3Determining the Necessity of Laboratory Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs

TRENDS IN DOG USE IN U.S. RESEARCH FACILITIES

Animals, including dogs, have been used in scientific demonstrations, teaching, and research since antiquity (Kinter and DeGeorge, 2016). Dog use increased dramatically in the late 19th and early 20th centuries, paralleling the development of increasingly sophisticated instrumentation for measuring physiological function, along with advances in analytic and organic chemistry that led to an explosion in the synthesis of small molecules requiring evaluation of their pharmacological properties¹ (Kinter and DeGeorge, 2016). These trends in molecule synthesis and animal use continued through the mid-20th century and were amplified by new considerations, including requirements for animal safety testing in order to obtain government approvals for clinical trials and marketing of regulated products and the growth and proliferation of international biomedical research stimulated by post–World War II industrial expansion. Several members of this committee recall the large number of sophisticated dog models that supported basic human and veterinary physiological research in the postwar decades, as well as dog bioassays for pharmacological and toxicological research and product discovery and development. The advent of new molecular techniques in the 1970s and 1980s likely played a role in replacing animal research models, particularly dogs. Data from U.S. Department of Agriculture (USDA) annual reports tracking dog use from 1973 to 2018 are illustrated in Figure 3_1. (See also Appendix B for further analysis of the USDA data.)

The specific factors leading to decreased dog use since the 1970s are uncertain but could include the advancement of molecular techniques, societal pressures and preferences, and the high cost of using dogs in biomedical research. It is also the case that while there has been a notable decrease in dog use since the 1970s, dog use in the past decade has been steady at around 60,000 dogs per year.

LABORATORY DOG USE IN BIOMEDICAL RESEARCH AT THE VA

The VA provided the committee with documentation from 44 research projects involving dogs conducted by its researchers over the past 50 years. Of these projects, 30 dated from the 1960s to 2017 and 14 were active in 2018–2019 (VA, 2018a,b). Among these studies, cardiovascular/renal was the most frequently cited application (17), followed by central nervous system (15), endocrine (4), respiratory (4), gastrointestinal (3), and animal/surgical models (4). Some VA projects covered more than one research area, hence the total number of areas exceeds the number of projects. One VA study, undertaken to test a treatment for a spontaneous melanoma that occurs in both dogs and humans, used companion rather than laboratory dogs (VA, 2018b). In research performed at or funded by the VA, 99 percent of animals used in 2017 were mice or rats, while fewer than 0.05 percent were dogs (VA ORD, 2018).

In the following three sections, the committee surveys the use of dogs in 10 biomedical research areas—CVD, SCI, imaging, diabetes, narcolepsy, chronic pain and OA, experimental pharmacology and toxicology, cancer, infectious disease, and Alzheimer's disease. The purpose of this overview is to establish a context for assessing both the current need for laboratory dogs in each of these fields and the likely need for dogs in future VA biomedical research. CVD, SCI, and imaging are the current areas of laboratory dog use at the VA. Diabetes, narcolepsy, chronic pain and OA, and experimental pharmacology and toxicology are areas in which dogs were recently used (since 2016), and the remaining three fields (cancer, infectious disease, and Alzheimer's disease) were chosen based on their potential for future use (primarily in companion dogs). As stated in the introduction to this chapter, the absence of a particular field of research should not be taken as a determination regarding the necessity of dog use in that field.

NEXT STEPS FOR THE USE OF LABORATORY DOGS IN BIOMEDICAL RESEARCH RELATED TO THE VA'S MISSION

Historically and across disease type, from the understanding and treatment of diabetes to the development of cardiac pacemakers and valve replacement, it would be challenging to find an area of biomedical research that has not benefitted from the involvement of laboratory dogs. The use of dogs in biomedical research peaked in the 1970s, with more than 200,000 dogs per year being used at USDA-regulated academic and industrial institutions. Since the 1970s, however, as molecular techniques and rodents have gained prominence, some biomedical research has moved away from using laboratory dogs. The focus has shifted toward a variety of alternatives, including rodents, pigs, companion dogs, and even sheep. Today, the majority of dog use in the United States is by companies and private research organizations engaging in applied biomedical research and product development, including testing that is required by regulatory agencies.

Nevertheless, a few areas remain in which laboratory dogs offer the potential for medically important discoveries that cannot currently be obtained elsewhere. These include subsets of CVD research, most notably cardiac rhythm disorders, that depend on anatomical and physiological features that humans share with dogs but not with other laboratory species or on the implantation of devices that rely on restricted growth in addition to some of these other features. They may also include a number of the complex treatments for SCI, particularly cervical injuries resulting in quadriplegia with its many systemic and life-altering effects, that cannot be modeled effectively in other animal or non-animal systems. Even in these limited fields, however, it will be crucial to remain vigilant for non-dog and non-animal alternatives and actively work to promote the development and use of alternatives, as described in Chapter 4.

Given the committee's inability to predict future biomedical research needs, it is not inconceivable that VA research in other fields may require use of laboratory dogs due to unique aspects of their physiology or behavior.

Conclusion 3-1: The laboratory dog is scientifically necessary for only a few areas of current U.S. Department of Veterans Affairs (VA) biomedical research. Based on the request from the VA to review areas of research from 2016 onward, the committee concludes that laboratory dogs currently remain scientifically necessary in these areas of active biomedical research at the VA:

• mechanistic insights of premature ventricular contraction-induced cardiomyopathy;
• autonomic nerve activity and cardiac arrhythmias;
• cardiovascular disease requiring functional modeling of the human Purkinje system; and
• development and testing of implantable devices to stimulate respiration and cough in spinal cord injury.

Laboratory dogs are no longer the preferred model for studies of diabetes or narcolepsy, for most imaging studies, or for primary pharmacological research. Responsibility lies with the principal investigator, scientific review committee, and institutional animal care and use committee to know the literature and accurately determine whether the laboratory dog is still the best model for any particular study.

Conclusion 3-2: A potential new approach or treatment may be developed that, for biological reasons, can only be tested in dogs. As yet unknown, new, or reemerging diseases or disorders may not be reproducible in non-dog models and could require the limited use of laboratory dogs to advance their prevention, treatment, or control. Conversely, alternatives may develop in the future that would make the laboratory dog unnecessary.

Conclusion 3-3: The U.S. Department of Veterans Affairs (VA) has an opportunity to expand the study of companion dogs in clinical trials. Companion dogs experience many of the same naturally occurring diseases as humans and stand to benefit from the results of the research in which they participate. Companion dogs are promising models for a range of disorders, including obesity, diabetes, infectious disease, Alzheimer's disease, osteoarthritis, hereditary glaucoma, cardiomyopathy, thoracic spinal cord injury, and cancer. While companion dog clinical trials can be challenging to conduct due, in part, to the financial and time costs of collecting an appropriate population of companion animals for a particular trial, these studies are possible and deserve priority consideration by VA researchers and leaders.

THE VA'S BIOMEDICAL RESEARCH REVIEW PROCESS

VA-funded biomedical research using laboratory dogs takes place either in VA medical centers or through partnerships with local academic centers (e.g., the St. Louis VA Medical Center no longer has an animal facility on the premises but partners with Washington University and St. Louis University to conduct animal research). VA funds support VA clinician–researchers, who initiate research projects based on the health care needs of veterans. Each laboratory dog research protocol undergoes several stages of VA review, as illustrated in Figure 3_2.

For VA-funded research, the investigator submits a proposal using the same technology infrastructure that is employed by NIH (Grants.gov, n.d.). The proposal is reviewed by a panel of experts who are recruited by the Office of Research and Development of the relevant VA service (primary review) and who score the proposal for scientific merit (see Figure 3_2, bottom left). Completed reviews are sent to the director of the service, who makes the final funding decision. Each facility then carries out a process of regulatory approval. This includes review by a local R&D committee and its subcommittees, which include the institutional animal care and use committee (IACUC) for animal research, the institutional review board for human research, and other committees, depending on the exact requirements of the study. For research with dogs, a secondary veterinary review is carried out by the Office of the Chief Veterinary Medical Officer. The Chief Research and Development Officer; the VA National Center for Ethics in Health Care; the Deputy Undersecretary for Discovery, Education, and Affiliate Networks; and the Undersecretary for Health also review the project before it is submitted to the Secretary of the VA for final approval before the work may begin. The secondary veterinary review was instituted in the 1970s for all VA-funded research involving animals and has been required for all proposed research involving dogs at the VA, regardless of funding source, since 2017 (VHA ORD, 2017). Only after all the regulatory requirements are met is the research permitted to begin. For canine research to be supported by non-VA sources, the same secondary review process applies, with the only difference being that the external funding source, and not the VA, is responsible for the primary review for scientific merit (Bever, 2019). Recent legislative developments related to oversight of VA biomedical research using laboratory dogs are discussed in Chapter 1 and later in this chapter.

OPERATIONALIZING “NECESSARY” AREAS OF AGREEMENT AND DISAGREEMENT WITHIN THE COMMITTEE

The committee offers the following recommendation for determining when it is scientifically necessary to use laboratory dogs in biomedical research funded by or conducted at the VA.

Recommendation 1: Adopt an expanded set of criteria for determining when it is scientifically necessary to use laboratory dogs in biomedical research funded by or conducted at the U.S. Department of Veterans Affairs (VA).

In order to conduct biomedical research that will lead to meaningful outcomes to support improved health of veterans, the VA should adopt an expanded set of criteria for determining if the use of laboratory dogs is scientifically necessary:⁴

1.

The scientific question and the knowledge anticipated will advance understanding or medical practices related to veterans' health;

2.

Based on unique physiological and other characteristics, there is no alternative to the laboratory dog that will yield scientifically valid results that meet proposed study objectives;

3.

The anticipated harms experienced by the laboratory dog are outweighed by the potential benefits for veterans; and

4.

Both the scientific review committee and institutional animal care and use committee have provided written statements attesting that the laboratory dog is the only species that can yield scientifically valid results.

After reaching agreement on Conclusion 3-1 and Recommendation 1, the committee found itself at an impasse. Ten committee members,⁵ a majority, believed that according to the Statement of Task, their job was not done and that a second recommendation linked to Recommendation 1 was warranted, while five committee members⁶ were equally convinced that this second recommendation would not be in keeping with the Statement of Task and thus should not be included in the report. The differing opinions of the two groups turn on the meaning of three specific sentences in the Statement of Task—and, in particular, on the meaning of one word that appears multiple times in those sentences.

The crucial word is “necessary,” and the portion of the Statement of Task that contains the three sentences reads as follows (with emphasis added):

Specifically, the committee will write a report to address the following:

1.

Explore recent past, current, and anticipated research questions directly related to the VA's mission to determine if dogs [rather than non-rodent (excluding non-human primates) or rodent species or non-animal alternatives] are or will continue to be necessary for relevant basic and translational research. The committee will:

a.

Make a determination as to whether dogs are or will continue to be necessary for any type of biomedical research directly related to the VA's mission. If it is determined that they are necessary, describe the unique physiological and other characteristics of dogs that currently make it the necessary animal model for use in these types of research.

In reading this portion of the Statement of Task, the majority and minority groups interpret the word “necessary” in different ways and, as a result, end up with differing opinions as to whether the report should include the recommendation in question. While there are other issues that the two groups do not agree on, the crux of their disagreement can be traced to that one word.

To understand the disagreement, some background is useful. Throughout the study process, the committee debated at great length how scientific, legal, ethical, and social considerations factor into the determination of the laboratory dog's necessity in VA biomedical research. In March 2018, prior to the VA's request that the National Academies of Sciences, Engineering, and Medicine undertake this study, the federal government enacted new restrictions on the VA's use of laboratory dogs, mandating that no federal funds “may be used to conduct research using canines unless: the scientific objectives of the study can only be met by research with canines.”⁷ Section 254 of the Consolidated Appropriations Act of 2018 further required the Secretary of the VA to “directly approve” any such studies, and to submit to the U.S. Congress within 180 days “a detailed report outlining under what circumstances canine research may be needed if there are no other alternatives.”⁸

In December 2019, as the committee neared the end of its deliberative process, the Further Consolidated Appropriations Act of 2020⁹ was enacted into law. This legislation reiterated the language from the 2018 Act and expanded it to include cats and non-human primates.¹⁰ The 2020 Act also added a new requirement that such scientific objectives must be “directly related to an illness or injury that is combat-related.”¹¹ Furthermore, the 2020 legislation now requires the Secretary of the VA to submit a report to the U.S. Congress for any such approved research “not later than 30 days before the commencement of such research.”¹² That report must describe the nature of the research and include “the justification for the determination of the Secretary that the scientific objectives of such research could only be met using canines, felines, or non-human primates.”¹³

In considering the Statement of Task in the context of this legislation, the members of the majority and minority disagreed about the scientific and ethical implications of this legislation and about its relevance to the committee's recommendations to the VA.

As noted, all members of the committee agreed on Recommendation 1, which addresses the Statement of Task—at least partially—by laying out a set of scientific criteria that provides the VA with a framework for deciding when it is scientifically necessary to use laboratory dogs in a proposed protocol. All of the committee members are satisfied that Recommendation 1 provides a framework for scientific grounds for determining whether the laboratory dog should be used. The issue that separates them is whether addressing the scientific grounds for using dogs in research is sufficient to satisfy the Statement of Task.

The five committee members in the minority assert that it is indeed sufficient, and they believe that the inquiry should end there. Referring to the definition of “necessary” from the Oxford English Dictionary—“required to be achieved” or “essential”—they assert that determining the use of dogs to be necessary in a line of VA research is equivalent to finding that the laboratory dog is the only animal model that can satisfy an important study objective. In short, they believe that the word “necessary” in the Statement of Task should be read as “scientifically necessary” and, in particular, that it was the VA's intention in its Statement of Task to ask only about scientific necessity. Thus, because Recommendation 1 addresses that aspect of the Statement of Task, the minority concludes that no further recommendations are necessary or warranted.

By contrast, the 10 committee members in the majority believe that the discussion of when the laboratory dog is “necessary” should not end with scientific or technical considerations related to the unique physiological and other characteristics of dogs and that parameters for guiding how and when to use laboratory dogs must include ethical, legal, and animal welfare concepts as well. In making this argument, they refer to another part of the Statement of Task, which specifically asks the committee to address other issues than the scientific ones:

1.

Identify ethical considerations, regulatory requirements, and currently accepted standards for the care, use and welfare of dogs in biomedical research, and make recommendations to enhance their well-being while achieving the research objectives.

If policy making on dog research is to be ethical, the ten members of the majority believe, a broader conceptualization of “necessary” than just “scientifically necessary” is required, and specifically they believe that if policy on dog research is to be ethical it must also take into consideration the implications for members of other species that might be substituted for dogs. In particular, the majority argues that while the Oxford English Dictionary provides a concise definition of “necessity,” that definition lacks sufficient conceptual or analytical clarity to guide action in this case. Instead they hold that the concept of “necessity” entails specifying at least two factors—the goals invoked and the conditions attached to such goals. The goal of the VA is to restore or improve the health and well-being of veterans, which is done in part by advancing scientific knowledge and the understanding of how diseases (e.g., SCI) affect veterans. Science is not the end goal, but rather science is the means of advancing the goals embedded in the mission of the VA. For research using laboratory dogs to be “necessary,” the research must not only advance a set of goals but do so under a set of conditions that include factors like time efficiency, law, and ethics. As described in Chapter 2, any policy that restricts research on dogs may transfer the burden of that research to other large animal models (e.g., pigs and sheep), and the alternative species could potentially experience greater harm than laboratory dogs, a scenario that could be considered unethical by some and a violation of the Three Rs—a set of well-established ethical principles that have also been embedded in many regulatory documents guiding the ethical use of animals in research.

The 10 committee members contend that there are no clear moral grounds for arguing that dogs have a “higher” moral status than other large animal species like pigs. Societal preferences, without additional ethical principles, do not confer greater moral value. Therefore, a rule that requires that scientists be more permissive about research on pigs than dogs or similar large animal species is not ethical. What matters most in selecting a particular species, from an ethical standpoint, is that (1) the biological characteristics of the non-human animal indicate that it will provide valuable knowledge in the context of the proposed research, and (2) the harm experienced by the animals is minimized. Some animal research protocols may be less harmful when conducted in dogs than in other species like pigs. Others might be the reverse. The majority of the committee believes these ethical considerations regarding minimizing the harm experienced by animals are part of evaluating scientific necessity.

In support of this contention the majority point to the 2011 Institute of Medicine report on chimpanzees, where the committee found itself in a similar position and took a very similar step. In particular, that committee wrote:

Neither the cost of using chimpanzees in research nor the ethical implications of that use were specifically in the committee's charge. Rather, the committee was asked for its advice on the scientific necessity of the chimpanzee model for biomedical and behavioral research. The committee agrees that cost should not be a consideration. However, the committee feels strongly that any assessment of the necessity for using chimpanzees as an animal model in research raises ethical issues, and any analysis of necessity must take these ethical issues into account. (IOM, 2011, p. 2)

The committee majority also point to similar ethical considerations being described in the Guide for the Care and Use of Laboratory Animals (the Guide) (NRC, 2011), which is an internationally accepted primary reference on animal care and use whose use is required in the United States by the U.S. Public Health Service (PHS) Policy. Many institutions, including the VA, are legally obligated to follow PHS Policy and therefore the recommendations in the Guide.

In light of such ethical considerations, the majority believes that where multiple species, including the laboratory dog, can be adequately used to answer the scientific question, the species that will incur the fewest burdens should be selected and that such considerations must play a role in determining when a proposed protocol is “necessary.”

The committee majority recognizes that this ethical consideration may at times be in conflict with the current law. Specifically, if the dog is the non-primate laboratory species that would incur the fewest burdens in a proposed protocol, ethical considerations would require its use, but that would be prohibited by law. In this case—or in any situation where the animal that would incur the fewest burdens cannot be selected, because of legal or funding restrictions or any other reason—the majority believes that the VA cannot ethically proceed and should consider forgoing the research. In some situations, this limitation might encourage researchers to find an alternative method or combination of methods that would accomplish the goals of the study and reduce harms to an acceptable level. It may require that the research be done by a different entity. It is also possible that if the current legal restrictions on the VA's dog research program are deemed to be hampering the advancement of science, research, and treatments for veterans, lawmakers will choose to remove or alter the current legal restrictions.

With this rationale the 10 committee members in the majority offer the following recommendation:

Recommendation 2: Adopt an expanded set of criteria for determining when to use laboratory dogs in U.S. Department of Veterans Affairs' (VA's) biomedical research when the dog is not scientifically necessary.^14,15

In order to conduct biomedical research that will lead to meaningful outcomes to support improved health of veterans, the following criteria should be met before approving the use of laboratory dogs when other animal models are also scientifically appropriate:

1.

The scientific question and the knowledge expected to be gained will advance understanding or medical practices related to veterans' health;

2.

The research objective cannot be adequately addressed using new approach methodologies or ethically using human subjects or companion animals;

3.

Where multiple species [excluding non-human primates],¹⁶ including the laboratory dog, can be used to adequately answer the scientific question, the non-primate species that will incur the fewest burdens should be selected. If the species that will incur the fewest burdens cannot be selected for any reason, including legal and/or funding restrictions (e.g., the laboratory dog), the VA cannot ethically proceed and should consider forgoing the research; and

4.

The expected harms experienced by the selected animals are sufficiently outweighed by the expected benefits for veterans. Both the institutional animal care and use committee and the VA's central office ethics review should concur in this assessment.

The five member committee minority dissents from this recommendation because they believe the recommendation strays beyond the Statement of Task. Where the majority grounds its arguments for the recommendations in ethical considerations, the minority points to the ethical, legal, regulatory, and institutional context in which the Statement of Task was prepared and argues that the VA clearly intended the committee to address only the scientific necessity of using dogs in research and that ethics-based recommendations are outside the scope of what the committee was asked to do.

To support its position, the minority offers several observations. First, turning to the Statement of Task, the minority points to the sentence “If it is determined that they [dogs] are necessary, describe the unique physiological and other characteristics of dogs that currently make it the necessary animal model for use in these types of research.” The implicit message in this sentence, the minority argue, is that the VA wanted the committee to focus on objective scientific criteria, such as physiological characteristics, in the determination of whether dogs are necessary in particular research projects. A second sentence in the Statement of Task asks the committee to “Provide recommendations for any new or revised scientific parameters to guide how and when to use dogs for biomedical research rather than non-rodent (excluding non-human primates) or rodent species or non-animal alternatives.” Again, only scientific parameters, not ethical ones, are mentioned. Thus, the minority believes that the VA's intention in its Statement of Task was that the committee address only the scientific necessity of using dogs in research. The minority also believes that the ethical considersations (#2 in the Statement of Task) were specific to the dog (rather than to a comparative ethical analysis).

More broadly, the minority contends that Recommendation 2 is in conflict with both existing VA policy and existing federal legislation. For example, during the public meeting held in Washington, DC, on February 14, 2019, the VA representative confirmed that the definition of “necessary” used by the VA holds that the VA should only continue using dogs in biomedical research when there is no other alternative that will yield scientifically valid results that meet proposed study objectives of importance to veterans (i.e., the definition it uses of “necessary” is essentially “scientifically necessary”). Furthermore, the federal appropriations legislation that places restrictions on the use of dogs in VA-funded research uses the same definition of necessity. Beyond that Recommendation 2 contradicts accepted policies of various other federal agencies, such as NIH, many of which treat some animals, such as the chimpanzee, differently from others, and the Animal Welfare Act privileges any “dog, cat, monkey (nonhuman primate mammal), guinea pig, hamster, rabbit, or such other warm-blooded animal” over every other type of sentient species, including rats and mice, birds used for research, and farmed animals, such as horses, livestock, and poultry.¹⁷

Thus, the minority members believe that while it is certainly important to grapple with the broad ethical issues surrounding animal research, this report is not the proper venue, as it was intended to address scientific questions and ethical and regulatory positions taken by the VA and the federal government specific to the laboratory dog. Furthermore, the minority contends that if a full ethical analysis of using various species of animals in biomedical research were to be undertaken, it would require a deeper analysis than this committee was equipped to perform and likely would require convening a committee that was not composed predominantly of scientists. If the dissenting minority believed a comparative ethical analysis had been requested in the Statement of Task, the minority would have proposed the use of a broader ethical framework that acknowledges the rapid changes in science (e.g., the sophistication of non-animal models), is inclusive of societal values (particularly when the research is publicly funded), is ethically defensible, and is ultimately useful to researchers.¹⁸ Regardless, the minority members still conclude that such comparative ethical questions remain outside the scope of the committee's Statement of Task. For these reasons they dissent from Recommendation 2.

To sum up, the disagreement between the majority and minority over Recommendation 2 is essentially a disagreement about whether that recommendation comports with the Statement of Task. The majority, taking a broad view of the meaning of “necessary,” believes it does. The minority, holding a more restricted view of the meaning of “necessary,” believes it does not. The practical effect of that definitional disagreement is that the majority believes that the interests of other laboratory animals than the dog must be taken into consideration when determining the necessity of research on laboratory dogs, while the minority believes that the question the committee was asked dealt not with other research animals but only with laboratory dogs.

OPPORTUNITIES TO IMPROVE BIOMEDICAL RESEARCH PROTOCOLS AND REVIEW PROCESSES AT THE VA

The committee is concerned that the current culture of justifying biomedical research in laboratory dogs favors the continued use of dogs, given that the previous experience of principal investigators and technical support staff, along with the availability of extensive historical data for dogs, are sometimes the sole justifications provided for the continued use of laboratory dogs in research. The current system has considerable momentum around scientific review committee and IACUC acceptance of the principal investigator's judgment regarding whether laboratory dogs are necessary. In the experience of some committee members, in general, if an investigator states that the harm to laboratory dogs used in a particular study would be less than the harm incurred by pigs or sheep because more pigs or sheep would be required to build the knowledge base to a level comparable to dogs, it is possible that scientific review committees and IACUCs will accept that logic. Perpetuating this reasoning favors the continued use of laboratory dogs in biomedical research, at the VA and elsewhere.

The committee could not fully evaluate or understand the institutional momentum at the VA for or against this reasoning for the continued use of laboratory dogs. Rather, this concern is based on review of ACORPs and the opinion and experience of some on the committee. The VA Chief Research and Development Officer, Rachel Ramoni, told the committee that the VA was committed to moving away from sensitive species, including dogs, even if that meant an additional investment of time and money (Ramoni, 2019). Indeed, the committee learned that a pilot study in pigs was under way at a VA center to potentially replace the use of laboratory dogs. Also during the course of this study, several VA protocols planned in laboratory dogs were switched to mice, pigs, or humans.

Justifying the use of laboratory dogs at the VA today requires significant paperwork and sign-offs but, in the committee's judgment, does not always require a thorough examination of alternatives nor an accurate accounting of harm and burden to study animals. For example, evidence from the ACORPs reviewed by the committee suggests that literature searches for relevant alternatives are of poor quality and seem to be primarily box-checking exercises (i.e., the decision to use laboratory dogs having been made prior to the literature search for alternatives). Also, some ACORPs lacked a written descripton of the perceived harm to laboratory dogs. A few ACORPs also seemed to misapply the Three Rs by prioritizing reduction in the number of dogs used over refinement.

REFERENCES

NOTE: An asterisk before the first author's name denotes that the publication was based on research conducted at or funded by the VA. For such references, details about the VA connection are appended after the reference.

• ACF (Animal Cancer Foundation). Home page. n.d. [March 2, 2020]. http://acfoundation​.org.
• Adin CA, Gilor C. The diabetic dog as a translational model for human islet transplantation. Yale Journal of Biology and Medicine. 2017;90(3):509–515. [PMC free article: PMC5612193] [PubMed: 28955189]
• Aguilar M, Qi XY, Huang H, Comtois P, Nattel S. Fibroblast electrical remodeling in heart failure and potential effects on atrial fibrillation. Biophysical Journal. 2014;107(10):2444–2455. [PMC free article: PMC4241450] [PubMed: 25418313]
• Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, Gillis AM, Granger CB, Hammill SC, Hlatky MA, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology. 2018;72(14):1677–1749. [PubMed: 29097294]
• Alilain WJ. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Workshop on the Uses of Dogs in Biomedical Research, March 27. Washington, DC: 2019.
• Allen AR. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column: A preliminary report. JAMA. 1911;57:878–880.
• Alzheimer's Association. Alzheimer's disease facts and figures. Alzheimer's & Dementia. 2019;15(3):321–387.
• Anderson JA, Kimmelman J. Should preclinical studies be registered? Nature Biotechnology. 2012;30(6):488–489. [PMC free article: PMC4516408] [PubMed: 22678379]
• Andics A, Miklosi A. Neural processes of vocal social perception: Dog-human comparative fMRI studies. Neuroscience and Biobehavioral Reviews. 2018;85:54–64. [PubMed: 29287629]
• Antz M, Scherlag BJ, Otomo K, Pitha J, Tondo C, Patterson E, Jackman WM, Lazzara R. Evidence for multiple atrio-AV nodal inputs in the normal dog heart. Journal of Cardiovascular Electrophysiology. 1998;9(4):395–408. [PubMed: 9581955]
• *Antz M, Otomo K, Nakagawa H, Yamanashi WS, Jackman WM, Kuck KH. Radiofrequency catheter ablation with the split-tip electrode in the temperature-controlled mode. Pacing and Clinical Electrophysiology. 2001;24(12):1765–1773. [This study included research performed at the VA Health Care System in Oklahoma City, OK.] [PubMed: 11817810]
• Ardell JL, Cardinal R, Beaumont E, Vermeulen M, Smith FM, Armour JA. Chronic spinal cord stimulation modifies intrinsic cardiac synaptic efficacy in the suppression of atrial fibrillation. Autonomic Neuroscience: Basic and Clinical. 2014;186:38–44. [PMC free article: PMC4607028] [PubMed: 25301713]
• Assari S. Veterans and risk of heart disease in the United States: A cohort with 20 years of follow up. International Journal of Preventive Medicine. 2014;5(6):703–709. [PMC free article: PMC4085922] [PubMed: 25013689]
• *Auerbach O, Hammond EC, Kirman D, Garfinkel L. Emphysema produced in dogs by cigarette smoking. JAMA. 1967;199(4):241–246. [Two of the authors conducted their research at the VA Medical Center in East Orange, NJ.] [PubMed: 6071181]
• *Avasthi PS, Greene ER, Voyles WF, Eldridge MW. A comparison of echo-doppler and electromagnetic renal blood flow measurements. Journal of Ultrasound in Medicine. 1984;3(5):213–218. [The first author was affiliated with the Raymond G. Murphy VA Medical Center in Albuquerque, NM.] [PubMed: 6233429]
• Babatunde OO, Jordan L, Van der Windt DA, Hill JC, Foster E, Protheroe J. PLOS ONE 12. 6. 2017. Effective treatment options for musculoskeletal pain in primary care: A systematic overview of current evidence; p. e0178621. [PMC free article: PMC5480856] [PubMed: 28640822]
• Babic RR, Stankovic Babic G, Babic SR, Babic NR. 120 years since the discovery of x-rays. Medicinski Pregled. 2016;69(9-10):323–330. [PubMed: 29693857]
• Baburin I, Varkevisser R, Schramm A, Saxena P, Beyl S, Szkokan P, Linder T, Stary-Weinzinger A, van der Heyden MAG, Houtman M, Takanari H, Jonsson M, Beekman JHD, Hamburger M, Vos MA, Hering S. Dehydroevodiamine and hortiamine, alkaloids from the traditional Chinese herbal drug Evodia rutaecarpa, are IKr blockers with proarrhythmic effects in vitro and in vivo. Pharmacological Research. 2018;131:150–163. [PubMed: 29477480]
• Baimel C, Bartlett SE, Chiou L-C, Lawrence AJ, Muschamp JW, Patkar O, Tung L-W, Borgland SL. Orexin/hypocretin role in reward: Implications for opioid and other addictions. British Journal of Pharmacology. 2015;172:334–348. [PMC free article: PMC4292951] [PubMed: 24641197]
• Baker TL, Foutz AS, McNerney V, Mitler MM, Dement WC. Canine model of narcolepsy: Genetic and developmental determinants. Experimental Neurology. 1982;75(3):729–742. [PubMed: 7199479]
• Barger AC. New technology for a new century: Walter B. Cannon and the invisible rays. American Journal of Roentgenology. 1981;136(1):187–195. [PubMed: 6779567]
• Barker PB, Blackband SJ, Chatham JC, Soher BJ, Samphilipo MA, Magee CA, Hilton JD, Strandberg JD, Anderson JH. Quantitative proton spectroscopy and histology of a canine brain tumor model. Magnetic Resonance in Medicine. 1993;30(4):458–464. [PubMed: 8255193]
• Bastijanic JM, Etscheidt J, Sattiraju M, Bonsignore C, Kopchok G, White R, Sarac TP. Fatigue and in vivo validation of a peritoneum-lined self-expanding nitinol stent-graft. Journal of Endovascular Therapy. 2014;21(5):735–746. [PMC free article: PMC5621711] [PubMed: 25290804]
• Baumeister RG, Mayo W, Notohamiprodjo M, Wallmichrath J, Springer S, Frick A. Microsurgical lymphatic vessel transplantation. Journal of Reconstructive Microsurgery. 2016;32(1):34–41. [PubMed: 26165882]
• Bekiari E, Kitsios K, Thabit H, Tauschmann M, Athanasiadou E, Karagiannis T, Haidich A-B, Hovorka R, Tsapas A. Artificial pancreas treatment for outpatients with type 1 diabetes: Systematic review and meta-analysis. BMJ (Clinical Research Edition). 2018;361:k1310. [PMC free article: PMC5902803] [PubMed: 29669716]
• Benavides FD, Santamaria AJ, Bodoukhin N, Guada LG, Solano JP, Guest JD. Characterization of motor and somatosensory evoked potentials in the Yucatan micropig using transcranial and epidural stimulation. Journal of Neurotrauma. 2017;34(18):2595–2608. [PubMed: 27251314]
• *Benthem L, Mundinger TO, Taborsky GJ Jr. Parasympathetic inhibition of sympathetic neural activity to the pancreas. American Journal of Physiology: Endocrinology and Metabolism. 2001;280(2):E378–E381. [VA research was conducted at the VA Puget Sound Health Care System in Seattle, WA.] [PubMed: 11158944]
• Bernstein SA. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Workshop on the Uses of Dogs in Biomedical Research, March 27. Washington, DC: 2019.
• Bert B, Heinl C, Chmielewska J, Schwarz F, Grune B, Hensel A, Greiner M, Schönfelder G. Refining animal research: The Animal Study Registry. PLOS Biology. 2019;17(10):e3000463. [PMC free article: PMC6793840] [PubMed: 31613875]
• Betton GR, Owen LN. Allogeneic grafts of spontaneous canine melanomas and their cell culture strains in neonatal immunosuppressed dogs. British Journal of Cancer. 1976;34(4):374–380. [PMC free article: PMC2025258] [PubMed: 974003]
• Bever C. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs meeting open session, March 28. Washington, DC: 2019.
• Billman GE. Cardiac autonomic neural remodeling and susceptibility to sudden cardiac death: Effect of endurance exercise training. American Journal of Physiology: Heart and Circulatory Physiology. 2009;297(4):H1171–H1193. [PubMed: 19684184]
• Bloom F, Paff GH, Noback CR. The transmissible venereal tumor of the dog: Studies indicating that the tumor cells are mature end cells of reticulo-endothelial origin. American Journal of Pathology. 1951;27(1):119–139. [PMC free article: PMC1937229] [PubMed: 14799618]
• *Boehmer LN, Wu M-F, John J, Siegel LM. Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity. Experimental Neurology. 2004;188:292–299. [Research was conducted at the VA Greater Los Angeles Healthcare System.] [PMC free article: PMC8788643] [PubMed: 15246829]
• Boggiatto PM, Ramer-Tait AE, Metz K, Kramer EE, Gibson-Corley K, Mullin K, Hostetter JM, Gallup JM, Jones DE, Petersen CA. Immunologic indicators of clinical progression during canine Leishmania infantum infection. Clinical and Vaccine Immunology. 2010;17(2):267–273. [PMC free article: PMC2815526] [PubMed: 20032217]
• Bonilla IM, Nishijima Y, Vargas-Pinto P, Baine SH, Sridhar A, Li C, Billman GE, Carnes CA. Chronic omega-3 polyunsaturated fatty acid treatment variably affects cellular repolarization in a healed post-MI arrhythmia model. Frontiers in Physiology. 2016;7:225. [PMC free article: PMC4906012] [PubMed: 27378936]
• Bosch F, Rosich L. The contributions of Paul Ehrlich to pharmacology: A tribute on the occasion of the centenary of his Nobel Prize. Pharmacology. 2008;82(3):171–179. [PMC free article: PMC2790789] [PubMed: 18679046]
• Boulay E, Abernathy MM, Chui R, Friedrichs GS, Gendron-Parra N, Greiter-Wilke A, Guillon JM, Koerner JE, Menard A, Steidl-Nichols J, Pierson J, Pugsley MK, Rossman EI, Strauss D, Troncy E, Valentin JP, Wisialowski T, Authier S. A proof-of-concept evaluation of JTPc and Tp-Tec as proarrhythmia biomarkers in preclinical species: A retrospective analysis by an HESI-sponsored consortium. International Journal of Toxicology. 2019;38(1):23–32. [PubMed: 30567462]
• *Bresler L, Walter JS, Jahoda A, Wheeler JS, Turk T, Wurster RD. Effective methods of pelvic plexus nerve and bladder stimulation in anesthetized animal model. Journal of Rehabilitation Research and Development. 2008;45:627–638. [VA research was performed at the Edward J. Hines Jr. VA Hospital in Hines, IL.] [PubMed: 18712648]
• Brodala N, Merricks EP, Bellinger DA, Damrongsri D, Offenbacher S, Beck J, Madianos P, Sotres D, Chang YL, Koch G, Nichols TC. Porphyromonas gingivalis bacteremia induces coronary and aortic atherosclerosis in normocholesterolemic and hypercholesterolemic pigs. Arteriosclerosis Thrombosis and Vascular Biology. 2005;25:1446–1451. [PubMed: 15845905]
• Brooks OW, King RM, Nossek E, Marosfoi M, Caroff J, Chueh JY, Puri AS, Gounis MJ. A canine model of mechanical thrombectomy in stroke. Journal of Neurointerventional Surgery. 2019;1(12):1243–1248. [PubMed: 31103992]
• Brott DA, Diamond M, Campbell P, Zuvich A, Cheatham L, Bentley P, Gorko MA, Fikes J, Saye J. An acute rat in vivo screening model to predict compounds that alter blood glucose and/or insulin regulation. Journal of Pharmacological and Toxicological Methods. 2013;68(2):190–196. [PubMed: 23835094]
• Brown DC, Agnello K. Intrathecal substance P-saporin in the dog: Efficacy in bone cancer pain. Anesthesiology. 2013;119(5):1178–1185. [PMC free article: PMC3868346] [PubMed: 24195949]
• Bruce CJ, Stanton CM, Asirvatham SJ, Danielsen AJ, Johnson SB, Packer DL, Friedman PA. Percutaneous epicardial left atrial appendage closure: Intermediate-term results. Journal of Cardiovascular Electrophysiology. 2011;22(1):64–70. [PubMed: 20662983]
• Bryant RM. How implantable cardioverter-defibrillators work and simple programming. Cardiology in the Young. 2017;27(S1):S121–S125. [PubMed: 28084970]
• Burkhart F. The New York Times, January 16. 1997. [September 19, 2019]. Oscar Auerbach, 92, dies; linked smoking to cancer. https://www​.nytimes.com​/1997/01/16/nyregion​/oscar-auerbach-92-dies-linked-smoking-to-cancer.html.
• Cai SV, Famula TR, Oberbauer AM, Hess RS. Heritability and complex segregation analysis of diabetes mellitus in American Eskimo dogs. Journal of Veterinary Internal Medicine. 2019;33(5):1926–1934. [PMC free article: PMC6766479] [PubMed: 31318104]
• Camacho P, Fan H, Liu Z, He JQ. Large mammalian animal models of heart disease. Journal of Cardiovascular Development and Diseases. 2016;3(4):30. [PMC free article: PMC5715721] [PubMed: 29367573]
• Carabello BA, Zile MR, Tanaka R, Cooper G 4th. Left ventricular hypertrophy due to volume overload versus pressure overload. Amerian Journal of Physiology. 1992;263(4 Pt 2):H1137–H1144. [PubMed: 1415762]
• Carapeba GO, Cavaleti P, Nicácio GM, Brinholi RB, Giuffrida R, Cassu RN. Intra-articular hyaluronic acid compared to traditional conservative treatment in dogs with osteoarthritis associated with hip dysplasia. Evidence-Based Complementary and Alternative Medicine. 2016;2016:2076921. [PMC free article: PMC5101385] [PubMed: 27847523]
• Casas CE, Guest JD. Percutaneous endoscopic cellular transplantation into the lower lumbar spinal cord. Neurosurgery. 2004;54(4):950–955. discussion 955. [PubMed: 15046663]
• CCOGC (Canine Comparative Oncology & Genomics Consortium). Home page. 2020. [March 2, 2020]. https://ccogc​.net.
• CDC (Centers for Disease Control and Prevention). National diabetes statistics report, 2020. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services; 2020. [March 6, 2020]. https://www​.cdc.gov/diabetes​/pdfs/data/statistics​/national-diabetes-statistics-report.pdf.
• Chapagain D, Range F, Huber L, Virányi Z. Cognitive aging in dogs. Gerontology. 2018;64(2):165–171. [PMC free article: PMC5841136] [PubMed: 29065419]
• Chardack WM. Heart block treated with an implantable pacemaker: Past experience and current developments. Progress in Cardiovascular Disease. 1964;6:507–537. [PubMed: 14171950]
• *Chardack WM, Gage AA, Greatbatch W. A transistorized, self-contained, implantable pacemaker for the long-term correction of complete heart block. Surgery. 1960;48:643–654. [Research was conducted at the VA Medical Center in Buffalo, NY.] [PubMed: 13692461]
• Chardack WM, Gage AA, Greatbatch W. Treatment of complete heart block with an implantable and self-contained pacemaker Bulletin de la Société Internationale Chirurgie. 1962;21:411–432. [PubMed: 14020217]
• Chardack WM, Gage AA, Schimert G, Thomson NB, Sanford CE, Greatbatch W. Two years' clinical experience with the implantable pacemaker for complete heart block. Diseases of the Chest. 1963;43:225–239. [PubMed: 14020218]
• Chatal JF, Rouzet F, Haddad F, Bourdeau C, Mathieu C, Le Guludec D. Story of rubidium-82 and advantages for myocardial perfusion PET imaging. Frontiers in Medicine (Lausanne). 2015;2:65. [PMC free article: PMC4566054] [PubMed: 26442267]
• Chen M, Zhou X, Yu L, Liu Q, Sheng X, Wang Z, Wang S, Jiang H, Zhou S. Low-level vagus nerve stimulation attenuates myocardial ischemic reperfusion injury by antioxidative stress and antiapoptosis reactions in canines. Journal of Cardiovascular Electrophysiology. 2016;27(2):224–231. [PubMed: 26546374]
• Chen SL, Zhang YJ, Zhou L, Xie DJ, Zhang FF, Jia HB, Wong SS, Kwan TW. Percutaneous pulmonary artery denervation completely abolishes experimental pulmonary arterial hypertension in vivo. EuroIntervention. 2013;9(2):269–276. [PubMed: 23466961]
• Cheriyan T, Ryan DJ, Weinreb JH, Cheriyan J, Paul JC, Lafage V, Kirsch T, Errico TJ. Spinal cord injury models: A review. Spinal Cord. 2014;52:588–595. [PubMed: 24912546]
• Chinda K, Tsai WC, Chan YH, Lin AY, Patel J, Zhao Y, Tan AY, Shen MJ, Lin H, Shen C, Chattipakorn N, Rubart-von der Lohe M, Chen LS, Fishbein MC, Lin SF, Chen Z, Chen PS. Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs. Heart Rhythm. 2016;13(3):771–780. [PMC free article: PMC4762711] [PubMed: 26607063]
• Cho H, Nango M, Sakai Y, Sohgawa E, Kageyama K, Hamamoto S, Kitayama T, Yamamoto A, Miki Y. Neointimal hyperplasia after stent placement across size-discrepant vessels in an animal study. Japanese Journal of Radiology. 2014;32(6):340–346. [PubMed: 24715330]
• Chueh J. Experimental models of vascular occlusions for evaluation of thrombectomy devices. Cardiovascular Engineering and Technology. 2013;4(4):309–322.
• Cimino Brown D. What can we learn from osteoarthritis pain in companion animals? Clinical and Experimental Rheumatology 35 Suppl. 2017;107(5):53–58. [PubMed: 28967360]
• Clarke SA, Goodman NC, Ailawadi G, Holmes JW. Effect of scar compaction on the therapeutic efficacy of anisotropic reinforcement following myocardial infarction in the dog. Journal of Cardiovascular Translational Research. 2015;8(6):353–361. [PMC free article: PMC4527936] [PubMed: 26077797]
• Clauss S, Bleyer C, Schüttler D, Tomsits P, Renner S, Klymiuk N, Wakili R, Massberg S, Wolf E, Kääb S. Animal models of arrhythmia: Classic electrophysiology to genetically modified large animals. Nature Reviews Cardiology. 2019;16(8):457–475. [PubMed: 30894679]
• COHA (Clinical and Translational Science Award One Health Alliance). Home page. 2020. [February 26, 2020]. https:​//ctsaonehealthalliance.org.
• Conn HL Jr, Detweiler DK, McGiff J, Luchi RJ. Why we have gone to the dogs. Transactions of the American Clinical and Climatological Association. 1966;77:34–47. [PMC free article: PMC2441100] [PubMed: 5894832]
• Cotman CW, Head E. The canine model of human aging and disease. Advances in Alzheimer's Disease. 2011;1:15–38.
• Danek M, Danek J, Araszkiewicz A. Large animals as potential models of human mental and behavioral disorders. Psychiatria Polska. 2017;51(6):1009–1027. [PubMed: 29432500]
• De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, Kotzin S, Laine C, Marusic A, Overbeke AJPM, Schroeder TV, Sox HC, Van Der Weyden MB. Clinical trial registration: A statement from the International Committee of Medical Journal Editors. Canadian Medical Association Journal. 2004;171(6):606–607. [PMC free article: PMC516198] [PubMed: 15367465]
• del Rio CL, Clymer BD, Billman GE. Myocardial electrotonic response to submaximal exercise in dogs with healed myocardial infarctions: evidence for beta-adrenoceptor mediated enhanced coupling during exercise testing. Frontiers in Physiology. 2015;6:25. [PMC free article: PMC4318283] [PubMed: 25698976]
• DiMarco AF, Kowalski KE. High-frequency spinal cord stimulation in a subacute animal model of spinal cord injury. Journal of Applied Physiology. 1985;127(1):98–102. [PMC free article: PMC6692743] [PubMed: 31095462]
• DiMarco AF, Geertman RT, Tabbaa K, Kowalski KE. Complete restoration of respiratory muscle function in three subjects with spinal cord injury: Pilot interventional clinical trial. American Journal of Physical Medicine and Rehabilitation. 2019a;98(1):43–50. [PMC free article: PMC8883340] [PubMed: 30119089]
• DiMarco AF, Geertman RT, Tabbaa K, Nemunaitis GA, Kowalski KE. Restoration of cough via spinal cord stimulation improves pulmonary function in tetraplegics. Journal of Spinal Cord Medicine. 2019b;6:1–7. [PMC free article: PMC7534376] [PubMed: 31809251]
• Dixon JA, Spinale FG. Large animal models of heart failure: A critical link in the translation of basic science to clinical practice. Circulation: Heart Failure. 2009;2(3):262–271. [PMC free article: PMC2762217] [PubMed: 19808348]
• Efimov I. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs meeting open session, March 28. Washington, DC: 2019.
• Eisenbrey JR, Sridharan A, Liu J-B, Forsberg F. Recent experiences and advances in contrast-enhanced subharmonic ultrasound. BioMed Research International. 2015;2015:640397. [PMC free article: PMC4450275] [PubMed: 26090430]
• Eknoyan G, Nagy J. A history of diabetes mellitus, or how a disease of the kidneys evolved into a kidney disease. Advances in Chronic Kidney Disease. 2005;12:223–229. [PubMed: 15822058]
• Estrada JA, Williams AG Jr, Sun J, Gonzalez L, Downey HF, Caffrey JL, Mallet RT. δ-opioid receptor (DOR) signaling and reactive oxygen species (ROS) mediate intermittent hypoxia induced protection of canine myocardium. Basic Research in Cardiology. 2016;111(2):17. [PubMed: 26879900]
• Fan L, Mao C, Hu X, Zhang S, Yang Z, Hu Z, Sun H, Fan Y, Dong Y, Yang Shi J, Xu Y. New insights into the pathogenesis of Alzheimer's disease. Frontiers in Neurology. 2020;10:1312. [PMC free article: PMC6965067] [PubMed: 31998208]
• FDA (U.S. Food and Drug Administration). FDA approves first automated insulin delivery device for type 1 diabetes. 2016. [March 4, 2020]. https://www​.fda.gov/news-events​/press-announcements​/fda-approves-first-automated-insulin-delivery-device-type-1-diabetes.
• Floyd CL. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs meeting open session, March 28. Washington, DC: 2019.
• Foutz A, Mitler M, Cavalli-Sforza L, Dement WC. Genetic factors in canine narcolepsy. Sleep. 1979;1(4):413–421. [PubMed: 574310]
• Frampton D, Schwenzer H, Marino G, Butcher LM, Pollara G, Kriston-Vizi J, Venturini C, Austin R, de Castro KF, Ketteler R, Chain B, Goldstein RA, Weiss RA, Beck S, Fassati A. Molecular signatures of regression of the canine transmissible venereal tumor. Cancer Cell. 2018;33(4):620–633. [PMC free article: PMC5896242] [PubMed: 29634949]
• Friedli L, Rosenzweig ES, Barraud Q, Schubert M, Dominici N, Awai L, Nielson JL, Musienko P, Nout-Lomas Y, Zhong H, Zdunowski S, Roy RR, Strand SC, van den Brand R, Havton LA, Beattie MS, Bresnahan JC, Bézard E, Bloch J, Edgerton VR, Ferguson AR, Curt A, Tuszynski MH, Courtine G. Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates. Science Translational Medicine. 2015;7(302):302ra134. [PMC free article: PMC5669362] [PubMed: 26311729]
• Fumoto H, Gillinov AM, Saraiva RM, Horai T, Anzai T, Takaseya T, Shiose A, Arakawa Y, Vince DG, Dessoffy R, Fukamachi K. Left atrial appendage occlusion: Pilot study of a fourth-generation, minimally invasive device. Innovations (Phila). 2012;7(3):195–200. [PubMed: 22885461]
• Gabel BC, Curtis EI, Marsala M, Ciacci JD. A review of stem cell therapy for spinal cord injury: Large animal models and the frontier in humans. World Neurosurgery. 2017;98:438–443. [PubMed: 27876663]
• *Ganey T, Libera J, Moos V, Alasevic O, Fritsch K-G, Meisel HJ, Hutton WC. Disc chondrocyte transplantation in a canine model: A treatment for degenerated or damaged intervertebral disc. Spine. 2003;28(23):2609–2620. [VA research was conducted at the Atlanta VA Medical Center in Atlanta, GA.] [PubMed: 14652478]
• *Gasser TC, Graversen PH, Madsen PO. Fleroxacin (Ro 23-6240) distribution in canine prostatic tissue and fluids. Antimicrobial Agents and Chemotherapy. 1987;31(7):1010–1013. [VA research for this project was conducted at the William S. Middleton Memorial Veterans Hospital in Madison, WI.] [PMC free article: PMC174862] [PubMed: 3116916]
• Gerstenfeld EP, Lavi N, Bazan V, Gojraty S, Kim SJ, Michele J. Mechanism of complex fractionated electrograms recorded during atrial fibrillation in a canine model. Pacing and Clinical Electrophysiology. 2011;34(7):844–857. [PubMed: 21418250]
• Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on experimental hypertension: I. The production of persistent elevation of systolic blood pressure by means of renal ischemia. Journal of Experimental Medicine. 1934;59(3):347–379. [PMC free article: PMC2132360] [PubMed: 19870251]
• González-Martínez Á, Rosado B, Pesini P, Suárez ML, Santamarina G, García-Belenguer S, Villegas A, Monleón I, Sarasa M. Plasma β-amyloid peptides in canine aging and cognitive dysfunction as a model of Alzheimer's disease. Experimental Gerontology. 2011;46(7):590–596. [PubMed: 21377518]
• Gordon I, Paoloni M, Mazcko C, Khanna C. The Comparative Oncology Trials Consortium: Using spontaneously occurring cancers in dogs to inform the cancer drug development pathway. PLOS Medicine. 2009;6(10):e1000161. [PMC free article: PMC2753665] [PubMed: 19823573]
• Gordon IK, Khanna C. Modeling opportunities in comparative oncology for drug development. ILAR Journal. 2010;51(3):214–220. [PMC free article: PMC7303812] [PubMed: 21131722]
• Granada JF, Kaluza GL, Wilensky RL, Biedermann BC, Schwartz RS, Falk E. Porcine models of coronary atherosclerosis and vulnerable plaque for imaging and interventional research. EuroIntervention. 2009;5(1):140–148. [PubMed: 19577996]
• Granger N, Blamires H, Franklin RJ, Jeffery ND. Autologous olfactory mucosal cell transplants in clinical spinal cord injury: A randomized double-blinded trial in a canine translational model. Brain. 2012;135(Pt 11):3227–3237. [PMC free article: PMC3501977] [PubMed: 23169917]
• Grants.gov. Home page. n.d. [March 5, 2020]. https://www​.grants.gov/web/grants.
• *Grozdanic SD, Kecova H, Harper MM, Nilaweera W, Kuehn MH, Kardon RH. Functional and structural changes in a canine model of hereditary primary angle-closure glaucoma. Investigative Opthalmology & Visual Science. 2010;51(1):255–263. VA research was conducted at the Iowa City VA Center. [PMC free article: PMC3258664] [PubMed: 19661222]
• Gruenstein DH, Bass JL. Experimental evaluation of a new articulated Amplatzer ductal occluder device without fabric. Catheterization and Cardiovascular Interventions. 2009;74(3):482–487. [PubMed: 19405162]
• Guest J. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Webinar, May 7. 2019.
• *Gunda S, Akyeampong D, Gomez-Arroyo J, Jovin DG, Kowlgi NG, Kaszala K, Tan AY, Koneru JN, Kron J, Ellenbogen KA, Huizar JF. Consequences of chronic frequent premature atrial contractions: Association with cardiac arrhythmias and cardiac structural changes. Journal of Cardiovascular Electrophysiology. 2019;30(10):1952–1959. VA research was conducted at the Hunter Holmes McGuire VA Medical Center in Richmond, VA. [PMC free article: PMC6786912] [PubMed: 31310360]
• Hadrian R, Palmes D. Animal models of secondary lymphedema: New approaches in the search for therapeutic options. Lymphatic Research and Biology. 2017;15(1):2–16. [PubMed: 28128668]
• Halsey JT. The digitalized dog's heart as affected by amyl nitrite or atropine, studied electrocardiographically. Journal of Experimental Medicine. 1917;25(5):729–754. [PMC free article: PMC2125513] [PubMed: 19868120]
• Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, Ferreira C, Willhite A, Rejc E, Grossman RG, Edgerton VR. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: A case study. Lancet. 2011;377(9781):1938–1947. [PMC free article: PMC3154251] [PubMed: 21601270]
• Harrison D. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Workshop on the Uses of Dogs in Biomedical Research, March 27. Washington, DC: 2019.
• Harzmann R, Gericke D, Altenähr E, Bichler KH. Induction of a transplantable urinary bladder carcinoma in dogs. Investigations in Urology. 1980;18(1):24–28. [PubMed: 7410009]
• Hasdemir C, Scherlag BJ, Yamanashi WS, Lazzara R, Jackman WM. Endovascular stimulation of autonomic neural elements in the superior vena cava using a flexible loop catheter. Japanese Heart Journal. 2003;44(3):417–427. [PubMed: 12825809]
• Hasler-Rapacz J, Prescott MF, Von Linden-Reed J, Rapacz JM, Hu Z, Rapacz J. Elevated concentrations of plasma lipids and apolipoproteins B, C-III, and E are associated with the progression of coronary artery disease in familial hypercholesterolemic swine. Arteriosclerosis Thrombosis and Vascular Biology. 1995;15:583–592. [PubMed: 7749872]
• *Havel PJ, Mundinger TO, Taborsky GJ Jr. Pancreatic sympathetic nerves contribute to increased glucagon secretion during severe hypoglycemia in dogs. American Journal of Physiology: Endocrinology and Metabolism. 1996;270(1 Pt 1):E20–E26. VA research was conducted at the VA Puget Sound Health Care System in Seattle, WA. [PubMed: 8772469]
• Hayashida KI. Substance P-saporin for bone cancer pain in dogs: Can man's best friend solve the lost in translation problem in analgesic development? Anesthesiology. 2013;119(5):999–1000. [PMC free article: PMC3827733] [PubMed: 24195943]
• Head E. Oxidative damage and cognitive dysfunction: Antioxidant treatments to promote healthy brain aging. Neurochemical Research. 2009;34(4):670–678. [PMC free article: PMC4392815] [PubMed: 18683046]
• Head E. Neurobiology of the aging dog. Age. 2011;33(3):485–496. [PMC free article: PMC3168593] [PubMed: 20845082]
• Head E. A canine model of human aging and Alzheimer's disease. Biochimica et Biophysica Acta. 2013;1832(9):1384–1389. [PMC free article: PMC3937962] [PubMed: 23528711]
• *Heiner JP, Manley P, Kohles S, Ulm M, Bogart L, Vanderby R Jr. Ingrowth reduces implant-to-bone relative displacements in canine acetabular prostheses. Journal of Orthopaedic Research. 1994;12:657–664. VA research was conducted at the William S. Middleton Memorial Veterans Hospital in Madison, WI. [PubMed: 7931782]
• Heinl C, Chmielewska J, Olevska A, Grune B, Schönfelder G, Bert B. Rethinking the incentive system in science: Animal study registries: Preregistering experiments using animals could greatly improve transparency and reliability of biomedical studies and improve animal welfare. EMBO Reports. 2020;21(1):e49709. [PMC free article: PMC6945056] [PubMed: 31867805]
• Heron M. Deaths: Leading causes for 2017. Hyattsville, MD: National Center for Health Statistics; National Vital Statistics Reports. 2019;68(6):1–76. [PubMed: 32501203]
• Hill AC, Guy TS. Minimally invasive surgical implantation of the percutaneous left atrial appendage transcatheter occlusion device: initial experience in a canine model. Innovations (Phila). 2012;7(1):52–58. [PubMed: 22576036]
• Hong LTA, Kim YM, Park HH, Hwang DH, Cui Y, Lee EM, Yahn S, Lee JK, Song SC, Kim BG. An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling. Nature Communications. 2017;8(1):533. [PMC free article: PMC5599609] [PubMed: 28912446]
• Hoyer D, Jacobson LH. Orexin in sleep, addiction and more: Is the perfect insomnia drug at hand? Neuropeptides. 2013;47(6):477–488. [PubMed: 24215799]
• Hu HZ, Granger N, Pai SB, Bellamkonda RV, Jeffery ND. Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine clinical model of spinal cord injury. Brain. 2018;141(4):1017–1027. [PubMed: 29444239]
• Huang J, Dosdall DJ, Cheng KA, Li L, Rogers JM, Ideker RE. The importance of Purkinje activation in long duration ventricular fibrillation. Journal of the American Heart Association. 2014;3(1):e000495. [PMC free article: PMC3959715] [PubMed: 24584738]
• Huang Y, Gnanadurai CW, Fu ZF. Rabies virus vaccines. In: Pattnaik AK, Whitt MA, editors. Biology and pathogenesis of rhabdo- and filoviruses. Singapore: World Scientific Publishing Co Pte Ltd; 2015. pp. 387–426.
• *Huizar JF, Kaszala K, Potfay J, Minisi AJ, Lesnefsky EJ, Abbate A, Mezzaroma E, Chen Q, Kukreja RC, Hoke NN, Thacker LR 2nd, Ellenbogen KA, Wood MA. Left ventricular systolic dysfunction induced by ventricular ectopy: A novel model for premature ventricular contraction-induced cardiomyopathy. Circulation: Arrhythmia and Electrophysiology. 2011;4(4):543–549. Research was conducted at the Hunter Holmes McGuire VA Medical Center in Richmond, VA. [PMC free article: PMC3175603] [PubMed: 21576277]
• Huizar JF, Ellenbogen KA, Tan AY, Kaszala K. Arrhythmia-induced cardiomyopathy: JACC state-of-the-art review. Journal of the American College of Cardiology. 2019;73(18):2328–2344. [PMC free article: PMC6538508] [PubMed: 31072578]
• Iadarola MJ, Sapio MR, Raithel SJ, Mannes AJ, Brown DC. Long-term pain relief in canine osteoarthritis by a single intra-articular injection of resiniferatoxin, a potent TRPV1 agonist. Pain. 2018;159(10):2105–2114. [PMC free article: PMC8121156] [PubMed: 30015705]
• IOM (Institute of Medicine). Chimpanzees in biomedical and behavioral research: Assessing the necessity. Washington, DC: The National Academies Press; 2011. [PubMed: 22514816]
• Ishibashi Y, Rembert JC, Carabello BA, Nemoto S, Hamawaki M, Zile MR, Greenfield JC Jr, Cooper G. Normal myocardial function in severe right ventricular volume overload hypertrophy. American Journal of Physiology: Heart and Circulatory Physiology. 2001;280(1):H11–H16. [PubMed: 11123212]
• Ishihara K, Zile MR, Tomita M, Tanaka R, Kanazawa S, Carabello BA. Left ventricular hypertrophy in a canine model of reversible pressure overload. Cardiovascular Research. 1992;26(6):580–585. [PubMed: 1451137]
• Ito D, Carwardine D, Prager J, Wong LF, Kitagawa M, Jeffery N, Granger N. Methods of olfactory ensheathing cell harvesting from the olfactory mucosa in dogs. PLOS ONE. 2019;14(3):e0213252. [PMC free article: PMC6402693] [PubMed: 30840687]
• Jackman WM, Zipes DP. Low-energy synchronous cardioversion of ventricular tachycardia using a catheter electrode in a canine model of subacute myocardial infarction. Circulation. 1982;66(1):187–195. [PubMed: 7083506]
• Jackman WM, Kuck KH, Naccarelli GV, Carmen L, Pitha J. Radiofrequency current directed across the mitral anulus with a bipolar epicardial-endocardial catheter electrode configuration in dogs. Circulation. 1988;78(5 Pt 1):1288–1298. [PubMed: 3180385]
• Jäkel L, Van Nostrand WE, Nicoll JAR, Werring DJ, Verbeek MM. Animal models of cerebral amyloid angiopathy. Clinical Science (London). 2017;131(19):2469–2488. [PubMed: 28963121]
• Jalal Z, Seguela PE, Baruteau AE, Benoist D, Bernus O, Villemain O, Boudjemline Y, Iriart X, Thambo JB. Role of animal models for percutaneous atrial septal defect closure. Journal of Thoracic Disease. 2018;10(Suppl 24):S2966–S2974. [PMC free article: PMC6174152] [PubMed: 30305957]
• Janardhan AH, Gutbrod SR, Li W, Lang D, Schuessler RB, Efimov IR. Multistage electrotherapy delivered through chronically-implanted leads terminates atrial fibrillation with lower energy than a single biphasic shock. Journal of the American College of Cardiology. 2014;63(1):40–48. [PMC free article: PMC4123180] [PubMed: 24076284]
• Jeffery N. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Workshop on the Uses of Dogs in Biomedical Research, March 27. Washington, DC: 2019.
• Jeremy JY, Thomas AC. Animal models for studying neointima formation. Current Vascular Pharmacology. 2010;8(2):198–219. [PubMed: 19485916]
• Jiang M, Zhang M, Howren M, Wang Y, Tan A, Balijepalli RC, Huizar JF, Tseng GN. JPH-2 interacts with Cai-handling proteins and ion channels in dyads: Contribution to premature ventricular contraction-induced cardiomyopathy. Heart Rhythm. 2016;13(3):743–752. [PMC free article: PMC4762763] [PubMed: 26538326]
• Jilaihawi H, Virmani R, Nakagawa H, Ducharme A, Shi Y-F, Carter-Monroe N, Ladich E, Iyer M, Ikeda A, Asgar A, Bonan R. Mitral annular reduction with subablative therapeutic ultrasound: Pre-clinical evaluation of the ReCor device. EuroIntervention. 2010;6(1):54–62. [PubMed: 20542798]
• Jordan J, Heusser K, Brinkmann J, Tank J. Electrical carotid sinus stimulation in treatment resistant arterial hypertension. Autonomic Neuroscience: Basic and Clinical. 2012;172(1-2):31–36. [PubMed: 23146623]
• Joscht M, Martin M, Henin M, Nisolle JF, Kirschvink N, Dugdale A, Godart B, Coulon H, Simon V, Hontoir F, Graffin R, De Raeve Y, Vandeweerd JM. Angiographic anatomy of external iliac arteries in the sheep. Anatomia, Histologia, Embryologia. 2016;45(6):443–449. [PubMed: 26680154]
• Kaeberlein M, Creevy KE, Promislow DE. The dog aging project: Translational geroscience in companion animals. Mammalian Genome. 2016;27(7-8):279–288. [PMC free article: PMC4936929] [PubMed: 27143112]
• Kakino T, Saku K, Sakamoto T, Sakamoto K, Akashi T, Ikeda M, Ide T, Kishi T, Tsutsui H, Sunagawa K. Prediction of hemodynamics under left ventricular assist device. American Journal of Physiology: Heart and Circulatory Physiology. 2017;312(1):H80–H88. [PubMed: 27793856]
• Kalder J, Isfort P, Reinartz SD, Gremse F, Yamoah GG, Gesche V, Kotelis D, Tolba R, Jacobs MJ, Jalaie H. New large animal model for aortic aneurysms in the viscerorenal segment. Journal of Surgical Research. 2019;240:156–164. [PubMed: 30933829]
• Kaplan JL, Stern JA, Fascetti AJ, Larsen JA, Skolnik H, Peddle GD, Kienle RD, Waxman A, Cocchiaro M, Gunther-Harrington CT, Klose T, LaFauci K, Lefbom B, Machen Lamy M, Malakoff R, Nishimura S, Oldach M, Rosenthal S, Stauthammer C, O'Sullivan L, Visser LC, Williams R, Ontiveros E. Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets. PLOS ONE. 2018;13(12):e0209112. [PMC free article: PMC6292607] [PubMed: 30543707]
• Kar S, Hou D, Jones R, Werner D, Swanson L, Tischler B, Stein K, Huibregtse B, Ladich E, Kutys R, Virmani R. Impact of Watchman and Amplatzer devices on left atrial appendage adjacent structures and healing response in a canine model. JACC: Cardiovascular Interventions. 2014;7(7):801–809. [PubMed: 25060026]
• Kara T, Leinveber P, Vlasin M, Jurak P, Novak M, Novak Z, Chrastina J, Czechowicz K, Belehrad M, Asirvatham SJ. Endovascular brain intervention and mapping in a dog experimental model using magnetically-guided micro-catheter technology. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czech Republic. 2014;158(2):221–226. [PubMed: 23154541]
• Karczmar AG, Longo VG, De Carolis AS. A pharmacological model of paradoxical sleep: The role of cholinergic and monoamine systems. Physiology & Behavior. 1970;5(2):175–182. [PubMed: 5525792]
• Karlson AG, Mann FC. The transmissible venereal tumor of dogs: Observations on forty generations of experimental transfers. Annals of the New York Academy of Sciences. 1952;54(6):1197–1213. [PubMed: 12977017]
• Katsouras G, Sakabe M, Comtois P, Maguy A, Burstein B, Guerra PG, Talajic M, Nattel S. Differences in atrial fibrillation properties under vagal nerve stimulation versus atrial tachycardia remodeling. Heart Rhythm. 2009;6(10):1465–1472. [PubMed: 19968926]
• Kawajiri H, Mizuno T, Moriwaki T, Ishibashi-Ueda H, Yamanami M, Kanda K, Yaku H, Nakayama Y. Development of tissue-engineered self-expandable aortic stent grafts (bio stent grafts) using in-body tissue architecture technology in beagles. Journal of Biomedical Materials Research, Part B: Applied Biomaterials. 2015a;103(2):381–386. [PubMed: 24895150]
• Kawajiri H, Mizuno T, Moriwaki T, Iwai R, Ishibashi-Ueda H, Yamanami M, Kanda K, Yaku H, Nakayama Y. Implantation study of a tissue-engineered self-expanding aortic stent graft (bio stent graft) in a beagle model. Journal of Artificial Organs. 2015b;18(1):48–54. [PubMed: 25320016]
• Khanna C, London C, Vail D, Mazcko C, Hirschfeld S. Guiding the optimal translation of new cancer treatments from canine to human cancer patients. Clinical Cancer Research. 2009;15(18):5671–5677. [PMC free article: PMC2748812] [PubMed: 19737961]
• *Kijas JMH, Bauer TR Jr, Gäfvert S, Marklund S, Trowald-Wigh G, Johannisson A, Hedhammar Å, Binns M, Juneja RK, Hickstein DD, Andersson L. A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics. 1999;61(1):101–107. Two of the authors were affiliated with the VA Puget Sound Health Care System in Seattle, WA. [PubMed: 10512685]
• Kim BG, Kang YM, Phi JH, Kim YH, Hwang DH, Choi JY, Ryu S, Elastal AE, Paek SH, Wang KC, Lee SH, Kim SU, Yoon BW. Implantation of polymer scaffolds seeded with neural stem cells in a canine spinal cord injury model. Cytotherapy. 2010;12(6):841–845. [PubMed: 20629485]
• Kinter LB, DeGeorge JJ. Scientific knowledge and technology, animal experimentation, and pharmaceutical development. ILAR Journal. 2016;57(2):101–108. [PubMed: 28053064]
• Kleinert M, Clemmensen C, Hofmann S, Moore M, Renner S, Woods SC, Huypens P, Beckers J, de Angelis MH, Schürmann A, Bakhti M, Klingenspor M, Heiman M, Cherrington AD, Ristow M, Lickert H, Wolf E, Havel PJ, Müller TD, Tschöp MH. Animal models of obesity and diabetes mellitus. Nature Reviews Endocrinology. 2018;14(3):140–162. [PubMed: 29348476]
• *Kowalski KE, Romaniuk JR, Brose S, Richmond MA, Kowalski T, DiMarco AF. High frequency spinal cord stimulation—New method to restore cough. Respiratory Physiology & Neurobiology. 2016;232:54–56. VA research was performed at the Louis Stokes Cleveland VA Medical Center in Cleveland, OH. [PMC free article: PMC5012955] [PubMed: 27395446]
• Kowalski KE, Romaniuk JR, Kirkwood PA, DiMarco AF. Inspiratory muscle activation via ventral lower thoracic high-frequency spinal cord stimulation. Journal of Applied Physiology (1985). 2019;126(4):977–983. [PubMed: 30763163]
• Krueger E, Magri LMS, Botelho AS, Bach FS, Rebellato CLK, Fracaro L, Fragoso FYI, Villanova JA Jr, Brofman PRS, Popovi-Maneski L. Effects of low-intensity electrical stimulation and adipose derived stem cells transplantation on the time-domain analysis-based electromyographic signals in dogs with SCI. Neuroscience Letters. 2019;696:38–45. [PubMed: 30528708]
• Kubota Y, Miyagawa S, Fukushima S, Saito A, Watabe H, Daimon T, Sakai Y, Akita T, Sawa Y. Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model. Journal of Thoracic and Cardiovascular Surgery. 2014;147(3):1081–1087. [PubMed: 24131787]
• Kukielka M, Holycross BJ, Billman GE. Endurance exercise training reduces cardiac sodium/calcium exchanger expression in animals susceptible to ventricular fibrillation. Frontiers in Physiology. 2011;2:3. [PMC free article: PMC3059610] [PubMed: 21423413]
• Kumar A, Green JD, Sykes JM, Ephrat P, Carson JJ, Mitchell AJ, Wisenberg G, Friedrich MG. Detection and quantification of myocardial reperfusion hemorrhage using T2*-weighted CMR. JACC: Cardiovascular Imaging. 2011;4(12):1274–1283. [PubMed: 22172784]
• Kumar S, Singh R, Vasudeva N, Sharma S. Acute and chronic animal models for the evaluation of anti-diabetic agents. Cardiovascular Diabetology. 2012;11:9. [PMC free article: PMC3286385] [PubMed: 22257465]
• Kutikov AB, Moore SW, Layer RT, Podell PE, Sridhar N, Santamaria AJ, Aimetti AA, Hofstetter CP, Ulich TR, Guest JD. Method and apparatus for the automated delivery of continuous neural stem cell trails into the spinal cord of small and large animals. Neurosurgery. 2019;85(4):560–573. [PubMed: 30169668]
• *Kwofie MA, Chaudhary AK, Martins JB. Association among intracardiac T-wave alterans, ischemia, and spontaneous ventricular arrhythmias after coronary artery occlusion in a canine model. Translational Research. 2011;158(5):265–272. A co-author held an appointment at the VA Health Care System in Iowa City, IA. [PubMed: 22005265]
• Lafleur RL, Callister SM, Dant JC, Jobe DA, Lovrich SD, Warner TF, Wasmoen TL, Schell RF. One-year duration of immunity induced by vaccination with a canine lyme disease bacterin. Clinical and Vaccine Immunology. 2010;17(5):870–874. [PMC free article: PMC2863397] [PubMed: 20237200]
• Larsen M, Holm R, Jensen KG, Brodin B, Nielsen CU. Intestinal gaboxadol absorption via PAT1 (SLC36A1): Modified absorption in vivo following co-administration of L-tryptophan. British Journal of Pharmacology. 2009;157(8):1380–1389. [PMC free article: PMC2765307] [PubMed: 19594759]
• Lascelles BDX, Brown DC, Maixner W, Mogil JS. Spontaneous painful disease in companion animals can facilitate the development of chronic pain therapies for humans. Osteoarthritis and Cartilage. 2018;26(2):175–183. [PubMed: 29180098]
• Lee JY, Lucchesi BR. HBI-3000 prevents secondary sudden cardiac death. Journal of Cardiovascular Pharmacology and Therapeutics. 2013;18(5):453–459. [PubMed: 23615576]
• Lee N, Authier S, Pugsley MK, Curtis MJ. The continuing evolution of torsades de pointes liability testing methods: Is there an end in sight? Toxicolicology and Applied Pharmacology. 2010a;243(2):146–153. [PubMed: 20005885]
• Lee RJ, Bartus K, Yakubov SJ. Catheter-based left atrial appendage (LAA) ligation for the prevention of embolic events arising from the LAA: Initial experience in a canine model. Circulation: Cardiovascular Interventions. 2010b;3(3):224–229. [PubMed: 20484100]
• Lee SH, Chung YN, Kim YH, Kim YJ, Park JP, Kwon DK, Kwon OS, Heo JH, Kim YH, Ryu S, Kang HJ, Paek SH, Wang KC, Kim SU, Yoon BW. Effects of human neural stem cell transplantation in canine spinal cord hemisection. Neurological Research. 2009;31(9):996–1002. [PubMed: 19138477]
• Lequoy P, Savoji H, Saoudi B, Bertrand-Grenier A, Wertheimer MR, De Crescenzo G, Soulez G, Lerouge S. In vitro and pilot in vivo evaluation of a bioactive coating for stent grafts based on chondroitin sulfate and epidermal growth factor. Journal of Vascular and Interventional Radiology. 2016;27(5):753–760. [PubMed: 27036642]
• Li CH, Gao BL, Wang JW, Liu JF, Li H, Yang ST. Construction of aneurysmal models on a curved vascular segment of a carotid siphon model for testing endovascular devices. World Neurosurgery. 2019;123:e581–e587. [PubMed: 30529529]
• Lim JH, Piedrahita JA, Jackson L, Ghashghaei T, Olby NJ. Development of a model of sacrocaudal spinal cord injury in cloned Yucatan minipigs for cellular transplantation research. Cellular Reprogramming. 2010;12(6):689–697. [PMC free article: PMC3004133] [PubMed: 21108536]
• Lopshire JC, Zhou X, Dusa C, Ueyama T, Rosenberger J, Courtney N, Ujhelyi M, Mullen T, Das M, Zipes DP. Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model. Circulation. 2009;120(4):286–294. [PubMed: 19597055]
• Loría-Cervera EN, Andrade-Narváez FJ. Animal models for the study of leishmaniasis immunology. Revista do Instituto de Medicina Tropical de Sao Paulo. 2014;56(1):1–11. [PMC free article: PMC4085833] [PubMed: 24553602]
• Luo J, Lu G, Ye S, Ou J, Fu C, Zhang X, Wang X, Huang J, Wu P, Xu H, Wu L, Li S. Comparative pathogenesis of H3N2 canine influenza virus in beagle dogs challenged by intranasal and intratracheal inoculation. Virus Research. 2018;255:147–153. [PubMed: 29860092]
• MacFarlane PM, Vinit S, Mitchell GS. Enhancement of phrenic long-term facilitation following repetitive acute intermittent hypoxia is blocked by the glycolytic inhibitor 2-deoxyglucose. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. 2018;314(1):R135–R144. [PMC free article: PMC5866367] [PubMed: 29021191]
• Mahoney CE, Cogswell A, Koralnik IJ, Scammell TE. The neurobiological basis of narcolepsy. Nature Reviews Neuroscience. 2019;20(2):83–93. [PMC free article: PMC6492289] [PubMed: 30546103]
• Makary S, Voigt N, Maguy A, Wakili R, Nishida K, Harada M, Dobrev D, Nattel S. Differential protein kinase C isoform regulation and increased constitutive activity of acetylcholine-regulated potassium channels in atrial remodeling. Circulation Research. 2011;109(9):1031–1043. [PubMed: 21903936]
• Marcus DA, Bernstein CD, Constantin JM, Kunkel FA, Breuer P, Hanlon RB. Animal-assisted therapy at an outpatient pain management clinic. Pain Medicine. 2012;13(1):45–57. [PubMed: 22233395]
• Marostica E, Van Ammel K, Teisman A, Gallacher D, Van Bocxlaer J, De Ridder F, Boussery K, Vermeulen A. PK/PD modelling of the QT interval: A step towards defining the translational relationship between in vitro, awake beagle dogs, and humans. AAPS Journal. 2016;18(4):1000–1012. [PubMed: 27116025]
• Martinez Moreno R, Bhogal P, Lenz-Habijan T, Bannewitz C, Siddiqui A, Lylyk P, Hannes R, Monstadt H, Henkes H. In vivo canine study of three different coatings applied to p64 flow-diverter stents: Initial biocompatibility study. European Radiology Experimental. 2019;3(1):3. [PMC free article: PMC6342750] [PubMed: 30671686]
• Matsuo T, Carabello BA, Nagatomo Y, Koide M, Hamawaki M, Zile MR, McDermott PJ. Mechanisms of cardiac hypertrophy in canine volume overload. American Journal of Physiology. 1998;275(1 Pt 2):H65–H74. [PubMed: 9688897]
• Mazzatenta A, Carluccio A, Robbe D, Giulio CD, Cellerino A. The companion dog as a unique translational model for aging. Seminars in Cell and Developmental Biology. 2017;70:141–153. [PubMed: 28803893]
• Melby SJ, Lee AM, Zierer A, Kaiser SP, Livhits MJ, Boineau JP, Schuessler RB, Damiano RJ Jr. Atrial fibrillation propagates through gaps in ablation lines: Implications for ablative treatment of atrial fibrillation. Heart Rhythm. 2008;5(9):1296–1301. [PMC free article: PMC2923579] [PubMed: 18774106]
• Mendis S, Puska P, Norrving B, editors. Global atlas on cardiovascular disease prevention and control. Geneva, Switzerland: World Health Organization; 2011.
• Merkely B, Molnar L, Geller L, Neuzil P, Skoda J, Bednarek J, Bartus K, Reddy VY, Sanders WE Jr. Chronic implantation of intravascular cardioverter defibrillator in a canine model: Device stability, vascular patency, and anchor histology. Pacing and Clinical Electrophysiology. 2013;36(10):1251–1258. [PubMed: 23952482]
• Meurs KM. Arrhythmogenic right ventricular cardiomyopathy in the boxer dog: An update. Veterinary Clinics of North America: Small Animal Practice. 2017;47(5):1103–1111. [PubMed: 28647112]
• Meurs KM, Lahmers S, Keene BW, White SN, Oyama MA, Mauceli E, Lindblad-Toh K. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher. Human Genetics. 2012;131(8):1319–1325. [PubMed: 22447147]
• Mieda M. The roles of orexins in sleep/wake regulation. Neuroscience Research. 2017;118:56–65. [PubMed: 28526554]
• Mignot EJM. Genetica of narcolepsy and other sleep disorders. American Journal of Human Genetics. 1997;60(6):1289–1302. [PMC free article: PMC1716121] [PubMed: 9199548]
• Mignot EJM. History of narcolepsy at Stanford University. Immunologic Research. 2014;58(2-3):315–339. [PMC free article: PMC4028550] [PubMed: 24825774]
• Millon A, Canet-Soulas E, Boussel L, Fayad Z, Douek P. Animal models of atherosclerosis and magnetic resonance imaging for monitoring plaque progression. Vascular. 2014;22(3):221–237. [PubMed: 24907292]
• Mody RM, Lakhal-Naouar I, Sherwood JE, Koles NL, Shaw D, Bigley DP, Co E-MA, Copeland NK, Jagodzinski LL, Mukbel RM, Smiley RA, Duncan RC, Kamhawi S, Jeronimo SMB, DeFraites RF, Aronson NE. Asymptomatic visceral Leishmania infantum infection in U.S. soldiers deployed to Iraq. Clinical Infectious Diseases. 2019;68(12):2036–2044. [PMC free article: PMC6769235] [PubMed: 30239631]
• Moore S. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Workshop on the Uses of Dogs in Biomedical Research, March 27. Washington, DC: 2019.
• Moore SA, Granger N, Olby NJ, Spitzbarth I, Jeffery ND, Tipold A, Nout-Lomas Y S, da Costa RC, Stein VM, Noble-Haeusslein LJ, Blight AR, Grossman RG, Basso DM, Levine JM. Targeting translational successes through CANSORT-SCI: Using pet dogs to identify effective treatments for spinal cord injury. Journal of Neurotrauma. 2017;34(12):2007–2018. [PMC free article: PMC5467140] [PubMed: 28230415]
• Moore SA, Zidan N, Spitzbarth I, Nout-Lomas YS, Granger N, da Costa RC, Levine JM, Jeffery ND, Stein VM, Tipold A, Olby NJ. Development of an International Canine Spinal Cord Injury observational registry: A collaborative data-sharing network to optimize translational studies of SCI. Spinal Cord. 2018;56(7):656–665. [PMC free article: PMC6035082] [PubMed: 29795173]
• Mori K. Double cisterna magna blood injection model of experimental subarachnoid hemorrhage in dogs. Translational Stroke Research. 2014;5(6):647–652. [PubMed: 24986149]
• Myers DD. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Workshop on the Uses of Dogs in Biomedical Research, March 27. Washington, DC: 2019.
• *Nagatsu M, Zile MR, Tsutsui H, Schmid PG, DeFreyte G, Cooper GT, Carabello BA. Native beta-adrenergic support for left ventricular dysfunction in experimental mitral regurgitation normalizes indexes of pump and contractile function. Circulation. 1994;89(2):818–826. This study included research performed at the Ralph H. Johnson VA Medical Center in Charleston, SC. [PubMed: 8313571]
• Nagatsu M, Spinale G, Koide M, Tagawa H, DeFreitas G, Cooper GT, Carabello BA. Bradycardia and the role of beta-blockade in the amelioration of left ventricular dysfunction. Circulation. 2000;101(6):653–659. [PubMed: 10673258]
• Nakagawa H, Wittkampf FH, Yamanashi WS, Pitha JV, Imai S, Campbell B, Arruda M, Lazzara R, Jackman WM. Inverse relationship between electrode size and lesion size during radiofrequency ablation with active electrode cooling. Circulation. 1998;98(5):458–465. [PubMed: 9714097]
• Nakatani Y, Nishida K, Sakabe M, Kataoka N, Sakamoto T, Yamaguchi Y, Iwamoto J, Mizumaki K, Fujiki A, Inoue H. Tranilast prevents atrial remodeling and development of atrial fibrillation in a canine model of atrial tachycardia and left ventricular dysfunction. Journal of the American College of Cardiology. 2013;61(5):582–588. [PubMed: 23273396]
• NASEM (National Academies of Sciences, Engineering, and Medicine). The role of clinical studies for pets with naturally occurring tumors in translational cancer research: Workshop summary. Washington, DC: The National Academies Press; 2015. [PubMed: 26803853]
• Nasi-Er BG, Lou X, Zhang Y, Sun H, Zhou X, Li Y, Zhou Q, Zhang J, Tang B, Lu Y. Renal sympathetic denervation improves outcomes in a canine myocardial infarction model. Medical Science Monitor. 2019a;25:3887–3893. [PMC free article: PMC6556070] [PubMed: 31127792]
• Nasi-Er BG, Wenhui Z, HuaXin S, Xianhui Z, Yaodong L, Yanmei L, Hongli W, TuEr-Hong ZL, Qina Z, BaoPeng T. Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability. Pacing and Clinical Electrophysiology. 2019b;42(2):247–256. [PubMed: 30552763]
• NCHS (National Center for Health Statistics). Leading causes of death. 2017. [March 17, 2020]. https://www​.cdc.gov/nchs​/fastats/leadingcauses-of-death.htm.
• NCI (National Cancer Institute). Cancer statistics. n.d. [August 5, 2019]. https://www​.cancer.gov​/about-cancer/understanding/statistics.
• NCI CCR (Center for Cancer Research). Comparative oncology program. n.d. [March 2, 2020]. https://ccr​.cancer.gov​/Comparative-Oncology-Program.
• Nemoto S, Hamawaki M, De Freitas G, Carabello BA. Differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation. Journal of the American College of Cardiology. 2002;40(1):149–154. [PubMed: 12103269]
• Neubauer DN. Almorexant, a dual orexin receptor antagonist for the treatment of insomnia. Current Opinion in Investigational Drugs (London, England: 2000). 2010;11(1):101–110. [PubMed: 20047164]
• Neumann U, Ufer M, Jacobson LH, Rouzade-Dominguez ML, Huledal G, Kolly C, Lüönd RM, Machauer R, Veenstra SJ, Hurth K, Rueeger H, Tintelnot-Blomley M, Staufenbiel M, Shimshek DR, Perrot L, Frieauff W, Dubost V, Schiller H, Vogg B, Beltz K, Avrameas A, Kretz S, Pezous N, Rondeau J-M, Beckmann N, Hartmann A, Vormfelde S, David OJ, Galli B, Ramos R, Graf A, Lopez CL. The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease. EMBO Molecular Medicine. 2018;10(11):e9316. [PMC free article: PMC6220303] [PubMed: 30224383]
• NHGRI (National Human Genome Research Institute). The NHGRI Dog Genome Project. 2019. [February 28, 2020]. https://research​.nhgri​.nih.gov/dog_genome.
• Nishida K, Maguy A, Sakabe M, Comtois P, Inoue H, Nattel S. The role of pulmonary veins vs. autonomic ganglia in different experimental substrates of canine atrial fibrillation. Cardiovascular Research. 2011;89(4):825–833. [PubMed: 20962102]
• NRC (National Research Council). Guide for the care and use of laboratory animals, 8th edition. Washington, DC: The National Academies Press; 2011. [PubMed: 21595115]
• NSCISC (National Spinal Cord Injury Statistical Center). Facts and figures at a glance. Birmingham, AL: University of Alabama at Birmingham; 2019. [January 16, 2020]. https://www​.nscisc.uab​.edu/Public/Facts%20and​%20Figures%202019%20-%20Final.pdf.
• O'Kell AL, Wasserfall C, Catchpole B, Davison LJ, Hess RS, Kushner JA, Atkinson MA. Comparative pathogenesis of autoimmune diabetes in humans, NOD mice, and canines: Has a valuable animal model of type 1 diabetes been overlooked? Diabetes. 2017;66:1443–1452. [PMC free article: PMC5440022] [PubMed: 28533295]
• Ono N, Yamaguchi T, Ishikawa H, Arakawa M, Takahashi N, Saikawa T, Shimada T. Morphological varieties of the Purkinje fiber network in mammalian hearts, as revealed by light and electron microscopy. Archives of Histology and Cytology. 2009;72(3):139–149. [PubMed: 20513977]
• *Otterson MF, Leming SC, Fox CJ, Moulder JE. Propagation of giant migrating contractions between the small intestine, cecum and colon during radiation. Neurogasteroenterology and Motility. 2010;22(8):919–926. VA research was conducted at the Clement J. Zablocki VA Medical Center in Milwaukee, WI. [PMC free article: PMC4520439] [PubMed: 20529206]
• Paciello O, Oliva G, Gradoni L, Manna L, Foglia Manzillo V, Wojcik S, Trapani F, Papparella S. Canine inflammatory myopathy associated with Leishmania infantum infection. Neuromuscular Disorders. 2009;19(2):124–130. [PubMed: 19084398]
• Panfilov AV. Is heart size a factor in ventricular fibrillation? Or how close are rabbit and human hearts? Heart Rhythm. 2006;3(7):862–864. [PubMed: 16818223]
• *Pang Y, Wang X, Ucuzian AA, Brey EM, Burgess WH, Jones KJ, Alexander TD, Greisler HP. Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering. Biomaterials. 2010;31(5):878–885. VA research was conducted at the Edward J. Hines Jr. VA Hospital in Hines, IL. [PMC free article: PMC2789982] [PubMed: 19853908]
• Paoloni MC, Khanna C. Comparative oncology today. Veterinary Clinics of North America: Small Animal Practice. 2007;37(6):1023–1032. [PMC free article: PMC2174910] [PubMed: 17950880]
• Paoloni M, Webb C, Mazcko C, Cherba D, Hendricks W, Lana S, Ehrhart EJ, Charles B, Fehling H, Kumar L, Vail D, Henson M, Childress M, Kitchell B, Kingsley C, Kim S, Neff M, Davis B, Khanna C, Trent J. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials. PLOS ONE. 2014;9(3):e90028. [PMC free article: PMC3956546] [PubMed: 24637659]
• Paul A, Shao W, Shum-Tim D, Prakash S. The attenuation of restenosis following arterial gene transfer using carbon nanotube coated stent incorporating TAT/DNA(Ang1+Vegf) nanoparticles. Biomaterials. 2012;33(30):7655–7664. [PubMed: 22818986]
• Paul A, Elias CB, Shum-Tim D, Prakash S. Bioactive baculovirus nanohybrids for stent based rapid vascular re-endothelialization. Science Reports. 2013;3:2366. [PMC free article: PMC3734445] [PubMed: 23917680]
• Pedrosa S, Aguado D, Canfrán S, Torres J, Miró J. Dog-assisted therapy in the treatment of people with chronic pain: A systematic review. Revista de la Sociedad Española del Dolor. 2017;24(1):11–18.
• Perez TD, Figueiredo FB, Velho Junior AAM, Silva VL, de M, Madeira F, Brazil RP, Coura JR. Prevalence of American trypanosomiasis and leishmaniases in domestic dogs in a rural area of the municipality of São João Do Piauí, Piauí State, Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo. 2016;58:79. [PMC free article: PMC5096633] [PubMed: 27828620]
• Petersen C. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Webinar, May 7. 2019.
• Piktel JS, Wilson LD. Translational models of arrhythmia mechanisms and susceptibility: Success and challenges of modeling human disease. Frontiers in Cardiovascular Medicine. 2019;6:135. [PMC free article: PMC6748164] [PubMed: 31552276]
• Pleticha J, Malkmus SA, Heilmann LF, Veesart SL, Rezek R, Xu Q, Yaksh TL, Beutler AS. High cerebrospinal fluid levels of interleukin-10 attained by AAV in dogs. Gene Therapy. 2015;22(2):202–208. [PMC free article: PMC5079622] [PubMed: 25354684]
• Pomba C, Rantala M, Greko C, Baptiste KE, Catry B, van Duijkeren E, Mateus A, Moreno MA, Pyörälä S, Ružauskas M, Sanders P, Teale C, Threlfall EJ, Kunsagi Z, Torren-Edo J, Jukes H, Törneke K. Public health risk of antimicrobial resistance transfer from companion animals. Journal of Antimicrobial Chemotherapy. 2017;72(4):957–968. [PubMed: 27999066]
• Prier JE, Brodey RS. Canine neoplasia: A prototype for human cancer study. Bulletin of the World Health Organization. 1963;29:331–344. [PMC free article: PMC2554964] [PubMed: 14058226]
• *Prkic I, Mustapic S, Radocaj T, Stucke AG, Stuth EAE, Hopp FA, Dean C, Zuperku EJ. Pontine μ-opioid receptors mediate bradypnea caused by intravenous remifentanil infusions at clinically relevant concentrations in dogs. Journal of Neurophysiology. 2012;108:2430–2441. VA research was conducted at the Clement J. Zablocki VA Medical Center in Milwaukee, WI. [PMC free article: PMC3545180] [PubMed: 22875901]
• Qi XY, Diness JG, Brundel BJ, Zhou XB, Naud P, Wu CT, Huang H, Harada M, Aflaki M, Dobrev D, Grunnet M, Nattel S. Role of small-conductance calcium-activated potassium channels in atrial electrophysiology and fibrillation in the dog. Circulation. 2014;129(4):430–440. [PubMed: 24190961]
• Ramoni R. VA Office of Research and Development: Organization, mission, and funding process. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs meeting open session, March 28. Washington, DC: 2019. [June 9, 2020]. https://www​.nationalacademies​.org/event/03-27-2019​/assessment-of-the-care-and-use-of-dogs-in-biomedical-research-funded-by-or-conducted-at-the-us-department-of-veterans-affairs---public-workshop-on-the-uses-of-dogs-in-biomedical-research---public-workshop.
• Regier Y, O'Rourke F, Kempf VAJ. Bartonella spp.—A chance to establish One Health concepts in veterinary and human medicine. Parasites and Vectors. 2016;9(1):261. [PMC free article: PMC4862191] [PubMed: 27161111]
• Riemenschneider K, Liu J, Powers JG. Skin cancer in the military: A systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel. Journal of the American Academy of Dermatology. 2018;78(6):1185–1192. [PMC free article: PMC7262574] [PubMed: 29291955]
• Ripley B, Fujiki N, Okura M, Mignot E, Nishino S. Hypocretin levels in sporadic and familial cases of canine narcolepsy. Neurobiology of Disease. 2001;8(3):525–534. [PubMed: 11442359]
• Ross J Jr, Franklin D. Analysis of regional myocardial function, dimensions, and wall thickness in the characterization of myocardial ischemia and infarction. Circulation. 1976;53(3 Suppl):I88–I92. [PubMed: 1253375]
• *Ruaengsri C, Schill MR, Lancaster TS, Khiabani AJ, Manghelli JL, Carter DI, Greenberg JW, Melby SJ, Schuessler RB, Damiano RJ Jr. The hemodynamic and atrial electrophysiologic consequences of chronic left atrial volume overload in a controllable canine model. Journal of Thoracic and Cardiovascular Surgery. 2018;156(5):1871–1879. A co-author held an appointment at the VA St. Louis Health Care System. The VA is continuing to fund this work. [PMC free article: PMC6935371] [PubMed: 30336917]
• Rusbridge C, Salguero FJ, David MA, Faller KME, Bras JT, Guerreiro RJ, Richard-Londt AC, Grainger D, Head E, Brandner SGP, Summers B, Hardy J, Tayebi M. An aged canid with behavioral deficits exhibits blood and cerebrospinal fluid amyloid beta oligomers. Frontiers in Aging Neuroscience. 2018;10:7. [PMC free article: PMC5797595] [PubMed: 29441010]
• Sabbah HN, Wang M, Gupta RC, Rastogi S, Ilsar I, Viole T, Brewer R. Acute left ventricular unloading in dogs with chronic heart failure: Continuous aortic flow augmentation versus intra-aortic balloon pumping. Journal of Cardiac Failure. 2009;15(6):523–528. [PubMed: 19643364]
• Sakabe M, Fujiki A, Sakamoto T, Nakatani Y, Mizumaki K, Inoue H. Xanthine oxidase inhibition prevents atrial fibrillation in a canine model of atrial pacing-induced left ventricular dysfunction. Journal of Cardiovascular Electrophysiology. 2012;23(10):1130–1135. [PubMed: 22587612]
• Saku K, Kakino T, Arimura T, Sakamoto T, Nishikawa T, Sakamoto K, Ikeda M, Kishi T, Ide T, Sunagawa K. Total mechanical unloading minimizes metabolic demand of left ventricle and dramatically reduces infarct size in myocardial infarction. PLOS ONE. 2016;11(4):e0152911. [PMC free article: PMC4849631] [PubMed: 27124411]
• Sakurai T. Orexin deficiency and narcolepsy. Current Opinion in Neurobiology. 2013;23(5):760–766. [PubMed: 23663890]
• Sakurai T, Mieda M. Connectomics of orexin-producing neurons: Interface of systems of emotion, energy homeostasis, and arousal. Trends in Pharmacological Sciences. 2011;32(8):451–462. [PubMed: 21565412]
• Salcman M, Scott EW, Schepp RS, Knipp HC, Broadwell RD. Transplantable canine glioma model for use in experimental neuro-oncology. Neurosurgery. 1982;11(3):372–381. [PubMed: 6290929]
• Sanders WE Jr, Richey MW, Malkin RA, Masson SC, Ransbury TJ, Urtz MW, Ideker RE. Novel intravascular defibrillator: Defibrillation thresholds of intravascular cardioverter-defibrillator compared to conventional implantable cardioverter-defibrillator in a canine model. Heart Rhythm. 2011;8(2):288–292. [PubMed: 21034853]
• Schauerte P, Scherlag BJ, Pitha J, Scherlag MA, Reynolds D, Lazzara R, Jackman WM. Catheter ablation of cardiac autonomic nerves for prevention of vagal atrial fibrillation. Circulation. 2000;102(22):2774–2780. [PubMed: 11094046]
• Schol J, Sakai D. Cell therapy for intervertebral disk herniation and degenerative disc disease: Clinical trials. International Orthopaedics. 2019;43:1011–1025. [PubMed: 30498909]
• Schwartz RS, Holmes DR, Van Tassel RA, Hauser R, Henry TD, Mooney M, Matthews R, Doshi S, Jones RM, Virmani R. Left atrial appendage obliteration: mechanisms of healing and intracardiac integration. JACC: Cardiovascular Interventions. 2010;3(8):870–877. [PubMed: 20723861]
• Scorza BM, Carvalho EM, Wilson ME. Cutaneous manifestations of human and murine leishmaniasis. International Journal of Molecular Sciences. 2017;18(6):1296. [PMC free article: PMC5486117] [PubMed: 28629171]
• Shah K, Drury T, Roic I, Hansen P, Malin M, Boyd R, Sumer H, Ferguson R. Outcome of allogeneic adult stem cell therapy in dogs suffering from osteoarthritis and other joint defects. Stem Cells International. 2018;2018:7309201. [PMC free article: PMC6046133] [PubMed: 30050578]
• Sharif-Alhoseini M, Khormali M, Rezaei M, Safdarian M, Hajighadery A, Khalatbari MM, Safdarian M, Meknatkhah S, Rezvan M, Chalangari M, Derakhshan P, Rahimi-Movaghar V. Animal models of spinal cord injury: A systematic review. Spinal Cord. 2017;55(8):714–721. [PubMed: 28117332]
• Shorofsky M, Maguy A, Nattel S. Consequences of atrial or ventricular tachypacing on the heat shock proteins (HSP) level of expression and phosphorylation. McGill Journal of Medicine. 2009;12(2):34. [PMC free article: PMC2997257] [PubMed: 21264054]
• Shumway NE, Lower RR, Hurley EJ, Dong E Jr, Stofer RC. Congenital heart disease. Changing concepts in the surgical treatment. California Medicine. 1962;97:148–151. [PMC free article: PMC1575247] [PubMed: 13912411]
• Sigwart U. Living history of medicine: Vascular scaffolding, from dream to reality. European Heart Journal. 2017;38(16):1245–1248. [PubMed: 26792876]
• Simpson S, Edwards J, Ferguson-Mignan TF, Cobb M, Mongan NP, Rutland CS. Genetics of human and canine dilated cardiomyopathy. International Journal of Genomics. 2015;2015:204823. [PMC free article: PMC4525455] [PubMed: 26266250]
• Simpson S, Dunning MD, Brownlie S, Patel J, Godden M, Cobb M, Mongan NP, Rutland CS. Multiple genetic associations with Irish wolfhound dilated cardiomyopathy. Biomedical Research International. 2016;2016:6374082. [PMC free article: PMC5187458] [PubMed: 28070514]
• Smolek T, Madari A, Farbakova J, Kandrac O, Jadhav S, Cente M, Brezovakova V, Novak M, Zilka N. Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment. Journal of Comparative Neurology. 2016;524(4):874–895. [PubMed: 26239295]
• *Soon-Shiong P, Feldman E, Nelson R, Komtebedde J, Smidsrod O, Skjak-Braek G, Espevik T, Heintz R, Lee M. Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets. Transplantation. 1992;54(5):769–774. VA research was performed at the VA Greater Los Angeles Healthcare System. [PubMed: 1440841]
• *Starzl TE, Marchioro TL, Waddell WR. The reversal of rejection in human renal homografts with subsequent development of homograft tolerance. Surgery, Gynecology, and Obstetrics. 1963;117:385–395. VA research was conducted at the Rocky Mountain Regional VA Medical Center in Aurora, CO and the VA Pittsburgh Healthcare Center in Pittsburgh, PA. [PMC free article: PMC2581919] [PubMed: 14065716]
• *Sun Y, Song G-Q, Yin J, Lei Y, Chen JDZ. Effects and mechanisms of gastrointestinal electrical stimulation on slow waves: A systematic canine study. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. 2009;297(5):R1392–R1399. VA research was conducted at the VA Medical Center in Oklahoma City, OK. [PMC free article: PMC2777781] [PubMed: 19710395]
• Sunagawa G, Karimov JH, Breitbach M, Robinson NA, Fukamachi K. Impact of a refined advanced design for left atrial appendage exclusion. European Journal of Cardiothoracic Surgery. 2017;52(6):1098–1103. [PubMed: 28633397]
• Suo J, Ferrara DE, Sorescu D, Guldberg RE, Taylor WR, Giddens DP. Hemodynamic shear stresses in mouse aortas: Implications for atherogenesis. Arteriosclerosis Thrombosis and Vascular Biology. 2007;27(2):346–351. [PubMed: 17122449]
• Tafti M, Nishino S, Aldrich MS, Liao W, Dement WC, Mignot E. Major histocompatibility class II molecules in the CNS: Increased microglial expression at the onset of narcolepsy in a canine model. Journal of Neuroscience. 1996;16(15):4588–4595. [PMC free article: PMC6579009] [PubMed: 8764647]
• Takaseya T, Fumoto H, Saraiva RM, Shiose A, Arakawa Y, Park M, Rao S, Dessoffy R, Kramer LD Jr, Juravic M, Lombardi P, Fukamachi K. Acute feasibility study of a novel device for the treatment of mitral regurgitation in a normal canine model. Innovations (Phila). 2010;5(1):28–32. [PubMed: 22437273]
• Tan AY, Hu YL, Potfay J, Kaszala K, Howren M, Sima AP, Shultz M, Koneru JN, Ellenbogen KA, Huizar JF. Impact of ventricular ectopic burden in a premature ventricular contraction-induced cardiomyopathy animal model. Heart Rhythm. 2016;13(3):755–761. [PMC free article: PMC4762722] [PubMed: 26586453]
• Thannickal TC, John J, Shan L, Swaab DF, Wu M-F, Ramanathan L, McGregor R, Chew K-T, Cornford M, Yamanaka A, Inutsuka A, Fronczek R, Lammers GJ, Worley PF, Siegel JM. Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy. Science Translational Medicine. 2018;10:eaao4953. [PMC free article: PMC8235614] [PubMed: 29950444]
• Toepp AJ, Bennett C, Scott B, Senesac R, Oleson JJ, Petersen CA. Maternal Leishmania infantum infection status has significant impact on leishmaniasis in offspring. PLOS Neglected Tropical Diseases. 2019;13(2):e0007058. [PMC free article: PMC6391032] [PubMed: 30759078]
• Toledo-Pereyra LH. Heart transplantation. Journal of Investigative Surgery. 2010;23(1):1–5. [PubMed: 20232998]
• Triani F, Tramutola A, Di Domenico F, Sharma N, Butterfield DA, Head E, Perluigi M, Barone E. Biliverdin reductase-A impairment links brain insulin resistance with increased Aβ production in an animal model of aging: Implications for Alzheimer disease. Biochimica et Biophysica Acta. Molecular Basis of Disease. 2018;1864(10):3181–3194. [PubMed: 29981845]
• Tsujino N, Sakurai T. Role of orexin in modulating arousal, feeding, and motivation. Frontiers in Behavioral Neuroscience. 2013;7:28. [PMC free article: PMC3629303] [PubMed: 23616752]
• Tsutsui H, Spinale FG, Nagatsu M, Schmid PG, Ishihara K, DeFreyte G, Cooper G, Carabello BA. Effects of chronic beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation. Journal of Clinical Investigation. 1994;93(6):2639–2648. [PMC free article: PMC294505] [PubMed: 7911128]
• Uminski K, Kadkhoda K, Houston BL, Lopez A, MacKenzie LJ, Lindsay R, Walkty A, Embil J, Zarychanski R. Anaplasmosis: An emerging tick-borne disease of importance in Canada. IDCases. 2018;14:e00472. [PMC free article: PMC6278667] [PubMed: 30524954]
• VA (U.S. Department of Veterans Affairs). Health services research and development: Cancer. 2017. [March 17, 2020]. https://www​.research​.va.gov/topics/cancer.cfm.
• VA. Appendix 8: Current VA dog projects. Submitted to the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs on November 28, 2018. 2018a. [March 2, 2020]. https://www​.research​.va.gov/programs/animal_research​/canine_research​/active_projects.cfm.
• VA. Appendix 6: Sample accomplishments of VA research with dogs, 1960-current decade. Submitted to the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs on November 28, 2018. The list of 30 past research studies is available at. 2018b. [February 11, 2020]. https://www​.research​.va.gov/programs/animal_research​/canine_research​/accomplishments.cfm.
• VA. U.S. Department of Veterans Affairs FY 2018-2024 strategic plan. 2019. [February 27, 2020]. https://www​.va.gov/oei​/docs/VA20182024strategicPlan.pdf.
• VA. Public health: Infectious diseases. 2020. [March 2, 2020]. https://www​.publichealth​.va.gov/exposures​/infectious-diseases.
• VA ORD (Office of Research and Development). VA canine documents submitted to the National Academies of Sciences, Engineering, and Medicine. 2018. [November 19, 2019]. https://www​.research​.va.gov/programs/animal_research​/canine_research​/VA-CanineResearch-NAS.pdf.
• VA ORD. VA research on cardiovascular disease. n.d.a. [February 12, 2020]. https://www​.research​.va.gov/topics/cardio.cfm.
• VA ORD. VA research on spinal cord injury. n.d.b. [October 9, 2019]. https://www​.research​.va.gov/topics/sci.cfm.
• VA ORD. VA research on diabetes. n.d.c. [November 14, 2019]. https://www​.research​.va.gov/topics/diabetes.cfm.
• VA ORD. Overview of VA research on Alzheimer's disease. n.d.d. [November 19, 2019]. https://www​.research​.va.gov/topics/alzheimers.cfm.
• Vainio O. Translational animal models using veterinary patients—An example of canine osteoarthritis (OA). Scandinavian Journal of Pain. 2012;3(2):84–89. [PubMed: 29913782]
• Van Dam D, De Deyn PP. Animal models in the drug discovery pipeline for Alzheimer's disease. British Journal of Pharmacology. 2011;164(4):1285–1300. [PMC free article: PMC3229762] [PubMed: 21371009]
• van der Linde HJ, Van Deuren B, Somers Y, Loenders B, Towart R, Gallacher DJ. The electro-mechanical window: A risk marker for Torsade de Pointes in a canine model of drug induced arrhythmias. British Journal of Pharmacology. 2010;161(7):1444–1454. [PMC free article: PMC3010558] [PubMed: 21054337]
• Vargas HM. A new preclinical biomarker for risk of Torsades de Pointes: Drug-induced reduction of the cardiac electromechanical window. British Journal of Pharmacology. 2010;161(7):1441–1443. [PMC free article: PMC3010557] [PubMed: 20698854]
• Vasilevko V, Head E. Immunotherapy in a natural model of A pathogenesis: The aging beagle. CNS & Neurological Disorders—Drug Targets. 2009;8(2):98–113. [PubMed: 19355931]
• VHA ORD (Veterans Health Administration Office of Research and Development). Guidance document AR2017-001 (rev3): Canine, feline and non-human primate research protocols. 2017. [February 12, 2020]. https://www​.research​.va.gov/programs/animal_research​/CanineFelineNHP.pdf.
• Vilahur G, Padro T, Badimon L. Atherosclerosis and thrombosis: Insights from large animal models. Journal of Biomedicine and Biotechnology. 2011;2011:907575. [PMC free article: PMC3022266] [PubMed: 21274431]
• Vischer AS, Connolly DJ, Coats CJ, Fuentes VL, McKenna WJ, Castelletti S, Pantazis AA. Arrhythmogenic right ventricular cardiomyopathy in boxer dogs: The diagnosis as a link to the human disease. Acta Myologica. 2017;36(3):135–150. [PMC free article: PMC5953225] [PubMed: 29774304]
• Voorhees IEH, Dalziel BD, Glaser A, Dubovi EJ, Murcia PR, Newbury S, Toohey-Kurth K, Su S, Kriti D, Van Bakel H, Goodman LB, Leutenegger C, Holmes EC, Parrish CR. Multiple incursions and recurrent epidemic fade-out of H3N2 canine influenza A virus in the United States. Journal of Virology. 2018;92(16):e00323–18. [PMC free article: PMC6069211] [PubMed: 29875234]
• Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seáñez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018;563(7729):65–71. [PubMed: 30382197]
• Wakili R, Yeh YH, Qi XY, Greiser M, Chartier D, Nishida K, Maguy A, Villeneuve LR, Boknik P, Voigt N, Krysiak J, Kaab S, Ravens U, Linke WA, Stienen GJ, Shi Y, Tardif JC, Schotten U, Dobrev D, Nattel S. Multiple potential molecular contributors to atrial hypocontractility caused by atrial tachycardia remodeling in dogs. Circulatoin: Arrhythmia and Electrophysiology. 2010;3(5):530–541. [PubMed: 20660541]
• *Walter JS, Dunn RB, Wurster RD, Laghi F. Microstimulators and intramuscular hook electrodes for the stimulation of respiratory muscles. Journal of Spinal Cord Medicine. 2007;30:338–345. VA research was performed at the Edward J. Hines Jr. VA Hospital in Hines, IL. [PMC free article: PMC2031938] [PubMed: 17853655]
• Walton MB, Cowderoy E, Lascelles D, Innes JF. Evaluation of construct and criterion validity for the Liverpool Osteoarthritis in Dogs (LOAD) clinical metrology instrument and comparison to two other instruments. PLOS ONE. 2013;8(3):e58125. [PMC free article: PMC3591443] [PubMed: 23505459]
• Wang S, Zhou X, Huang B, Wang Z, Liao K, Saren G, Lu Z, Chen M, Yu L, Jiang H. Spinal cord stimulation protects against ventricular arrhythmias by suppressing left stellate ganglion neural activity in an acute myocardial infarction canine model. Heart Rhythm. 2015;12(7):1628–1635. [PubMed: 25778432]
• Wang X, Li G. Angiotensin-(1-7) prevent atrial tachycardia induced sodium channel remodeling. Pacing and Clinical Electrophysiology. 2014;37(10):1349–1356. [PubMed: 24861429]
• Wang Y, Eltit JM, Kaszala K, Tan A, Jiang M, Zhang M, Tseng GN, Huizar JF. Cellular mechanism of premature ventricular contraction-induced cardiomyopathy. Heart Rhythm. 2014;11(11):2064–2072. [PMC free article: PMC4252777] [PubMed: 25046857]
• Warren PM, Alilain WJ. Plasticity induced recovery of breathing occurs at chronic stages after cervical contusion. Journal of Neurotrauma. 2019;36(12):1985–1999. [PMC free article: PMC6599385] [PubMed: 30565484]
• Warren PM, Steiger SC, Dick TE, MacFarlane PM, Alilain WJ, Silver J. Rapid and robust restoration of breathing long after spinal cord injury. Nature Communications. 2018;9(1):4843. [PMC free article: PMC6258702] [PubMed: 30482901]
• Watanabe Y, Miyagawa S, Fukushima S, Daimon T, Shirakawa Y, Kuratani T, Sawa Y. Development of a prostacyclin-agonist-eluting aortic stent graft enhancing biological attachment to the aortic wall. Journal of Thoracic and Cardiovascular Surgery. 2014;148(5):2325–2334. [PubMed: 25224552]
• Watkins L Jr, Burton JA, Haber E, Cant JR, Smith FW, Barger AC. The rennin-angiotensin-aldosterone system in congestive failure in conscious dogs. Journal of Clinical Investigations. 1976;57(6):1606–1617. [PMC free article: PMC436820] [PubMed: 180056]
• Weaver ME, Pantely GA, Bristow JD, Ladley HD. A quantitative study of the anatomy and distribution of coronary arteries in swine in comparison with other animals and man. Cardiovascular Research. 1986;20(12):907–917. [PubMed: 3802126]
• Wei J, Zhang Y, Li Z, Wang X, Chen L, Du J, Liu J, Liu J, Hou Y. GCH1 attenuates cardiac autonomic nervous remodeling in canines with atrial-tachypacing via tetrahydrobiopterin pathway regulated by microRNA-206. Pacing and Clinical Electrophysiology. 2018;41(5):459–471. [PubMed: 29436714]
• Weina PJ, Neafie RC, Wortmann G, Polhemus M, Aronson NE. Old world leishmaniasis: An emerging infection among deployed U.S. military and civilian workers. Clinical Infectious Diseases. 2004;39(11):1674–1680. [PubMed: 15578370]
• White R. Presentation at the Committee on Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Workshop on the Uses of Dogs in Biomedical Research, March 27. Washington, DC: 2019.
• White RA, Fogarty TJ, Kopchok GE, Wilson E, Ayres B, Zalewski M, Donayre CE. Evaluation of a modular endovascular bifurcated prosthesis in a canine aortic aneurysm model. Journal of Vascular Surgery. 1996;24:1034–1042. [PubMed: 8976358]
• Wiersma AC, Stabej P, Leegwater PA, Van Oost BA, Ollier WE, Dukes-McEwan J. Evaluation of 15 candidate genes for dilated cardiomyopathy in the Newfoundland dog. Journal of Heredity. 2008;99(1):73–80. [PubMed: 17998275]
• Wiersma M, Meijering RAM, Qi XY, Zhang D, Liu T, Hoogstra-Berends F, Sibon OCM, Henning RH, Nattel S, Brundel B. Endoplasmic reticulum stress is associated with autophagy and cardiomyocyte remodeling in experimental and human atrial fibrillation. Journal of the American Heart Association. 2017;6(10):e006458. [PMC free article: PMC5721854] [PubMed: 29066441]
• Wieschowski S, Silva DS, Strech D. Animal study registries: Results from a stakeholder analysis on potential strengths, weaknesses, facilitators, and barriers. PLOS Biology. 2016;14(11):e2000391. [PMC free article: PMC5104355] [PubMed: 27832101]
• Wiese AJ, Rathbun M, Butt MT, Malkmus SA, Richter PJ, Osborn KG, Xu Q, Veesart SL, Steinauer JJ, Higgins D, Lappi DA, Russell B, Yaksh TL. Intrathecal substance P-saporin in the dog: Distribution, safety, and spinal neurokinin-1 receptor ablation. Anesthesiology. 2013;119(5):1163–1177. [PubMed: 24051388]
• Wilson EP, White RA, Kopchok GE, Donayre CE, deVirgilio C, Geselschap J. Deployment and healing of an e-PTFE encapsulated stent endograft in the canine aorta. Annals of Vascular Surgery. 1997;11:354–358. [PubMed: 9236990]
• Wilson S, Nagel SJ, Frizon LA, Fredericks DC, DeVries-Watson NA, Gillies GT, Howard MA 3rd. The hemisection approach in large animal models of spinal cord injury: Overview of methods and applications. Journal of Investigative Surgery. 2018;31:1–12. [PubMed: 30380340]
• Wilson S, Fredericks DC, Safayi S, DeVries-Watson NA, Holland MT, Nagel SJ, Gillies GT, Howard MA 3rd. Ovine hemisection model of spinal cord injury. Journal of Investigative Surgery. 2019;15:1–13. [PubMed: 31304811]
• Witt CM, Dalton S, O'Neil S, Ritrivi CA, Sanders R, Sharma A, Seifert G, Berhow S, Beinborn D, Witz A, McCaw T, Scott CG, Padmanabhan D, Killu AM, Naksuk N, Asirvatham SJ, Friedman PA. Termination of atrial fibrillation with epicardial cooling in the oblique sinus. JACC: Clinical Electrophysiology. 2018;4(10):1362–1368. [PubMed: 30336883]
• Wittkampf FH, Nakagawa H, Yamanashi WS, Imai S, Jackman WM. Thermal latency in radiofrequency ablation. Circulation. 1996;93(6):1083–1086. [PubMed: 8653827]
• Yaksh TL, Hobo S, Peters C, Osborn KG, Richter PJ Jr, Rossi SS, Grafe MR, Eisenach JC. Preclinical toxicity screening of intrathecal oxytocin in rats and dogs. Anesthesiology. 2014;120(4):951–961. [PMC free article: PMC5392224] [PubMed: 24492326]
• Yamashita K, Silvernagel J, Kwan E, Kamali R, Ghafoori E, MacLeod R, Dosdall DJ, Ranjan R. Changes in atrial electrophysiological and structural substrate and their relationship to histology in a long-term chronic canine atrial fibrillation model. Pacing and Clinical Electrophysiology. 2019;42(7):930–936. [PubMed: 31127633]
• Yu CH, Song GS, Yhee JY, Kim JH, Im KS, Nho WG, Lee JH, Sur JH. Histopathological and immunohistochemical comparison of the brain of human patients with Alzheimer's disease and the brain of aged dogs with cognitive dysfunction. Journal of Comparative Pathology. 2011;145(1):45–58. [PubMed: 21256508]
• Zeira O, Scaccia S, Pettinari L, Ghezzi E, Asiag N, Martinelli L, Zahirpour D, Dumas MP, Konar M, Lupi DM, Fiette L, Pascucci L, Leonardi L, Cliff A, Alessandri G, Pessina A, Spaziante D, Aralla M. Intra-articular administration of autologous micro-fragmented adipose tissue in dogs with spontaneous osteoarthritis: Safety, feasibility, and clinical outcomes. Stem Cells Translational Medicine. 2018;7(11):819–828. [PMC free article: PMC6216453] [PubMed: 30035380]
• Zeitzer JM, Nishino S, Mignot E. The neurobiology of hypocretins (orexins), narcolepsy, and related therapeutic interventions. Trends in Pharmacological Sciences. 2006;27(7):368–374. [PubMed: 16766052]
• Zhang WH, Zhou QN, Lu YM, Li YD, Zhang L, Zhang JH, Xing Q, Lv WK, Cheng XC, Zhang GG, Wang XS, Gu Q, Lou X, Guli B, Tang BP, Zhou XH. Renal denervation reduced ventricular arrhythmia after myocardial infarction by inhibiting sympathetic activity and remodeling. Journal of the American Heart Association. 2018;7(20):e009938. [PMC free article: PMC6474949] [PubMed: 30371294]
• Zhang X, Chen Z, Sun Y, Xu M, Pan G. Influence of iliac vein stent implantation on the contralateral iliac vein. Vascular and Endovascular Surgery. 2015;49(5-6):119–123. [PubMed: 26335993]
• Zhou M, Liu Y, Xiong L, Quan D, He Y, Tang Y, Huang H, Huang C. Cardiac sympathetic afferent denervation protects against ventricular arrhythmias by modulating cardiac sympathetic nerve activity during acute myocardial infarction. Medical Science Monitor. 2019;25:1984–1993. [PMC free article: PMC6436207] [PubMed: 30877783]
• Zile MR, Tomita M, Nakano K, Mirsky I, Usher B, Lindroth J, Carabello BA. Effects of left ventricular volume overload produced by mitral regurgitation on diastolic function. American Journal of Physiology. 1991;261(5 Pt 2):H1471–H1480. [PubMed: 1951734]
• *Zuleger CL, Kang C, Ranheim EA, Kurzman ID, Macklin MD, Newton MA, Wolchok JD, Vail DM, Eriksson E, Albertini MR. Pilot study of safety and feasibility of DNA microseeding for treatment of spontaneous canine melanoma. Veterinary Medicine and Science. 2017;3(3):134–145. The VA is funding the continuation of this work at the William S. Middleton Memorial VA Medical Center in Madison, WI. [PMC free article: PMC5645840] [PubMed: 29067210]
• Zullig LL, Sims KJ, McNeil R, Williams CD, Jackson GL, Provenzale D, Kelley MJ. Cancer incidence among patients of the U.S. Veterans Affairs health care system: 2010 update. Military Medicine. 2017;182(7/8):e1883–e1891. [PMC free article: PMC5650119] [PubMed: 28810986]