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| Status |
Public on Oct 19, 2011 |
| Title |
The role of sepsis in the development of limb muscle weakness in a porcine ICU model |
| Organism |
Sus scrofa |
| Experiment type |
Expression profiling by array
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| Summary |
Background : The aim of this study is to improve our understanding of the mechanisms underlying the role of sepsis in the limb muscles of ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factor triggering AQM that is endotoxin-induced sepsis.
Results : An increased expression of genes involved in chemokine activity and transcriptional regulation. A decreased expression in genes regulating heat shock proteins, cytoskeletal & sarcomeric and oxidative stress response were also apparent. Therefore, it appears that sepsis has an additive deleterious role in acute quadriplegic myopathy. Sepsis-induced molecular mechanisms involving chemokine/innate immunity and heat shock proteins are forwarded as probable mechanisms underlying the decreased force generating capacity.
Conclusions : This sepsis had significant effect on biceps femoris muscle force-generation capacity but not on fiber size. However, significant differences were observed between the MV and MV+SEP in the transcriptional regulation of an increased expression of genes involved in chemokine activity genes like MCP-1 and transcriptional regulation genes like JUNB, STAT3 and BHLHB2. A decreased expression in genes regulating heat shock proteins like HSP 90, HSP 70 and αB-crystallin, cytoskeletal & sarcomeric like MAP1A, MyBP-C1 and MYH7 and oxidative stress response like SRXN1 and SOD2 were also apparent. Therefore, it appears that sepsis has an additive negative role in acute quadriplegic myopathy.
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| Overall design |
Four female domestic piglets (Sus scrofa, average body weight 25.5 kg) were used in this study. Piglets were immobilized by anesthesia and mechanically ventilated via a tracheotomy for a period of five days. During this study period, the animals were sedated using isoflurane inhalation (Abbott Laboratories, Chicago, Il, USA, 0.8 – 1.3% end-tidal concentration) supplemented by intravenous bolus doses of morphine and ketamine as needed. Core body temperature (blood) was maintained in the range of 38.5 – 40°C by a servo controlled heating pad. The animals received intravenous crystalloid fluid (Ringeracetat) to maintain stable blood pressure and urinary output and a glucose infusion (Rehydrex, Fresenius Kabi, Stockholm, Sweden, 25 mg glucose /mL) in the range of 0.5 – 1.5 mg/kg/minute to decrease the effects of catabolism. Each animal received prophylactic streptomycin 750 mg/d and bensylpenicillin 600 mg/d (Streptocillin Vet, Boeringer-Ingelheim, Hellerup, Denmark). Arterial blood gas analysis as well as electrolytes and blood glucose levels were monitored regularly and kept in the normal range throughout the study period. A neuromuscular blocking agent (NMBA) was administered as a continuous infusion of pancuronium bromide 0.1mg/kg/h (Pavolun; Organon, Boxtel, The Netherlands) for 5days while a corticosteroid (CS) was given as bolus doses of betamethasone 0.1 mg/kg (Betapred; GSK, Slona, Sweden) twice daily for 5days. Endotoxemia was induced by a continuous infusion of Escherichia coli endotoxin, serotype O26:B6 (Sigma Labkemi, Stockholm, Sweden) at 36 µg/kg/h for 1h.
Key words : Treatment, immobilization, muscle function.
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| Contributor(s) |
Aare S, Radell P, Eriksson LI, Chen Y, Hoffman EP, Larsson L |
| Citation(s) |
22851759 |
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| Submission date |
Oct 18, 2011 |
| Last update date |
May 03, 2013 |
| Contact name |
sudhakar reddy aare |
| Organization name |
uppsala university
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| Department |
neuroscience
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| Lab |
clinical neurophysiology
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| Street address |
Ing 85, 3 tr, Akademiska sjukhuset
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| City |
uppsala |
| ZIP/Postal code |
751 85 |
| Country |
Sweden |
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| Platforms (1) |
| GPL3533 |
[Porcine] Affymetrix Porcine Genome Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA149533 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33037_RAW.tar |
25.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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