We investigated if increasing propofol's dosage to augment its antioxidant capacity during cardiopulmonary bypass (CPB) could confer cardiac protection. Fifty-four coronary artery bypass graft surgery patients were randomly assigned to small-dose propofol (Group P; n = 18), large-dose propofol (Group HiP; n = 18), or isoflurane Group (Group I; n = 18). After the induction, anesthesia was maintained with an inspired concentration of isoflurane 1%-3.5% (Group I) or a continuous infusion of propofol 60 microg x kg(-1) x min(-1) (Group P) throughout the surgery. In Group HiP, this dose of propofol was increased to 120 microg x kg(-1) x min(-1) for 10 min before the onset of CPB until 15 min after aortic unclamping and then decreased to 60 microg x kg(-1) x min(-1) until the end of surgery. The duration of aortic cross-clamping was 83 +/- 24, 88 +/- 22, and 81 +/- 20 min in Group P, Group HiP, and Group I, respectively (P > 0.1). Plasma malondialdehyde, a marker of oxidative stress, was significantly lower at 8 h after CPB, and Troponin I was lower at 24 h after CPB in Group HiP compared with Group P and Group I (P < 0.05). There was a significant reduction in inotropic requirements for separation from CPB in Group HiP compared with Group I. Postoperative systemic vascular resistance was significantly reduced in Group HiP as compared with Group I. Mean cardiac index was significantly higher at 24 h after CPB in Group HiP compared with Group P and Group I (P < 0.05) (Group I, 2.2 +/- 0.1; Group P, 2.3 +/- 0.2; and Group HiP, 2.8 +/- 0.3 L x min(-1) x m(-2), respectively). The duration of intensive care unit stay was significantly shorter in Group Hi-P compared with Group I. We conclude that administration of a large dose of propofol during CPB attenuates postoperative myocardial cellular damage as compared with isoflurane or small-dose propofol anesthesia.