The effects of ischemia and reperfusion on arterial and coronary sinus vitamin E and thiobarbituric acid reactive substance levels were investigated in 10 patients undergoing routine coronary artery bypass grafting. Serial sampling was performed during bypass operations, before the initial period of crossclamping and at 30 seconds and 2, 5, and 10 minutes after final crossclamp removal. A net myocardial loss of vitamin E occurred in the first 5 minutes of myocardial reperfusion (0.84 +/- 0.21 mumol/mmol cholesterol; p < 0.01). Myocardial vitamin E loss correlated positively with the total crossclamp time (rho = -0.695; p < 0.05) but was independent of cardiac enzyme release and duration of cardiopulmonary bypass. The concentration of thiobarbituric acid reactive substance rose significantly in the systemic circulation (+14 nmol/gm albumin; F > 17; p < 0.002) at 2 and 5 minutes after crossclamp removal. A significant increase of thiobarbituric acid reactive substance levels was also found in the coronary sinus blood 10 minutes after crossclamp removal (+8 nmol/gm albumin; F > 14; p < 0.004). However, there was no net arterial-coronary sinus difference in thiobarbituric acid reactive substance levels. The change in arterial thiobarbituric acid reactive substance levels in each patient was inversely correlated with their control vitamin E level (F = 9.53; p < 0.01). Our findings suggest that systemic lipid peroxidation occurs during bypass and that vitamin E may play a protective role during routine bypass grafting by attenuating the degree of peroxidative damage.