Superoxide generation during cardiopulmonary bypass: Is there a role for vitamin E?

The cytotoxic metabolites of oxygen [superoxide (O₂^-), hydrogen peroxide (H₂O₂), and hydroxyl (OH^•)] have been demonstrated to be involved in the peroxidation of membrane lipids consequently altering membrane composition, morphology, and function. Of all the lines of defense adopted by living organisms against toxic oxygen free radicals, vitamin E is most effective in the prevention of membrane damage. Cardiopulmonary bypass (CPB) has been shown to activate complement and cause sequestration of leukocytes which can recruit, adhere, and stimulate release of cytotoxic oxygen radicals. A prospective study of 30 patients evaluated the effects of CPB with and without an exogenous free radical scavenger (Group I, N = 20, control) and (Group II, N = 10, vitamin E) on H₂O₂ (a marker of oxygen free radicals) malonaldehyde (a marker of lipid peroxidation), transpulmonary leukosequestration, and plasma levels of vitamins E and C. Group I showed a progressive increase in H₂O₂ during CPB from 65 ± 6 to 130 ± 11 μm/ml (P < 0.0001); plasma vitamin E decreased from 15 ± 3 to 6 ± 1 mg/liter (P < 0.0001) while vitamin C increased from 1.6 ±.3 to 2.3 ±.3 mg/dl (P < 0.0001). Group II showed no significant increase in H₂O₂ (from 78 ± 8 to 93 ± 5 μm/ml) during CPB and a significant reduction in H₂O₂ levels compared to Group I (P < 0.001); plasma vitamins E and C did not change significantly in Group II. Transpulmonary leukosequestration, expressed as median cell difference (MCD), occurred in Group I (MCD = 1700) and Group II (MCD = 1900) (P < 0.001 vs pre-CPB). We conclude that (1) cytotoxic oxygen radicals liberated during CPB can be reduced by pretreatment with vitamin E despite complement activation and pulmonary sequestration of white blood cells. (2) Vitamin E pretreatment prevented a clinically overt vitamin E deficiency during CPB. (3) The rise in vitamin C post-CPB demonstrates the direct effect on oxidized vitamin E by vitamin C in vivo.