STUDIES OF HYPOXEMIC/REOXYGENATION INJURY - WITHOUT AORTIC CLAMPING .10. EXOGENOUS ANTIOXIDANTS TO AVOID NULLIFICATION OF THE CARDIOPROTECTIVE EFFECTS OF BLOOD CARDIOPLEGIA

This study tests the hypothesis that reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass produces an ''unintended'' reoxygenation injury that (1) nullifies the cardioprotective effects of blood cardioplegia and (2) is avoidable by adding antioxidants N-(2-mercaptopropionyl)-glycine plus catalase to the cardiopulmonary bypass prime. Twenty immature piglets (2 to 3 weeks) underwent 30 minutes of aortic clamping with a blood cardioplegic solution that was hypocalcemic, alkalotic, hyperosmolar, and enriched with glutamate and aspartate during 1 hour of cardiopulmonary bypass. Of these, six piglets did not undergo hypoxemia (blood cardioplegic control) and 14 others remained hypoxemic (oxygen tension about 25 mm Hg) for up to 2 hours by lowering ventilator fraction of inspired oxygen before reoxygenation on cardiopulmonary bypass. The primary solution of the cardiopulmonary bypass circuit was unchanged in eight piglets (no treatment) and supplemented with the antioxidants N-(2-mercaptopropionyl)-glycine 80 mg/kg) and catalase (5 mg/kg) in six others (N-(2-mercaptopropionyl)-glycine and catalase), Myocardial function (end-systolic elastance), lipid peroxidation (myocardial conjugated diene production), and antioxidant reserve capacity were evaluated. Blood cardioplegic arrest produced no biochemical or functional changes in nonhypoxemic control piglets. Reoxygenation caused an approximate 10-fold increase in conjugated production that persisted throughout cardiopulmonary bypass, lowered antioxidant reserve capacity 86% +/- 12%, and produced profound myocardial dysfunction, because end-systolic elastance recovered only 21% +/- 2%. Supplementation of the cardiopulmonary bypass prime with N-(2-mercaptopropionyl)-glycine and catalase reduced lipid peroxidation, restored antioxidant reserve capacity, and allowed near complete functional recovery (80% +/- 8%).** Lipid peroxidation (conjugated diene) production was lower during warm blood cardioplegic reperfusion than during induction in all reoxygenated hearts, which suggests that blood cardioplegia did not injure reoxygenated myocardium. We conclude that reoxygenation of the hypoxemic immature heart causes cardiac functional and antioxidant damage that nullifies the cardioprotective effects of blood cardioplegia that can be avoided by supplementation of the cardiopulmonary bypass prime with antioxidants (*p < 0.05 vs blood cardioplegic control; **p < 0.05 vs reoxygenation).