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 immatur e hearts when starting cardiopulmonary bypass produces an ''unintended '' reoxygenation injury that (1) nullifies the cardioprotective effect s of blood cardioplegia and (2) is avoidable by adding antioxidants N- (2-mercaptopropionyl)-glycine plus catalase to the cardiopulmonary byp ass prime. Twenty immature piglets (2 to 3 weeks) underwent 30 minutes of aortic clamping with a blood cardioplegic solution that was hypoca lcemic, alkalotic, hyperosmolar, and enriched with glutamate and aspar tate during 1 hour of cardiopulmonary bypass. Of these, six piglets di d not undergo hypoxemia (blood cardioplegic control) and 14 others rem ained hypoxemic (oxygen tension about 25 mm Hg) for up to 2 hours by l owering ventilator fraction of inspired oxygen before reoxygenation on cardiopulmonary bypass. The primary solution of the cardiopulmonary b ypass circuit was unchanged in eight piglets (no treatment) and supple mented 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 pe roxidation (myocardial conjugated diene production), and antioxidant r eserve capacity were evaluated. Blood cardioplegic arrest produced no biochemical or functional changes in nonhypoxemic control piglets. Reo xygenation caused an approximate 10-fold increase in conjugated produc tion that persisted throughout cardiopulmonary bypass, lowered antioxi dant reserve capacity 86% +/- 12%, and produced profound myocardial dy sfunction, because end-systolic elastance recovered only 21% +/- 2%. S upplementation of the cardiopulmonary bypass prime with N-(2-mercaptop ropionyl)-glycine and catalase reduced lipid peroxidation, restored an tioxidant reserve capacity, and allowed near complete functional recov ery (80% +/- 8%).* Lipid peroxidation (conjugated diene) production w as lower during warm blood cardioplegic reperfusion than during induct ion in all reoxygenated hearts, which suggests that blood cardioplegia did not injure reoxygenated myocardium. We conclude that reoxygenatio n of the hypoxemic immature heart causes cardiac functional and antiox idant damage that nullifies the cardioprotective effects of blood card ioplegia that can be avoided by supplementation of the cardiopulmonary bypass prime with antioxidants (p < 0.05 vs blood cardioplegic contr ol; *p < 0.05 vs reoxygenation).