Myocardial apoptosis prevention by radical scavenging in patients undergoing cardiac surgery.

Abstract

Reactive oxygen-derived species, including those generated during myocardial ischemia and reperfusion induced by cardioplegia, have been suggested to be involved in myocardial apoptosis induction. The purpose of our study was to investigate (1) whether cardioplegic arrest initiates apoptosis in the hearts of cardiac surgery patients and (2) whether reactive oxygen-derived species scavenging with N-acetylcysteine attenuates myocardial apoptosis initiation. In transmural left ventricular biopsy samples collected before and at the end of cardiopulmonary bypass, we densitometrically determined cardiac myocyte staining intensity for active caspases-3 and -7, the apoptosis signal pathway central effector enzymes. The left ventricular biopsy samples had been obtained from 36 coronary artery bypass graft patients randomized in a double-blind fashion to receive either N-acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg.kg(-1).h(-1); n = 18) or placebo (n = 18). The change in left ventricular cardiac myocyte staining (end of cardiopulmonary bypass minus before cardiopulmonary bypass) differed significantly between groups for both measures: caspase-3, -3.1 +/- 4.5 gray units (mean +/- SD; N-acetylcysteine group) versus 7.1 +/- 8.1 gray units (placebo); 95% confidence interval, 6.4 to 14.4; P <.0001; caspase-7, -5.1 +/- 6.1 gray units (N-acetylcysteine) versus 5.1 +/- 5.7 gray units (placebo); 95% confidence interval, 6.3 to 15.0; P <.0001. Clinical outcome did not differ between N-acetylcysteine and placebo. Our data show that cardioplegic arrest initiates the apoptosis signal cascade in human left ventricular cardiac myocytes. This apoptosis induction can effectively be prevented by N-acetylcysteine.