The influence of N-acetylcysteine on cardiac function and rhythm disorders during ischemia and reperfusion

To assess the ability of N-acetylcysteine to reduce the vulnerability of the heart to arrhythmias and improve its mechanical function during ischemia and reperfusion, groups of Langendorff-perfused rat hearts (15 per group) were subjected to 20 minutes of aerobic perfusion, 10 minutes of regional ischemia and 10 minutes of reperfusion. The hearts were perfused with N-acetylcysteine throughout the study. The incidences of ventricular premature beats and ventricular tachycardia induced by ischemia fell from 93% and 67%, in the N-acetylcysteine-free control group, to 40% and 27% with 8 microM N-acetylcysteine, to 33% and 27% with 80 microM N-acetylcysteine, and to 40% and 13% with 2000 microM N-acetylcysteine. The incidence of ventricular fibrillation induced by reperfusion was reduced from 93% to 60%, 67% and 47%, respectively. N-acetylcysteine had no significant effect upon the coronary flow and heart rate. When the ischemic period was prolonged to 30 minutes, N-acetylcysteine (8 microM) was shown to delay the time of onset of arrhythmias during ischemia and reperfusion. Thus, the incidences of ventricular premature beats and ventricular tachycardia were greatest after 15 minutes of ischemia in controls but were maximal after 18 minutes in hearts treated with N-acetylcysteine. N-acetylcysteine (8 microM) also improved the recovery of mechanical function after ischemia both in Langendorff preparations and in working preparations. In the working heart the post-ischemic recovery of aortic flow, coronary flow, cardiac output and aortic developed pressure after ischemia was improved from their control values of 30 +/- 5%, 82 +/- 2%, 43 +/- 2% and 63 +/- 4% to 59 +/- 7%, 98 +/- 5%, 71 +/- 3% and 80 +/- 6% respectively. Our results support the concept that agents which can alter redox state may exert protective effects against myocardial injury during both ischemia and reperfusion.