Beneficial effects of N-acetylcysteine and cysteine in stunned myocardium in perfused rat heart.

Abstract

1. The objective of this study was to evaluate the effects of three sulphydryl (SH) compounds, N-acetylcysteine (NAC), cysteine (Cys) and cystamine, on functional recovery and ventricular arrhythmias (VF) in stunned myocardium in the isolated perfused heart of the rat. 2. Hearts (n = 7-8 per group) were perfused by the Langendorff procedure for 20 min to stabilize and then assigned to one of five groups: saline, sham, NAC, Cys and cystamine. After the stabilizing period, the drugs (at 3.6 microM min-1) or their vehicle (saline) were infused into coronary vessels throughout the experimental period. Ten min after administration of drugs, the left anterior descending coronary artery (LAD) was ligatured for 20 min and then untied to reperfuse for 30 min. In the sham group, a ligature was placed around the LAD but not tied. 3. NAC and Cys had a significant effect in attenuating myocardial stunning: the percentage recovery of rate-pressure product measured 30 min after reperfusion as an index of heart function, was improved with the NAC (98.3 +/- 4.5) and Cys groups (104.0 +/- 6.5) compared with the saline (only 73.6 +/- 3.8, P < 0.01) group. Cystamine did not show these beneficial effects. This may be due to the difference in chemical structure between NAC, Cys and cystamine since the latter does not have a free SH group with a disulphide bond formed. This phenomenon suggests that a free SH group is essential for the protective effects of compounds like NAC and Cys in myocardial injury. 4. NAC and Cys prevented the fall in coronary flow during the LAD occlusion and enhanced coronary flow during reperfusion but cystamine did not have such a beneficial effect. 5. The incidence of VF in the saline, cystamine, Cys and NAC groups was 6/8 (75.0%), 4/7 (57.1%), 3/8 (37.5%) and 2/7 (28.6%), respectively, and no significant differences (P > 0.05) were noted between the saline- and drug-treated groups. 6. An in vitro study with electron spin resonance indicated that Cys effectively scavenged the hydroxyl radical (-OH) generated by Fenton's reaction but did not scavenge superoxide generated in an irradiated riboflavin system. NAC and cystamine showed a scavenging effect on -OH to a certain extent but this effect did not reach statistical significance (P > 0.05 vs saline). 7. Our results demonstrate that NAC and Cys treatment before ischaemia and reperfusion can reduce myocardial stunning. This beneficial effect may be mainly due to their ability to preserve and enhance coronary flow during coronary occlusion and reperfusion and in part due to scavenging -OH and/or replenishing intracellular glutathione. The results also indicate that the condition of coronary perfusion can produce a great impact on postischaemic ventricular performance.