6533b854fe1ef96bd12ae14e

RESEARCH PRODUCT

Protective effect of N-acetylcysteine on ischaemia-induced myocardial damage in canine heart.

subject

description

The glutathione redox pathway is an important antioxidant system in the myocardium. N-Acetylcysteine is a low molecular weight glutathione precursor that has been used clinically to replenish glutathione stores. The present study was aimed at evaluating the protective effect of N-acetylcysteine on myocardial damage resulting from permanent coronary occlusion (without reperfusion) in anaesthetized dogs. N-Acetylcysteine (150 mg kg−1 i.v.) administered 2 min before occlusion rerduced infarct size in dogs subjected to 24 h ischemia. The infarct size as a percentage of the area at risk was 86.8 ± 3.6% (n = 11) in control (salinetreated) dogs and 68.2 ± 2.4% (n = 7; P < 0.05 vs control) in N-acetylcysteine-treated animals. Haemodynamic variables (heart rate, mean arterial pressure and ratepressure product) were similar in the control and the treated group. Regional myocardial blood flow was determined with radioactive microspheres in ischaemic and non-ischaemic zones before occlusion and 3 h post-ocelusion. N-Acetylcysteine did not influence the regional distribution of myocardial blood flow. The myocardial content of reduced glutathione was significantly (P < 0.05) decreased 3 h post-occlusion (0.53 ± 0.19 μmol/ g−1 ; n = 5) compared to either pre-occlusion values (0.94 ± 0.03 μmol/g−1; n = 8) or values 3 h post-ocelusion in sham-operated animals (0.93 ± 0.15 μmo1/g−1 ; n = 5). Depletion of myocardial glutathione 3 h post-ocelusion was not observed in dogs treated with N-acetylcysteine (0.87 ± 0.11 μmol/g−1; n = 5). Superoxide dismutase activity and malondialdehyde levels were determined in blood samples obtained from the coronary vein draining the ischaemic zone. Superoxide dismutase activity increased 10 min post-occlusion in control but not in N-acetylcysteine-treated dogs. Malondialdehyde levels were elevated in both groups after occlusion but this increase failed to reach statistical significance in the animals treated with N-acetylcysteine. This study demon strates that N-acetylcysteine treatment reduces myocardial damage after permanent coronary occlusion. The beneficial effect may be due to maintenance of myocardial glutathione and to protection against free-radicalmediated damage during the early phase of ischaemia.