Protective effect of N-acetylcysteine on ischaemia-induced myocardial damage in canine heart.
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 reduced 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 (saline-treated) dogs and 68.2 +/- 2.4% (n = 7; P less than 0.05 vs control) in N-acetylcysteine-treated animals. Haemodynamic variables (heart rate, mean arterial pressure and rate-pressure 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-occlusion. N-Acetylcysteine did not influence the regional distribution of myocardial blood flow. The myocardial content of reduced glutathione was significantly (P less than 0.05) decreased 3 h post-occlusion (0.53 +/- 0.19 mumol/g-1; n = 5) compared to either pre-occlusion values (0.94 +/- 0.03 mumol/g-1; n = 8) or values 3 h post-occlusion in sham-operated animals (0.93 +/- 0.15 mumol/g-1; n = 5). Depletion of myocardial glutathione 3 h post-occlusion was not observed in dogs treated with N-acetylcysteine (0.87 +/- 0.11 mumol/g-1; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Alberola
A
A
Departamento de Fisiología, Facultad de Medicina, Universitat de Valencia, Spain.
Such
L
L
Gil
F
F
Zaragoza
R
R
Morcillo
E J
EJ
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
D005978:Glutathione; D000111:Acetylcysteine