Chronic administration of allopurinol fails to exert any cardioprotective effect in rats submitted to permanent coronary artery ligation.
It has been shown that allopurinol, an inhibitor of xanthine oxidase, may limit the extent of myocardial infarction in dogs. In the present work, we studied the effect of a chronic administration of allopurinol on myocardial infarct size measured histochemically 48 h after in situ left coronary artery ligation in the rat. Our results indicate that allopurinol pretreatment does not produce any limitation of the extent of necrosis, but induces a significant increase in the volume of the non-ischemic portion of the myocardium, accompanied by an increase in protein content. This phenomenon, which could be due to the development of an edema in the non-ischemic portion of the myocardium, may well explain some discrepancies reported in previous experimental studies in which the infarct size was conventionally expressed as a percentage of the total volume of ventricular tissue. We have also shown that allopurinol pretreatment failed to improve the residual cardiac function in rats after left coronary artery ligation. We conclude that the enzyme xanthine oxidase is probably not involved in the pathophysiology of myocardial infarction in the rat because of the absence of collateral vasculature in this species which prevents any oxygen supply to the ischemic zone. In most other mammals such as the dog, the existence of a collateral system maintains a residual blood flow and oxygen supply to the ischemic portion of ligated hearts, allowing the xanthine oxidase-induced production of superoxide anions to be activated, thereby initiating peroxidative lesions in membrane lipids.
Boucher
F
F
Laboratoire de physiologie cellulaire cardiaque, URA CNRS 632, Université Joseph Fourier, Grenoble, France.
de Leiris
J
J
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D003331:Coronary Vessels / Q000601:surgery*; D006321:Heart / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D009336:Necrosis; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D000493:Allopurinol