Oxypurinol limits myocardial infarct size in closed chest dogs without pretreatment.
The authors tested whether allopurinol or oxypurinol could limit infarct size when treatment was started just prior to reperfusion and continued until sacrifice. In closed chest, anesthetized dogs, a branch of the left coronary artery was reversibly occluded for 90 mins followed by 24 h of reperfusion. Fifteen minutes prior to reperfusion, dogs received a bolus of either allopurinol (10 dogs), or oxypurinol (nine dogs), 10 mg/kg intravenously, followed by a 24 h infusion, 55 mg/kg/day. Eleven control dogs received equal volumes of saline. Investigators were blinded to the identity of the agent. Hearts were removed 24 h after reperfusion. Arrhythmias for 30 mins after reperfusion were quantitated. Oxypurinol caused 28% less of the risk zone to infarct for any level of collateral flow than that seen in the controls. This difference was significant. Allopurinol-treated hearts averaged only 18% less infarction and did not achieve significance. Ventricular arrhythmias and mortality did not differ among the three groups. Therefore, unlike allopurinol, oxypurinol with continued administration can limit tetrazolium-indicated necrosis in the dog heart in the absence of pretreatment.
Matsuki
T
T
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36608.
Shirato
C
C
Cohen
M V
MV
Downey
J M
JM
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D010117:Oxypurinol / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012307:Risk Factors
D011743:Pyrimidines; D000493:Allopurinol; D010117:Oxypurinol