Limitation of infarct size for 24 hours by combined treatment with allopurinol plus verapamil during acute myocardial infarction in the dog.
This study examined whether combination therapy with allopurinol plus verapamil would enhance limitation of myocardial infarct size compared with either allopurinol or verapamil alone in closed-chest dogs subjected to 24 hr of permanent coronary occlusion. Four groups were studied: control, dogs receiving allopurinol (400 mg po 24 and 2 hr before coronary occlusion and 10 mg/kg iv 6 hr after occlusion), dogs receiving verapamil (200 micrograms/kg iv bolus, then continuous administration of 5 micrograms/kg/min), and dogs receiving allopurinol plus verapamil as indicated above. The anatomic risk zone and regional myocardial blood flow were measured with radioactive microspheres administered intraventricularly 1 min after coronary occlusion. Necrotic tissue was visualized by triphenyl tetrazolium chloride staining and the risk zone by autoradiography of the microspheres. Infarct size, expressed as a percentage of the risk zone, was 75.9 +/- 13.7% (mean +/- SD) in the control group, 44.1 +/- 13.3% in the allopurinol group (p less than .05 vs control), 40.6 +/- 11.1% in the verapamil group (p less than .05 vs control), and 37.9 +/- 13.6% in the allopurinol plus verapamil group (p less than .05 vs control; p = NS vs drug-treated groups). In controls, there was a close correlation (r = -.83) between infarct size and subepicardial collateral blood flow. As a result the expected infarct size in the treatment group that would have occurred without drug-treatment could be reliably predicted based on the correlation between infarct size and subepicardial collateral blood flow. The ratio of the actual and predicted infarct size provides a "salvage index".(ABSTRACT TRUNCATED AT 250 WORDS)
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D012306:Risk; D013997:Time Factors; D014700:Verapamil / Q000627:therapeutic use*
D000493:Allopurinol; D014700:Verapamil