Protection afforded by allopurinol in the first 24 hours of coronary occlusion is diminished after 48 hours.
Experiments were performed to test whether the reduction in infarct size afforded by allopurinol following 24 h of permanent coronary artery occlusion is sustained over the subsequent 24 h. A dog's coronary artery was occluded with an embolus followed by injection of radiomicrospheres into the left ventricle to mark the ischemic region and to measure regional blood flow. Dogs were sacrificed either 24 h or 48 hours after embolization. The infarcts were delineated by failure to stain with triphenyl tetrazolium chloride and the ischemic zones were visualized by autoradiography of the heart slices. Dogs in the treatment groups received 600 mg of allopurinol PO 18 h before surgery, and a 10 mg/kg IV bolus 15 minutes before embolization followed by constant IV infusion of 55 mg/kg/24 h until sacrifice. A close correlation in the control animals between the percent of the ischemic zone which infarcted and collateral blood flow was used to predict a nonintervention infarct size in each treatment animal. Allopurinol treatment caused 17.9 +/- 3.3% less of the risk zone to be tetrazolium negative after 24 hours of ischemia than that seen in untreated animals. Less allopurinol induced salvage was observed in the 48 hour drug group with only a 11.1 +/- 3.3% limitation in infarct size. Furthermore, the effect was inconsistent at 48 h with only 2 dogs showing salvage. We conclude that allopurinol delays but does not prevent infarction in the permanent occlusion model.
Miura
T
T
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
Yellon
D M
DM
Kingma
J
J
Downey
J M
JM
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D003097:Collateral Circulation; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
D000493:Allopurinol