Limitation of infarct size for 24 hours by combined treatment with allopurinol plus verapamil during acute myocardial infarction in the dog

Circulation. 1987 Jun;75(6 Pt 2):V25-33.

Abstract

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)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / therapeutic use*
  • Animals
  • Coronary Circulation / drug effects
  • Disease Models, Animal
  • Dogs
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Male
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocardium / pathology
  • Risk
  • Time Factors
  • Verapamil / therapeutic use*

Substances

  • Allopurinol
  • Verapamil