Rabbit hearts for the critical evaluation of drugs to reduce the size of experimentally produced acute myocardial infarction.

Using more than 500 rabbits, we found that the rabbit heart is a good model for the evaluation of drugs which affect acute myocardial infarction (AMI) size. When the ratio of the epicardial coloration area to the long axis length of the left ventricle was controlled immediately after the ligation of the left anterior descending coronary artery and small branches of the left circumflex artery, it was possible to estimate the size of the ischemic region because AMI region in rabbit heart was always transmural. The necrotic region in the left ventricle was determined by phosphorylase histochemistry 24 hours after the operation. The incidence of arrhythmia and death following the operation was negligible. Then, we evaluated several drugs to examine their effects on AMI size. Propranolol (1, 2, and 4 mg/Kg) and verapamil (0.25, 0.5, and 1.0 mg/Kg) reduced AMI size, although the mortality and AMI size increased at higher doses of verapamil. Another Ca2+ antagonist, diltiazem (2 mg/Kg) and an adenosine potentiator, dilazep (2 mg/Kg) also decreased AMI size, while nicardipine, a water soluble, photoresistant nifedipine analogue (0.01, 0.05, and 0.1 mg/Kg) did not show a significant effect. These data suggest that this rabbit model is useful for assessing drug effects on AMI size and that the mechanism(s) of action of nicardipine may differ from other Ca2+ antagonists.