The effect of beta-adrenoceptor blocking agents on evolving myocardial necrosis in coronary ligated rats with and without reperfusion

Abstract

The left coronary artery of rats was ligated either permanently, or for a period of 40 or 60 min, with subsequent reperfusion. In experiments with permanent occlusion, the hearts were removed and investigated 5 h after the coronary ligation, or immediately after death in animals which died earlier. The hearts from the reperfusion experiments were investigated 60 min after reopening the occluded artery. The extent of the ischaemic and necrotic areas of the hearts was determined. A quantitative photometric method was developed for this purpose, using "negative staining" with Evans blue for the ischaemic area, and "negative staining" with triphenyltetrazolium chloride for the necrotic area. In experiments in which ligation was permanent, the percentage of the ischaemic area which underwent necrosis increased with the time after coronary occlusion. In reperfusion experiments, myocardial necrosis was detected earlier than in experiments with permanent coronary ligation. The beta-adrenoceptor blocking agents pindolol, propranolol, and metoprolol significantly decreased the percentage of necrosis in experiments with permanent ligation of the coronary artery. The most selective of the beta-adrenoceptor blockers, i.e. metoprolol was tested in the reperfusion experiments. In these experiments, the amount of necrosis was also significantly decreased.