Comparative investigation of the effects of metoprolol, propranolol, practolol, and verapamil in the acute phase of experimental myocardial infarction.

Myocardial infarction in rats was produced by ligation of the left coronary artery. To ensure exact comparison of drug effect, the extent of the myocardial zone excluded from the coronary circulation was determined in each animal, and the experimental data were related to it. For this purpose, the hearts were perfused with Evans blue, and after the photometric determination of the dye content of the hearts the percentage of ischemic myocardium was calculated. With metoprolol, propranolol, and verapamil a significant increase of the survival times was obtained (min/% of non-ischemic myocardium). Metoprolol and propranolol also significantly increased the survival rates. None of the beta-blockers exerted an antiarrhythmic effect. The arrhythmias were prevented by higher doses of the calcium antagonist verapamil which, however, decreased the survival times. All beta-blocking agents delayed the typical elevation of the ST-segment in the electrocardiogram, and reduced the increase of the activity of the serum creatine kinase. Propranolol and metoprolol antagonized the blood pH decrease obtained after coronary occlusion. Results concerning heart rate, and arterial and central venous pressures are also reported. - The findings with metoprolol, especially, indicate that the essential mechanism in the therapeutic action of beta-blockers is their ability to block the cardiac beta 1-receptors.