Effects of dimethyl quaternary propranolol (UM-272) on oxygen consumption and ischemic ST segment changes in the canine heart.

The effect of dimethyl quarternary propranolol, UM-272, on myocardial oxygen consumption was determined experimentally in anesthetized, open-chest dogs in which the left anterior descending and circumflex coronary arteries were cannulated and perfused at a constant pressure. Coronary arterial and venous blood samples were collected and their oxygen content were measured. Myocardial oxygen consumption was calculated and expressed as milliliters per minute per 100 grams of left ventricle. Mean control myocardial oxygen consumption in five animals was 11.7 +/- 1.9. This was significantly reduced to 7.6 +/- 1.1 after UM-272, 10 mg/kg (P less than 0.5). In separate experiments, hearts were excised from anesthetized dogs and were perfused with oxygenated whole blood via the aorta. Coronary blood flow was held constant and oxygen consumption was calculated and expressed as milliliters per minute per 100 g of myocardium. Mean control oxygen consumption in five hearts was significantly reduced from 3.1 +/- 0.2 to 2.1 +/- 0.1 (P less than 0.01). In addition, the effect of UM-272 on myocardial ischemic injury produced in response to acute coronary artery ligation was assessed. The sum ST segment elevations from six epicardial recording sites was reduced from 34.8 +/- 4.9 to 11.3 +/- 2.1 mV (P less than .05). These data suggest that UM-272 would aid in ischemic heart disease by reducing both oxygen utilization and ischemic damage. These data, although suggestive, do not exclude other mechanisms as being related to the reduction in ST segment elevation, mechanisms which may not involve a reduction in myocardial oxygen consumption.