The relationship between coronary blood flow, myocardial oxygen consumption and cardiac work as influenced by Persantin∗☆

A SERIES of explanations have been suggested to elucidate the origin of angina pectoris, but it appears most likely that angina pectoris is the result of anoxia of the heart muscle.1*2 The question arises whether the condition can be treated by drug induced dilatation of the coronary vessels. While hypoxemia itself may lead to near maximal dilatation of the coronary vessels, it is postulated that vasodilator drugs may eliminate possible vascular spasm, dilate preexisting anastomoses or collaterals, and increase coronary blood flo~.~*” Frequently drugs which dilate coronary arteries cause an increase in myocardial oxygen consumption. Katz4 has stressed the fact that coronary blood flow must be correlated with other parameters, such as oxygen consumption of the heart. The latter should be correlated with the work of the heart and heart rate levels, as well as the kind of work performed. These considerations must be kept in mind when the effect of a coronary dilator drug is being investigated. Agents such as epinephrine, norepinephrine, aminophyllin, coramine, khellin, quinidine, Arlidin@ and salicylates increase coronary blood flow and oxygen supply to the myocardium ; in addition they increase the oxygen consumption and cardiac work.5 According to Gregg,6 the coronary dilatation induced by these agents is not desirable, since the oxygen demands of the heart may be increased without a proportionate increase in the oxygen supply. On the other hand, coronary dilatation which results in an increase in coronary blood flow and oxygen supply in the presence of unchanged or decreased myocardial work and oxygen consumption is more desirable. Agents which fall into this category include nitroglycerin, papaverine, serotonin and the active pharmacologic agent in urine.5 Numerous pharmacologic agents have been suggested as coronary vasodilators. Their evaluation has been largely based on clinical trials employing as criteria alleviation of chest pain and improvement in electrocardiographic response following exercise. However, a recent symposium on the diagnosis of thoracic pain from the Mayo Clinic lists 78 different conditions other than coronary insufficiency that might simulate the angina1 syndrome.? Therefore, more objective methods have been undertaken by a series of investigators to evaluate the drugs used in the treatment of angina pectoris.4 s8 -11 The present report deals with the effect of a new coronary vasodilator agent, Persantinat, on coronary blood flow, myocardial oxygen consumption and cardiac work. Parent substances of this drug were first synthesized by Fischer and Roth in 1951.12 By means of pharmacologic studies in animals Persantin was shown to increase coronary blood flow without significant change in blood pressure, heart rate, or myocardial oxygen consumption, even when the dosage was varied over a wide range (0.025 to 0.5 mg. per kg. of body weight) ,13 -17 Bretschneider et al.,r6 Kadatzr3 and Kiese and co-workers,lT using anesthetized dogs, demont Persantin was kindly supplied to us by the Geigy Chemical Company, Ardsley, New York.