Studies of the Antiadrenergic Effects of Nitroglycerin on the Dog Heart

Abstract

Using anesthetized dogs, the possible antiadrenergic effects of nitroglycerin upon the myocardium were studied. Observations were made upon changes in heart rate, myocardial oxygen consumption, systolic vigor, and the electrocardiograms. Data are presented showing the effects of nitroglycerin and adrenergic agents when given separately and in combination. Results indicate that in dogs, nitroglycerin produces no antiadrenergic effects on the myocardium. The suggestion is made that the T wtave changes seen after adrenergic stimulation in dogs may not be due to anoxia.T HE beneficial effects of nitroglycerin in the anginal syndrome have been considered to be due either to coronary dilation with an improvement in myocardial oxygenation, or to the reduction in peripheral resistance and cardiac work, or to both, resulting in a decrease in myocardial oxygen re-(luirement. However, in view of recent evidence of heart rate and electrocardiographic changes in atropinized cats, Raab'1 suggests that nitroglycerin acts in a different manner. He postulates that it interferes with the metabolic, anoxia producing effects of the sympathomimetic amines on the myocardium. Although this hypothesis is attractive, Raab admits that its proof depends upon further evidence.The question then arises as to the criteria required for more conclusive study of this problem. Large increases in myocardial oxygen (oasumption electrocardiogram which is seen after adrenergic stimulation is due to anoxia or to some other myocardial effect of adrenergic agents is more difficult to establish. (See Discussion.) There are, however, two changes induced by adrenergic agents which occur together, and which can serve as indicators for testing any deviation in the adrenergic effects upon the myocardium. These are (1) changes in vigor of contraction, as indicated in the aortic pressure pulse, and (2) changes in myocardial oxygen consumption.'-8 The present report deals with our attempts to modify these adrenergically induced myocardial changes in dogs by the use of nitroglycerin. METHODSDogs were anesthetized with pentobarlital, and under artificial respiration the left chest was opened between the third and fourth ribs. The blood was made noncoagulable with 100 to 150 mg. of heparin. The left jugular vein was cannulated to administer fluid and to return coronary sinus blood. The coronary sinus was cannulated via the right auricle, and the cannula was made secure in the sinus by the inflation of a small balloon at the cannula tip.The left common coronary artery was dissected free and was cannulated by means of the special cannula previously described.9 The cannula was connected to the constant pressure apparatus andl a Shiplev rotameter described elsewhere.8' 10 In a few cases adjustment of the position of the cannula was necessary to get adequate sealing without leakage or restriction of coronary inflow. The possibility of leakage was tested in two ways: (1) With perfusion pressure above aortic pressure, a ligature was tightened about the common left art...

The Effect of Levarterenol on Polarographic Myocardial Oxygen, the Epicardial Electrocardiogram and Contraction

“…In contrast to the experimental situation just described, denervated heart-lung preparations, 41 ' 43 fibrillating hearts 43 or hearts perfused by constant-pressure coronary reservoir systems 17 (table 2, lower portion) do not show increases of coronary sinus oxygen content; rather, there is a fall of both oxygen content 17 and tension. 43 There may also be an initial coronary flow decrease followed by a prolonged increase.…”

“…Essentially similar changes have been described for ventricular muscle strip preparations, 12 ' 13 and for the hearts of frogs, 14 guinea pigs, 18 rabbits,* eats 10 and dogs. 17 The combination of experimental localized ischemia and levarterenol or epinephrine electrocardiographic effects has not been studied by other investigative groups to our knowledge.…”