Coronary Blood Flow and Cardiac Oxygen Metabolism During Nicotine‐induced Increases in Left Ventricular Work*

Abstract

The authors of the second edition of The Pharmacological Basis of Therapeulics state: "There is no proof that the use of tobacco causes arteriosclerosis or results in angina pectoris. However in a rare individual, who already has coronary sclerosis and angina pectoris, over-indulgence in tobacco may occasionally be a factor in precipitating anginal attacks. It is probable that the nicotine-inducedincrease in blood pressure and in heart rate is the basis for the occasional precipitation of an anginal seizure by smoking."' In so far as we are aware the mechanism of anginal seizures has not been precisely defined in terms of the physiological derangements.In order to obtain more information on this problem, a study of cardiac metabolism was designed, using intravenous infusions of nicotine in intact but anesthetized animals, each dog serving as its own control and returning several times for retesting. Our objective was to simulate in this preparation, under morphine-Dial-urethane-pentobarbital anesthesia (MDUP), a type of investigation that might later be pursued in patients. Specifically, we measured coronary blood flow, using the nitrous oxide desaturation method, cardiac oxygen, glucose, lactate, and pyruvate utilization and left ventricular pressure work in young, healthy dogs with normal coronary arteries. Measurements were made before and during infusions of nicotine that were anticipated to increase heart rate and left ventricular work. The results are compared with data obtained in if study of a newly syiithesised pressor substance Hypertensin I1 peptiden,$ the same animals and the same experimental design being used in the latter series of experiments under MDUP anesthesia. Hypertensin did increase left ventricular work significantly in this preparation.We asked this question: When the work load of the left ventricle is increased acutely by an infusion of nicotine or Hypertensin, is the myocardial oxygen extraction coefficient [(A-VIA) x 1001 increased, unchanged or reduced? Put another way, the question asks whether, during the action of nicotine or Hypertensin, the heart muscle is able to increase its oxygen uptake without reducing the cardiac capillary mean oxygen tension as this might be reflected in cardiac venous blood.