Joseph H. Hafkenschiel

The measurement of coronary blood flow, oxygen consumption, and efficiency of the left ventricle in man.

Abstract The left ventricular coronary blood flow and left ventricular oxygen consumption per unit weight have been determined in twenty-six patients by means of the nitrous oxide method in conjunction with catheterization of the coronary sinus. The studies were performed on normal individuals and on patients with various forms of cardiovascular disease. The technique of coronary sinus catheterization and of the nitrous oxide method as applied to the coronary circulation in man have been presented. In the normal subject the left ventricular coronary blood flow per 100 grams per minute and the left ventricular oxygen consumption per 100 grams per minute averaged 65 c.c. and 7.8 c.c, respectively. The average oxygen extraction was 12 volumes per cent. In acutely anemic patients the left ventricular coronary blood flow per 100 grams per minute was slightly increased, whereas the left ventricular oxygen consumption per 100 grams per minute and the left ventricular oxygen extraction were reduced. In patients with essential hypertension, left ventricular coronary blood flow per 100 grams per minute, left ventricular oxygen consumption per 100 grams per minute, and left ventricular oxygen extraction were normal. In patients with coarctation of the aorta, the average left ventricular coronary blood flow per 100 grams per minute, left ventricular oxygen consumption per 100 grams per minute, and left ventricular oxygen extraction were all increased. In congestive failure due to mitral stenosis and insufficiency and to arteriosclerotic heart disease the left ventricular coronary blood flow per 100 grams per minute, was normal. The oxygen extraction was slightly elevated. Despite clinical and radiological evidence of marked left ventricular enlargement, the oxygen consumption per 100 grams per minute was only slightly elevated. Left ventricular coronary blood flows per 100 grams per minute were increased in patients with aortic insufficiency, arteriovenous fistula, and hyperthyroidism. The left ventricular coronary blood flow was normal in the patient with aortic stenosis. The left ventricular oxygen consumption per 100 grams per minute was normal in patients with aortic stenosis, with arteriovenous fistula, and with hyperthyroidism. It was elevated in the patient with aortic insufficiency. In one patient with clinical and electrocardiographic evidence of coronary occlusion with myocardial damage, the left ventricular coronary flow per 100 grams per minute, the oxygen extraction, and the left ventricular oxygen consumption per 100 grams per minute were markedly reduced. The results indicate that chronic increase in the energy requirements of the heart were met, not by an increase in the oxygen consumption per unit weight, but by an increase in the total oxygen consumption due to hypertrophy. The efficiency of the failing heart was low as a result of markedly decreased work in conjunction with slightly increased oxygen consumption.

THE EFFECTS OF DIHYDROERGOCORNINE ON THE CEREBRAL CIRCULATION OF PATIENTS WITH ESSENTIAL HYPERTENSION

The cerebral vascular resistance is increased in patients with essential hypertension as shown by cerebral blood flow measurements ( 1-3). Following differential spinal sympathetic block this high cerebral vascular resistance is reduced, coincident with a fall in arterial blood pressure (4, 5). However, the cerebral blood flow during the hypotensive period became significantly diminished. This inadequacy might be explained by the fact that differential spinal sympathetic anesthesia induces dilatation in the vascular beds of the regions blocked, and only indirectly affects the brain (6). Depressor drugs, such as adrenergic blocking agents administered parenterally, can act on the brain as well as on extracerebral areas and could have effects on cerebral blood flow and cerebral vascular resistance somewhat different from those of differential spinal block. The effects of dihydrogenated derivatives of ergot on the blood pressure of patients with essential hypertension were first reported in 1947 (7). Later studies concerning the effect of these drugs on the peripheral circulation of normal men (8) and hypertensive patients (9, 10) have suggested that the dihydrogenated compounds derived from the ergotoxin fraction of the crude extract have depressor, vasodilator, and adrenolytic properties (11, 12). Among the dihydrogenated ergot compounds studied by Freis and his associates, dihydroergocornine was found to have the greatest hypotensive effect in essential hypertension (9).

Observations on the results of subtotal adrenalectomy in the treatment of severe, otherwise intractable hypertension and their bearing on the mechanism by which hypertension is maintained.

Excerpt The desirability of more effective measures for the treatment of patients with severe arterial hypertension than those now available is conceded by most students of this subject. Although h...

CORONARY BLOOD FLOW AND CARDIAC OXYGEN METABOLISM DURING NICOTINE‐INDUCED INCREASES IN LEFT VENTRICULAR WORK*

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,

Effects of Hypertensin on Arterial Pressure, Heart Work and Cardiac Oxygen Utilization

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. * The work described in this article was supported in part by Research Grant H-1817 from the National Heart Institute, Public Health Service, Rethesda, Md., by Research Grant QH-17 from the Tobacco Industry Research Committee, New York, N. Y . , by Research Grant UV-25 from the Committee on Problems of Alcohol of the National Academy of Sciences--National Research Council, Washington, D. C., and hy a research grant from the Heart Association of Southeastern Pennsylvania, Philadelphia, Pa. t Postdoctoral Research Fellow of the National Heart Institutc (HF-6498) a t Lankenau Hospital, Philadelphia, Pa. (1956-1958).

The clinical course following adrenal resection and sympathectomy, of 82 patients with severe hypertension.

,Made available as Hypertensin-Ciba (BA19990.4) by Albert Plummer of Ciba Pharmaceutical Products, Inc., Summit, N. J.

Coronary Sinus Catheterization Technique for Studying Coronary Blood Flow and Myocardial Metabolism in vivo.

Pharmacodynamically induced changes in left ventricular work, using an intravenous infusion of Hypertensin, were studied in intact anesthetized dogs. Coronary and systemic hemodynamics and cardiac metabolism under a combined morphine- “Dial” -urethane-pentobarbital-sodium (MDUP) anesthesia were measured during the action of the drug. The significant hemodynamic changes induced were increased mean arterial pressure and increased left ventricular work. A greater cardiac lactate utilization during the Hypertensin infusion was the only change in cardiac metabolism. The oxygen tension in left ventricular venous blood was not reduced during the action of the drug.

Further observations on patients with severe hypertension subjected to adrenal resection and sympathectomy.

Excerpt INTRODUCTION Previous reports of our testing of operations for hypertension, combining adrenal resection with sympathectomy, have indicated encouraging results.1, 2, 3, 4The number of patie...

The oxygen content of coronary venous blood as affected by anoxia and cytochrome c.

Summary Coronary sinus catheterization technique has been developed in intact dogs in order to study coronary blood flow and myocardial metabolism, and to evaluate the safety and practicality of a similar procedure in man. The pathological findings, among 30 autopsies following the procedure, have been discussed. The authors are very much indebted to Drs. S. S. Kety, C. F. Schmidt, and E. J. Bing for their help and advice, and to W. P. McShane, E. C. Johnson, Miss Alice Willis, Miss Sarah Bederman, and Mrs. Pauline Wilson for skillful technical assistance.

Blood Flow and Oxygen Consumption of the Brain in Coarctation of the Aorta.

Excerpt INTRODUCTION It has now been four years since our first patient was submitted to adrenal resection and three years since the first report to this College.1We are aware that it may well requ...