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Journal of Pharmacology And Experimental Therapeutics, Vol. 91, Issue 4, 362-369, 1947
Copyright © 1947 by American Society for Pharmacology and Experimental Therapeutics

THE EFFECT OF NIKETHAMIDE ON CORONARY BLOOD FLOW AND CARDIAC OXYGEN METABOLISM

JAMES E. ECKENHOFF 1 and JOSEPH H. HAFKENSCHIEL 1

1 From the Department of Pharmacology and the Harrison Department of Surgical Research, School of Medicine, University of Pennsylvania and the Department of Anesthesiology, Hospital of the University of Pennsylvania

1. In anesthetized spontaneously breathing heparinized dogs with coronary blood flow measured by the bubble flowmeter, the effects of nikethamide, papaverine, aminophylline, amyl nitrite and nitroglycerine on coronary blood flow were measured. In order of their effectiveness these drugs could be listed as follows: papaverine, aminophylline, amyl nitrite, nitroglycerine and nikethamide.

2. An approach necessary for the proper evaluation of the effect of a drug on coronary blood flow is presented. This approach attempts to correlate a) the ratio beween the oxygen supplied to the myocardium and the oxygen demanded by the myocardium (nutritional index) and b) the efficiency of the muscle cells in making the energy transformations necessary to accomplish the work loads imposed on the heart.

3. Utilizing this approach, nikethamide when injected in large amounts was found to increase coronary blood flow but did so at the expense of a decreased mechanical efficiency.

4. In experiments on six unanesthetized dogs, nikethamide in amounts necessary to produce an increase in coronary blood flow produced convulsions in one dog and undesirable symptoms in the others. Repetition of the same or decreased dose in three animals produced convulsions and delayed death.

5. Our investigations give no indication as to why nikethamide should enjoy such a widespread clinical use in the treatment of cardiovascular disease.

Submitted on August 14, 1947




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