PT  - JOURNAL ARTICLE
AU  - JAMES E. ECKENHOFF
AU  - JOSEPH H. HAFKENSCHIEL
TI  - THE EFFECT OF NIKETHAMIDE ON CORONARY BLOOD FLOW AND CARDIAC OXYGEN METABOLISM
DP  - 1947 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 362--369
VI  - 91
IP  - 4
4099  - http://jpet.aspetjournals.org/content/91/4/362.short
4100  - http://jpet.aspetjournals.org/content/91/4/362.full
SO  - J Pharmacol Exp Ther1947 Dec 01; 91
AB  - 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.