Effects of a 2',3',5'-substituted adenosine derivative on systemic and coronary hemodynamics and on cardiac metabolism in the anesthetized dog.

Hemodynamic and metabolic effects of 2',3'-O-methoxyethylidene-adenosine-5'-(Nethyl-carboxamide) (744-98), an adenosine analogue with long-lasting coronary dilator activity, were studied in the anesthetized, closed-chest dog. The coronary sinus outflow increased 5fold following administration of the compound (5 microgram/kg i.v.) and still remained three thimes higher than the control level after 4 h. Total peripheral resistance decreased markedly, accompanied by a baroreceptor-mediated increase in heart rate, left ventricular dp/dtmax and myocardial oxygen consumption. Blood glucose levels and glucose uptake by the heart increased concomitantly, whereas plasma free fatty acid (FFA) levels decreased markedly, without consistent changes in myocardial FFA balance. These effects are explained by antilipolytic and glucagon-releasing activities of the adenosine analogue. The myocardial oxygen extraction ratio for glucose greatly exceeded the aerobic metabolic requirement, a finding already previously obtained with coronary dilators.