Dissociation of adenosine from metabolic regulation of coronary flow in the lamb

Abstract

The objective of these studies was to evaluate the contribution of an adenosine mechanism to metabolic regulation of coronary flow. Cardiac O2 metabolism (MVO2) was altered by changing cardiac output while aortic pressure and heart rate were held constant (paced). Ganglionic (tetraethylammonium chloride) and beta blockade (propranolol) were employed. Relationships of coronary flow to MVO2 were determined in control and alloxan diabetic animals. The latter have previously been shown to have reduced sensitivity to adenosine [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H252-H258, 1982]. In each group, responses were measured before and after adenosine receptor blockade with aminophylline (10 mg/kg). Responses to infused adenosine were also compared. A linear relationship between adenosine infusion rate and flow was found in all conditions. Aminophylline caused a 70% reduction in adenosine sensitivity in controls. In the diabetics, adenosine sensitivity was much reduced and was identical with blocked controls. A close correlation between left ventricular work and MVO2 was found in both groups. Coronary flow increased linearly with MVO2, and the slopes before and after aminophylline were identical. Myocardial O2 extraction remained unchanged. The same relationships were found in the diabetics, and responses did not differ from controls. Thus, in two conditions of sharply reduced sensitivity to exogeneous adenosine, coronary flow (and resistance) were as equally well matched to MVO2 as in controls. These data suggest that mechanisms other than, or in addition to, adenosine provide the close link between MVO2 and coronary flow with changing cardiac work loads.