Adenosine modifies canine myocardial blood flow response to hypocapnia and hypercapnia, while aminophylline and verapamil do not

Variations of arterial Pco2 and pH are known to influence myocardial blood flow (MBF) in that hypercapnia results in a coronary vasodilatation, while hypocapnia possibly decreases MBF. The present study was performed to examine if hypocapnia and hypercapnia might influence the sensitivity to exogenous administration of adenosine. Aminophylline, an adenosine receptor blocking agent, was administered to rule out the effect of endogenously liberated adenosine during variations of Pco2 and pH. In the last part of the study, it was examined whether verapamil, a calcium-channel blocker, might influence the MBF response to variations in Pco2 and pH. Closed-chest dogs were anaesthetized with pentobarbital, and hypocapnia induced by hyperventilation. Carbon dioxide was added to the inspiratory gas to create normocapnia and hypercapnia. In the control group hypocapnia did not significantly reduce MBF although a decrease in coronary sinus (CS) So2 indicated a coronary vasoconstriction. During continuous adenosine infusion (7.5 ± 0.3 mg kg h) which increased MBF 116% during normocapnia, creating hypocapnia caused a 40% decrease in MBF. Hypercapnia seemed to potentiate the vasodilating effect of adenosine. During administration of aminophylline hypocapnia did not cause any decrease in MBF, while hypercapnia increased MBF by 39%, and these results are in harmony with the results obtained in the control group without aminophylline. Verapamil did not result in any altered MBF response to hypocapnia and hypercapnia when compared to the unblocked control group. These observations do not support the idea of any major influence of the Ca2+ fluxes blocked by verapamil as the cause of MBF changes during variations in Pco2 and pH. In conclusion, the findings following aminophylline administration indicate that MBF regulation during variations in Pco2 and pH is not determined by altered endogenous adenosine formation. The altered sensitivity to exogenously administered adenosine observed during hypocapnia and hypercapnia indicates another mechanism by which adenosine might regulate MBF. Verapamil, a calcium-channel blocker, did not influence the response of MBF to variations of Pco2 and pH.