Comparative hemodynamic effects of hypotension induced by diadenosine tetraphosphate (AP4A) and ATP in dogs

Abstract

ATP and diadenosine tetraphosphate (AP4A) have been shown to produce vasodilation mediated by P1- and P2-purinoceptor, respectively. The differing mechanisms involved in this vasodilating activity may induce different systemic hemodynamic changes. We compared the hemodynamic effects of AP4A-induced hypotension with those induced by ATP. Fourteen mongrel dogs were anesthetized with 0.87% halothane in oxygen (1 MAC). After the baseline period, mean arterial pressure was reduced to 60 mmHg for 60 min by the infusion of AP4A or ATP. The ATP- and AP4A-induced hypotension resulted in a maximum reduction in systemic vascular resistance of 43% and 46%, respectively (P<0.01), associated with a significant increase in stroke volume index. With ATP, a 20% of maximum increase (P<0.05) in cardiac index (CI) was observed during the induced hypotension. In contrast, AP4A-induced hypotension did not result in any changes in CI throughout the observation period. The varying results concerning CI during the ATP- and AP4A-induced hypotension were probably due to differences in ventricular filling pressure, since AP4A-induced hypotension was associated with decreases (P<0.01) in both right atrial and pulmonary capillary wedge pressures, whereas neither of these variables significantly changed with ATP. The hypotension induced by either ATP or AP4A was associated with a significant decrease in heart rate (HR). However, both the magnitude and duration of decreases in HR due to ATP-induced hypotension were more pronounced than those seen with AP4A. In conclusion, while both drugs were equally capable of inducing hypotension, our results suggest that AP4A was more suitable for induced hypotension because of its potent vasodilatory action with venodilation and less negative chronotropic action.