Clinical application of diadenosine tetraphosphate (Ap(4)A : F-1500) for controlled hypotension

Background: In our animal study, it was revealed that diadenosine tetraphos phate (Ap(4)A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg min(-1) was confi rmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in or der to examine its hypotensive effect and modulating action on the blood pr essure. Methods: Ten patients who required controlled hypotension and who were sche duled for elective surgery under general anesthesia were studied. Anesthesi a was maintained with isoflurane (n=7) or sevoflurane(n=3) in oxygen-nitrou s oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 mu g kg(-1) min-l. The dose was adjusted at a maximum rate of 80 m u g kg(-1) min(-1) until the target blood pressure was achieved. Arterial b lood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. Results: The time required for attaining the target blood pressure after in itiation of Ap(4)A infusion was about 16 min, and the time lapse between wi thdrawal of infusion to recovery of blood pressure was about 18 min. No ref lex tachycardia was observed during infusion of Ap(4)A and no rebound hyper tension was evident after withdrawal. The plasma Ap(4)A concentration incre ased in response to the acceleration rate of Ap(4)A administration with a t endency of augmented hypotensive effect. Conclusion: As it produces an excellent hypotensive effect together with a modulating action on blood pressure, AP(4)A was assessed as useful in produ cing controlled hypotension.