Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate

1 The structural conformation of diadenosine tetraphosphate (Ap(4)A) and pe ntaphosphate (Ap(5)A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac effects of Ap(4)A and Ap(5)A vary during a cidosis and myocardial ischaemia due to changes in ligand structure, recept or proteins or intracellular signalling. 2 We investigated whether the cardiac electrophysiological and coronary vas omotor effects of Ap(4)A and Ap(5)A are preserved under conditions of extra cellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap(4)A has an y electrophysiological or antiarrhythmic effects during ischaemia. 3 Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendorff-perfu sed guinea-pig hearts under constant flow conditions. The effects of 1 nM a nd 1 muM Ap(4)A and Ap(5)A were studied at pH 7.4, 6.5 and 8.5. The effects of 1 muM Ap(4)A were studied during global low-flow ischaemia and reperfus ion. 4 At pH 7.4, Ap(4)A and Ap(5)A increased action potential duration (APD(95) ) and refractory period (RP) and reduced coronary perfusion pressure. The e lectrophysiological effects were absent at pH 6.5 while the reductions in p erfusion pressure were attenuated. At pH 8.5, Ap4A increased RP but the eff ects of Ap(4)A and Ap(5)A on perfusion pressure were attenuated. During isc haemia, Ap(4)A had no antiarrhythmic or electrophysiological effects. 5 These data demonstrate the importance of extracellular pH in influencing the effects of Ap(4)A and Ap(5)A on the heart and indicate that any potenti ally cardioprotective effects of these compounds during normal perfusion at physiological pH are absent during ischaemia.