EFFECT OF ADO A(1)-RECEPTOR AND A(2)-RECEPTOR ACTIVATION ON VENTRICULAR-FIBRILLATION DURING HYPOXIA-REOXYGENATION

We examined the hypothesis that adenosine (Ado)-induced alterations in ventricular electrophysiology may contribute to arrhythmogenesis in a setting of myocardial hypoxia through activation of Ado AI and A(2) receptors in the rabbit isolated perfused heart. There was a 20% incidence of ventricular fibrillation (VF) in control hearts subjected to perfusion conditions of hypoxia and reoxygenation. The incidence of VF was increased to 50% in the presence of 1 mu M Ado when hearts were exposed to hypoxia-reoxygenation. The incidence of VF was 20% when Ado was increased to 10 mu M. Inhibition of the Ado A(2) receptor with 3,7-dimethyl-l-propargylxanthine (DMPX; 10 mu M) increased the incidence of VF to 100% when 10 mu M Ado was added to the perfusion medium. The Al antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 mu M), attenuated (from 100% to 20%) VF induced by Ado + DMPX (10 mu M each). The ventricular refractory period and monophasic action potential duration were determined in a separate group of hearts. Our findings indicate that 1) Ado AL-receptor stimulation facilitates VF by decreasing action potential duration and refractoriness in hearts subjected to hypoxia and reoxygenation and 2) the arrhythmogenic potential of Ado A(1)-receptor stimulation is modulated by simultaneous activation of the ventricular A(2) Ado receptor.