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 A1 and A2 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 microM Ado when hearts were exposed to hypoxia-reoxygenation. The incidence of VF was 20% when Ado was increased to 10 microM. Inhibition of the Ado A2 receptor with 3,7-dimethyl-l-propargylxanthine (DMPX; 10 microM) increased the incidence of VF to 100% when 10 microM Ado was added to the perfusion medium. The A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM), attenuated (from 100% to 20%) VF induced by Ado + DMPX (10 microM each). The ventricular refractory period and monophasic action potential duration were determined in a separate group of hearts. Our findings indicate that 1) Ado A1-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 A1-receptor stimulation is modulated by simultaneous activation of the ventricular A2 Ado receptor.
The Protective Effect of H2-Receptor Activation Against the Duration of Myocardial Hypoxia/Reoxygenation-Induced Ventricular Fibrillation in Sensitized Guinea-Pig Hearts
