Adrenergic-dependent Effect of Adenosine-induced Ventricular Fibrillation in the Isolated Rabbit Heart

Abstract

Background: The present study examined the contributory role of endogenous cate cholamines in adenosine-induced ventricular fibrillation in isolated rabbit hearts. Methods and Results: Cardiac catecholamine depletion was induced in eleven rabbits by the administration of 6-hydroxydopamine (2 x 30 mg/kg, every 12 hours intramuscularly). Hearts were removed 24 hours later, and subjected to 12 minutes of hypoxic perfusion fol lowed by 40 minutes of reoxygenation while heart rate was maintained with atrial pacing. One of six, and one of five hearts from 6-hydroxydopamine treated rabbits developed ventric ular fibrillation during hypoxia-reoxygenation when exposed to 3,7-dimethyl-1-propar gylzanthine (DMPX) (10 μM) + adenosine (ADO) (1 μM) and DMPX (10 μM) + ADO (10 μM), respectively. In hearts from a control group, not exposed to 6-hydroxydopamine, ven tricular fibrillation developed in each of five (100% incidence) hearts when perfused in the presence of DMPX (10 μM) + ADO (10 μM) ( P < .05). Nadolol (1 μM), a β-adrenoceptor antagonist, decreased the incidence of ventricular fibrillation (30%) in a separate group of DMPX (10 μM) + ADO (10 μM) treated hearts (n = 6, P < .05 vs DMPX + ADO treated hearts). To ensure catecholamine depletion. spontancously beating isolated hearts from vehi cle and 6-hydroxydopamine treated rabbits were perfused under normoxic conditions while exposed to increasing concentrations of tyramine ( 1, 3, 10 mM) and the change in heart rate was determined. A concentration-related, positive chronotropic response to tyramine was obtained in hearts from the vehicle treated group that was absent in hearts from 6-hydroxy dopamine treated rabbits or hearts perfused in the presence of nadolol. Conclusions: The results demonstrate that inhibition of the cardiac adenosine A2 receptor, unmasks an adenosine A1 receptor profibrillatory effect that is dependent upon endogenous cardiac catecholamines and β-adrenoreceptor activation during myocardial hypoxia-reoxy genation.