Adrenergic-dependent Effect of Adenosine-induced Ventricular Fibrillation in the Isolated Rabbit Heart.
BACKGROUND: The present study examined the contributory role of endogenous catecholamines in adenosine-induced ventricular fibrillation in isolation 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 followed 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 ventricular fibrillation during hypoxia-reoxygenation when exposed to 3,7-dimethyl-1-propargylzanthine (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, ventricular 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 beta-adrenoceptor DMPX (10 µM) + ADO (10 µM) treated hearts (n = 6, P <.05 vs DMPX + ADO treated hearts). To ensure catecholamine depletion, spontaneously beating isolated hearts from vehicle 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 chronotorpic 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 A(2) receptor, unmasks an adenosine A(1) receptor profibrillatory effect that is dependent upon endogenous cardiac catecholamines and beta-adrenoreceptor activation during myocardial hypoxia-reoxygenation.
Friedrichs
GS
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA
Chi
L
Park
JL
Lucchesi
BR