Effect of Ado A1- and A2-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 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.
Chi
L
L
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Friedrichs
G S
GS
Oh
J Y
JY
Green
A L
AL
Lucchesi
B R
BR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D004573:Electrolytes / Q000097:blood / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006706:Homeostasis; D066298:In Vitro Techniques; D007700:Kinetics; D011651:Pulmonary Artery / Q000502:physiology; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D011897:Random Allocation; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology*; D014970:Xanthines / Q000494:pharmacology*
D004573:Electrolytes; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine