In
halothane-
nitrous oxide-anesthetized pigs, the effect of the competitive
adenosine antagonist,
BW-A1433U (a derivative of 1,3-dipropyl-8-phenylxanthine), on postdefibrillation
bradyarrhythmia and hemodynamic depression was investigated. In protocol 1, repetitive episodes of
ventricular fibrillation lasting 15 seconds before transthoracic DC
shock were performed in five animals, before (control) and after the administration of
BW-A1433U (5 mg/kg i.v.). An unsuccessful initial
shock was immediately followed by a rescue
shock of 40 A. In
ventricular fibrillation episodes requiring rescue shocks, nine of 19 episodes (47%) exhibited second- or third-degree
atrioventricular block at 15 seconds postdefibrillation compared with only one of 16
BW-A1433U episodes (6%). In protocol 2, the effect of
BW-A1433U was determined in the presence of
dipyridamole, a
nucleoside uptake blocker known to potentiate the cardiac actions of
adenosine. To counter the hypotensive effect of
dipyridamole,
methoxamine was continuously infused at 0.015 mg/kg/min i.v. Sequential episodes of
ventricular fibrillation lasting 45 seconds were terminated by shocks of 40 A in the presence of
methoxamine alone, after
dipyridamole (1.5-7.5 mg i.v.), and after
BW-A1433U (5 mg/kg i.v.). Over the first 15 seconds postdefibrillation,
BW-A1433U significantly (p less than 0.05) increased the number of spontaneous beats (31 +/- 2) and systolic/diastolic blood pressure (111 +/- 4/67 +/- 5 mm Hg; mean +/- SEM; n = 9) compared with both
methoxamine (16 +/- 2 beats; 98 +/- 14/52 +/- 12 mm Hg; n = 5) and
dipyridamole (8 +/- 3 beats; 58 +/- 11/27 +/- 6 mm Hg; n = 9), respectively. Rapid infusion of
BW-A1433U during
dipyridamole postdefibrillation periods raised heart rate and blood pressure to preventricular fibrillation levels within 30 seconds. Thus,
BW-A1433U can reverse and prevent postdefibrillation
bradyarrhythmia and hemodynamic depression. Endogenous
adenosine may be an important mediator of postdefibrillation cardiovascular collapse.