title: Role of endogenous adenosine in postdefibrillation bradyarrhythmia and hemodynamic depression.
abstract: 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.
authors.affiliation: Department of Medicine, University of Virginia Medical Center, Charlottesville.
authors.forename: R C
authors.initials: RC
authors.lastname: Wesley
authors.forename: L
authors.initials: L
authors.lastname: Belardinelli
mesh_terms: D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000209:etiology* / Q000503:physiopathology; D004176:Dipyridamole / Q000494:pharmacology; D004554:Electric Countershock / Q000009:adverse effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects; D013552:Swine; D014970:Xanthines / Q000494:pharmacology
chemical_list: D014970:Xanthines; D004176:Dipyridamole; C053414:BW A1433U; D008729:Methoxamine; D000241:Adenosine