ADENOSINE-DEAMINASE AND BW A1433U ATTENUATE HYPOXIA-INDUCED VENTRICULAR ECTOPY

Twenty-six beagles of either sex, weighing 10.4 +/- 0.3 kg, were used to investigate the role of adenosine in the genesis of ventricular arr hythmias during systemic hypoxia. After instrumentation dogs were rand omly assigned to one of four treatment groups: 14 dogs were pretreated before hypoxia with adenosine deaminase (n = 7, group I) or its vehic le (n = 7, group II) while 12 other dogs were pretreated with the A1 s elective adenosine receptor antagonist BW A1433U (n = 6, group III) or its vehicle (n = 6, group IV). Each dog was exposed to a 3-min period of hypoxic ventilation [3% O2-5% CO2-92% N2; PO2 in arterial blood 96 +/- 3 Torr (before hypoxia), 21 +/- 1 Torr (during hypoxia)]. The per centages of ventricular ectopic beats (19) experienced in the four gro ups after 3 min of hypoxia were 21 +/- 10% (group I, P < 0.05 relative to group II), 50 +/- 2% (group II), 15 +/- 8% (group III, P < 0.05 re lative to group IV), and 42 +/- 7% (group IV). Ventricular bigeminy, t he most prominent arrhythmia seen in this study, was significantly red uced by adenosine deaminase and BW A1433U. No significant differences in other monitored cardiovascular variables were seen between adenosin e deaminase and BW A1433U treatment groups and their corresponding veh icles. These findings implicate endogenous adenosine as an arrhythmoge nic mediator during hypoxia and point to a mechanism involving the A1 adenosine receptor.