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 arrhythmias during systemic hypoxia. After instrumentation dogs were randomly assigned to one of four treatment groups: 14 dogs were pretreated before hypoxia with adenosine deaminase (n = 7, group I) or its vehicle (n = 7, group II) while 12 other dogs were pretreated with the A1 selective 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 percentages of ventricular ectopic beats (19) experienced in the four groups 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 relative to group IV), and 42 +/- 7% (group IV). Ventricular bigeminy, the most prominent arrhythmia seen in this study, was significantly reduced by adenosine deaminase and BW A1433U. No significant differences in other monitored cardiovascular variables were seen between adenosine deaminase and BW A1433U treatment groups and their corresponding vehicles. These findings implicate endogenous adenosine as an arrhythmogenic mediator during hypoxia and point to a mechanism involving the A1 adenosine receptor.
Leone
R J
RJ
Department of Biological Sciences, Rutgers, State University of New Jersey, New Brunswick 08903-0231.
Friedrichs
G S
GS
Merrill
G F
GF
D000243:Adenosine Deaminase / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006352:Heart Ventricles; D000860:Hypoxia / Q000150:complications; D008297:Male; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology*
D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D014970:Xanthines; C053414:BW A1433U; D000243:Adenosine Deaminase