title: Inhibition of adenosine deaminase and administration of adenosine increase hypoxia induced ventricular ectopy.
abstract: Eighteen anesthetized, instrumented beagles (both genders, 10.4 +/- 0.5 kg) were used to investigate the effects of administered adenosine (n = 6), erythro-9-(2-hydroxy, 3-nonyl)adenine (EHNA), a potent inhibitor of endogenous adenosine deaminase (n = 6), and saline (n = 6), on the incidence of ventricular arrhythmias caused by systemic hypoxia (5% O2, 95% N2, PaO2 = 21 +/- 3 mmHg). After dogs were instrumented and monitored variables were in the steady-state, the above compounds were infused continuously into the cannulated left anterior descending (LAD) coronary artery for three minutes before, and throughout a four-minute period of hypoxia. After approximately 4 min of hypoxia the rates of ventricular ectopy [(total beats-normal beats)/total beats x 100 = % ectopy] were 73 +/- 9%, 73 +/- 11%, and 35 +/- 8% for the three groups, respectively. The percent ectopy of the adenosine- and EHNA-treated dogs was significantly greater (p < 0.05) than that for the saline-treated controls. These findings suggest that adenosine contributes to the ventricular arrhythmias of experimental systemic hypoxia.
authors.affiliation: Department of Biological Sciences, Busch Campus, Piscataway, New Jersey 08855-1059, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Leone
authors.forename: G F
authors.initials: GF
authors.lastname: Merrill
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D004285:Dogs; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000201:enzymology / Q000503:physiopathology*; D006439:Hemodynamics; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000201:enzymology
chemical_list: D058892:Adenosine Deaminase Inhibitors; D004791:Enzyme Inhibitors; C010192:9-(2-hydroxy-3-nonyl)adenine; D000225:Adenine; D000241:Adenosine