This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Friedrichs, G. S. Articles by Lucchesi, B. R. Search for Related Content PubMed Articles by Friedrichs, G. S. Articles by Lucchesi, B. R. Social Bookmarking                         What's this?

Adrenergic-dependent Effect of Adenosine-induced Ventricular Fibrillation in the Isolated Rabbit Heart

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Liguo Chi

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

James L. Park

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Benedict R. Lucchesi

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Background: The present study examined the contributory role of endogenous cate cholamines in adenosine-induced ventricular fibrillation in isolated rabbit hearts.

Methods and Results: Cardiac catecholamine depletion was induced in eleven rabbits by the administration of 6-hydroxydopamine (2 x 30 mg/kg, every 12 hours intramuscularly). Hearts were removed 24 hours later, and subjected to 12 minutes of hypoxic perfusion fol lowed by 40 minutes of reoxygenation while heart rate was maintained with atrial pacing. One of six, and one of five hearts from 6-hydroxydopamine treated rabbits developed ventric ular fibrillation during hypoxia-reoxygenation when exposed to 3,7-dimethyl-1-propar gylzanthine (DMPX) (10 µM) + adenosine (ADO) (1 µM) and DMPX (10 µM) + ADO (10 µM), respectively. In hearts from a control group, not exposed to 6-hydroxydopamine, ven tricular fibrillation developed in each of five (100% incidence) hearts when perfused in the presence of DMPX (10 µM) + ADO (10 µM) (P < .05). Nadolol (1 µM), a ß-adrenoceptor antagonist, decreased the incidence of ventricular fibrillation (30%) in a separate group of DMPX (10 µM) + ADO (10 µM) treated hearts (n = 6, P < .05 vs DMPX + ADO treated hearts). To ensure catecholamine depletion. spontancously beating isolated hearts from vehi cle and 6-hydroxydopamine treated rabbits were perfused under normoxic conditions while exposed to increasing concentrations of tyramine ( 1, 3, 10 mM) and the change in heart rate was determined. A concentration-related, positive chronotropic response to tyramine was obtained in hearts from the vehicle treated group that was absent in hearts from 6-hydroxy dopamine treated rabbits or hearts perfused in the presence of nadolol.

Conclusions: The results demonstrate that inhibition of the cardiac adenosine A₂ receptor, unmasks an adenosine A₁ receptor profibrillatory effect that is dependent upon endogenous cardiac catecholamines and ß-adrenoreceptor activation during myocardial hypoxia-reoxy genation.

Key Words: adenosine receptors • cardiac electrophysiology • isolated perfused heart • myocar dial hypoxia • catecholamines.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 2, No. 4, 299-308 (1997)
DOI: 10.1177/107424849700200408


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?