Pharmacological delayed preconditioning against ischaemia-induced ventricular arrhythmias: effect of an adenosine A(1)-receptor agonist

Br J Pharmacol. 2001 Dec;134(7):1532-8. doi: 10.1038/sj.bjp.0704407.

Abstract

1. The goal of this study was to investigate the effects of the delayed pharmacological preconditioning produced by an adenosine A(1)-receptor agonist (A(1)-DPC) against ventricular arrhythmias induced by ischaemia and reperfusion, compared to those of ischaemia-induced delayed preconditioning (I-DPC). 2. Eighty-nine instrumented conscious rabbits underwent a 2 consecutive days protocol. On day 1, rabbits were randomly divided into four groups: 'Control' (saline, i.v.), 'I-DPC' (six 4-min coronary artery occlusion/4-min reperfusion cycles), 'A(1)-DPC(100)' (N(6)-cyclopentyladenosine, 100 microg kg(-1), i.v.), and 'A(1)-DPC(400)' (N(6)-cyclopentyladenosine, 400 microg kg(-1), i.v.). On day 2, i.e., 24 h later, the incidence and severity of ventricular arrhythmias during a 30-min coronary artery occlusion and subsequent reperfusion were analysed in all animals, using an arrhythmia score. 3. I-DPC, A(1)-DPC(100) and A(1)-DPC(400) significantly reduced the infarct size (34+/-5, 42+/-3 and 43+/-7% of the area at risk, respectively) as compared to Control (55+/-3% of the area at risk). 4. During both ischaemia and reperfusion, neither the incidence nor the severity of ventricular arrhythmias were altered by A(1)-DPC(100), A(1)-DPC(400) or I-DPC as compared to Control. 5. Thus, despite reduction of infarct size induced by delayed preconditioning, A(1)-DPC as well as I-DPC failed to exert any anti-arrhythmic effect in the conscious rabbit model of ischaemia-reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / physiopathology*
  • Blood Pressure / drug effects
  • Coronary Disease / complications
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Heart Rate / drug effects
  • Heart Ventricles / drug effects
  • Heart Ventricles / physiopathology
  • Hemodynamics / drug effects
  • Ischemic Preconditioning, Myocardial*
  • Male
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / pathology
  • Myocardial Ischemia / complications*
  • Myocardial Reperfusion / adverse effects
  • Purinergic P1 Receptor Agonists
  • Rabbits

Substances

  • Purinergic P1 Receptor Agonists
  • N(6)-cyclopentyladenosine
  • Adenosine