Ventricular fibrillation induced by ischemia-reperfusion is not prevented by the NPY Y2 receptor antagonist BIIE0246

J Cardiovasc Pharmacol Ther. 2006 Sep;11(3):177-83. doi: 10.1177/1074248406292709.

Abstract

Neuropeptide Y is released together with norepinephrine from sympathetic nerve terminals during conditions of increased sympathetic activity. Neuropeptide Y is known to inhibit vagal activity, and accordingly, it might increase the risk for ventricular fibrillation during myocardial ischemia-reperfusion, with concomitant sympathetic stimulation. Counteracting the inhibiting effect of neuropeptide Y by the specific neuropeptide Y2 antagonist, BIIE0246, we expected occurrence of ventricular fibrillation in association with repeated periods of myocardial ischemia-reperfusion to decrease. The midleft anterior descending coronary artery was repeatedly occluded in 16 open-chest pigs. Eight pigs received BIIE0246, and the controls received the vehicle only. Ventricular fibrillation developed in 2 animals of the control group, but in 4 pigs receiving BIIE0246. Occurrence of ventricular fibrillation and ventricular tachycardia did not differ significantly between the 2 groups, and in association with repeated periods of regional myocardial ischemia, did not decline in pigs treated by the specific neuropeptide Y2-receptor antagonist BIIE0246.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Arginine / pharmacology
  • Benzazepines / blood
  • Benzazepines / pharmacology*
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Body Temperature / drug effects
  • Carbon Dioxide / analysis
  • Carbon Dioxide / blood
  • Cardiac Output / drug effects
  • Coronary Circulation / drug effects
  • Coronary Stenosis / complications
  • Disease Models, Animal
  • Female
  • Heart Rate / drug effects
  • Hematocrit
  • Male
  • Myocardial Reperfusion / adverse effects*
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / prevention & control
  • Oxygen / analysis
  • Oxygen / blood
  • Potassium / blood
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Receptors, Neuropeptide Y / blood
  • Swine
  • Tachycardia, Ventricular / etiology
  • Tachycardia, Ventricular / physiopathology
  • Tachycardia, Ventricular / prevention & control
  • Ventricular Fibrillation / etiology*
  • Ventricular Fibrillation / physiopathology
  • Ventricular Fibrillation / prevention & control*

Substances

  • Benzazepines
  • Biomarkers
  • Receptors, Neuropeptide Y
  • neuropeptide Y2 receptor
  • Carbon Dioxide
  • Arginine
  • BIIE 0246
  • Potassium
  • Oxygen