biie-0246 and Coronary-Stenosis

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.

Topics: Animals; Arginine; Benzazepines; Biomarkers; Blood Pressure; Body Temperature; Carbon Dioxide; Cardiac Output; Coronary Circulation; Coronary Stenosis; Disease Models, Animal; Female; Heart Rate; Hematocrit; Male; Myocardial Reperfusion; Myocardial Reperfusion Injury; Oxygen; Potassium; Receptors, Neuropeptide Y; Swine; Tachycardia, Ventricular; Ventricular Fibrillation