Ventricular fibrillation induced by ischemia-reperfusion is not prevented by the NPY Y2 receptor antagonist BIIE0246.
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.
Ilebekk
Arnfinn
A
Institute for Experimental Medical Research, University of Oslo, Oslo, Norway. arnfinn.ilebekk@medisin.uio.no
Eriksen
Morten
M
Sevre
Knut
K
Aspelin
Trude
T
Björkman
Jan-Arne
JA
Lyberg
Torstein
T
Nordlander
Margareta
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D001552:Benzazepines / Q000097:blood / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002245:Carbon Dioxide / Q000032:analysis / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D023921:Coronary Stenosis / Q000150:complications; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D008297:Male; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control; D010100:Oxygen / Q000032:analysis / Q000097:blood; D011188:Potassium / Q000097:blood; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000097:blood; D013552:Swine; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*
D001552:Benzazepines; D015415:Biomarkers; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D002245:Carbon Dioxide; D001120:Arginine; C403256:BIIE 0246; D011188:Potassium; D010100:Oxygen