Expressed monophasic action potential alternans before the onset of ventricular arrhythmias induced by intracoronary bolus administration of endothelin-1 in dogs.
We showed previously a direct arrhythmogenic effect of the intracoronary infusion of endothelin-1 (ET-1). We aimed to examine the electrophysiological effects of intracoronary bolus administration of ET-1 using monophasic action potential (MAP) recordings. Eight mongrel dogs received boli of ET-1 (1 and 2 nmol) into the left anterior descending coronary artery. These intracoronary ET-1 boli rapidly caused a marked decrease in coronary blood flow (1 nmol, 78+/-7%; 2 nmol, 89+/-7%). Ischaemic changes of MAP morphology, a decrease in upstroke velocity (baseline, 1.78+/-0.2 V/s; 1 nmol, 0.95+/-0.18 V/s; 2 nmol, 0.45+/-0.21 V/s; P<0.01) and a decrease in MAP duration at 90% repolarization (MAPD(90)) [1 nmol, from 191+/-3 to 176+/-5 ms (P<0.05); 2 nmol, from 212+/-4 to 180+/-8 ms (P<0.05)] occurred after ET-1 bolus administration. However, at 7-10 min after the 1 nmol bolus, a significant increase in MAPD(90) was observed (10 min, in the left ventricular anterior epicardial region: from 191+/-3 to 206+/-6 ms; P<0.05). The incidence of ventricular arrhythmias was as follows: after the 1 nmol ET-1 bolus: ventricular tachycardia, 3/8 animals; ventricular fibrillation, 1/8; after the 2 nmol ET-1 bolus: ventricular tachycardia, 5/7; ventricular fibrillation, 5/7. MAP alternans was present in each animal (1 nmol, 18.2+/-5.8%; 2 nmol, 10.8+/-2.5%). Thus electrophysiological and coronary blood flow changes indicate the predominance of an ischaemic arrhythmogenic effect of the bolus administration of ET-1 (shortening of action potential duration; appearance of MAP alternans), whereas the observed delayed prolongation of MAPD(90) suggests a direct arrhythmogenic effect of ET-1. The expressed MAP alternans could have a pathogenic role in the onset of ventricular arrhythmias induced by an intracoronary bolus of ET-1.
Department of Cardiovascular Surgery, Semmelweis University, Városmajor u. 68, Budapest H-1122, Hungary. merkbe@hermes.sote.hu
Béla
B
Merkely
Hajnalka
H
Vágó
Orsolya
O
Kiss
Endre
E
Zima
Gábor
G
Szücs
László
L
Gellér
Alexander
A
Juhász-Nagy
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004285:Dogs; D019332:Endothelin-1 / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019332:Endothelin-1; D014662:Vasoconstrictor Agents