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 2nmol) into the left anterior descending coronary artery. These intracoronary ET-1 boli rapidly caused a marked decrease in coronary blood flow (1nmol, 78±7%; 2nmol, 89±7%). Ischaemic changes of MAP morphology, a decrease in upstroke velocity (baseline, 1.78±0.2V/s; 1nmol, 0.95±0.18V/s; 2nmol, 0.45±0.21V/s; P<0.01) and a decrease in MAP duration at 90% repolarization (MAPD₉₀) [1nmol, from 191±3 to 176±5ms (P<0.05); 2nmol, from 212±4 to 180±8ms (P<0.05)] occurred after ET-1 bolus administration. However, at 7–10min after the 1nmol bolus, a significant increase in MAPD₉₀ was observed (10min, in the left ventricular anterior epicardial region: from 191±3 to 206±6ms; P<0.05). The incidence of ventricular arrhythmias was as follows: after the 1nmol ET-1 bolus: ventricular tachycardia, 3/8 animals; ventricular fibrillation, 1/8; after the 2nmol ET-1 bolus: ventricular tachycardia, 5/7; ventricular fibrillation, 5/7. MAP alternans was present in each animal (1nmol, 18.2±5.8%; 2nmol, 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 MAPD₉₀ 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.