Intracoronary endothelin-1 infusion combined with systemic isoproterenol treatment: antagonistic arrhythmogenic effects

Endothelin-1 secretion and sympathetic activation may play important role in cardiovascular pathophysiology. In vivo interactions between these systems are not defined. We aimed to study the electrophysiological and haemodynamic effects of simultaneous intracoronary endothelin-1 and intravenous isoproterenol infusions. 18 anaesthetised open chest dogs were studied after AV-ablation. Mean arterial blood pressure, coronary blood flow, left ventricular contractility, standard electrocardiograms, right and left ventricular epi- and endocardial monophasic action potential (MAP) signals were recorded. Intracoronary endothelin-1 (30 pmol/min) was given to Group ET (n=6), intravenous isoproterenol (0.2 microg/kg/min) to Group ISO (n=6), both endothelin-1 and isoproterenol to Group ET+ISO (n=6) for 30 min. MAP duration increased in all studied regions of Group ET, decreased in all studied regions of Group ISO and ET+ISO (control vs. maximal changes of left ventricular epicardial MAP 90% duration, Group ET: 296+/-22 vs 369+/-20 ms, p<0.05, Group ISO: 298+/-18 vs 230+/-27 ms, p<0.01, Group ET+ISO: 302+/-18 vs 231+/-10 ms, p<0.01). In Group ET, early after depolarisations (3/6), polymorphic non-sustained ventricular tachycardias (6/6), and ventricular fibrillation (3/6) could be observed. In Group ISO, monomorphic non-sustained ventricular tachycardias (5/6) and atrial fibrillation (3/6) appeared. In Group ET+ISO, mono- and polymorphic non-sustained ventricular tachycardias occurred (5/6), neither ventricular fibrillation nor atrial fibrillation developed. An additive effect of endothelin-1 and isoproterenol on left ventricular contractility was observed. Isoproterenol treatment showed antagonistic effect against endothelin-1 induced MAP duration prolongation, early after depolarisation and ventricular fibrillation formation, while endothelin-1 showed protective effect against the development of isoproterenol induced atrial fibrillation.