ELECTROPHYSIOLOGICAL EFFECTS OF INTRAPERICARDIAL INFUSION OF ENDOTHELIN-1

Recently, extremely high levels of endothelin-l (ET-I) were detected i n the pericardial fluid of patients undergoing open-heart surgery. ET- I has been suggested to have direct arrhythmogenic effect on myocardiu m. The aim of the present study was to examine the putative arrhythmog enic effect of intrapericardial infusion of ET-1 in anesthetized dogs (n=15). In preliminary experiments, ET-I (0.125-1.0 nmol/min, n=7) was infused into the closed pericardial sack for 40 min. ET-I induced non -sustained and/or sustained ventricular tachyarrhythmias in all but th e lowest dose. For detailed arrhythmia analysis in addition to standar d ECG ventricular endocardial and epicardial monophasic action potenti als (MAP) were recorded. ET-I (0.250 nmol/min, n=7) induced mono- and polymorphic ventricular tachycardias, which degenerated into ventricul ar fibrillation in two instances. Moderate if any ischemic signs could be detected before the onset of arrhythmias. The arrhythmias spontane ously disappeared in all instances with the exception when ventricular fibrillation terminated the experiment. Qr interval (260+/-23ms vs. 3 17+/-31ms, P<0.05), and endo- and epicardial MAPD(90) (at 300 ms cycle length) prolonged significantly (in average 182+/-12ms vs. 224+/-25ms , P<0.05). Using MAP recording afterdepolarizations were detected in t hree instances. In control animals (n=3) arrhythmias were not observed and all electrophysiological parameters remained unchanged The presen t results show that intrapericardial administration of ET-1 can induce ventricular arrhythmias in dogs. The arrhythmogenic effect of ET-1 ma y be based on prolongation of MAP duration and development of afterdep olarizations. However the elucidation of the precise mechanism needs f urther investigation.