Intrapericardial infusion of endothelin-1 induces ventricular arrhythmias in dogs

Objectives: Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients with heart disease; however, the pathophysiological importance of this finding is not known. The present study was designed to characterize ET-1 levels in canine pericardial fluid and to investigate the effects of local high concentrations of exogenous ET-1 in vivo. Methods: In anesthetized, open-chest dogs ET-1 (Groups 1 and 2: 11 and 33 pmol·kg−1·min−1; n =6 and 6, respectively) or physiological saline (Group 3, n =5) were infused into the closed pericardial sac for 40 min. In serial pericardial fluid and aortic blood plasma samples, ET-1 levels were measured by radioimmunoassay, and analysed by high-performance liquid chromatography (HPLC). Systemic arterial blood pressure, heart rate, cardiac output (CO), standard ECG and right ventricular endocardial monophasic action potentials (MAPs) were recorded. Results: Basal pericardial fluid ET-1 levels were significantly higher than respective plasma levels (342±210 vs. 8.0±5.2 pmol·l−1, n =14, P