Effects of tedisamil (KC-8857) on cardiac electrophysiology and ventricular fibrillation in the rabbit isolated heart

摘要: 1. The direct cardiac electrophysiological and antifibrillatory actions of tedisamil (KC-8857) were studied in rabbit isolated hearts. 2. Tedisamil (1, 3, 10 microM), prolonged the ventricular effective refractory period (VRP) from 120 +/- 18 ms (baseline) to 155 19, 171 20, 205 14 ms, respectively. Three groups hearts (n = 6 each) used test action tedisamil. Hearts perfused with 1.25 microM pinacidil, a KATP channel activator. subjected hypoxia for 12 min followed by 40 reoxygenation. Ventricular fibrillation (VF) developed during reoxygenation both control 1 tedisamil-treated (5/6 4/6, respectively). (3 microM) reduced incidence VF (0/6, P 0.007 vs. control). 3. In separate group hearts, was initiated electrical stimulation. administration 0.3 ml mM tedisamil, via aortic cannula, terminated all converting them normal sinus rhythm. 4. reversed pinacidil-induced negative inotropic effects atrial muscle which equilibrated under normoxia, as well 5. results demonstrate vitro. mechanism responsible observed may involve modulation ATP-regulated potassium channel, addition its antagonism IK Ito.