[The new potassium channel blocker tedisamil and its hemodynamic, anti-ischemic and neurohumoral effect in patients with coronary heart disease]

Abstract

Thirty-two patients with angiographically proven coronary artery disease and reproducible ST-segment depression in the exercise ECG took part in this open dose-finding study on the hemodynamic and anti-ischemic effects of tedisamil, using right heart catheterization and bicycle exercise testing. Tedisamil--a bispidine derivative--is a new potassium channel blocking agent with negative chronotropic (i.e., direct effects on sinus node automaticity) and class III antiarrhythmic properties. Four groups of 8 patients each received rising doses of 0.1, 0.2, 0.3, and 0.4 mg/kg BW tedisamil intravenously. Being well tolerated, tedisamil was found to be dose-linear with the dose of 0.3 mg/kg BW having the most favorable anti-ischemic effects accompanied by a significant decrease in heart rate at rest (-13%, p < 0.001) and maximum exercise (-9%, p < 0.05). There was a consecutive fall of CO (by 10%, p < 0.05), while stroke volume remained unaltered. Despite singular significant changes, PCWPm and RV-EF, as indirect parameters of ventricular function, showed different responses without a clear tendency. PAPm increased slightly in accordance with peripheral and pulmonary vascular resistance, being significant at 3.3 mm Hg (p < 0.05) only at the dose of 0.4 mg/kg BW. Mean arterial pressure demonstrated a slight increase at rest (9% at 0.4 mg/kg BW; p < 0.05). Plasma catecholamine levels fell in a dose-dependent way by a maximum of 115-150 pg/ml (p < 0.01) on treatment with 0.4 mg/kg BW. QTc was found significantly prolonged by 16% (p < 0.001) on 0.4 mg/kg BW. During treatment with 0.3 mg/kg BW, tedisamil produced a dose-dependent reduction of ST segment depression at a maximum of 42% (p < 0.001) as well as a decrease in myocardial oxygen consumption, pressure rate product, and plasma lactate concentrations. In conclusion, tedisamil lowered heart rate and showed favorable hemodynamic, anti-ischemic, and neurohumoral effects in patients with coronary artery disease.