HEMODYNAMIC, ANTIISCHEMIC, AND NEUROHUMOR AL EFFECTS OF THE NEW POTASSIUM CHANNEL BLOCKING-AGENT TEDISAMIL IN PATIENTS WITH CORONARY-ARTERYDISEASE

Thirty-two patients with angiographically proven coronary artery disea se and reproducible ST-segment depression in the exercise ECG took par t in this open dose-finding study on the hemodynamic and antiischemic effects of tedisamil, using right heart catheterization and bicycle ex ercise testing. Tedisamil - a bispidine derivative - is a new potassiu m channel blocking agent with negative chronotropic (i.e., direct effe cts on sinus node automaticity) and class III antiarrhythmic propertie s. 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, te disamil was found to be dose-linear with the dose of 0.3 mg/kg BW havi ng the most favorable antiischemic effects accompanied by a significan t decrease in heart rate at rest (-13 %, p < 0.001) and maximum exerci se (-9 %, p < 0.05). There was a consecutive fall of CO (by 10%, p < 0 .05), while stroke volume remained unaltered. Despite singular signifi cant changes, PCWPm and RV-EE as indirect parameters of ventricular fu nction, showed different responses without a clear tendency. PAPm incr eased slightly in accordance with peripheral and pulmonary vascular re sistance, being significant at 3.3 mm Hg (p < 0.05) only at the dose o f 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 f ell in a dose-dependent way by a maximum of 115-150 pg/ml (p < 0.01) o n treatment with 0.4 mg/kg BW. QTc was found significantly prolonged b y 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 depressio n at a maximum of 42% (p < 0.001) as well as a decrease in myocardial oxygen consumption, pressure rate product, and plasma lactate concentr ations. In conclusion, tedisamil lowered heart rate and showed favorab le hemodynamic, antiischemic, and neurohumoral effects in patients wit h coronary artery disease.