Hemodynamic and antiischemic effects of tedisamil in humans

Abstract

Twenty-four patients with angiographically documented coronary artery disease, chronic stable angina, and reproducible ST-segment depression took part in this openlabel, baseline-controlled study on the hemodynamic, antiischemic, metabolic, and neurohumoral effects of tedisamil following IV doses of 0.1, 0.2, and 0.3 mg/kg (eight patients in each dose group). Tedisamil produced a dose-dependent decrease in both heart rate [rest: 2.4, 7.5 (p .01), resp.]. While cardiac output was found decreased due to the heart-rate reduction both at rest [−8.5%, −5.7%, and −10.2% (p<.05), respectively] and during exercise (2–8%), being significant only at rest in the highest dose group, stroke volume remained unaltered. Pulmonary artery pressure, pulmonary capillary wedge pressure, right-ventricular ejection fraction, and pulmonary vascular resistance were without significant changes. Blood pressure and systemic vascular resistance tended to increase, associated with a decrease in plasma catecholamines (20–40%). Tedisamil produced a dose-dependent prolongation of QTc duration [+2%, +6%, +12% (p<.05), respectively] with PQ and QRS unaltered. The elimination half-life of tedisamil IV ranges between 6.8 and 7.8 hours. In conclusion, tedisamil, at a dose of 0.3 mg/kg IV, was well tolerated and was found to have favorable hemodynamic and antiischemic effects in patients with ischemic heart disease.