Mitrovic V, Oehm E, Strasser R, Schlepper M, Pitschner H F
Kerckhoff-Klinik, Bad Nauheim.
Z Kardiol. 1996 Dec;85(12):961-72.
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.
32例经血管造影证实患有冠状动脉疾病且运动心电图有可重复性ST段压低的患者参与了这项关于替地沙米血流动力学和抗缺血作用的开放剂量探索性研究，采用右心导管插入术和自行车运动试验。替地沙米——一种联吡啶衍生物——是一种新型钾通道阻滞剂，具有负性变时作用（即对窦房结自律性有直接作用）和Ⅲ类抗心律失常特性。四组，每组8例患者，静脉注射递增剂量的0.1、0.2、0.3和0.4mg/kg体重的替地沙米。结果发现，替地沙米耐受性良好，其剂量与效应呈线性关系，0.3mg/kg体重的剂量具有最有利的抗缺血作用，同时静息心率显著降低（-13%，p<0.001），最大运动时心率降低（-9%，p<0.05）。心输出量连续下降（10%，p<0.05），而每搏输出量保持不变。尽管有个别显著变化，但作为心室功能间接参数的肺毛细血管楔压均值和右室射血分数显示出不同的反应，无明显趋势。肺动脉平均压随外周和肺血管阻力略有升高，仅在0.4mg/kg体重剂量时升高3.3mmHg有显著性差异（p<0.05）。平均动脉压在静息时略有升高（0.4mg/kg体重时升高9%；p<0.05）。血浆儿茶酚胺水平在使用0.4mg/kg体重治疗时呈剂量依赖性下降，最多下降115 - 150pg/ml（p<0.01）。发现0.4mg/kg体重时QTc显著延长16%（p<0.001）。在使用0.3mg/kg体重治疗期间，替地沙米使ST段压低呈剂量依赖性降低，最大降低42%（p<0.001），同时心肌耗氧量、压力心率乘积和血浆乳酸浓度降低。总之，替地沙米可降低心率，对冠心病患者显示出有利的血流动力学、抗缺血和神经体液作用。
