Papp Julius Gy, Pollesello Piero, Varró András, Végh Agnes, Udvary Eva
Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, H-6701 Szeged, Hungary.
Basic Clin Pharmacol Toxicol. 2006 Jul;99(1):27-32. doi: 10.1111/j.1742-7843.2006.pto_394.x.
The haemodynamic and electrophysiological effects of levosimendan were studied in conscious dogs receiving long-term oral amiodarone treatment. Instrumented dogs were administered increasing doses of levosimendan (up to 0.9 microg/kg/min. intravenously) in three successive 30 min. infusions. This schedule was repeated on the 21st day of treatment with oral amiodarone 100 mg/kg/day. The extent of increase in left ventricular systolic pressure (LVSP) and the decrease in left ventricular end-diastolic pressure (LVEDP) seen with levosimendan were similar before and after long-term treatment with amiodarone. The levosimendan-induced increases in isovolumic contraction (+dP/dt) and in left ventricular contractility (dP/dt/P) seen prior to amiodarone administration were augmented during amiodarone treatment, an effect that was statistically significant (P<0.05) at the highest doses of levosimendan. A tendency towards a shortening of the QT interval and a rise in heart rate was observed for levosimendan alone but they did not exceed the physiological range when the drug was given in combination with amiodarone. QTc value was unaffected by levosimendan either alone or with amiodarone. These effects were apparent in animals with therapeutically meaningful plasma levels of levosimendan, amiodarone and desethylamiodarone levels. The results of this study show that the improvement in ventricular contractile performance usually associated with administration of levosimendan was somewhat enhanced by chronic oral treatment with amiodarone. It seems reasonable to infer that the inotropic potency and electrophysiological safety of parenteral levosimendan will be maintained in patients with heart failure during long-term treatment with oral amiodarone.
在接受长期口服胺碘酮治疗的清醒犬中研究了左西孟旦的血流动力学和电生理效应。对植入仪器的犬连续3次静脉输注递增剂量的左西孟旦（静脉注射剂量高达0.9μg/kg/min），每次输注30分钟。在口服胺碘酮100mg/kg/天治疗的第21天重复此给药方案。胺碘酮长期治疗前后，左西孟旦引起的左心室收缩压（LVSP）升高程度和左心室舒张末期压力（LVEDP）降低程度相似。在给予胺碘酮之前，左西孟旦引起的等容收缩期（+dP/dt）和左心室收缩性（dP/dt/P）增加在胺碘酮治疗期间增强，在左西孟旦最高剂量时这种效应具有统计学意义（P<0.05）。单独使用左西孟旦时观察到QT间期缩短和心率升高的趋势，但与胺碘酮联合使用时，这些变化未超过生理范围。单独使用或与胺碘酮联合使用时，左西孟旦均不影响QTc值。在左西孟旦、胺碘酮和去乙基胺碘酮血浆水平具有治疗意义的动物中，这些效应明显。本研究结果表明，长期口服胺碘酮治疗可使通常与左西孟旦给药相关的心室收缩性能改善有所增强。可以合理推断，在口服胺碘酮长期治疗的心力衰竭患者中，静脉注射左西孟旦的正性肌力作用和电生理安全性将得以维持。
