Department of Anaesthesiology, Germany bInstitute for Laboratory Animal Science, Germany.
Eur J Anaesthesiol. 2009 Nov;26(11):946-53. doi: 10.1097/EJA.0b013e328330e9a0.
Patients in cardiac surgery and critically ill patients often demonstrate either hypothermia or fever. In addition, owing to heart failure, they frequently require inotropic support. The relative effectiveness of modern inotropic agents at various temperatures has not yet been evaluated. Therefore, we investigated the influence of levosimendan, dobutamine and milrinone on the contractile response of myocardial trabeculae at various temperatures.
A total of 120 guinea pig ventricular trabeculae were placed in oxygenated 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid (HEPES) buffer, stimulated at a frequency of 1.3 Hz and randomly assigned to a temperature of 31 degrees C, 34 degrees C, 37 degrees C or 40 degrees C. Concentrations of all substances were increased stepwise from 10(-9) to 10(-5) mol l(-1) (milrinone up to 10(-4) mol l(-1)). Maximum developed force, time to peak tension, Tsystolic(50%) and Tdiastolic(50%) were continuously recorded.
All agents showed a dose-dependent positive inotropic effect (P < 0.0001 for all). Levosimendan acted at every temperature as a positive inotrope (P = 0.0643). Dobutamine-related inotropy showed a clear trend towards temperature dependence, although statistical evaluation did not prove this (P = 0.0624). Milrinone-related inotropy was abolished at 31 degrees C and 34 degrees C, and temperature dependence was significant (P < 0.0001). Hypothermia induced a positive inotropic effect.
Our results suggest no modulation of levosimendan-induced inotropy under the experimental temperatures tested. This observation is possibly due to its Ca2+-sensitizing mechanism, which might not be influenced by temperature-related changes in intracellular Ca2+ levels. In contrast, the inotropic effect of cyclic AMP-coupled dobutamine and milrinone is suppressed under hypothermia-related interaction with intracellular Ca2+ homeostasis. Hence, levosimendan might prove to be the preferred inotropic drug in hypothermic patients.
心脏手术患者和重症患者常表现为体温过低或发热。此外，由于心力衰竭，他们经常需要正性肌力支持。不同温度下现代正性肌力药物的相对有效性尚未得到评估。因此，我们研究了左西孟旦、多巴酚丁胺和米力农在不同温度下对心肌小梁收缩反应的影响。
共将 120 个豚鼠心室小梁置于充氧的 4-(2-羟乙基)-1-哌嗪乙磺酸（HEPES）缓冲液中，以 1.3 Hz 的频率刺激，并随机分配到 31℃、34℃、37℃或 40℃。所有物质的浓度均从 10(-9)增加至 10(-5) mol l(-1)（米力农增加至 10(-4) mol l(-1)）。连续记录最大收缩力、达峰时间、Tsystolic(50%)和 Tdiastolic(50%)。
所有药物均表现出剂量依赖性正性肌力作用（所有 P < 0.0001）。左西孟旦在所有温度下均作为正性肌力药物起作用（P = 0.0643）。多巴酚丁胺相关的正性肌力作用表现出明显的温度依赖性趋势，但统计学评估未证明这一点（P = 0.0624）。米力农相关的正性肌力作用在 31℃和 34℃时被消除，且温度依赖性显著（P < 0.0001）。低温诱导正性肌力作用。
我们的结果表明，在实验温度下，左西孟旦诱导的正性肌力作用没有受到调节。这一观察结果可能是由于其 Ca2+增敏机制，而该机制可能不受细胞内 Ca2+水平与温度相关变化的影响。相比之下，与细胞内 Ca2+稳态相关的低温相关相互作用抑制了环 AMP 偶联的多巴酚丁胺和米力农的正性肌力作用。因此，左西孟旦可能是低温患者的首选正性肌力药物。
