Influence of hypothermia on the positive inotropic effect of levosimendan, dobutamine and milrinone

Objectives: Patients in cardiac surgery are at high risk to become dependent to inotropic support. Beside this, they frequently develop hypothermia. The effectiveness of modern inotropic agents under hypothermia have not been yet compared. Therefore we investigated the influence of levosimendan, dobutamine and milrinone on the contractile response of myocardial trabeculae under hypothermia. Methods: Guinea pig ventricular trabeculae were placed in oxygenated HEPES-buffer, stimulated at a frequency of 1.3Hz and randomized to a temperature of 31°C, 34°C and 37°C. All substances were stepwise increased from 10–9M to 10–4M. Maximum developed force was continuously recorded. Results: The inotropic effect of dobutamine was suppressed at 31°C. Milrinone related inotropy was abolished at 31°C and 34°C. Levosimendan acted at each temperature positive inotropic. At 31°C it was significant superior to dobutamine (p=0.0185) and to milrinone (p=0.0266). At 34°C it was significant superior to milrinone (p=0.0143), compared to dobutamine was no difference evident at 34°C (p=0.6305). levosimendan 10–6M dobutamine 10–5M milrinone 10–4M 31°C 125.1±13.7 107.5±18.2 101.1±20.2 34°C 126.5±14.7 147.2±69.5 103.9±16.7 Conclusion: Our results show no modulation of levosimendan induced inotropy under hypothermia. This observation is possibly due to its Ca2+-sensitizing mechanism, which might not be influenced by temperature related change of intracellular Ca2+-levels. In contrast, the inotropic effect of cAMP coupled dobutamine and milrinone is suppressed under hypothermia related interaction to intracellular Ca2+-homeostasis. Hence levosimendan might prove to be the favourable inotropic drug in hypothermic patients.