Electrophysiological properties of levosimendan during rewarming from severe hypothermia in vivo

Abstract

Introduction: Hypothermia, defined as measured core temperature below 35°C, is a lethal condition associated with complications such as hypothermia-induced cardiac dysfunction (HCD). Recent studies have shown that administration of the PDE3-inhbitor and calcium-sensitizer levosimendan might alleviate HCD. Hypothermia is also associated with proarrhythmic activity and novel ECG-markers have been able to predict ventricular arrythmias in hypothermic patients and animals. In order to evaluate the safety of levosimendan during hypothermia, it is important to investigate if it has any pro-arrhythmic effects during hypothermia and rewarming.

Material and methods: Male Wistar rats were administered levosimendan (n=7) or 5% glucose (n=7) and ECG-recordings were obtained. The hypothermic protocol included cooling from 37°C down to 15°C, a stable period at 15°C for 3 hours before rewarming to 37°C.

Results: No significant differences between levosimendan group and control group were detected for ECG-markers predicting ventricular arrythmias during the protocol. The PR-interval (40ms ± 3ms vs. 42ms ± 2ms), QRS-interval (20ms ± 1ms vs. 26ms ± 1ms) and QT-interval (49ms ± 1ms vs. 57ms ± 2ms) were significantly decreased for the levosimendan group compared to the control group when rewarmed to 37°C.

Conclusion: Levosimendan remains a promising pharmacological strategy to alleviate HCD as it shows no proarrhythmic potential in rats during the hypothermic protocol. Further studies are needed to obtain pharmacodynamic and pharmacokinetic properties of levosimendan, as well as the physiological effects during hypothermia.