Levosimendan during Cardiac Surgery Deteriorates Cardiac Function in Rats

Introductions: Levosimendan as a calcium sensitizer has been shown to have no or low effects in patients undergoing cardiac surgery in clinical studies. To investigate the reason for these results, we wanted to evaluate the influence of Levosimendan administered 24 hours before cardiac arrest on myocardial cell function.

Materials and Methods: In 24 rats, a pump was implanted subcutaneously 24 hours before cardiac arrest and filled with Levosimendan (experimental group Levo 24) or with NACl (control group NaCl). For investigation of cardiac function, the hearts were excised after 24 hours and inserted in a Langendorff apparatus with a cardioplegia time of 90 minutes or a global cardiac arrest time of 45 minutes in the Levo 24 group and compared to 90 min perfusion in the NaCl or in the Levo 24 group. During reperfusion, cardiac function parameters were measured. To evaluate cell function, the cardiomyocytes of the rat hearts were isolated and their function was measured.

Results: Before cardiac arrest, the hearts treated with Levo had better LVPsys (121 ± 20 mm Hg), and similar heart frequency (194 ± 52 bpm) compared with NACl (90 ± 29 mm Hg, 215 ± 75 bpm). After 45 minutes ischemia and 90 minutes cardioplegic arrest, Levo hearts (45 minutes: LVDP 21 ± 3% BL, 90 minutes: 12 ± 10% BL) showed worse cardiac function than NaCl hearts (LVDP 126 ± 17% BL) or Levo hearts without ischemia (128 ± 15%). In isolated cardiomyocytes, velocity of shortening and cell shortening were significantly better in NaCl24 (183 ± 5 µm/s and 8.03 ± 0.15%) than in the Levo24 (105 ± 4 µm/s and 5.46 ± 0.18%) group with 45 min ischemia. Especially in the cardiomyocytes undergoing cardioplegic arrest, velocity of shortening and contraction was impaired (94 ± 3 µm/s and 4.26 ± 0.18%).

Conclusion: Levosimendan applied before ischemia/reperfusion showed worse cardiac function recovery from ischemia than NaCl, especially when cardioplegic arrest was included.