Levosimendan during Cardiac Surgery Improves Cardiac Function in Ischemic Rat Hearts

Objectives: Levosimendan as a calcium sensitizer has been shown to have minor effects in patients undergoing cardiac surgery in clinical studies. To investigate this experimentally, we evaluated the influence of Levosimendan administered 24 hour before cardiac arrest on myocardial cell function.

Methods: In 53 rats, levosimendan (Levo oral group) or NaCl (control group) was administered via drinking water 24 hours before the experiment. For investigation of cardiac function, the rats' hearts were inserted in a Langendorff apparatus with a cardioplegia time (90 minutes) or a global cardiac arrest (45 minutes) in the Levo oral group and compared with the same experiments in the control group. During reperfusion, cardiac function parameters were measured, these values were normalized to baseline (% BL). To evaluate cell function, the cardiomyocytes of the rat hearts were isolated and their function was measured.

Result: Oral application of levosimendan resulted in therapeutic plasma concentrations. Before cardiac arrest, the hearts treated with Levo had similar LVPsys (113 ± 32 mm Hg), and similar heart rate (188 ± 43 bpm) compared with NACl (113 ± 28 mm Hg, 218 ± 48 bpm), but cell shortening was increased in the Levo group (ΔL/L: 7.80 ± 1.79% vs. 6.50 ± 1.87%; +20%). After 45-minute ischemia and 90-minute reperfusion, Levo hearts showed better recovery than NaCl hearts (LVDP: 63 ± 34 vs. 44 ± 37 mm Hg; p = 0.03). In isolated cardiomyocytes, cell shortening was also significantly better (+22%) in the Levo group (ΔL/L: 7.65 ± 1.95%) than in the NaCl group (ΔL/L: 6.28 ± 1.67%). In hearts treated with cardioplegia, LVDP recovery in the Levo group was slightly improved (57.9 ± 13.3 vs. 47.8 ± 25.2 mm Hg; p = 0.33) but not in cells isolated from hearts after cardioplegia (ΔL/L: 6.64 ± 1.85% vs. 6.65 ± 2.427%; ±0%).

Conclusion: Levosimendan applied orally more than 24 hours before ischemia/reperfusion led to better cardiac recovery from ischemia than NaCl, but only to minimal improvement when cardioplegic arrest was induced. Thus, the ability of levosimendan to improve cardiac recovery is slightly lost when clinical conditions are mimicked.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
19 February 2021