The Dose-Dependent Cardioprotective Effect of Levosimendan against Ischemia/Reperfusion Injury in an Isolated Rat Heart Experimental Model

Background: This study aims to investigate the dose-dependent effect of levosimendan in an experimental model of ischemia–reperfusion injury in isolated rat hearts.

Method: The Langendorff's isolated heart perfusion model was used. The isolated rat hearts underwent 30 minutes of perfusion, a 30-minute period of regional ischemia, and a 120-minute period of reperfusion. Animals were randomly divided into eight experimental groups of nine animals in each group: (1) control, (2) sham, (3) digox (negative control, digoxin of 1.67 μg/min), (4) levo 1 (levosimendan: 0.01 μg/min), (5) levo 2 (levosimendan: 0.03 μg/mL), (6) levo 3 (levosimendan: 0.1 μg/min), (7) levo 4 (levosimendan: 0.3 μg/min), (8) levo 5 (levosimendan: 1 μg/min). Hemodynamic parameters were recorded throughout the experiment. Occurrence of arrhythmias and coronary flow were also studied. At the end of every experiment, the infarct size was measured and evaluated. Markers of myocardial injury were also recorded. Finally, reactive oxygen species were measured.

Results: A dose-dependent improvement of the hemodynamic response was observed after the administration of levosimendan in various concentrations. Levosimendan offered a significant increase of the coronary flow and a reduction of arrhythmias. A dose-dependent reduction of the size of myocardial infarction, myocardial injury was also demonstrated.

Conclusion: The administration of levosimendan offers a significant improvement in the hemodynamic response of isolated hearts, an increase of the coronary flow, and a significant reduction of the occurrence of arrhythmias, of the size of myocardial infarction and oxidative stress in isolated rat hearts.

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Artikel online veröffentlicht:
28. Januar 2023