The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury.

Autor: Leivaditis V; Department of Cardiothoracic and Vascular Surgery, Westpfalz-Klinikum, Hellmut-Hartert-Strasse 1, 67655 Kaiserslautern, Germany.; Department of Cardiothoracic Surgery, University Hospital of Patras, 26504 Patras, Greece., Koletsis E; Department of Cardiothoracic Surgery, University Hospital of Patras, 26504 Patras, Greece., Tsopanoglou N; Department of Pharmacology, School of Medicine, University of Patras, 26504 Patras, Greece., Charokopos N; Department of Cardiothoracic Surgery, University Hospital of Patras, 26504 Patras, Greece., D'Alessandro C; Laboratory of Biomechanics & Biomedical Engineering, Department of Mechanical Engineering & Aeronautics, University of Patras, 26504 Patras, Greece., Grapatsas K; Department of Thoracic Surgery, Medical Center-University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany., Apostolakis E; Department of Cardiothoracic Surgery, University Hospital of Ioannina, 45500 Ioannina, Greece., Choleva E; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504 Patras, Greece., Plota M; Department of Microbiology, School of Medicine, University of Patras, 26504 Patras, Greece., Emmanuil A; Laboratory of Hematology, University Hospital of Patras, 26504 Patras, Greece., Dahm M; Department of Cardiothoracic and Vascular Surgery, Westpfalz-Klinikum, Hellmut-Hartert-Strasse 1, 67655 Kaiserslautern, Germany., Dougenis D; Department of Cardiothoracic Surgery, Attikon University Hospital of Athens, 12462 Athens, Greece.
Jazyk: angličtina
Zdroj: Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2022 Aug 12; Vol. 9 (8). Date of Electronic Publication: 2022 Aug 12.
DOI: 10.3390/jcdd9080263
Abstrakt: (1) Background: The present study aims to investigate the effect of administration of Levosimendan and Exenatide in various concentrations, as well as of the coadministration of those agents in an ischemia-reperfusion injury isolated heart model. (2) Methods: After 30 min of perfusion, the hearts underwent a 30 min period of regional ischemia followed by a 120 min period of reperfusion. All animals were randomly divided into 12 experimental groups of nine animals in each group: (1) Control, (2) Sham, (3) Digox (Negative control, Digoxin 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), (9) Exen 1 (Exenatide 0.001 μg/min), (10) Exen 2 (Exenatide 0.01 μg/min), (11) Exen 3 (Exenatide 0.1 μg/min) and (12) Combi (Levosimendan 0.1 µg/mL + Exenatide 0.001 μg/min). The hemodynamic parameters were recorded throughout the experiment. Arrhythmias and coronary flow were also evaluated. After every experiment the heart was suitably prepared and infarct size was measured. Markers of myocardial injury were also measured. Finally, oxidative stress was evaluated measuring reactive oxygen species. (3) Results: A dose-dependent improvement of the haemodynamic response was observed after the administration of both Levosimendan and Exenatide. The coadministration of both agents presented an even greater effect, improving the haemodynamic parameters further than the two agents separately. Levosimendan offered an increase of the coronary flow and both agents offered a reduction of arrhythmias. A dose-dependent reduction of the size of myocardial infarction and myocardial injury was observed after administration of Levosimendan and Exenatide. The coadministration of both agents offered a further improving the above parameters. Levosimendan also offered a significant reduction of oxidative stress. (4) Conclusions: The administration of Levosimendan and Exenatide offers a significant benefit by improving the haemodynamic response, increasing the coronary flow and reducing the occurrence of arrhythmias, the size of myocardial injury and myocardial oxidative stress in isolated rat hearts.
Databáze: MEDLINE