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

(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 un...

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Main Authors: Vasileios Leivaditis, Efstratios Koletsis, Nikolaos Tsopanoglou, Nikolaos Charokopos, Cristian D’Alessandro, Konstantinos Grapatsas, Efstratios Apostolakis, Effrosyni Choleva, Maria Plota, Andreas Emmanuil, Manfred Dahm, Dimitrios Dougenis
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Journal of Cardiovascular Development and Disease
Subjects:
Online Access:https://www.mdpi.com/2308-3425/9/8/263
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author Vasileios Leivaditis
Efstratios Koletsis
Nikolaos Tsopanoglou
Nikolaos Charokopos
Cristian D’Alessandro
Konstantinos Grapatsas
Efstratios Apostolakis
Effrosyni Choleva
Maria Plota
Andreas Emmanuil
Manfred Dahm
Dimitrios Dougenis
author_facet Vasileios Leivaditis
Efstratios Koletsis
Nikolaos Tsopanoglou
Nikolaos Charokopos
Cristian D’Alessandro
Konstantinos Grapatsas
Efstratios Apostolakis
Effrosyni Choleva
Maria Plota
Andreas Emmanuil
Manfred Dahm
Dimitrios Dougenis
author_sort Vasileios Leivaditis
collection DOAJ
description (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.
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spelling doaj.art-f6373c38de914005a23102c7a0a132392023-11-30T21:39:58ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252022-08-019826310.3390/jcdd9080263The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion InjuryVasileios Leivaditis0Efstratios Koletsis1Nikolaos Tsopanoglou2Nikolaos Charokopos3Cristian D’Alessandro4Konstantinos Grapatsas5Efstratios Apostolakis6Effrosyni Choleva7Maria Plota8Andreas Emmanuil9Manfred Dahm10Dimitrios Dougenis11Department of Cardiothoracic and Vascular Surgery, Westpfalz-Klinikum, Hellmut-Hartert-Strasse 1, 67655 Kaiserslautern, GermanyDepartment of Cardiothoracic Surgery, University Hospital of Patras, 26504 Patras, GreeceDepartment of Pharmacology, School of Medicine, University of Patras, 26504 Patras, GreeceDepartment of Cardiothoracic Surgery, University Hospital of Patras, 26504 Patras, GreeceLaboratory of Biomechanics & Biomedical Engineering, Department of Mechanical Engineering & Aeronautics, University of Patras, 26504 Patras, GreeceDepartment of Thoracic Surgery, Medical Center-University of Freiburg, Faculty of Medicine, 79106 Freiburg, GermanyDepartment of Cardiothoracic Surgery, University Hospital of Ioannina, 45500 Ioannina, GreeceLaboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504 Patras, GreeceDepartment of Microbiology, School of Medicine, University of Patras, 26504 Patras, GreeceLaboratory of Hematology, University Hospital of Patras, 26504 Patras, GreeceDepartment of Cardiothoracic and Vascular Surgery, Westpfalz-Klinikum, Hellmut-Hartert-Strasse 1, 67655 Kaiserslautern, GermanyDepartment of Cardiothoracic Surgery, Attikon University Hospital of Athens, 12462 Athens, Greece(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.https://www.mdpi.com/2308-3425/9/8/263LevosimendanExenatideischemia-reperfusion injuryisolated rat heartcardioprotection
spellingShingle Vasileios Leivaditis
Efstratios Koletsis
Nikolaos Tsopanoglou
Nikolaos Charokopos
Cristian D’Alessandro
Konstantinos Grapatsas
Efstratios Apostolakis
Effrosyni Choleva
Maria Plota
Andreas Emmanuil
Manfred Dahm
Dimitrios Dougenis
The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury
Journal of Cardiovascular Development and Disease
Levosimendan
Exenatide
ischemia-reperfusion injury
isolated rat heart
cardioprotection
title The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury
title_full The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury
title_fullStr The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury
title_full_unstemmed The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury
title_short The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury
title_sort coadministration of levosimendan and exenatide offers a significant cardioprotective effect to isolated rat hearts against ischemia reperfusion injury
topic Levosimendan
Exenatide
ischemia-reperfusion injury
isolated rat heart
cardioprotection
url https://www.mdpi.com/2308-3425/9/8/263
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