Exploring the Pleiotropic Effects of Levosimendan
Moritz Benjamin Immohr, Alexander Jenke, Annika Jahn, Laura Döhrn, Markus Kornfeld, Antonio Pinto, Artur Lichtenberg, Payam Akhyari
Affiliation
Department of Cardiovascular Surgery, Heinrich-Heine-University Medical School, Moorenstrasse 5, Duesseldorf, Germany
Corresponding Author
Udo Boeken, Department of Cardiovascular Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, 40225 Duesseldorf, Germany, Tel: +49-(0)211-8118331; Fax: +49-(0)211-8118333; E-mail: Udo.Boeken@med.uni-duesseldorf.de
Citation
Udo Boeken, et al. CARDIA Exploring the Pleiotropic Effects of Levosimendan – Impact on Systemic Inflammatory Parameters and Molecular Salvage Pathways by Modulation of Cytokine Levels and Tissue Apoptosis Rate. (2017) J Heart Cardiol 3(1): 22-30.
Copy rights
© 2017 Udo Boeken. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Keywords
Abstract
Introduction: Although levosimendan is commonly used, recent clinical trials remain ambiguous. Extra-corporeal circulation induces Ischemia/Reperfusion Injury (IRI) and inflammation.
Methods: In our study, male rats (400 - 500 g) were cannulated, intravenously treated with 12 μg/kg body weight levosimendan (n = 4) or vehicle solution (n = 5) and connected to a heart-lung machine. To induce IRI, 45 min circulatory arrest was performed. After reperfusion, rats were euthanized. Cytokines were analyzed by ELISA and salvage pathways and apoptosis by western blot.
Results: After circulatory arrest, heart rate and blood pressure recovered faster in the levosimendan group. The need for buffering solution and catecholamines was 40% lower in the levosimendan group. Cytokines increased in both groups during the procedure but levosimendan diminished the increase of IL-6(- 44 %). Whereas activation of AKT did not differ between groups, p44-42 MAPK (+ 29%) and p38 MAPK (+ 17%) increased and STAT3 (- 55%) decreased in levosimendan heart samples. PARP-cleavage was 35% decreased in the levosimendan group indicating lower apoptosis.
Conclusions: Application of levosimendan seems to affect salvage pathways, cytokines and apoptosis. Levosimendan treated rats recovered faster and showed beneficial changes. These findings may serve our understanding of levosimendan in the context of IRI, allowing better patient tailored drug application.
