Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction

Author:

Plotnikov Mark B.12ORCID,Chernysheva Galina A.1,Smol’yakova Vera I.1,Aliev Oleg I.1,Fomina Tatyana I.1,Sandrikina Lyubov A.1,Sukhodolo Irina V.3,Ivanova Vera V.3ORCID,Osipenko Anton N.4ORCID,Anfinogenova Nina D.5ORCID,Khlebnikov Andrei I.6ORCID,Atochin Dmitriy N.67,Schepetkin Igor A.8,Quinn Mark T.8ORCID

Affiliation:

1. Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, Russia

2. Faculty of Radiophysics, National Research Tomsk State University, 634050 Tomsk, Russia

3. Department of Morphology and General Pathology, Siberian State Medical University, 634050 Tomsk, Russia

4. Department of Pharmacology, Siberian State Medical University, 634050 Tomsk, Russia

5. Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, Russia

6. Kizhner Research Center, Tomsk Polytechnic University, 634050 Tomsk, Russia

7. Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02115, USA

8. Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA

Abstract

Activation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11H-indeno [1,2-b]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI. On day 60 after MI, a significant (2.6-fold) decrease in LV scar size, a 2.2-fold decrease in the size of the LV cavity, a 2.9-fold decrease in the area of mature connective tissue, and a 1.7-fold decrease in connective tissue in the interventricular septum were observed compared with the control group. The improved contractile function of the heart resulted in a significant (33%) increase in stroke size, a 40% increase in cardiac output, a 12% increase in LV systolic pressure, a 28% increase in the LV maximum rate of pressure rise, a 45% increase in the LV maximum rate of pressure drop, a 29% increase in the contractility index, a 14% increase in aortic pressure, a 2.7-fold decrease in LV end-diastolic pressure, and a 4.2-fold decrease in LV minimum pressure. We conclude that IQ-1 has cardioprotective activity and reduces the severity of HF after MI.

Funder

Ministry of Science and Higher Education of the Russian Federation

Tomsk Polytechnic University development program

National Institutes of Health

Montana State University Agricultural Experiment Station

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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