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Oxidative Medicine and Cellular LongevityVolume 2013 2013, Article ID 279847, 9 pages

Research Article

Department of Emergency Medicine, The Davis Heart Lung Research Institute, The Ohio State University Wexner Medical Center, 750 Prior Hall, 376 W. 10th Avenue, Columbus, OH 43210, USA

The Division of Cardiovascular Medicine, The Davis Heart Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA

Received 5 March 2013; Accepted 13 April 2013

Academic Editor: Narasimham L. Parinandi

Copyright © 2013 Sverre E. Aune et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The neutrophil elastase inhibitor sivelestat ONO-5046 possesses unknown mechanisms of cardioprotection when infused following global ischemia, even in the absence of neutrophils. Since myocardial ischemia-reperfusion injury is strongly associated with endothelial dysfunction and reactive oxygen species ROS generation during reperfusion, we have tested the hypothesis that infusion of sivelestat during postischemic low flow would preserve endothelial and contractile function and reduce infarct size through an ROS-mediated mechanism. Isolated male rat hearts, subjected to global ischemia of 25 minutes, were reperfused with low flow with or without sivelestat followed by a full flow reperfusion. Hearts treated with sivelestat showed a significant improvement of LV contractile function and a reduction in infarct size. Infusion of L-NAME nonspecific blocker of endothelial nitric oxide synthase eNOS along with sivelestat during reperfusion reversed the preservation of contractile function and infarct size. In vitro EPR spin trapping experiments showed that sivelestat treatment decreased superoxide adduct formation in bovine aortic endothelial cells BAECs subjected to hypoxia-reoxygenation. Similarly, dihydroethidine DHE staining showed decreased superoxide production in LV sections from sivelestat-treated hearts. Taken together, these results indicate that sivelestat infusion during postischemic low flow reduces infarct size and preserves vasoreactivity in association with decreased ROS formation and the preservation of nitric oxide.





Autor: Sverre E. Aune, Steve T. Yeh, Periannan Kuppusamy, M. Lakshmi Kuppusamy, Mahmood Khan, and Mark G. Angelos

Fuente: https://www.hindawi.com/



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