Attenuation of neutrophil-mediated myocardial ischemia-reperfusion injury by a calpain inhibitor

Document Type

Article

Publication Date

2002

Abstract

Calpains are ubiquitous neutral cysteine proteases. Although their physiological role has yet to be clarified, calpains seem to be involved in the expression of cell adhesion molecules. Therefore, we hypothesized that a selective calpain inhibitor could attenuate polymorphonuclear (PMN) leukocyte-induced myocardial ischemia-reperfusion (I/R) injury. We examined the effects of the calpain inhibitor Z-Leu-Leu-CHO in isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Z-Leu-Leu-CHO (10 and 20 μM, respectively) significantly improved left ventricular developed pressure (LVDP) (P < 0.01) and the maximal rate of development of LVDP (P < 0.01) compared with I/R hearts perfused without Z-Leu-Leu-CHO. In addition, Z-Leu-Leu-CHO significantly reduced PMN adherence to the vascular endothelium and subsequent infiltration into the postischemic myocardium (P < 0.01). Moreover, Z-Leu-Leu-CHO significantly inhibited expression of P-selectin on the rat coronary microvascular endothelium (P < 0.01). These results provide evidence that Z-Leu-Leu-CHO significantly attenuates PMN-mediated I/R injury in the isolated perfused rat heart to a significant extent via downregulation of P-selectin expression.

Publication Title

American Journal of Physiology - Heart and Circulatory Physiology

Volume

282

Issue

4 51-4

First Page

H1421

Last Page

H1426

Comments

This article was published in American Journal of Physiology - Heart and Circulatory Physiology, Volume 282, Issue 4 51-4, Pages H1421-H1426.

The published version is available at http://dx.doi.org/10.1152/ajpheart.00626.2001 .

Copyright © 2002 AJP.

This document is currently not available here.

COinS