Orphan targets for reperfusion injury.

Abstract:

:Cardiomyocyte death secondary to transient ischaemia occurs mainly during the first minutes of reperfusion in the form of contraction band necrosis. Research on the mechanisms leading to sarcolemmal rupture and necrosis during initial reperfusion identified several promising pharmacological targets directed either to correct the alterations in Ca(2+) handling occurring during this period (Na(+)/H(+)-exchanger, reverse mode of Na(+)/Ca(2+)-exchanger, sarcoplasmic reticulum) or to interfere with its consequences [hypercontracture, calpain activation, and mitochondrial permeability transition pore (mPTP) opening]. However, despite the fact that pharmacological tools against some of these targets have consistently demonstrated that it is possible to reduce infarct size in experimental studies by interventions applied at the time of reperfusion, the translation of these approaches to clinical practice has failed due in part to the lack of drugs able to be tested in humans. Recently, the benefits of both post-conditioning and inhibition of mPTP have been supported by proof-of-concept trials demonstrating the clinical applicability of strategies aimed at preventing lethal reperfusion injury. These promising results should stimulate efforts to develop drugs testable in humans against known, unexploited targets involved in reperfusion injury and to identify and validate additional ones.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Inserte J,Barrabés JA,Hernando V,Garcia-Dorado D

doi

10.1093/cvr/cvp109

subject

Has Abstract

pub_date

2009-07-15 00:00:00

pages

169-78

issue

2

eissn

0008-6363

issn

1755-3245

pii

cvp109

journal_volume

83

pub_type

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