Calpain inhibitor MDL 28170 protects against the Ca2+ paradox in rat hearts.

Clinical and Experimental Pharmacology & Physiology
Sheng-Hui BiJun Ren

Abstract

The calcium paradox represents an important model in which to study myocardial injuries due to intracellular Ca(2+) overload. In a previous study, calpain was transiently activated in Ca(2+) -paradoxic hearts. The aim of the present study was to determine the role of calpain in myocardial dysfunction in hearts subjected to the Ca(2+) paradox and to elucidate the underlying mechanisms. Rat hearts were isolated, Langendorff perfused and subjected to the Ca(2+) paradox, which was induced by 3 min Ca(2+) depletion followed by 30 min Ca(2+) repletion, in the presence or absence of the calpain inhibitor 10 umol/L MDL 28170. Cardiac function was evaluated. Furthermore, cell death and the degradation of troponin I (TnI) were assessed and calpain activity was determined by measurement of the α-fodrin fragment and confocal image analysis. Upon Ca(2+) repletion, the hearts immediately deteriorated, exhibiting a marked depression in cardiac function and an enlarged myocardial injury area. This was accompanied by significant increases in lactate dehydrogenase, mitochondrial release of cytochrome c, the apoptotic index and degraded TnI. These changes were significantly inhibited by MDL 28170, with the exception of TnI degradation. Comp...Continue Reading

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Citations

Dec 3, 2013·Canadian Journal of Physiology and Pharmacology·Ioanna-Katerina AggeliIsidoros Beis
Dec 3, 2013·Canadian Journal of Physiology and Pharmacology·Kamel CharradiEzzedine Aouani
Jun 10, 2016·Clinical and Experimental Pharmacology & Physiology·Jian-Ying ZhangJing-Jun Zhou
Sep 25, 2021·Canadian Journal of Physiology and Pharmacology·Fatma AlatragAsfree Gwanyanya

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