Calpain inhibition attenuates right ventricular contractile dysfunction after acute pressure overload.

Calpain inhibition attenuates right ventricular contractile dysfunction after acute pressure overload. Research Abstract Details 

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Calpain inhibition attenuates right ventricular contractile dysfunction after acute pressure overload. Abstract Text:

Clifford R Greyson,Gregory G Schwartz,Li Lu,Shuyu Ye,Steve Helmke,Ya Xu,Hasan Ahmad,Clifford R Greyson,Gregory G Schwartz,Li Lu,Shuyu Ye,Steve Helmke,Ya Xu,Hasan Ahmad,

Right ventricular contractile failure from acute RV pressure overload is an important cause of morbidity and mortality, but the mechanism of RV failure in this setting is incompletely defined. We hypothesized that RV dysfunction from acute RV pressure overload is, in part, due to activation of calpain, and that calpain inhibition would therefore attenuate RV dysfunction. Anesthetized, open chest pigs were treated with the calpain inhibitor MDL-28170 or with inactive vehicle, and then subjected to acute RV pressure overload for 90 min. RV contractile function was assessed by the regional Frank-Starling relation. RV myocardial tissue was analyzed for evidence of calpain activation and calpain-mediated proteolysis. RV pressure overload caused severe contractile dysfunction, along with significant alterations in the endogenous calpain inhibitor calpastatin typical of calpain activation. MDL-28170 attenuated RV free wall dysfunction by more than 50%. However, there were no differences in degradation of spectrin, desmin, troponin-I or SERCA2 between SHAM operated pigs and pigs subjected to acute RV pressure overload, or between vehicle and MDL-28170 treated pigs. Acute RV pressure overload causes calpain activation, and RV contractile dysfunction from acute RV pressure overload is attenuated by the calpain inhibitor MDL-28170; however, the effect is not explained by inhibition of calpain-mediated degradation of spectrin, desmin, troponin-I or SERCA2. Because this is the first report of any agent that can directly attenuate RV contractile dysfunction in acute RV pressure overload, further investigation of the mechanism of action of MDL-28170 in this setting is warranted.

Calpain inhibition attenuates right ventricular contractile dysfunction after acute pressure overload. Publishing Authors By Initials

CR Greyson,GG Schwartz,L Lu,S Ye,S Helmke,Y Xu,H Ahmad,CR Greyson,GG Schwartz,L Lu,S Ye,S Helmke,Y Xu,H Ahmad,

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Calpain inhibition attenuates right ventricular contractile dysfunction after acute pressure overload. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of molecular and cellular cardiology

VOLUME: 44

Page Numbers: 59-68

Journal Abbreviation: J. Mol. Cell. Cardiol.

ISSN: 0022-2828

DAY: 23

MONTH: 10

YEAR: 2007

Calpain inhibition attenuates right ventricular contractile dysfunction after acute pressure overload. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Calpain inhibition attenuates right ventricular contractile dysfunction after acute pressure overload.

AFFILIATION: Cardiology Section, VA Medical Center and the University of Colorado Health Sciences Center, Denver, CO, USA.

Country: England

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MEDLINETA: J Mol Cell Cardiol

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