Differential effects of caspase inhibitors on endotoxin-induced myocardial dysfunction and heart apoptosis.

Content Provider	Semantic Scholar
Author	Fauvel, Harold Marchetti, Philippe Chopin, Claude Formstecher, Pierre Neviere, Remi R.
Copyright Year	2001
Abstract	Endotoxin is one of the major factors causing myocardial depression and death during sepsis in humans. Recently, it was reported that endotoxin may induce cardiomyocyte apoptosis. Also, multiple caspase activation has been implicated in endotoxin-induced apoptosis in several organ systems. In this study, we investigated whether endotoxin would increase myocardial caspase activities and evaluated the effects of in vivo administration (3 mg/kg) of the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone(z-VAD.fmk), the caspase-3-like inhibitor benzyloxycarbonyl-Asp-Glu-Val-Asp-chloromethylketone (z-DEVD.cmk), and the caspase-1-like inhibitor acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD. fmk), on endotoxin-induced myocardial dysfunction and apoptosis. Endotoxin administration (10 mg/kg iv) induced myocardial contractile dysfunction that was associated with caspase activity increases and nuclear apoptosis. Broad-spectrum z-VAD.fmk and z-DEVD.cmk improved endotoxin-induced myocardial dysfunction and reduced caspase activation and nuclear apoptosis when given immediately and 2 h after endotoxin. In contrast, no effects of Ac-YVAD.fmk were observed on myocardial function and caspase-induced apoptosis. Administration of caspase inhibitors 4 h after endotoxin treatment was not able to protect the rat heart from myocardial dysfunction and nuclear apoptosis. These observations provide evidence that in our model, caspase activation plays a role in endotoxin-induced myocardial apoptosis. Caspase inhibition strategy may represent a therapeutic approach to endotoxin-induced myocardial dysfunction.
Starting Page	11
Ending Page	16
Page Count	6
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://ajpheart.physiology.org/content/ajpheart/280/4/H1608.full.pdf
PubMed reference number	11247771v1
Volume Number	280
Issue Number	4
Journal	American journal of physiology. Heart and circulatory physiology
Language	English
Access Restriction	Open
Subject Keyword	Alanine Apoptosis Cardiomyopathies Caspase Activation Caspase Inhibitors Cessation of life Glutamic Acid Myocardium Myocytes, Cardiac Sepsis Tyrosine Valine body system
Content Type	Text
Resource Type	Article