Role of extracellular histones in the cardiomyopathy of XXXX .

@entity295 @entity35 @entity19 @entity409 @entity325 @entity299 @entity141 @entity6198
The purpose of this study was to define the relationship in @entity325 (in adult male C57BL/6 @entity19 ) between @entity299 and the appearance in plasma of extracellular histones. Procedures included induction of @entity295 by cecal ligation and puncture and measurement of heart function using echocardiogram/Doppler parameters. We assessed the ability of histones to cause disequilibrium in the redox status and intracellular [ @entity141 ]i levels in cardiomyocytes (CMs) (from @entity19 and @entity35 ). We also studied the ability of histones to disturb both functional and electrical responses of hearts perfused with histones. Main findings revealed that extracellular histones appearing in septic plasma required C5a receptors, polymorphonuclear leukocytes (PMNs), and the @entity6198 ( @entity6198 ) inflammasome. In vitro exposure of CMs to histones caused loss of homeostasis of the redox system and in [ @entity141 ]i, as well as defects in mitochondrial function. Perfusion of hearts with histones caused @entity409 . Finally, in vivo neutralization of histones in septic @entity19 markedly reduced the parameters of @entity299 . Histones caused dysfunction in hearts during @entity325 . These events could be attenuated by histone neutralization, suggesting that histones may be targets in the setting of @entity295 to reduce @entity299 .
