OBJECTIVE: To investigate the impact of circulating histones on @entity299 in a @entity19 model and @entity1 with @entity295 . DESIGN: Prospective, observational clinical study with in vivo and ex vivo translational laboratory investigations. SETTING: General ICU and university research laboratory. SUBJECTS: Sixty-five septic @entity1 and 27 healthy volunteers. Twelve-week-old male C57BL/6 @entity19 . INTERVENTIONS: Serial blood samples from 65 @entity1 with @entity295 were analyzed, and left ventricular function was assessed by echocardiography. @entity1 ' sera were incubated with cultured cardiomyocytes in the presence or absence of antihistone antibody, and cellular viability was assessed. @entity19 @entity295 was initiated by intraperitoneal @entity526 injection (10 colony-forming unit/ @entity19 ) in 12-week-old male C57BL/6 @entity19 , and the effect of antihistone antibody (10 mg/kg) was studied. @entity19 blood samples were collected serially, and left ventricular function was assessed by intraventricular catheters and electrocardiography. MEASUREMENTS AND MAIN RESULTS: Circulating histones and cardiac troponins in @entity1 and @entity19 plasma were quantified. In 65 @entity1 with @entity295 , circulating histones were significantly elevated compared with healthy controls (n = 27) and linearly correlated with cardiac troponin T levels (rs = 0.650; p < 0.001), @entity1063 doses required to achieve hemodynamic stability (rs = 0.608; p < 0.001), Sequential Organ Failure Assessment scores (p = 0.028), and mortality (p = 0.008). In a subset of 36 septic @entity1 without prior @entity299 , high histone levels were significantly associated with new-onset @entity1002 (p = 0.001) and @entity943 (p = 0.01). @entity1002 only predicted adverse outcomes when combined with elevated histones or cardiac troponin levels. Furthermore, @entity1 ' sera directly induced histone-specific @entity204 ex vivo, which was abrogated by antihistone antibodies. In vivo studies on septic @entity19 confirmed the cause-effect relationship between circulating histones and the development of @entity299 , @entity943 , and @entity1002 . CONCLUSION: Circulating histones are novel and important mediators of @entity296 , which can potentially be utilized for prognostic and therapeutic purposes.

Circulating Histones Are Major Mediators of @entity299 in @entity1 With XXXX .

@entity1 :: ('9606', 'Species') :: ['Patients', 'human', 'patients'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity296 :: ('MESH:D009202', 'Disease') :: ['septic cardiomyopathy'] @entity943 :: ('MESH:D001145', 'Disease') :: ['arrhythmias'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse', 'N mice', 'murine', 'Murine'] @entity1002 :: ('MESH:D018487', 'Disease') :: ['Left ventricular dysfunction', 'left ventricular dysfunction'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac injury and dysfunction', 'cardiac injury', 'cardiac disease'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['noradrenaline'] @entity204 :: ('MESH:D003643', 'Disease') :: ['cardiomyocyte death'] @entity526 :: ('562', 'Species') :: ['Escherichia coli']
@entity295 :: (MESH:D018805,Disease) :: ['Sepsis']
