title: Cardiomyocyte function after burn injury and lipopolysaccharide exposure: single-cell contraction analysis and cytokine secretion profile.
abstract: A component of multiorgan dysfunction in burned patients is heart failure. Burn trauma induces cytokine synthesis of interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) which can negatively impact cardiac function. Infectious complications are common following severe burn injury. We hypothesized that burn injury and lipopolysaccharide (LPS) exposure independently influence peak cardiomyocyte contraction and cytokine secretion. Rats underwent a full-thickness 30% total body surface area scald or sham burn. At 1, 6, 12, and 24 h after burn, cardiomyocytes were isolated and incubated with increasing LPS doses. Peak sarcomere shortening and contractile velocity parameters were recorded using a variable-rate video camera with sarcomere length detection software. Supernatants were assayed for IL-1beta, IL-6, and TNF-alpha by ELISA. Peak sarcomere shortening was decreased in the burn group at 1, 6, 12, and 24 h after burn. IL-1beta, IL-6, and TNF-alpha levels were increased in cardiomyocytes isolated 1 h after burn compared with sham controls, but returned to sham levels at 6, 12, and 24 h after burn. LPS exposure caused dose-dependent decreases in sarcomere shortening in sham and burn animals. LPS exposure did not produce increased cardiomyocyte cytokine expression. Burn injury diminished peak sarcomere shortening. Whereas exposure to LPS did not have an effect on cardiomyocyte cytokine expression, LPS significantly inhibited sarcomere shortening in a dose-dependent fashion. Combined burn and LPS exposure inhibited sarcomere shortening more than each alone. These results demonstrate that LPS exposure and burn injury independently decrease peak cardiac shortening. These decreases did not directly correlate with the levels of cytokines released in response to each stressor.
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Niederbichler
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Westfall
authors.forename: Grace L
authors.initials: GL
authors.lastname: Su
authors.forename: Julia
authors.initials: J
authors.lastname: Donnerberg
authors.forename: Asad
authors.initials: A
authors.lastname: Usman
authors.forename: Peter M
authors.initials: PM
authors.lastname: Vogt
authors.forename: Kyros R
authors.initials: KR
authors.lastname: Ipaktchi
authors.forename: Saman
authors.initials: S
authors.lastname: Arbabi
authors.forename: Stewart C
authors.initials: SC
authors.lastname: Wang
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hemmila
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides