title: Myocardial inflammatory responses to sepsis complicated by previous burn injury.
abstract: BACKGROUND
  It is generally accepted that an initial injury such as burn trauma alters immune function such that a second insult increases the morbidity and mortality over that observed with each individual insult. We have shown previously that either burn trauma or sepsis promotes cardiomyocyte secretion of TNF-alpha and IL-1beta, cytokines that have been shown to produce myocardial contractile dysfunction. This study determined whether a previous burn injury (given eight days prior to sepsis) (1) provides a preconditioning phenomenon, decreasing inflammatory responses to a second insult or (2) exacerbates inflammatory response observed with either injury alone.
  
  
  METHODS
  Anesthetized Sprague-Dawley rats were given either burn injury over 40% total body surface area, sepsis alone (intratracheal S. pneumoniae, 4 x 10(6) colony forming units) or sepsis eight days after burn; all rats received lactated Ringer's solution. Hearts harvested 24 h after onset of sepsis alone or sepsis plus eight-day burn were used to (1) isolate cardiomyocytes (collagenase) or (2) assess contractile function (Langendorff). Cardiomyocytes loaded with 2 microg/mL Fura-2AM or sodium-binding benzofuran isophthalate were used to measure intracellular calcium and sodium concentrations (Nikon inverted microscope, Grooney optics, InCyt Im2 Fluorescence Imaging System). Additional cardiomyocytes were used to measure myocyte-secreted TNFalpha, IL-1, IL-6, IL-10 (pg/ml, ELISA).
  
  
  RESULTS
  Either burn trauma alone or sepsis alone promoted TNF-alpha, IL-1beta, nitric oxide, IL6 and IL-10 secretion by cardiomyocytes (p < 0.05). Producing aspiration-related pneumonia eight days postburn produced myocardial pro- and anti-inflammatory responses and increased myocyte Ca2+/Na+ concentrations to a significantly greater degree than the responses observed after either insult alone.
  
  
  CONCLUSIONS
  A previous burn injury alters myocardial inflammatory responses, predisposing the burn-injured subject to exaggerated inflammation, which correlates with greater myocardial dysfunction.
authors.affiliation: Department of Surgery, UT Southwestern Medical Center, Dallas, Texas 75390-9160, USA. jureta.horton@utsouthwestern.edu
authors.forename: Jureta W
authors.initials: JW
authors.lastname: Horton
authors.forename: David L
authors.initials: DL
authors.lastname: Maass
authors.forename: Jean
authors.initials: J
authors.lastname: White
authors.forename: Billy
authors.initials: B
authors.lastname: Sanders
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology* / Q000503:physiopathology; D013296:Streptococcus pneumoniae; D013997:Time Factors
chemical_list: D016207:Cytokines