A model of myocardial inflammation and dysfunction in burn complicated by sepsis.
Numerous studies have described that an initial injury alters immune function, disposing the injured subject to infectious complications. The mechanisms by which an initial injury primes the subject, exacerbating the responses to a second injury, remain unclear; however, inflammatory cytokines have been implicated. The development of "2-hit" models has allowed investigators to determine the role of inflammatory mediators in susceptibility to infection after injury. A high incidence rate of pneumonia after burn injury and a significant increase in postburn mortality led us to develop models of either Gram-positive (Streptococcus pneumoniae) or Gram-negative (Klebsiella pneumoniae) sepsis after burn injury on 40% of total body surface area in rodents. In this present model, we used adult Sprague-Dawley rats to evaluate cardiac function in vitro (using Langendorff method) and myocardial inflammation (myocyte secretion of cytokines measured using enzyme-linked immunosorbent assay) after burn complicated by sepsis. Either burn injury alone or sepsis alone produced myocardial inflammatory responses and contractile dysfunction. Either Gram-negative or Gram-positive infection exacerbated the myocardial inflammation (increased myocyte secretion of tumor necrosis factor alpha, interleukin 1beta, and interleukin 6) above that which occurred with burn alone or with infection alone. Burn complicated by sepsis exacerbated the myocardial contraction and relaxation defects observed with either sepsis alone or burn alone. Inasmuch as sepsis, which occurs after a previous injury, increases myocardial inflammation/dysfunction and mortality, the development of therapeutic strategies that either decrease inflammatory response to the initial injury or provide cardiac support during the postinjury period may improve the outcome in injured patients who are at risk for developing sepsis.
Horton
Jureta W
JW
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9136, USA. jureta.horton@utsouthwestern.edu
D000818:Animals; D002056:Burns / Q000150:complications*; D002118:Calcium / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003971:Diastole; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology; D007710:Klebsiella Infections / Q000150:complications; D007711:Klebsiella pneumoniae; D009200:Myocardial Contraction; D009205:Myocarditis / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D011008:Pneumococcal Infections / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications*; D012964:Sodium / Q000378:metabolism
D016207:Cytokines; D012964:Sodium; D002118:Calcium