Bactericidal/permeability increasing protein attenuates the myocardial inflammation/dysfunction that occurs with burn complicated by subsequent infection.
Intubation and mechanical ventilation after burn contribute to pneumonia-related infection. Although postburn presence or absence of endotoxin has been described, inactivation of Toll-like receptor 4 signaling has been shown to improve postburn organ function, suggesting that LPS participates in burn-related susceptibility to infection. We hypothesized that bactericidal/permeability-increasing protein (rBPI) given postburn would attenuate myocardial inflammation/dysfunction associated with postburn septic challenge given 7 days postburn. Rats were given burn over 40% total body surface area, lactated Ringer 4 ml.kg(-1).% burn(-1); burns received either vehicle or rBPI, 1 mg.kg(-1).h(-1) for 48 h postburn. Postburn day 7, subgroups of burns and shams were given intratracheal Klebsiella pneumoniae, 4 x 10(6) CFU to produce burn complicated by sepsis; additional sham and burn subgroups received intratracheal vehicle to produce sham sepsis. Vehicle-treated groups: 1) sham burn + sham sepsis 2) sham burn + sepsis, 3) burn + sham sepsis, 4) burn + sepsis. rBPI-treated groups: 5) sham burn + sham sepsis, 6) sham burn + sepsis, 7) burn + sham sepsis, 8) burn + sepsis. Cardiomyocyte cytokine secretion and myocardial function were studied 24 h after septic challenge, postburn day 8. Pneumonia-related infection 8 days after vehicle-treated burn produced myocyte cytokine secretion (pg/ml), indicated by increased myocyte TNF-alpha, 549 +/- 46; IL-1beta, 50 +/- 8; IL-6, 286 +/- 3 levels compared with levels in sham myocytes (TNF-alpha, 88 +/- 11; IL-1beta, 7 +/- 1; IL-6, 74 +/- 10; P < 0.05). Contractile dysfunction was evident from lower left ventricular pressure +/-dP/dt values in this group compared with sham. rBPI attenuated myocyte cytokine responses to septic challenge and improved contractile function, suggesting that burn-related mobilization of microbial-like products contribute to postburn susceptibility to infection.
Horton
Jureta W
JW
Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9136, USA. jureta.horton@utsouthwestern.edu
Maass
David L
DL
White
D Jean
DJ
Minei
Joseph P
JP
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D016470:Bacteremia / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D001798:Blood Proteins / Q000627:therapeutic use*; D002056:Burns / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D007710:Klebsiella Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D007711:Klebsiella pneumoniae; D008565:Membrane Proteins / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D011014:Pneumonia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D016207:Cytokines; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein; D012964:Sodium; D002118:Calcium