Effect of Aspiration Pneumonia-Induced Sepsis on Post-Burn Cardiac Inflammation and Function in Mice

Abstract

Introduction: Numerous studies have found that burn injury alters immune function, predisposing the subject to infectious complications. We developed a mouse model of burn injury complicated by either gram-positive or gram-negative infection and hypothesized that post-burn infection would exacerbate the myocardial cytokine responses and contractile dysfunction characteristic of either sepsis alone or burn alone. Methods: Adult C57 BL6 mice were given burn injury over 40% of the total body surface area and conventional fluid resuscitation (lactated Ringer's solution, 4 mL/kg/% burn) followed on day 7 by intratracheal administration of 1 × 10⁵ cfu of either Streptococcus pneumoniae or Klebsiella pneumoniae or saline. Mice received fluid resuscitation (2 mL of lactated Ringer's intraperitoneally) again after bacterial challenge. Cardiomyocyte cytokine secretion and the contractile function of isolated hearts (Langendorff perfusion) were examined in vitro 24 h after bacterial challenge. Results: Infectious challenge seven days after burn injury exaggerated the inflammatory cytokine responses over those observed with either burn alone or gram-positive or gram-negative infection alone (tumor necrosis factor-α: sham, 72 ± 9 pg/mL; burn alone, 176 ± 6 pg/mL, Klebsiella pneumoniae alone, 337 ± 8 pg/mL; Streptococcus pneumoniae alone, 184 ± 2 pg/mL; burn + Klebsiella, 476 ± 14 pg/mL; burn + Streptococcus, 351 ± 6 pg/mL). Myocardial contractile depression was evident in the burn alone, infection alone, and burn plus infection groups, regardless of the organism selected to produce pneumonia-related sepsis. Conclusions: Gram-negative or gram-positive infection exacerbated the myocardial inflammation seen with burn alone or infection alone. The availability of a mouse model of burn injury complicated by pneumonia-related sepsis will allow use of genetically engineered mice to examine further the mechanisms by which burn injury increases susceptibility to infection.