Myocardial Inflammatory Responses to Sepsis Complicated by Previous Burn Injury

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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-α and IL-1β, 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 × 106 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 μg/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 TNFα, IL-1, IL-6, IL-10 (pg/ml, ELISA). Results: Either burn trauma alone or sepsis alone promoted TNF-α, IL-1β, 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.