The effects of early excision and grafting on myocardial inflammation and function after burn injury.

Background: Sepsis is a frequent complication of burn injury despite absence of confirmed infection. Numerous investigators have proposed that the burn wound itself is a primary stimulus for postburn inflammation, and that early excision of the burn wound attenuates the hypermetabolic and inflammatory responses to burn injury. However, others have suggested that aggressive fluid resuscitation and correction of postburn fluid and electrolyte deficits should be the primary focus of intervention in the first 24 hours postburn.

Effect of aspiration pneumonia-induced sepsis on post-burn cardiac inflammation and function in mice.

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 x 10(5) cfu of either Streptococcus pneumoniae or Klebsiella pneumoniae or saline.

Cardiac myocyte accumulation of calcium in burn injury: cause or effect of myocardial contractile dysfunction.

Myocardial calcium accumulation and myocardial injury occur after burn trauma. However, whether altered calcium dyshomeostasis occurs as a result of myocardial injury/dysfunction or whether altered calcium handling initiates myocardial injury and contractile abnormalities remains unclear. In addition, the specific mechanisms by which burn injury promotes calcium entry into cardiac myocytes, specifically L-type channels and the sodium-calcium exchanger, remain unclear.

Effects of burn serum on myocardial inflammation and function.

Large cutaneous burns are clearly recognized to produce acute myocardial contractile dysfunction. This study used a model of burn serum challenge in either primary cardiomyocyte cultures or isolated perfused hearts to examine several aspects of burn-serum-related contractile dysfunction as well as myocardial inflammatory responses. Despite the absence of detectable LPS in burn serum, pretreating isolated cells or perfused hearts with recombinant bactericidal permeability-increasing protein (rBPI21) prevented both the inflammatory cytokine cascade and the cardiac contractile dysfunction induced by burn serum treatment of myocytes or ventricular muscle preparations.

Role of cytosolic vs. mitochondrial Ca2+ accumulation in burn injury-related myocardial inflammation and function.

This study was designed to examine the role of mitochondrial Ca2+ homeostasis in burn-related myocardial inflammation. We hypothesized that mitochondrial Ca2+ is a primary modulator of cardiomyocyte TNF-alpha, IL-1beta, and IL-6 responses to injury and infection. Ventricular myocytes were prepared by Langendorff perfusion of hearts from adult rats subjected to sham burn or burn injury over 40% of total body surface area to produce enzymatic (collagenase) digestion.

Myocardial inflammatory responses to sepsis complicated by previous burn injury.

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.

Molecular and pharmacological approaches to inhibiting nitric oxide after burn trauma.

Whereas controversial, several studies have suggested that nitric oxide (NO) alters cardiac contractility via cGMP, peroxynitrite, or poly(ADP ribose) synthetase (PARS) activation. This study determined whether burn-related upregulation of myocardial inducible NO synthase (iNOS) and NO generation contributes to burn-mediated cardiac contractile dysfunction. Mice homozygous null for the iNOS gene (iNOS knockouts) were obtained from Jackson Laboratory.

Cardiomyocyte intracellular calcium and cardiac dysfunction after burn trauma.

Objective: To examine the effects of pharmacologic agents designed to limit burn-mediated calcium overload on cardiomyocyte [Ca2+] and cardiac contractile function.

Design: Experimental, comparative study.

Setting: Cellular biology and physiology laboratory.