Hypertonic saline-dextran suppresses burn-related cytokine secretion by cardiomyocytes

Whereas hypertonic saline-dextran (HSD, 7.5% NaCl in 6% D70) improves cardi ac contractile function after burn trauma, the mechanisms of HSD-related ca rdioprotection remain unclear. We recently showed that cardiomyocytes secre te tumor necrosis factor-alpha (TNF-alpha), a response that was enhanced by burn trauma. This study addressed the question: does HSD modulate cardiac contraction/relaxation by altering cardiomyocyte TNF-alpha secretion? Wista r-Furth rats (325 g) were given a burn injury over 40% of the total body su rface area and were then randomized to receive a bolus of either isotonic s aline or HSD (4 ml/kg, n = 14 rats/group). Sham burn rats were given either isotonic saline or HSD (n = 14 rats/group) to provide appropriate controls for the two burn groups. Hearts were isolated 24 h postburn for either Lan gendorff perfusion (n = 8 hearts/group) or to prepare cardiomyocytes (n = 6 hearts/group). Myocytes were stimulated with lipopolysaccharide (LPS) (0, 10, 25, or 50 mg for 18 h) to measure cytokine secretion. Burn trauma incre ased myocyte TNF-alpha and interleukin-1 beta and -6 secretion, exacerbated cytokine response to LPS stimulus, and impaired cardiac contraction. HSD t reatment of burns decreased cardiomyocyte cytokine secretion, decreased res ponsiveness to LPS challenge with regard to cytokine secretion, and improve d ventricular function. These data suggest that HSD mediates cardioprotecti on after burn trauma, in part, by downregulating cardiomyocyte secretion of inflammatory cytokines.