Hypertonic saline-dextran suppresses burn-related cytokine secretion by cardiomyocytes.
Whereas hypertonic saline-dextran (HSD, 7.5% NaCl in 6% D70) improves cardiac contractile function after burn trauma, the mechanisms of HSD-related cardioprotection remain unclear. We recently showed that cardiomyocytes secrete 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? Wistar-Furth rats (325 g) were given a burn injury over 40% of the total body surface area and were then randomized to receive a bolus of either isotonic saline 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 Langendorff perfusion (n = 8 hearts/group) or to prepare cardiomyocytes (n = 6 hearts/group). Myocytes were stimulated with lipopolysaccharide (LPS) (0, 10, 25, or 50 microg for 18 h) to measure cytokine secretion. Burn trauma increased myocyte TNF-alpha and interleukin-1 beta and -6 secretion, exacerbated cytokine response to LPS stimulus, and impaired cardiac contraction. HSD treatment of burns decreased cardiomyocyte cytokine secretion, decreased responsiveness to LPS challenge with regard to cytokine secretion, and improved ventricular function. These data suggest that HSD mediates cardioprotection after burn trauma, in part, by downregulating cardiomyocyte secretion of inflammatory cytokines.
Horton
J W
JW
Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9160, USA. JURETA.HORTON@utsouthwestern.edu
Maass
D L
DL
White
J
J
Sanders
B
B
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002056:Burns / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D003911:Dextrans / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006982:Hypertonic Solutions / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011920:Rats, Inbred WF; D012965:Sodium Chloride / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D002316:Cardiotonic Agents; D016207:Cytokines; D003911:Dextrans; D006982:Hypertonic Solutions; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C104375:hypertonic saline-dextran solution; D012965:Sodium Chloride