Topical application of cerium nitrate prevents burn edema after burn plasma transfer.

Thermal injuries of more than 20% body surface area (BSA) result in systemic capillary leakage with subsequent edema. This can similarly be induced by burn plasma transfer (BPT) from burned individuals to healthy rats. We evaluated if cerium nitrate (CN) bathing can prevent edema after BPT. Therefore, donor rats (DR) underwent thermal injury (100 degrees C water, 30%BSA, 12 s) for positive controls and were additionally bathed in CN (0.05M, at 10 and 120 min) for study groups. For negative controls DR underwent shamburn (37 degrees C water, 30%BSA, 12 s). DR-plasma (harvested 4 h post trauma) was transferred to healthy individuals. Intravital microscopy was performed in mesenteric venules (0/60/120 min). Edema was assessed by FITC-albumin extravasation. Additionally, leukocyte sticking (cells/mm(2)) and micro hemodynamic parameters were assessed. Significant systemic capillary leakage was observed after BPT at 120 min. Edema formation was significantly lower in negative controls. Topical CN application after 10 and 120 min reduced FITC-efflux to baseline levels. Adherent leukocytes increased slightly in all groups. Leukocyte-sticking tended to be reduced after CN bathing. In conclusion, BPT induces burn edema in healthy individuals. CN bathing after 10 and 120 min reduces mediator levels in burned individuals. Therefore, BPT after CN application does not induce burn shock anymore. Burn edema is partially independent from leukocyte activation because CN significantly influences macromolecular leakage whereas leukocyte activation is not significantly altered.

[1]  Ph.D. Tjøstolv Lund M.D.,et al.  Pathogenesis of edema formation in burn injuries , 2005, World Journal of Surgery.

[2]  Y. Huang,et al.  Serial experimental and clinical studies on the pathogenesis of multiple organ dysfunction syndrome (MODS) in severe burns. , 1998, Burns : journal of the International Society for Burn Injuries.

[3]  W. Boeckx,et al.  Predictors of mortality: a comparison between two burn wound treatment policies. , 2007, Burns : journal of the International Society for Burn Injuries.

[4]  D. Ross,et al.  The use of cerium nitrate-silver sulphadiazine as a topical burns dressing. , 1993, British journal of plastic surgery.

[5]  A. Arbor,et al.  Molecular determinants of reperfusion-induced leukocyte adhesion and vascular protein leakage. , 1994, Circulation research.

[6]  R. Good,et al.  T-cell subpopulations following thermal injury. , 1982, Surgery, gynecology & obstetrics.

[7]  Y. Chen,et al.  Plasma tumor necrosis factor-α, its soluble receptors and interleukin-1β levels in critically burned patients , 1998 .

[8]  David N. Herndon,et al.  Modern burn care. , 2001, Annales chirurgiae et gynaecologiae.

[9]  R. Sheridan,et al.  What's new in burns and metabolism. , 2004, Journal of the American College of Surgeons.

[10]  F. Deitz,et al.  Cerium nitrate: a new topical antiseptic for extensive burns. , 1976, Surgery.

[11]  C. Ryan,et al.  Death in the burn unit: sterile multiple organ failure. , 1998, Burns : journal of the International Society for Burn Injuries.

[12]  W. Monafo,et al.  'Lethal' burns. A progress report. , 1978, Archives of surgery.

[13]  D. Heimbach,et al.  Current status of burn wound pathophysiology. , 2000, Clinics in plastic surgery.

[14]  D. Maass,et al.  The Time Course of Cardiac NF-&kgr;B Activation and TNF-&agr; Secretion by Cardiac Myocytes After Burn Injury: Contribution to Burn-Related Cardiac Contractile Dysfunction , 2002, Shock.

[15]  W. Cioffi What's new in burns and metabolism. , 2001, Journal of the American College of Surgeons.

[16]  D. White,et al.  EFFECTS OF BURN SERUM ON MYOCARDIAL INFLAMMATION AND FUNCTION , 2004, Shock.

[17]  D. Maass,et al.  IL-1beta and IL-6 act synergistically with TNF-alpha to alter cardiac contractile function after burn trauma. , 2002, Shock.

[18]  W. Cioffi,et al.  Leukocyte responses to injury. , 1993, Archives of surgery.

[19]  G Arturson,et al.  Forty years in burns research - the postburn inflammatory response. , 2000, Burns : journal of the International Society for Burn Injuries.

[20]  P. Heppell,et al.  Cerium nitrate in the management of burns. , 2005, Burns : journal of the International Society for Burn Injuries.

[21]  S. Yuan,et al.  A ROLE FOR LONG CHAIN MYOSIN LIGHT CHAIN KINASE (MLCK-210) IN MICROVASCULAR HYPERPERMEABILITY DURING SEVERE BURNS , 2007, Shock.

[22]  M. Yoshida,et al.  Plasma tumour necrosis factor-α (TNF-α) levels in patients with burns , 1993 .

[23]  P. Blondeel,et al.  Effect of cerium nitrate-silver sulphadiazine on deep dermal burns: a histological hypothesis. , 1992, Burns : journal of the International Society for Burn Injuries.

[24]  M. Allgöwer,et al.  The present status of research in burn toxins , 2005, Intensive Care Medicine.

[25]  Thomas Kremer,et al.  BURN PLASMA TRANSFER INDUCES BURN EDEMA IN HEALTHY RATS , 2008, Shock.

[26]  S. Modak,et al.  Topical chemotherapy for burns using cerium salts and silver sulfadiazine. , 1977, Surgery, gynecology & obstetrics.

[27]  W. Boeckx,et al.  Application of cerium nitrate-silver sulphadiazine allows for postponement of excision and grafting. , 2006, Burns : journal of the International Society for Burn Injuries.

[28]  C. Burri,et al.  TOXICITY OF BURNED MOUSE SKIN IN RELATION TO BURN TEMPERATURE. , 1963, Surgical forum.

[29]  B. G. Sparkes Immunological responses to thermal injury. , 1997, Burns : journal of the International Society for Burn Injuries.

[30]  S. Langer,et al.  New model for in vivo investigation after microvascular breakdown in burns: use of intravital fluorescent microscopy. , 2005, Burns : journal of the International Society for Burn Injuries.

[31]  C. G de Gracia,et al.  An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns. , 2001 .

[32]  P. Kubes,et al.  Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion. , 1995, The Journal of clinical investigation.

[33]  C G de Gracia,et al.  An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns. , 2001, Burns : journal of the International Society for Burn Injuries.

[34]  M. Şengezer,et al.  Effects of cerium nitrate bathing and prompt burn wound excision on IL-6 and TNF-alpha levels in burned rats. , 2000, Burns : journal of the International Society for Burn Injuries.

[35]  F. Korompai,et al.  Ventral burn in rats: an experimental model for intravital microscopic study of microcirculation. , 2002, Burns : journal of the International Society for Burn Injuries.

[36]  G. Arturson Pathophysiology of the burn wound and pharmacological treatment. The Rudi Hermans Lecture, 1995. , 1996, Burns : journal of the International Society for Burn Injuries.

[37]  E. Martin,et al.  Role of Nitric Oxide in Leukocyte-Independent Endothelial Damage During Experimental Endotoxemia , 2003, Shock.

[38]  S. Yuan,et al.  Myosin Light Chain Kinase-Dependent Microvascular Hyperpermeability in Thermal Injury , 2003, Shock.

[39]  D. Schoenfeld,et al.  Prompt Eschar Excision: A Treatment System Contributing to Reduced Burn Mortality , 1986, Annals of surgery.

[40]  J. Hansbrough,et al.  Postburn immunosuppression in an animal model. III. Maintenance of normal splenic helper and suppressor lymphocyte subpopulations by immunomodulating drugs. , 1985, Surgery.

[41]  M. Allgöwer,et al.  Burning the largest immune organ. , 1995, Burns : journal of the International Society for Burn Injuries.

[42]  E. Helvig,et al.  Cerium nitrate-silver sulfadiazine cream in the treatment of burns: a prospective evaluation. , 1980, Surgery.

[43]  M. Allgöwer,et al.  Survival in major burn injuries treated by one bathing in cerium nitrate. , 1992, Burns : journal of the International Society for Burn Injuries.

[44]  S. D. House,et al.  Leukocyte-endothelium adhesion: microhemodynamics in mesentery of the cat. , 1987, Microvascular research.

[45]  E. Martin,et al.  Leukocyte-independent plasma extravasation during endotoxemia , 2000, Critical care medicine.

[46]  E. Lightfoot,et al.  BURN PLASMA MEDIATES CARDIAC MYOCYTE APOPTOSIS VIA ENDOTOXIN: 96 , 2001 .

[47]  G. Arturson Neutrophil granulocyte functions in severely burned patients. , 1985, Burns, including thermal injury.

[48]  P. Horan,et al.  Fluorescent cell labeling for in vivo and in vitro cell tracking. , 1990, Methods in cell biology.

[49]  A. Mason,et al.  A standard animal burn. , 1968, The Journal of trauma.

[50]  M. Deveci,et al.  Treatment with cerium nitrate bathing modulate systemic leukocyte activation following burn injury: an experimental study in rat cremaster muscle flap. , 2001, Burns : journal of the International Society for Burn Injuries.

[51]  J. Hansbrough,et al.  Topical cerium nitrate prevents postburn immunosuppression. , 1985, The Journal of trauma.