title: Burn plasma transfer induces burn edema in healthy rats.
abstract: Thermal injuries greater than 20% body surface area (BSA) result in systemic shock with generalized edema in addition to local tissue destruction. Burn shock is induced by a variety of mediators, mainly immunomodulative cytokines. This experimental study evaluates if burn shock can be induced in healthy rats by transfer of burn plasma (BP) with mediators. Thermal injury was induced by hot water (100 degrees C water, 12 s, 30% BSA) in male syngenic Wistar rats. Donor rats were killed 4 h posttrauma, and BP was harvested. Burn plasma was transferred to healthy animals by continuous intravenous infusion in three types of dilution (100%, 10%, and 1%). Positive controls were directly examined 4 h after thermal injury, and negative control rats had a continuous infusion done with sham burn (SB) plasma (37 degrees C water, 12 s, 30% BSA). Afterwards, intravital fluorescence microscopy was performed in postcapillary mesenteric venules at 0, 60, and 120 min. Edema formation was assessed by relative changes over time in fluorescence intensity of fluorescein isothiocyanate-albumin in the intravascular versus the extravascular space. The interactions of leucocytes and endothelium were evaluated by quantification of leukocyte sticking. Additionally, microhemodynamic (volumetric blood flow, erythrocyte velocity, venular wall shear rate, venular diameters) and macrohemodynamic parameters (blood pressure, heart frequency, temperature) were assessed online (arterial catheter). For statistics, an ANOVA was performed with Bonferroni adjustment procedure. Differences were considered significant when P < 0.05. There are no statistically significant differences in microhemodynamics or macrohemodynamics between study groups. Burn plasma infusion and thermal injury lead to significant increases in fluorescein isothiocyanate-albumin extravasation, whereas SB plasma shows no significant changes. Even BP diluted in 0.9% saline (10% and 1%) results in a similar transvascular flux of plasma proteins as direct thermal injury. Differences between positive controls and BP infusion are not significant, whereas all groups are statistically different from the SB group (P<0.05). Leukocyte sticking is significantly increased in all groups except the SB group, and the number of adherent leukocytes is dose dependent. The present study demonstrates that as early as 4 h after thermal injury, there are sufficient factors (e.g., cytokines) in BP to induce systemic burn shock in healthy rats even in diluted plasma (1%). However, the "key" cytokines are not identified at this point. The burned tissue is no longer required for burn shock induction, and the pathophysiologic process seems to be self-perpetuating as early as 4 h posttrauma. Leukocytes are activated by thermal injury and BP infusion. The role of leukocyte-endothelium interactions for edema formation remains uncertain and requires further investigation.
authors.affiliation: Department of Hand, Plastic and Reconstructive Surgery, Burn Center-BG Trauma Center Ludwigshafen, Plastic and Hand Surgery, University of Heidelberg, Ludwigshafen, Germany. tkremer@bgu-ludwigshafen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Kremer
authors.forename: Dorotheé
authors.initials: D
authors.lastname: Abé
authors.forename: Marc
authors.initials: M
authors.lastname: Weihrauch
authors.forename: Christopher
authors.initials: C
authors.lastname: Peters
authors.forename: Martha Maria
authors.initials: MM
authors.lastname: Gebhardt
authors.forename: Guenter
authors.initials: G
authors.lastname: Germann
authors.forename: Christoph
authors.initials: C
authors.lastname: Heitmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Walther
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002056:Burns / Q000097:blood* / Q000473:pathology*; D004487:Edema / Q000473:pathology*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000378:metabolism; D006439:Hemodynamics; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D013997:Time Factors