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.

Molecular mechanisms of trauma-induced acute kidney injury: Inflammatory and metabolic insights from animal models

“…Indeed, this may constitute the major difference between HS and burn injuries, as burn-induced AKI may occur in the absence of hypovolemia/hypoperfusion. Infusion of plasma from burned rats into healthy animals causes leukocyte activation and enhanced fluid extravasation and edema [45]. While the burn eschar itself may be a nidus for inflammatory substances, this study indicates that it is not necessary for the induction of systemic inflammation.…”

Influence of Cdp-Choline Administration on Early Burn Edema in Rats

“…General aspects of animal preparation used in this study are similar to those described previously by our group. 14,19,20 To expose a dorsal area that equals 30% TBSA to 100°C for 12 seconds the rat was placed in a special plastic mold. 14 This experimental setting provides a clearly defined full thickness burn avoiding any detectable visceral injury.…”

Mikrovaskuläre Effekte des Verbrennungsplasma­transfers und therapeutische Optionen im Tiermodell

“…o.). In der Burnplasmagruppe (B1) erhielten die Tiere während der Intravitalmikroskopie Burnplasma in 10 % Verdünnung (Ringer-Lactat) infundiert, was ebenfalls zur Ausprägung der Verbrennungskrankheit führt, wie die Autoren in früheren Arbeiten zeigen konnten [ 16 ] ( • ▶ Abb. 2 ).…”

“…Unter anderem wurde der als "Lipoproteinkomplex" (LPC) beschriebene Faktor als mögliche Ursache der Leukozytenaktivierung genannt [ 26 , 43 ] . In der aktuellen Arbeit wurde in Übereinstimmung mit vorangegangenen Arbeiten [ 16 ] , sowohl in der Verbrennungstraumagruppe, als auch in der Plasmatransfergruppe signifi kant erhöhte Werte adhärenter Leukozyten beobachtet. Die bereits zu Beginn des Experimentes stark gesteigerte Anzahl der Leukozyten in der Positivkontrollgruppe (Verbrennungsgruppe) mag darin ihre Ursache haben, dass hier das Verbrennungstrauma zum Zeitpunkt der ersten Messung bereits 4 Stunden zurück liegt.…”

“…An diesem Modell wurden dann unterschiedliche therapeutische Optionen am Spendertier (topisches Ceriumnitrat) und im Empfängerorganismus (hoch dosiert Vitamin C) untersucht. In der hier vorgestellten Übersichtsarbeit werden daher in 2 Abschnitten zunächst die Ergebnisse unserer Studie zur methodischen Etablierung [ 16 ] und anschließend die Evaluation der genannten therapeutischen Optionen [ 17 , 18 ] …”