Recombinant thrombomodulin improves the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat LPS model

IntroductionAbnormalities in vascular endothelial function play an important role in the development of septic organ dysfunction. The aim of this study was to examine the effect of recombinant thrombomodulin (rTM) on leukocyte-endothelial interaction and subsequent malcirculation in endotoxemia.Materials and MethodsWistar rats were administered with either low, medium or high dose of rTM (n = 7 each) 2 hours after lipopolysaccharide (LPS) infusion. Mesenteric microcirculation after the treatment was observed under the intravital microscopy. In another series (n = 5 each), plasma levels of high-mobility group box 1 (HMGB1) levels were measured at 5 hours after LPS infusion.ResultsMicroscopic findings revealed suppression in leukocyte adhesion, thrombus formation and endothelial damage with the treatment by rTM. However, high-dose rTM tended to increase the bleeding events. Thus, blood flow was better maintained with medium-dose rTM (P < 0.05). The increase in HMGB1 level was significantly suppressed by medium and high-dose rTM (P < 0.05, respectively).ConclusionsrTM demonstrated a protective effect on microcirculation through the inhibition of leukocyte-endothelial interaction and suppression of HMGB1.