Leucocyte sequestration in endotoxemia and the effect of low-molecular-weight dextran

Abstract

Leucocyte sequestration in various organs during endotoxin-induced shock in sheep was studied using leucocytes labelled with indium 111 oxine. A moderate dose of Escherichia coli endotoxin (10 micrograms/kg body weight) was slowly infused intravenously in 16 sheep, 9 of which subsequently received a continuous i.v. infusion of low-molecular-weight dextran (LMWD) given at an infusion rate of 15 ml/h over 4 h, starting 30 min after administration of the endotoxin. By that time, signs of acute lung injury had developed, thus mimicking a clinical situation. The remaining animals were untreated and served as controls. A marked increase in lung, liver and kidney leucocyte sequestration, together with a sharp, corresponding drop in splenic activity and leucocyte count in peripheral blood, occurred shortly after the endotoxin infusion in both groups. However, after 90 min there was a significantly lower leucocyte activity in the lungs, liver and kidneys of LMWD-treated animals as compared with controls. Less marked hemodynamic and respiratory alterations were also observed in animals treated with LMWD. The present study confirms previous reports that significant leucocyte sequestration in the lungs occurs early during endotoxemia. Furthermore, we found that leucocyte sequestration also occurs in the liver and kidneys, which could explain the development of multi-organ failure, frequently described in clinical sepsis. Even after injury to organs, LMWD infusion seems to be beneficial by significantly lowering leucocyte sequestration and could therefore be justified as an addition to the arsenal of interventions used in the treatment of endotoxemia.