Effect of hydroxyethyl starch on vascular leak syndrome and neutrophil accumulation during hypoxia.
OBJECTIVE
Several studies have suggested that intravenous hydroxyethyl starch treatment may dampen acute inflammatory responses. It is well documented that limited oxygen delivery to tissues (hypoxia) is common in acute inflammation, and numerous parallels exist between acute responses to hypoxia and to inflammation, including the observation that both are associated with increased vascular leakage and neutrophil infiltration of tissues. Therefore, we compared functional influences of hydroxyethyl starch on normoxic or posthypoxic endothelia.


METHODS
Laboratory study.


METHODS
University hospital.


METHODS
Cultured human microvascular endothelial cells and mice (C57BL/6/129 svj).


METHODS
We measured functional influences of hydroxyethyl starch on normoxic or posthypoxic endothelia.


RESULTS
Studies to assess endothelial barrier function in vitro indicated that the addition of hydroxyethyl starch promotes endothelial barrier in a dose-dependent fashion and hydroxyethyl starch-barrier effects are increased following endothelial hypoxia exposure (human microvascular endothelial cells, 48 hrs, 2% oxygen). Treatment of human microvascular endothelial cells with hydroxyethyl starch resulted in a dose-dependent increase in 157-phosphorylated vasodilator-stimulated phosphoprotein, a protein responsible for controlling the geometry of actin-filaments. Neutrophil adhesion was decreased in the presence of physiologically relevant concentrations of hydroxyethyl starch in vitro, particularly after endothelial hypoxia exposure. Using a murine model of normobaric hypoxia, increases in vascular leakage and pulmonary edema associated with hypoxia exposure (4 hrs at 8% oxygen) were decreased in animals treated with intravenous hydroxyethyl starch. Increases of tissue neutrophil accumulation following hypoxia exposure were dampened in hydroxyethyl starch-treated mice.


CONCLUSIONS
Taken together, these results indicate that hypoxia-induced increases in vascular leakage and acute inflammation are attenuated by hydroxyethyl starch treatment.
Dieterich
Hans-Jürgen
HJ
Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
Weissmüller
Thomas
T
Rosenberger
Peter
P
Eltzschig
Holger K
HK
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology*; D010952:Plasma Substitutes / Q000494:pharmacology*; D013577:Syndrome; D014471:Umbilical Veins / Q000166:cytology
D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes