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Effect of hydroxyethyl starch on vascular leak syndrome and neutrophil accumulation during hypoxia.

Abstract：

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. DESIGN:Laboratory study. SETTING:University hospital. SUBJECTS:Cultured human microvascular endothelial cells and mice (C57BL/6/129 svj). INTERVENTIONS:We measured functional influences of hydroxyethyl starch on normoxic or posthypoxic endothelia. MEASUREMENTS AND MAIN 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.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

Dieterich HJ,Weissmüller T,Rosenberger P,Eltzschig HK

doi

10.1097/01.CCM.0000218814.77568.BC

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

1775-82

issue

eissn

0090-3493

issn

1530-0293

journal_volume

pub_type

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Effect of hydroxyethyl starch on vascular leak syndrome and neutrophil accumulation during hypoxia.