Hydroxyethyl starch (130 kD), but not crystalloid volume support, improves microcirculation during normotensive endotoxemia.
BACKGROUND
Increased leukocyte-endothelial cell interaction (LE) and deterioration of capillary perfusion represent key mechanisms of septic organ dysfunction. The type of volume support, however, which may be used during septic disorders, remains controversial. Using intravital microscopy, the authors studied the effect of different regimens of clinically relevant volume support on endotoxin-induced microcirculatory disorders, including the synthetic colloid hydroxyethyl starch (HES, 130 kD) and a crystalloid regimen with isotonic saline solution (NaCl).


METHODS
In Syrian Golden hamsters, normotensive endotoxemia was induced by intravenous application of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg). The microcirculation was analyzed in striated muscle of skinfold preparations. HES 130 kD (Voluven(R), 16 ml/kg, n = 7) or isotonic saline (NaCl, 66 ml/kg, n = 6) were infused 3 h after LPS exposure over a 1-h period (posttreatment mode). Animals receiving LPS without volume therapy served as control subjects (n = 8, control). LE, functional capillary density (FCD), and macromolecular leakage were repeatedly analyzed in the awake animals during a 24-h period using intravital fluorescence microscopy.


RESULTS
HES 130 kD significantly reduced LPS-induced arteriolar and venular leukocyte adherence (P < 0.05), whereas NaCl resuscitation had no effect when compared with nontreated control animals. The LPS-induced decrease in FCD and increase in macromolecular leakage were also significantly attenuated by HES 130 kD but not by NaCl. Improvement of LPS-induced microcirculatory disorders by HES was unlikely the result of macro- and microhemodynamic changes because arterial blood pressure, heart rate, and venular wall shear rate did not differ between HES- and NaCl-treated animals.


CONCLUSIONS
Thus, our study provides microhemodynamic and cellular mechanisms of HES 130 kD-mediated protection on microcirculation during endotoxemia, even when used in a clinically relevant posttreatment mode during normotensive conditions.
Hoffmann
Johannes N
JN
Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany. Johannes.Hoffmann@gch.med.uni-muenchen.de
Vollmar
Brigitte
B
Laschke
Matthias W
MW
Inthorn
Dietrich
D
Schildberg
Friedrich W
FW
Menger
Michael D
MD
D000818:Animals; D006224:Cricetinae; D000077324:Crystalloid Solutions; D019446:Endotoxemia / Q000628:therapy*; D006439:Hemodynamics / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D007552:Isotonic Solutions; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects*; D010952:Plasma Substitutes / Q000627:therapeutic use*; D012151:Resuscitation / Q000379:methods*
D000077324:Crystalloid Solutions; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D010952:Plasma Substitutes