title: Hydroxyethyl starch normalizes platelet and leukocyte adhesion within pulmonary microcirculation during LPS-induced endotoxemia.
abstract: Growing evidence supports substantial pathophysiological impact of platelets and their interactions on the development of septic lung failure. We developed a rat model of endotoxemia for direct in situ visualization of pulmonary microcirculation by in vivo fluorescence videomicroscopy. Male Sprague-Dawley rats were assigned to control, endotoxemia (Escherichia coli LPS, 15 mg/kg, i.v.), and fluid management for treatment of LPS-induced hypovolemia (Ringer lactate, hydroxyethyl starch [HES] 6%) groups (n = 7 each). Leukocytes were labeled in vivo by rhodamine, and 5 x 10(6) Calcein-AM-labeled nonactivated platelets were injected. Microcirculatory parameters (vessel diameter, ventilation-perfusion ratio) and adhesive characteristics of platelets and leukocytes (velocity, rolling, sticking) within the pulmonary microcirculation were quantified after endotoxin application under various regimens of fluid substitution for 60 min. A reduction of cell velocity and enhanced cell adhesion was seen in leukocytes and platelets (P < 0.05) after LPS injection. Fluid treatment with HES 6% resulted in a significant increase of platelet's velocity compared with the LPS group (442.86 +/- 20.60 vs. 343.93 +/- 11.17; P < 0.05), whereas Ringer lactate showed no beneficial effects. Similarly, HES 6% normalized LPS-induced platelet rolling and sticking as well as alterations in ventilation-perfusion ratio. Using direct visualization of the pulmonary microcirculation, we observed that platelet and leukocyte interactions are enhanced in the lung during LPS endotoxemia. Fluid therapy with HES 6% seems to have restorative effects on these cellular functions within the pulmonary microcirculation.
authors.affiliation: Molecular Biology Laboratory, Department of General Surgery, University Hospital Münster, Münster, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Küpper
authors.forename: Soeren Torge
authors.initials: ST
authors.lastname: Mees
authors.forename: Peter
authors.initials: P
authors.lastname: Gassmann
authors.forename: Martin F
authors.initials: MF
authors.lastname: Brodde
authors.forename: Beate
authors.initials: B
authors.lastname: Kehrel
authors.forename: Joerg
authors.initials: J
authors.lastname: Haier
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure; D002448:Cell Adhesion / Q000187:drug effects*; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides; D008168:Lung / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology*; D019007:P-Selectin / Q000096:biosynthesis; D015539:Platelet Activation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D008070:Lipopolysaccharides; D019007:P-Selectin