title: Glycocalyx degradation causes microvascular perfusion failure in the ex vivo perfused mouse lung:  hydroxyethyl starch 130/0.4 pretreatment attenuates this response.
abstract: The endothelial glycocalyx (GLX) is pivotal to vascular barrier function. We investigated the consequences of GLX degradation on pulmonary microvascular perfusion and, prompted by evidence that hydroxyethyl starch (HES) improves microcirculation, studied the effects of two HES preparations during GLX diminution. C57 BL/6 black mice lungs were explanted and perfused with 1-mL/min buffer solution containing autologous erythrocytes (red blood cells) at a hematocrit of 5%. Microvessel perfusion was quantified by video fluorescence microscopy at 0 and 90 min. To register interstitial edema, alveolar septal width was quantified. Pulmonary artery pressure (PAP), airway pressure, and left atrial pressure were recorded continuously. Lungs were randomly assigned to four groups (each n = 5): (i) control: no treatment, (ii) HEP1: heparinase I (1 mU/mL) was injected for GLX degradation, (iii) HES 130, and (iv) HES 200: one third of perfusion fluid was exchanged for 6% HES 130/0.4 or 10% HES 200/0.5 before GLX degradation. Analysis of variance on ranks and pairwise multiple comparisons were used for statistics, P < 0.05. Compared with control, GLX degradation effected perfusion failure in microvessels, increased PAP, and facilitated interstitial edema formation after a 90-min period of perfusion. In contrast to HES 200/0.5, pretreatment with HES 130/0.4 attenuated all of these consequences. Sequelae of GLX degradation in lung include perfusion failure in microvessels, interstitial edema formation, and increase in PAP. We assume that these effects are a consequence of vascular barrier dysfunction. Beneficial effects of HES 130/0.4 are presumably a result of its lower red blood cell bridging capacity compared with HES 200/0.5.
authors.affiliation: Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. m.strunden@uke.de
authors.forename: Mike Sebastian
authors.initials: MS
authors.lastname: Strunden
authors.forename: Anika
authors.initials: A
authors.lastname: Bornscheuer
authors.forename: Anke
authors.initials: A
authors.lastname: Schuster
authors.forename: Rainer
authors.initials: R
authors.lastname: Kiefmann
authors.forename: Alwin E
authors.initials: AE
authors.lastname: Goetz
authors.forename: Kai
authors.initials: K
authors.lastname: Heckel
mesh_terms: D000818:Animals; D015824:Blood-Air Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019276:Glycocalyx / Q000378:metabolism*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000187:drug effects*; D010477:Perfusion; D010952:Plasma Substitutes / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology
chemical_list: C485123:HES 130-0.4; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes