title: Severe microcirculatory abnormalities elicited by E. coli hemolysin in the rabbit ileum mucosa.
abstract: Decreased capillary flow and heterogeneity of microvascular perfusion are hallmarks of septic circulatory disturbances, and the gastrointestinal mucosa is considered to be particularly prone to such abnormalities. We investigated the impact of Escherichia coli hemolysin (HlyA), a medically relevant pore-forming bacterial toxin, on the mucosal microvasculature in a constant-flow blood-perfused rabbit ileum model. Microsensor techniques were employed to assess spatial distribution of mucosal hemoglobin oxygenation and relative mucosal hemoglobin content, as well as mucosal-arterial PCO(2) gap. Administration of low doses of HlyA (0.005 to 0.1 hemolytic units [HU]/ml) into the mesenteric artery provoked a transient vasoconstrictor response. Whereas physiological mucosal oxygenation is homogeneous, severe heterogeneity in capillary blood flow distribution appeared, paralleled by a marked increase in the mucosal-arterial PCO(2) gap. In addition, HlyA provoked a dose-dependent increase in relative hemoglobin concentration (rel Hb(conc)) values and edema formation, suggesting postcapillary vasoconstriction and capillary leakage. The observed changes occurred while fully maintaining mesenteric oxygen delivery. We conclude that low doses of HlyA may elicit severe mucosal microcirculatory disturbances in the rabbit ileum under maintenance of global hemodynamics, reminiscent of septic perfusion abnormalities. Pore-forming bacterial toxins may thus be considered as contributors to splanchnic mucosal damage under conditions of severe infection and sepsis.
authors.affiliation: Department of Internal Medicine, Justus-Liebig-University, Giessen, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Mayer
authors.forename: B
authors.initials: B
authors.lastname: Temmesfeld-Wollbrück
authors.forename: A
authors.initials: A
authors.lastname: Friedland
authors.forename: H
authors.initials: H
authors.lastname: Olschewski
authors.forename: M
authors.initials: M
authors.lastname: Reich
authors.forename: W
authors.initials: W
authors.lastname: Seeger
authors.forename: A F
authors.initials: AF
authors.lastname: Grimminger
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001783:Blood Flow Velocity; D002199:Capillary Permeability; D002245:Carbon Dioxide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins; D006454:Hemoglobins / Q000032:analysis; D006460:Hemolysin Proteins / Q000494:pharmacology*; D007082:Ileum / Q000098:blood supply*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000378:metabolism; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology; D008833:Microcirculation; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D011817:Rabbits; D018805:Sepsis / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D006454:Hemoglobins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; D002245:Carbon Dioxide; D010100:Oxygen