Am. J. Respir. Crit. Care Med.,
Volume 160, Number 4, October 1999, 1171-1178
Severe Microcirculatory Abnormalities Elicited by
E. coli Hemolysin in the Rabbit Ileum Mucosa
KONSTANTIN
MAYER,
BETTINA
TEMMESFELD-WOLLBRÜCK,
ALEXANDER
FRIEDLAND,
HORST
OLSCHEWSKI,
MICHAEL
REICH,
WERNER
SEEGER,
and
AND FRIEDRICH
GRIMMINGER
Department of Internal Medicine, Justus-Liebig-University, Giessen, and Department of Internal Medicine, Charité,
Humboldt-University, Berlin, Germany
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 PCO2
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 PCO2 gap. In addition, HlyA provoked a dose-dependent increase in relative hemoglobin concentration (rel Hbconc) 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.
