Am. J. Respir. Crit. Care Med., Volume 163, Number 4, March 2001, 1002-1009

Liver-Lung Interactions Following Escherichia coli Bacteremic Sepsis and Secondary Hepatic Ischemia/Reperfusion Injury

GEORGE M. MATUSCHAK, KURT A. HENRY, CHERYL A. JOHANNS, and ANDREW J. LECHNER

Division of Pulmonary, Critical Care, and Occupational Medicine, Department of Internal Medicine, and Department of Pharmacological and Physiological Science, Saint Louis University Health Sciences Center, St. Louis, Missouri; and Department of Critical Care Medicine, Saint John's Mercy Medical Center, St. Louis, Missouri

We hypothesized that ischemia/reperfusion (I/R) injury of the liver during normotensive gram-negative bacteremic sepsis alters the kinetics of circulating endotoxin, tumor necrosis factor-alpha (TNF-), and coinduced mediators, thereby exacerbating sepsis-induced lung inflammation. Liver and lung dysfunction were studied after hematogenous infection of Sprague-Dawley rats with 10⁹ Escherichia coli serotype O55:B5 (EC) and 90 min of secondary hepatic ischemia in EC + I/R and saline-infused (normal saline NS) × I/R rats, followed by brief (1 h) or longer reperfusion (24 h). TNF- :leukotriene interactions in this model were examined using the 5-lipoxygenase-activating protein inhibitor MK-886. Compared with sham-operated EC + Sham animals, peak serum endotoxin, TNF-, alanine aminotransferase, interleukin-6 (IL-6), and hepatic neutrophil (PMN) influx were higher in EC + I/R rats through 24 h (p < 0.05) despite comparable arterial pressure. Lung PMN influx and wet/dry weight ratios were likewise enhanced in EC + I/R versus EC + Sham or NS + I/R rats. MK-886 attenuated TNF- concentrations and ischemic liver injury but not mortality. Thus, focal hepatic I/R augments circulating endotoxin, TNF-, and postbacteremic lung inflammation early after normotensive E. coli bacteremic sepsis.

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