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

2001; American Thoracic Society; Volume: 163; Issue: 4 Linguagem: Inglês

10.1164/ajrccm.163.4.2003020

1535-4970

George M. Matuschak, KURT A. HENRY, Cheryl A. Johanns, Andrew J. Lechner,

Thermal Regulation in Medicine

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- α ), 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- α :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- α , 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- α concentrations and ischemic liver injury but not mortality. Thus, focal hepatic I/R augments circulating endotoxin, TNF- α , and postbacteremic lung inflammation early after normotensive E. coli bacteremic sepsis.