Liver-lung interactions following Escherichia coli bacteremic sepsis and secondary hepatic ischemia/reperfusion injury.
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-alpha), and coinduced mediators, thereby exacerbating sepsis-induced lung inflammation. Liver and lung dysfunction were studied after hematogenous infection of Sprague-Dawley rats with 10(9) Escherichia coli serotype O55:B5 (EC) and 90 min of secondary hepatic ischemia in EC + I/R and saline-infused (normal saline NS) x I/R rats, followed by brief (1 h) or longer reperfusion (24 h). TNF- alpha: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-alpha, 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-alpha concentrations and ischemic liver injury but not mortality. Thus, focal hepatic I/R augments circulating endotoxin, TNF-alpha, and postbacteremic lung inflammation early after normotensive E. coli bacteremic sepsis.
Division of Pulmonary, Critical Care, and Occupational Medicine, Saint Louis University Health Sciences Center, St. Louis, Missouri 63110-0250, USA. Matuscgm@slu.edu
G M
GM
Matuschak
K A
KA
Henry
C A
CA
Johanns
A J
AJ
Lechner
D000818:Animals; D016470:Bacteremia / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000032:analysis; D004927:Escherichia coli Infections / Q000150:complications / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000032:analysis; D007511:Ischemia / Q000150:complications / Q000503:physiopathology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000187:drug effects; D008107:Liver Diseases / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D011014:Pneumonia / Q000150:complications / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004731:Endotoxins; D018836:Inflammation Mediators; D016859:Lipoxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha