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

Abstract

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.

High tidal volume ventilation induces lung injury after hepatic ischemia-reperfusion

“…Colletti et al (8,9) showed intra-alveolar PMN infiltration 12 h after reperfusion that followed 90 min of lobar hepatic ischemia. In contrast, Matuschak et al (22) showed a lung PMN influx 1 h after reperfusion that was not present 24 h after reperfusion. The reason for such diverse results is thought to be due to variations in the experimental design, including differences in: the duration of ischemia; the type of hepatic inflow obstruction (total or partial); respiration during the reperfusion period; the timing of the examinations after reperfusion; and the animal species that were studied.…”

Sodium Nitroprusside Regulates mRNA Expressions of LTC4 Synthesis Enzymes in Hepatic Ischemia/Reperfusion Injury Rats via NF-κB Signaling Pathway

“…In the I/R group, animals were anesthetized with pentobarbital 50 mg/kg intraperitoneally. An external jugular vein catheter was created using a polyethylene tube of 0.9 mm inner diameter (Becton Dickinson Medical Devices, Suzhou, China) and the rats were subjected to midline lapSodium Nitroprusside Regulates LTC4 Synthesis Enzyme mRNA Expressions Pharmacology 2007;80: [11][12][13][14][15][16][17][18][19][20] 13 arotomy. The liver was exposed, and the left lateral and median lobes were rendered ischemic by clamping the hepatic arterial and portal venous blood supply using a microaneurysm clamp.…”

Protective effects of nicotinamide against acetaminophen-induced acute liver injury

“…In the same vein, IL-6 is a pleotropic cytokine which was initially recognized for its regulation of acute protein synthesis and the acute inflammatory response [22,23]. Recently, IL-6 has been reported to be upregulated in several animal models of hepatic injury [24][25][26], and its mRNA expression was enhanced in the liver of wild-type mice injected with APAP [19]. Interestingly, these pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, could be blocked from release from hepatic cells treated with NAM [27][28][29][30][31].…”