A.K. van Vliet

Biliary drainage attenuates postischemic reperfusion injury in the cholestatic rat liver

BACKGROUND The combination of hepatic ischemia and cholestasis, both identified as risk factors for oxidative stress, potentially enhances postischemic reperfusion (I/R) injury. Preoperative biliary drainage relieves oxidative stress and therefore seems a worthwhile intervention in cholestatic patients undergoing major liver resection. AIM To assess the effect of biliary decompression on I/R injury in a reversible bile duct ligation (BDL) model in the rat. METHODS Male Wistar rats were randomized into 3 groups. The first group underwent 30 minutes of partial liver ischemia after 7 days BDL; the second group underwent internal drainage (ID) after 7 days BDL and after 5 days, were subjected to partial liver ischemia. The last group (control animals) underwent 2 sham laparotomies and subsequent ischemia. Inflammatory response (interleukin [IL]-6, IL-10, GRO/KC, and interferon-gamma), hepatic damage and oxidative stress were assessed during 24 hours of reperfusion. RESULTS Cholestatic rats, as compared with the ID and control groups, showed significantly increased I/R injury as determined by transaminase release, histologic injury score and neutrophil infiltration. Plasma IL-6, IL-10, and GRO/KC (a CXC chemokine) were significantly increased in the BDL group (P < .05 vs control and ID). Moreover, the hepatic antioxidant capacity was strongly decreased in the BDL group (P < .01 vs control and ID). No significant differences for most parameters were seen in the ID group as compared to the control group. CONCLUSION The cholestatic rat is more susceptible to postischemic liver injury and these injurious effects were significantly attenuated by biliary decompression.

Mild steatosis impairs functional recovery after liver resection in an experimental model

Mild steatosis has been thought not to affect outcome after liver resection. However, recent studies have reported impaired postoperative recovery of patients with mild steatosis. This study evaluated the recovery of hepatic functional reserve during regeneration in a rat model of mild steatosis and liver resection.

Alkaline phosphatase reduces hepatic and pulmonary injury in liver ischaemia–reperfusion combined with partial resection

Lipopolysaccharides mediate inflammation in liver ischaemia–reperfusion (I/R) and partial liver resection (PHX). Bovine intestinal alkaline phosphatase (BIAP) detoxifies lipopolysaccharides by dephosphorylation and reduces inflammation in models of sepsis. This study examined the protective effects of BIAP administration in models of partial (70 per cent) liver I/R with or without partial resection of all non‐ischaemic lobes during ischaemia (30 per cent).

Immunoglobulin M, C-Reactive Protein and Complement Activation in Rat Hepatic Ischemia-Reperfusion Injury

Background: Ischemia-reperfusion (I/R) models have shown that C-reactive protein (CRP) and immunoglobulin M (IgM) are involved in complement activation. Binding of CRP and IgM to damaged cell membranes initiates complement activation and aggravates I/R injury in various organs. However, the time course of CRP- and IgM-mediated complement activation and the relation to hepatocellular injury and inflammation in liver I/R are unknown. Aim: To evaluate the time course of IgM- and CRP-related complement activation and the relation to hepatocellular injury and inflammation in a hepatic I/R rat model. Methods: Male Wistar rats were allocated to (1) five groups of animals exposed to 60 min of partial ischemia (70%) induced via clamping of the left segmental portal triad, followed by 0, 3, 6, 12 or 24 h of reperfusion (n = 6 in each group); (2) five groups of sham-operated animals with corresponding reperfusion times (n = 5), and (3) a control group sacrificed before ischemia (n = 5). Hepatocellular injury, inflammatory response, rat plasma CRP and IgM levels and immunohistochemical depositions of CRP, IgM and C3 were assessed for each group. Results: Histopathological injury scores of hematoxylin and eosin sections of ischemic liver lobes demonstrated increasing values throughout the reperfusion time with a peak at 12 h. Plasma aminotransferases (alanine aminotransferase and aspartate aminotransferase) significantly increased after 3 h of reperfusion, peaking at 6 h (3,100 ± 800 U/l; p < 0.05). Hepatic neutrophil influx significantly increased from 3 to 6 h of reperfusion (p < 0.05) and demonstrated the highest value at 12 h (1.1 ± 0.2 U/mg of protein). Plasma IL-6 levels in the ischemia groups showed peak values after 6 h of reperfusion, decreasing significantly thereafter (p < 0.05). Plasma CRP values reached highest levels after 3 h of reperfusion (mean 91 ± 5% of control pool), decreasing significantly thereafter. Rat IgM concentrations in plasma did not significantly change throughout the reperfusion time. Immunohistochemical depositions of IgM, CRP and C3 in ischemic lobes demonstrated a similar pattern in time, reaching maximum values at 12 h of reperfusion. The percentages of depositions of CRP and IgM were significantly correlated [r(S) = 0.569; p < 0.001; Spearman test]. The time course of C3 and CRP depositions throughout reperfusion and C3 and IgM staining were significantly similar [r(S) = 0.797 and r(S) = 0.656, respectively; p < 0.0001; ANOVA]. Conclusions: CRP and IgM depositions demonstrate a parallel time course throughout the reperfusion to hepatocellular damage, inflammatory response and activated complement deposition in this rat hepatic I/R model. Furthermore, the time course of CRP and IgM depositions was significantly similar to that of activated complement depositions.