Effect of liver ischemic preconditioning in cirrhotic rats submitted to hepatic ischemia/reperfusion injury

Abstract

Purpose:The main aim of this study was to determine the influence of ischemic preconditioning (IPC) on rat liver cirrhosis. Methods: Cirrhosis was induced in Wistar rats by occlusion of the hepatic duct. The animals were divided into four groups of six animals each: non-cirrhotic group (simulated operation only), cirrhotic control group (simulated operation in cirrhotic rats), I/R group (40-minute ischemia without IPC), and IPC group (cirrhotic rats with ischemia, previously submitted to IPC). The IPC procedure consisted of partial hepatic ischemia for five minutes, followed by 10 minutes of reperfusion. In the case of the IPC group, the animals were submitted to liver ischemia for 40 minutes after the preconditioning procedure, followed by 2 hours of reperfusion. Blood samples were collected for measurement of serum aminotransferases (ALT and AST). The respiratory control ratio (RCR), the mitochondrial membrane potential (MMP), and malondialdehyde (MDA) values in the hepatic tissue were analyzed. Nonparametric statistical analysis was used and a value of p<0.05 was considered statistically significant. Results: Ischemia did not induce significant increase in ALT and AST levels. MDA values were significantly higher in cirrhotic animals. MMP did not significantly change in cirrhosis and liver ischemia. Mitochondrial RCR decreased in liver cirrhosis, accentuated upon liver ischemia, and did not significantly change with IPC. Conclusion: Ischemic preconditioning does not protect the liver from hepatic injury induced by the ischemia/ reperfusion process. Key words: Liver Cirrhosis. Hepatic Ischemia. Ischemic Preconditioning. RESUMOObjetivo: O objetivo deste estudo foi determinar a influência do pré-condicionamento isquêmico (IPC) em fígados de ratos cirróticos. Métodos: A cirrose hepática foi induzida em ratos Wistar machos (250 a 300g) por oclusão, durante 30 dias, do ducto hepático comum.A seguir, os animais cirróticos foram divididos em três grupos de seis; Grupo controle cirrótico (operação simulada para isquemia/reperfusão/pré-condicionamento), Grupo I/R, isquemia de 40 minutos sem pré-condicionamento (IPC) e grupo IPC com isquemia precedida por IPC. O IPC consistiu de uma isquemia parcial por cinco minutos, seguida por 10 minutos de reperfusão. No grupo IPC, após o pré-condicionamento, os animais foram submetidos à isquemia hepática de 40 minutos seguida de 2 horas de reperfusão. Foram colhidas amostras de sangue para dosagem sérica de aminotransferases (ALT e AST). Razão de controle respiratório (RCR), potencial de membrana das mitocôndrias (PMM) e dosagem de malondialdeído (MDA) foram analisadas no tecido hepático. Analise estatística não paramétrica foi utilizada com nível de significância de 5% para as comparações entre grupos.Resultados: A isquemia não induziu aumento significativo das aminotransferases. Houve aumento significativo de MDA nos animais cirróticos.O PMM não se alterou significativamente na cirrose e na isquemia hepática. A RCR mitocondrial diminuiu na cirrose hepática e acentuou-se ...

Topical hepatic hypothermia plus ischemic preconditioning: analysis of bile flow and ischemic injuries after initial reperfusion in rats

“…This observation, however, is similar to reports that used IPC in aged and cirrhotic rats, in liver donors to transplant or under total vascular exclusion 25,[34][35][36] . A possible explanation might be related to the protocol of 90 minutes of ischemia applied in this study, which could be beyond the limits of IPC protection.…”

Attenuation of Reperfusion-Induced Hepatocyte Apoptosis is Associated with Reversed bcl-2/bax Ratio in Hemi-Hepatic Artery-Preserved Portal Occlusion

“…As an organ susceptible to ischemia and hypoxia, the liver is less tolerant to systemic hypoperfusion and compromised inflow, especially in pathologic conditions, such as cirrhosis and steatohepatitis [1]. The minimization of hemorrhage in hepatic procedures is, therefore, critical for the outcome of hepatectomy and postoperative recovery of patients.…”

Portal vein clamping alone confers protection against hepatic ischemia–reperfusion injury via preserving hepatocyte function in cirrhotic rats

“…Several studies have shown that a liver with underlying disease, such as cirrhosis or steatosis, tolerates I/R injury poorly and that injury mechanisms differ from those of the normal liver [11,12]. In addition, most of the hepatocellular carcinoma tends to occur in the background of liver cirrhosis [13].…”