Effects of ischemic preconditioning on hepatic hemodynamics and metabolism in an experimental model of liver ischemia/ reperfusion injury in rats

• Grant number: 11/09434-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2011
• Effective date (End): September 30, 2013
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Estela Regina Ramos Figueira
• Grantee: Mauro Nakatani
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Background: The liver warm ischemia/ reperfusion injury (I/R) is associated with various medical conditions such as liver resection, hemorrhagic shock and liver transplantation. In cases submitted to warm liver ischemia, liver failure is a major cause of postoperatory death. To understand the mechanisms of I/R injury and associated factors, several studies have been developed, and some treatments to decrease liver injury has been suggested. The ischemic preconditioning (IPC) increases the production of endogenous NO, producing vasodilation, increasing sinusoidal blood flow, with consequent reduction of I/R injury. Alterations in the microcirculation can lead to variations in hepatic hemodynamics. Some studies correlate the portal flow with postoperatory patient survival. Aim: To evaluate the effects of ischemic preconditioning on hepatic hemodynamics and metabolism in a experimental model of ischemia/reperfusion injury in rats. Methods: We will study 76 male Wistar rats, four animals were used to evaluate the normal range (Group I - Normal control). The remaining rats will be divided into three groups (II, III and VI). Each group will be divided into three subgroups of 8 animals for analysis into three time points after reperfusion: 4h, 12h and 7 days. Group II (Sham group): rats that underwent resection of the right and caudate non-ischemic lobes, group III (C group): animals submitted to 60 min of warm ischemia and resection of non-ischemic lobes during reperfusion, and group IV (PCI group): animals submitted PCI for 10 min followed by 10 min of reperfusion and 60 min of warm ischemia, with subsequent resection of non-ischemic lobes. The following parameters will be evaluated: AST, ALT as an index of tissue injury, and lactate, potassium and glucose for metabolism analysis. For hemodynamic assessment will be recorded systemic blood pressure, central venous pressure, portal pressure and portal flow. Liver fragments will be sent for histological analysis. Animal survival will be evaluated during 7 days after surgery.