Effects of hypertonic saline solution on liver ischemia/reperfusion injury with topical hepatic hypothermia in rats

• Grant number: 12/22420-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2013
• End date: December 31, 2013
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Estela Regina Ramos Figueira
• Grantee: Eduardo Ryoiti Tatebe
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The liver ischemia/ reperfusion (IR) injury is characterized by the worsening of hepatocellular damage during revascularization. This occurs in various clinical situations such as liver resection, hemorrhagic shock, and liver transplantation (LT). Some strategies have been developed to minimize liver injury. Hypertonic saline solutions have antioxidant properties with effects on neutrophils, macrophages, and endothelial cells, that also have an impact on microcirculation. Meanwhile, hypothermia, which is the cornerstone of organ preservation, has a protective reducing IR injury. However, hypothermia may also increase cellular edema impairing microcirculation, which can disturb liver macrocirculation. Objective: the aim of this study is to evaluate the effects of saline hypertonic solution on liver hypothermic ischemia/ reperfusion. Methods: male Wistar rats will be randomly allocated into six groups. Sham group: rats will be submitted to sham operation; resection control group (RC): rats will be submitted to resection of the right and caudate liver lobes; warm ischemia group (WI): rats will be submitted to 40 min of partial normothermic liver ischemia and subsequent resection of non-ischemic right and caudate liver lobes; cold ischemia group (CI): rats will be submitted to 40 min of hypothermic (10ºC) liver ischemia and subsequent resection of non-ischemic lobes; warm ischemia + NaCl 7.5% group (WNaCl): rats will be submitted to 40 min of normothermic liver ischemia, and 15 min before reperfusion rats will receive intravenous NaCl 7.5%; cold ischemia + NaCl 7.5% group (CNaCl): rats will be submitted to 40 min of hypothermic (10ºC) liver ischemia, and 15 min before reperfusion rats will receive intravenous NaCl 7.5%. Hemodynamic parameters (blood pressure, heart rate, and venous portal flow) will be recorded before ischemia (T0), 5 min (T1) and 20 min (T2) during ischemia, 5 min before reperfusion (T3), 5 min (T4), 30 min (T5), 1 h (T6) and 4 h (T7) during reperfusion. Four hours after reperfusion the animals will be killed for blood and tissue collection. The levels of transaminases AST and ALT, the inflammatory mediators TNF-alpha, IL-6 and IL-10, and the malondialdehyde (MDA) will be assayed. Liver fragments will be sent for histological analysis.(AU)