Effects of hexafluoro-2-propanol on normothermic hepatic ischemia and reperfusion injury

• Grant number: 18/07000-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2018
• Effective date (End): August 31, 2019
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Joel Avancini Rocha Filho
• Grantee: Jonathan Augusto Venceslau Lima
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

One of the main clinical problems after liver transplantation and liver resections is hepatic dysfunction due to ischemia/reperfusion (RI) injury. Several strategies have been implemented to decrease the IR injury. Recent experimental studies have demonstrated protective effects in tissues with the use of sevoflurane metabolites, mainly related to the trifluorinated carbon (CF3) structural groups. Our hypothesis is that intravenous administration of the metabolite hexafluoro-2-propanol (HFIP) decreases liver ischemia/reperfusion injury. Objective: To evaluate the effects of hexafluoro-2-propanol administration in an experimental model of normothermic hepatic ischemia and reperfusion injury in rats. Methods: Sixty Wistar rats will be studied in four groups: Sham group (S); Control group (C), animals will be submitted to 30 min of normothermic liver ischemia; Sevoflurane group, animals submitted to IR will be treated with inhaled sevoflurane 2.5% for 30 min prior to ischemia; HFIP group, animals will be treated with intravenous infusion of HFIP, 67 mg / kg, prior to ischemia. Systemic hemodynamic evaluation and portal blood flow will be performed at the time after induction of anesthesia, 5 min after induction of ischemia, immediately before reperfusion, 5 min after reperfusion, 30 min and 4 h after reperfusion. Four hours after reperfusion the animals will be sacrificed for collection of blood and tissue. The levels of AST and ALT, TNF±, IL-6 and IL-10, mitochondrial functions, malondialdehyde and liver histology, thromboelastometry, platelets, permeability and pulmonary myeloperoxidase will be assessed. Statistically significant differences will be considered when p <0.05.