Histological evaluation and molecular effects of early ischemic preconditioning direct and remote in liver transplant in pigs

• Grant number: 16/18756-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2017
• Effective date (End): December 31, 2017
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Alessandro Rodrigo Belon
• Grantee: Alessandra Matheus da Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Liver transplantation (LT) is the only effective method of treatment and acceptable to patients with end-stage liver failure. The progress in the training of professionals involved in the trans management and postoperative combined with new regimens of immunosuppressive treatments, contributed to the improvement in the short and long-term results of these transplants. However, despite these advances, the ischemia and reperfusion (I / R) during the withdrawal and deployment of the graft remains a major cause of primary dysfunction and also relates to cases of acute and chronic rejection. In order to minimize the deleterious effects of I / R nsa grafts, Development and Use of New Conservation Solutions, for example, contributed positively to the success of Liver Transplantation. New strategies are being studied / developed. The ischemic preconditioning ( CIP) For the maneuver qua are generated brief ischemia followed by periods of brief periods of reperfusion, previously one hum ischemic injury can help the graft to tolerate hum Long ischemia period and subsequent reperfusion. The release of substances na bloodstream, after a PCI, CAN effects develop protective, like reduction of apoptosis and cell necrosis of the graft, increasing survival nsa TH .PCI can be direct (the target organ) or indirect (remote). In direct PCI (PCID), the biggest disadvantage is the mechanical stress in major vascular organ structures. Remote PCI (PCIR) is the procedure where the target organ does not suffer episodes of brief ischemia, another body is ischemic for a short period and the protective effect acts in the target organ. In the literature is scant research reporting the possible beneficial effect of PCI on liver transplantation in large animals. The objective of the project and observe the effects of different PCI in the model of orthotopic liver transplantation in pigs of similar weight. We will use 48 pigs (24 donors and 24 recipients). The animals will be allocated in the following groups: control group (GCT N = 6); PCID group donor (GPCID N = 6); Group PCIR the receiver (GPCIR N = 6) and PCID group donor and the recipient PCIR (GPCID + R, N = 6). After the transplantation, liver biopsy will be taken with 1h after arterialization graft, this material will be processed for histological analysis, molecular analysis (pro-apoptotic gene: Bax, anti-apoptotic gene: Bcl-XL, cell proliferation gene : IL-6 and nitric oxide generator gene: eNOS) and immunohistochemistry, to detect differences between groups. (AU)