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PORCINE LARGE-FOR-SIZE LIVER TRANSPLANTATION WITH MANIPULATION OF PORTAL VENOUS FLOW: A HEMODYNAMIC, HISTOLOGIC AND BIOMOLECULAR STUDY

Grant number: 12/13020-7
Support type:Regular Research Grants
Duration: October 01, 2012 - September 30, 2014
Field of knowledge:Health Sciences - Medicine - Surgery
Principal researcher:Ana Cristina Aoun Tannuri
Grantee:Ana Cristina Aoun Tannuri
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Alessandro Rodrigo Belon ; Daniel de Albuquerque Rangel Moreira ; Maria Cecília de Mendonça Coelho ; Uenis Tannuri

Abstract

Pediatric liver transplantation is considered a well-established therapeutic modality for treatment of progressive liver disease not subject to clinical management. With technical advances of liver transplants, continuing increase in the number of liver transplanted children weighing less than 10kg has occurred. The optimum size for a given cirrhotic receiver varies from 0.8% to 4% of their body weight. When it comes to performing liver transplantation with graft weight greater than 5% of the recipient body weight we have a situation called large-for-size. This increases the chance of complications such as abdominal compartmental syndrome, reduced portal blood flow and higher probability of dysfunction1-3.During liver transplantation the graft harvested from the donor suffers cellular, molecular and biochemical injury proportional to time and type of ischemia. When hepatic blood flow is restored after implantation of the graft, a lesion caused by a chain of events is initially mediated by Kupffer cells and then, carried on by a complex mechanism involving endothelial cell injury, apoptosis, and injury to the liver parenchyma by reactive oxygen species and poor perfusion of the hepatic microvasculature. The nitric oxide as a vasodilation molecule and endothelins as a vasoconstrictor mediator have a role in intensity of the lesion referred to as ischemia / reperfusion injury.Over time, several prognostic factors have been studied of the graft's long-term viability and clinical outcome after liver transplantation. The liver's ability to capture oxygen, to produce glucose and to maintain their metabolic functions immediately after reperfusion have been shown to be viable as predictors of outcome. As a prerequisite of the proper functioning of the graft it's also included the hemodynamic status of the receiver and the ability of this organism to maintain homeostasis after surgery and anesthesia injury.In this study we use a model of liver transplantation in pigs dividing them into three distinct groups. At first, we will carry out transplantation between animals of similar weight, the second group with donor's size twice of the recipient and in the third group we will perform a manipulated technique to increase the portal blood flow. During the transplant we will implant catheters in the portal and hepatic veins and a perivascular flowmeter on the hepatic artery and portal vein to monitor the hemodynamics of the graft after transplantation. To do this, we will measure the hepatic vascular resistance, supply and O2 uptake by the graft and the ability of the newly implanted organ to produce glucose. We will infer the liver's anaerobic metabolism from the amount of lactate released. Subsequent liver biopsies will be performed and submitted to histological, immunohistochemistry and molecular analysis in order to quantify the repercussions of ischemia and reperfusion lesion.This study is intended to increase knowledge about the hepatic vascular flow in a porcine large-for-size liver transplant model and its relationship with increased ischemia and reperfusion. Throughout the flowmeter assessment, biochemical, histological and molecular analysis we intend to quantify and identify the factors related to improving or worsening of ischemia / reperfusion injury before and after manipulation of the technique of evaluating changes of response in a better state of portal blood flow (porto-caval vein grafts in "H"). (AU)