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Normothermic ex-situ Liver Perfusion...

Linares Cervantes, Ivan de Jesus.

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Normothermic ex-situ Liver Perfusion and PPAR-γ Activation as Strategies to Reduce Liver Ischemia Reperfusion Injury.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Normothermic ex-situ Liver Perfusion and PPAR-γ Activation as Strategies to Reduce Liver Ischemia Reperfusion Injury./
作者:	Linares Cervantes, Ivan de Jesus.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	287 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Contained By:	Dissertations Abstracts International81-05B.
標題:	Medicine. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13901282
ISBN:	9781392575895

Normothermic ex-situ Liver Perfusion and PPAR-γ Activation as Strategies to Reduce Liver Ischemia Reperfusion Injury.
Linares Cervantes, Ivan de Jesus.

Normothermic ex-situ Liver Perfusion and PPAR-γ Activation as Strategies to Reduce Liver Ischemia Reperfusion Injury. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 287 p.

Source: Dissertations Abstracts International, Volume: 81-05, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

The liver ischemia-reperfusion injury (IRI) is a significant problem during liver transplantation. IRI leads to hepatocyte damage and a prominent inflammatory response that results in graft dysfunction, and high morbidity and mortality following transplantation. The pro-inflammatory Kupffer cell (KC) polarization and the cold ischemic injury are key factors that initiate and perpetuate the severity of IRI. In this dissertation, I explore strategies that address these factors. First, I aim to modify the pro-inflammatory KC-phenotype in an in-vitro and in-vivo model. Second, I focus on optimizing a model of normothermic ex-situ liver perfusion (NEsLP) as a preservation technique to reduce cold ischemic injury and as a platform to evaluate the liver viability before transplantation.The pro-inflammatory (M1) activation of KCs is thought to initiate the IRI event. In this dissertation, I utilize a peroxisome proliferator activated-receptor-gamma (PPAR-γ) agonist to ameliorate the M1 polarization of KCs. The PPAR-γ activation results in a significant decrease of the M1-Nitric oxide + KC-phenotype in-vitro (Chapter 3) and in-vivo (Chapter 4), which reflects in a significant reduction of hepatocyte injury, apoptosis and necrosis in a mouse model of IRI.As the next step in this dissertation, I aim to optimize NEsLP for its use in donation after circulatory death (DCD) organs. In Chapter 6, I evaluate the different clinical perfusates to identify the most suitable solution for the perfusion of DCD grafts. The use of a human albumin/ dextran solution during NEsLP displays a better endothelial function and reduces the levels of AST, apoptosis, and necrosis after transplantation compared to the other solutions. Finally, in Chapter 7, I evaluate the feasibility of using NEsLP biomarkers to predict liver viability after transplantation with marginal DCD grafts. The model identifies consistent biomarkers of hepatocellular (lactate clearance and urea production) and biliary viability (bile/perfusate glucose and sodium ratio) that reflect in successful liver transplantation.The results of this dissertation highlight the importance of addressing several targets during IRI and suggest that the combination of these strategies evaluated by consistent viability biomarkers during NEsLP might result in a reliable use of marginal DCD grafts in the future.

ISBN: 9781392575895Subjects--Topical Terms:

641104
Medicine.
Subjects--Index Terms:

Donation after circulatory death

Normothermic ex-situ Liver Perfusion and PPAR-γ Activation as Strategies to Reduce Liver Ischemia Reperfusion Injury.
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