Ischemic Preconditioning of Liver in Cadaver Donors
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Changes in INR/PT and serum AST, ALT and TB levels
研究概览
简要总结
The long-term goals of this proposal are to develop clinical protocols of donor preconditioning to improve liver graft function and ameliorate complications of poor graft function after liver transplantation. Achievement of these objectives would improve liver recipient outcomes, increase utilization of livers and alleviate the current critical shortage of livers for transplantation. More stringent liver donor selection intended to decrease the complications of poor graft function conflicts directly with efforts to maximize the use of donor livers. Ischemic preconditioning (IPC) of liver attenuates hepatic ischemia reperfusion injury (IRI) in animals. Preliminary data show hepatic IPC effectively decreases IRI following hepatic resection in humans.
The specific aims of this project are: AIM 1: To test the hypothesis that 10 minutes of hepatic ischemic preconditioning in deceased donors would improve liver graft function and decrease injury in the early post transplant period. AIM 2: To test the hypothesis that ischemic preconditioning of deceased donor livers would decrease systemic inflammatory response in liver recipients in the early post transplant period. AIM 3: To examine whether ischemic preconditioning of deceased donor livers decreases early post transplant pulmonary edema and acute rejection and shortens hospital stay.
详细描述
Specific Aims
- To test the hypothesis that 10 minutes of hepatic ischemic preconditioning in deceased donors would improve liver graft function and decrease injury in the early post transplant period.
To accomplish this aim, we will compare International Normalized Ratios of prothrombin time (INR/PT) and serum aspartate (AST) and alanine aminotransferase (ALT) and total bilirubin (TB) levels immediately post transplant and on day 1, 3, 7, 14 and 30 and injury score of reperfusion liver biopsies in recipients of livers from IPC and No IPC donors. 2. To test the hypothesis that ischemic preconditioning of deceased donor livers would decrease the systemic inflammatory response in liver recipients in the early post transplant period.
To accomplish this aim, we will compare plasma levels of cytokines tumor necrosis factor-alpha (TNF-alpha), interleukins-6, 8 and 10 (IL-6, 8 and 10) and soluble L-selectin, expression levels of adhesion molecules (CD11beta/CD18 and L-selectin) and oxidative burst of neutrophils, platelet P-selectin and platelet-neutrophil complexes (PNC) in the peripheral blood 3, 12, 24 and 48 hours following reperfusion in recipients of livers from IPC and No IPC donors. 3. To examine whether ischemic preconditioning of deceased donor livers decreases early post transplant pulmonary edema and acute rejection and shortens hospital stay.
To accomplish this aim, we will compare interstitial and alveolar edema in chest radiographs done after transplant and on post operative days 1, 2 and 3; biopsy confirmed acute rejection within 30 days post transplant, and number of days to discharge after transplantation in recipients of livers from IPC and No IPC donors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Deceased donor livers allocated to adult (> 18 years of age) recipients at the research site.
排除标准
- •Deceased donor livers allocated to recipients at centers other than the research site.
- •Deceased donor livers allocated to recipients < 18 years of age at the research site.
- •Non-heart beating donors
- •Deceased liver and small intestine donors
- •Live liver donors.
结局指标
主要结局
Changes in INR/PT and serum AST, ALT and TB levels
时间窗: Values immediately post-transplantation and on days 1 - 3 and days 7, 14 and 30 post-transplantation
次要结局
- Plasma levels of cytokines(Blood samples are collected at pre-incision of abdomen, cross-clamp of abdominal aorta; 3 hour postreprofusion and post-transplant day one in the recipient)
- Interstitial and alveolar edema in chest radiographs(days 1 - 3 post transplant)
- Length of Hospital stay(number of days from Liver transplant to hospital discharge on average 10 days)