Clinical Trial: Ischemic Preconditioning of Liver in Cadaver Donors

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Ischemic Preconditioning of Liver in Cadaver Donors

Brief Summary:

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.


Detailed Summary:

Specific Aims

  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.

    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 r
Sponsor: University of Medicine and Dentistry of New Jersey

Current Primary Outcome: Changes in INR/PT and serum AST, ALT and TB levels [ Time Frame: Values immediately post-transplantation and on days 1 - 3 and days 7, 14 and 30 post-transplantation ]

Original Primary Outcome:

  • 1). INR/PT and serum AST, ALT and TB levels
  • 2). Plasma levels of cytokines
  • 3). Interstitial and alveolar edema in chest radiographs


Current Secondary Outcome:

  • Plasma levels of cytokines [ Time Frame: 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 [ Time Frame: days 1 - 3 post transplant ]
  • Length of Hospital stay [ Time Frame: number of days from Liver transplant to hospital discharge on average 10 days ]


Original Secondary Outcome:

Information By: Rutgers, The State University of New Jersey

Dates:
Date Received: October 26, 2005
Date Started: October 2003
Date Completion:
Last Updated: January 16, 2015
Last Verified: January 2015