The Effects of Glucose/Ischemic Preconditioning on Reperfusion Injury in Deceased-Donor Liver Transplantation

The Effects of Glucose/Ischemic Preconditioning on Reperfusion Injury in Deceased-Donor Liver Transplantation

A Prospective, Randomized Trial to Investigate the Effects of Glucose/ Ischemic Preconditioning Donor Pre-treatment on Reperfusion Injury in Deceased-Donor Liver Transplantation

Standard liver retrieval procedures for transplantation from a deceased donor inevitably result in a "reperfusion injury" to the liver tissue. The purpose of this research study is to find out whether treatment of the liver with a "preconditioning" protocol before its removal from the donor will help reduce any of this injury. The "preconditioning" treatment being tested has two components. Firstly, a solution of glucose+insulin is infused and secondly, blood flow to the liver is stopped briefly (10 minutes) and then resumed. Both strategies, individually, have been shown to reduce liver tissue injury in human studies. We hypothesize that combining both strategies will have a clinical benefit to patients and will improve liver function following transplant.

Liver transplantation is the only chance of cure for patients with end-stage liver disease. Unfortunately, standard organ preservation results in an ischemic-reperfusion injury (IRI) at the time of graft implantation. Novel strategies have been proposed to decrease reperfusion injury and improve graft function. This study will be the first to combine both strategies in a randomized, prospective trial. The intervention will occur during the retrieval surgery prior to cold preservation. Briefly, a glucose and insulin solution will be infused via the mesenteric vein at a controlled rate. Immediately prior to cross-clamping, blood supply to the liver will be restricted for 10 minutes and then resumed for 10 minutes before beginning cold preservation. All remaining surgical procedures, including the recipient surgery, will be performed by standard techniques. The liver recipient does not directly receive any intervention during this study.

Deceased liver donors that are randomized to this arm will receive the Glucose/Ischemic Preconditioning pre-treatment intra-operatively prior to starting cold preservation of the organ

Neither donors nor recipients receive any intervention. All procedures will be performed according to our institution's standard of care.

A 20% dextrose+insulin infusion is administered to the liver via the mesenteric vein beginning after cannulation of the mesenteric vein and ending immediately prior to flushing with cold preservation fluid. Also, after completion of the visceral dissection but prior to cross-clamping, ischemic precondition will occur. This involves occluding the portal vein and hepatic artery to stop blood flow for 10 minutes, then restoring blood flow for 10 minutes.

Liver ATP and glycogen content; blood cytokine levels; liver gene expression of pro- and anti-apoptotic genes

Inclusion Criteria: Recipient 18 years of age or older Recipient with chronic end-stage liver disease Deceased donor liver transplant Recipient capable of providing written informed consent Whole organ graft from donors aged 60 years or older Exclusion Criteria: Fulminant liver failure Objection by any other member of the retrieval team Split-liver grafts Donor that has received total parenteral nutrition within 24hr of organ retrieval Donors from whom the pancreas and/or small bowel are also being retrieved