The ischemic preconditioning paradox in deceased donor liver transplantation-evidence from a prospective randomized single blind clinical trial

Am J Transplant. 2007 Dec;7(12):2788-96. doi: 10.1111/j.1600-6143.2007.02009.x. Epub 2007 Oct 19.

Abstract

While animal studies show that ischemic preconditioning (IPC) is beneficial in liver transplantation (LT), evidence from few smaller clinical trials is conflicting. From October 2003 to July 2006, 101 deceased donors (DD) were randomized to 10 min IPC (n = 50) or No IPC (n = 51). Primary objective was efficacy of IPC to decrease reperfusion (RP) injury. Both groups had similar donor risk index (DRI) (1.54 vs. 1.57). Aminotransferases on days 1 and 2 were significantly greater (p < 0.05) in IPC recipients. In multivariate analyses, IPC had an independent effect only on day 2 aspartate transferase. Prothrombin time, bilirubin and histological injury were similar in both groups. IPC had no significant effect on plasma TNF-alpha, IL-6 and IL-10 in the donor and TNF-alpha and IL-6 in the recipient. In contrast, IPC recipients had a significant rise in systemic IL-10 levels after RP (p < 0.05) and had fewer moderate/severe rejections within 30 days (p = 0.09). Hospital stay was similar in both groups. One-year patient and graft survival in IPC versus No IPC were 88% versus 78% (p = 0.1) and 86 versus 76% (p = 0.25), respectively. IPC increases RP injury after DDLT, an 'IPC paradox'. Other potential benefits of IPC are limited. IPC may be more effective in combination with other preconditioning regimens.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biopsy
  • Female
  • Graft Rejection / etiology*
  • Graft Rejection / metabolism
  • Graft Survival / physiology
  • Humans
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Ischemic Preconditioning / adverse effects*
  • Ischemic Preconditioning / methods
  • Liver / enzymology
  • Liver / pathology
  • Liver Transplantation / pathology
  • Liver Transplantation / physiology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Prospective Studies
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / metabolism
  • Single-Blind Method
  • Time Factors
  • Tissue Donors*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10