The ischemic preconditioning paradox in deceased donor liver transplantation-evidence from a prospective randomized single blind clinical trial.
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.
Koneru
B
B
Department of Surgery, University of Medicine and Dentistry, New Jersey Medical School, Newark, NJ, USA. koneruba@umdnj.edu
Shareef
A
A
Dikdan
G
G
Desai
K
K
Klein
K M
KM
Peng
B
B
Wachsberg
R H
RH
de la Torre
A N
AN
Debroy
M
M
Fisher
A
A
Wilson
D J
DJ
Samanta
A K
AK
D000328:Adult; D001706:Biopsy; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D019194:Ischemic Preconditioning / Q000009:adverse effects* / Q000379:methods; D008099:Liver / Q000201:enzymology / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism; D016037:Single-Blind Method; D013997:Time Factors; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10