Ischemic Pre-conditioning in Deceased Donor Liver Transplantation: A Prospective Randomized Clinical Trial

Abstract

To assess the immediate and long-term effects of ischemic preconditioning (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1alpha (HIF-1a ) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT.

Ischemic preconditioning of the liver: A few perspectives from the bench to bedside translation

“…However, a recent publication of that trial data did not address this issue of the IPC paradox. 28 In our own experience, both 5-minute and 10-minute IPC resulted in increased RP injury in DDLT. 24,29 Furthermore, a variant of the IPC paradox was reported by Azoulay et al 25 in DDLT.…”

“…Subsequently, others have reported results of clinical trial in LR and in deceased donor liver transplantation (DDLT). [21][22][23][24][25][26][27][28][29] It is fair to conclude that the overall clinical results have been less stellar than what was observed in experimental animals. Therefore, a critical evaluation of the available evidence from the initial translational attempts is needed.…”

“…20,21,[23][24][25][26][27][28][29]34 The biochemical parameters included serum AST and ALT, serum bilirubin, PT, and INR. The clinical parameters included PNF and initial poor graft function.…”

Recovering the Recovering Liver Graft

“…However, whether ischemic preconditioning of liver grafts has a protective effect is inconclusive [11]. Positive [12][13][14][15] and negative [16,17] views both exist. In a French study of 165 DDLTs, 34 of the donors had a history of cardiac arrest.…”

Hypoxia and reoxygenation of primary human hepatocytes induce proteome changes of glucose metabolism, oxidative protection and peroxisomal function

“…When low O 2 concentration is sustained longer adaptive alterations of gene expression take place and finally chronic hypoxia results in cell death when the adaptive mechanisms are exhausted (12). Short-term hypoxia can prime cells or organs to increase their tolerance to hypoxia (13,14) for example through downregulation of energy demanding pathways to reduce ATP requirements (15)(16)(17). Another compensatory factor is the upregulation of protective components against reactive oxygen species generated during reoxygenation.…”