Effect of remote ischemic preconditioning among donors and recipients following pediatric liver transplantation: A randomized clinical trial

Abstract

BACKGROUND Studies suggested that remote ischemic preconditioning (RIPC) may effectively lessen the harmful effects of ischemia reperfusion injury during organ transplantation surgery. AIM To investigate the protective effects of RIPC on living liver donors and recipients following pediatric liver transplantation. METHODS From January 2016 to January 2019 at Renji Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, 208 donors were recruited and randomly assigned to four groups: S-RIPC group (no intervention; n = 55), D-RIPC group (donors received RIPC; n = 51), R-RIPC group (recipients received RIPC, n = 51) and DR-RIPC group (both donors and recipients received RIPC; n = 51). We primarily evaluated postoperative liver function among donors and recipients and incidences of early allograft dysfunction, primary nonfunction and postoperative complications among recipients. RESULTS RIPC did not significantly improve alanine transaminase and aspartate aminotransferase levels among donors and recipients or decrease the incidences of early allograft dysfunction, primary nonfunction, and postoperative complications among recipients. Limited protective effects were observed, including a lower creatinine level in the D-RIPC group than in the S-RIPC group on postoperative day 0 ( P < 0.05). However, no significant improvements were found in donors who received RIPC. Furthermore, RIPC had no effects on the overall survival of recipients. CONCLUSION The protective effects of RIPC were limited for recipients who received living liver transplantation, and no significant improvement of the prognosis was observed in recipients.

Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury

“…The protective effect of IPC on IRI was initially discovered by Murry et al ( 72 ) in a canine myocardial ischemia model ( 72 ). A large number of experimental animal studies have provided strong preclinical evidence indicating that IPC can significantly improve the survival of hepatocytes and reduce the severity of liver IRI ( 11 , 65 ). In 2016, Liu et al ( 73 ) developed an IRI rat model indicating that inhibiting the activity of heme oxygenase-1 (HO-1) could reduce the autophagy induced by IPC, increase the activity of calpain2, and weaken the protective effect of IPC against liver IRI.…”

“…Although the protective effect of IPC on liver IRI has been verified in multiple animal model studies, contradictory results have emerged in ongoing clinical trials. A randomized clinical trial of 208 cases by Chinese scholars Qi et al ( 65 ) showed that RIPC neither significantly improved the levels of ALT and AST in donors and recipients nor decreased the incidence of early allograft dysfunction (EAD), primary non-function, and postoperative complications in liver recipients. Coincidently, another randomized clinical trial recently published in Ann Surg ( 66 ) reported that RIPC was not associated with any marked differences in postoperative transaminase levels and did not decrease the incidence of a delayed graft hepatic function among donors.…”

Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model

“…RIC is a simple procedure which creates short and repetitive cycles of non-damaging ischemia, usually applied to a leg or arm, which may reduce damaging effects caused by IRI in the target organ. RIC has shown various outcomes in pre-clinical studies in both kidney and other organs such as lung, liver, small intestine and in a variety of situations and species [6][7][8][9][10][11][12]. Several pre-clinical studies have demonstrated a reduction in IRI and improved early graft function in the recipient [13][14][15][16].…”