Luana Ricca1, Antoinette Lemoine, François Cauchy, Jocelyne Hamelin, Mylène Sebagh, Davide Degli Esposti, Chady Salloum, Eric Vibert, Genoveffa Balducci, Daniel Azoulay. 1. 1 Dipartimento di Scienze Medico-Chirurgiche e Medicina Traslazionale, Università degli Studi di Roma La Sapienza, Rome, Italy. 2 AP-HP Hôpital Paul Brousse-Centre Hépatobiliaire, Villejuif, France. 3 INSERM UMR-S 1004, Université Paris Sud, Villejuif, France. 4 AP-HP Hôpital Paul Brousse, Biochimie et Oncogénétique, Villejuif, France. 5 AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France. 6 INSERM UMR-S 785, Université Paris Sud, Villejuif, France. 7 AP-HP Hôpital Henri Mondor, Service de Chirurgie Digestive Hépatobiliaire, Creteil, France. 8 INSERM U 955, Université Paris Est, Créteil, France.
Abstract
BACKGROUND: Ischemia-reperfusion (I/R) injury is the main cause of graft failure in liver transplantation (LT). Ischemic postconditioning (IPo) has shown to be beneficial against I/R injury. Our objective was to compare the results of LT with or without IPo. METHODS: One hundred patients undergoing LT alternatively received IPo or not. At the time of arterial reperfusion, IPo consisted of three 1-minute arterial occlusions, interspersed with 1-minute reperfusion pauses. The primary endpoint was postoperative aspartate aminotransferase (AST) peak value; early graft dysfunction and histological I/R injury were secondary endpoints. RESULTS: Median postoperative AST peak values was similar in both groups (426 vs 463 IU/L, P = 0.21); no difference was found in other postoperative liver function tests. In the IPo group, fewer grafts presented severe histological I/R injury (12% vs 28%; P = 0.029). Ischemic postconditioning did not induce changes in cellular apoptosis but triggered autophagy in periportal areas. Independent predictors of severe I/R injury were IPo (odds ratio, 0.20; P = 0.008) and arterial warm ischemia duration (odds ratio, 1.05; P = 0.008). Early graft dysfunction rate was similar in both groups (20% versus 26%, P = 0.47) and was associated with severe histological I/R injury and longer cold ischemia. Morbidity, mortality, and 1-year graft and patient survival were similar in both groups. CONCLUSIONS: Ischemic postconditioning did not influence postoperative AST peak values or other liver function tests. However, our results showed a better tolerance to I/R injury on histological findings of grafts receiving IPo. Future studies are necessary to optimize the IPo protocol in LT, to clarify its clinical impact, and to deepen the molecular understanding.
BACKGROUND:Ischemia-reperfusion (I/R) injury is the main cause of graft failure in liver transplantation (LT). Ischemic postconditioning (IPo) has shown to be beneficial against I/R injury. Our objective was to compare the results of LT with or without IPo. METHODS: One hundred patients undergoing LT alternatively received IPo or not. At the time of arterial reperfusion, IPo consisted of three 1-minute arterial occlusions, interspersed with 1-minute reperfusion pauses. The primary endpoint was postoperative aspartate aminotransferase (AST) peak value; early graft dysfunction and histological I/R injury were secondary endpoints. RESULTS: Median postoperative AST peak values was similar in both groups (426 vs 463 IU/L, P = 0.21); no difference was found in other postoperative liver function tests. In the IPo group, fewer grafts presented severe histological I/R injury (12% vs 28%; P = 0.029). Ischemic postconditioning did not induce changes in cellular apoptosis but triggered autophagy in periportal areas. Independent predictors of severe I/R injury were IPo (odds ratio, 0.20; P = 0.008) and arterial warm ischemia duration (odds ratio, 1.05; P = 0.008). Early graft dysfunction rate was similar in both groups (20% versus 26%, P = 0.47) and was associated with severe histological I/R injury and longer cold ischemia. Morbidity, mortality, and 1-year graft and patient survival were similar in both groups. CONCLUSIONS: Ischemic postconditioning did not influence postoperative AST peak values or other liver function tests. However, our results showed a better tolerance to I/R injury on histological findings of grafts receiving IPo. Future studies are necessary to optimize the IPo protocol in LT, to clarify its clinical impact, and to deepen the molecular understanding.
Authors: Yanfeng Gao; Shuang Zhou; Fengfei Wang; Yue Zhou; Sen Sheng; Dan Qi; Jason H Huang; Erxi Wu; Yi Lv; Xiongwei Huo Journal: Int J Biol Sci Date: 2018-11-03 Impact factor: 6.580
Authors: Jordan R Yaron; Hao Chen; Sriram Ambadapadi; Liqiang Zhang; Amanda M Tafoya; Barbara H Munk; Dara N Wakefield; Jorge Fuentes; Bruno J Marques; Krishna Harripersaud; Mee Yong Bartee; Jennifer A Davids; Donghang Zheng; Kenneth Rand; Lisa Dixon; Richard W Moyer; William L Clapp; Alexandra R Lucas Journal: J Inflamm (Lond) Date: 2019-05-29 Impact factor: 4.981
Authors: Julia Schewe; Marie-Christine Makeschin; Andrej Khandoga; Jiang Zhang; Doris Mayr; Simon Rothenfußer; Max Schnurr; Alexander L Gerbes; Christian J Steib Journal: Dig Dis Sci Date: 2020-05-25 Impact factor: 3.199
Authors: Ana Isabel Álvarez-Mercado; Carlos Rojano-Alfonso; Marc Micó-Carnero; Albert Caballeria-Casals; Carmen Peralta; Araní Casillas-Ramírez Journal: Front Cell Dev Biol Date: 2021-06-01