The Significance of Preserving the Energy Status and Microcirculation in Liver Grafts from Non-Heart-Beating Donor

Abstract

To complete a successful liver transplantation (LTx) from non-heart-beating donors (NHBD), it is necessary to both improve the energy status in liver grafts and to reduce the exposure to free radicals. This study investigated the effects of short perfusion with oxygenated buffer on the grafts prior to cold preservation. In addition, the effects of the antioxidant, biliverdin, for reduction of free radicals was investigated. Male Wistar rats were used. Livers were retrieved, preserved in UW solution, and perfused for 60 min with oxygenated Krebs-Henseleit solution. Rats were allocated to six groups as follows (n=5): (i) control group-no warm ischemia (WI) and cold preservation, (ii) HBD group--no WI with cold preservation for 6 h; (iii) NHBD group--with 30 min of WI and cold preservation, (iv) NM group--with WI including nafamostat mesilate infusion before cardiac arrest and cold preservation; (v) PRE group--with WI, 30-min pre-cold preservation perfusion with oxygenated buffer after cardiac arrest, and cold preservation, (vi) BV group-with the same treatment as the PRE group plus the addition of biliverdin to the pre-cold preservation perfusion. The portal flow volume, bile production, AST, and TNF-alpha in perfusate, energy charge (EC), and ATP level in the tissue, and histological findings were investigated. The portal flow volume in the NM, PRE, and BV groups were higher than in the NHBD group. The bile production in the PRE and BV groups were also higher than in the NHBD group. The EC and ATP level of the BV group after reperfusion were higher than those of the NHBD group. Pre-cold preservation perfusion and addition of biliverdin to perfusate improved viability of grafts from NHBD. The results indicate that the preservation of the energy status and microcirculation of the graft is important for successful LTx from NHBD.

Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation

“…However, new devices are gaining support and may play a role in the near future (37). Post-procurement machine perfusion, particularly in the case of DCD livers, offers a recovery phase prior to cold preservation that may improve tolerance to extended cold ischemia (38). In this work and previous studies we employ SNMP with the aim of improving the final quality of the liver pre-implantation and, importantly, to allow for the most representative assessment of liver viability.…”

Improvement of liver injury and survival by JNK2 and iNOS deficiency in liver transplants from cardiac death mice

“…Kupffer cell activation, parenchymal cell killing, ROS and toxic cytokine production, and increased endothelin may be involved in CDD graft failure [4, 9, 28-31]. Maintaining energy status and microcirculation is crucial for successful transplantation of CDD grafts [9, 32].…”

“…Preserving bioenergetic status and microcirculation is important for successful transplantation of CDD grafts [9]. Mitochondria provide >90% of the cellular ATP during aerobic liver metabolism.…”

Hyperbaric oxygen therapy protects the liver from apoptosis caused by ischemia‐reperfusion injury in rats

“…7,13 Another event typical of ischemia involves changes in ion transport, with a loss of intracellular K þ and increased intracellular Na þ because of the inhibition of Na þ /K þ ATPase function. 25 The decrease in intracellular ATP correlated with the lower viability of cells. 26 During ischemia, when ATP stores are depleted, the transport mechanism of cell pump is inhibited, resulting in a significant loss of membrane potential, and the accumulation of intracellular Na þ promotes cell swelling.…”