2019Annals of TransplantationOpen access

Normothermic Machine Perfusion Protects Against Liver Ischemia-Reperfusion Injury During Reduced-Size Liver Transplantation in Pigs

Zhibin Zhang, Wei Gao, Lei Liu, Yuan Shi, Ning Ma, Ming-sheng Huai, Shen Zhong-yang

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Abstract

BACKGROUND Normothermic machine perfusion (NMP) preservation is superior to cold preservation during reduced-size liver transplantation (RSLT) in pigs. However, the mechanism of this protective effect has not been explained. We aimed to compare the effects of NMP preservation with that of cold preservation (CS) in protecting against ischemia-reperfusion injury (IRI) during RSLT in pigs. MATERIAL AND METHODS Twenty-four healthy Bama miniature pigs were randomized into 2 groups: 1) the NMP group in which donor livers harvested without warm ischemia time and cardiac activity were connected to the NMP system to reduce liver size under normothermic conditions, and 2) the CS group in which donor livers harvested without warm ischemia time and cardiac activity were perfused using the University of Wisconsin (UW) solution and then preserved in the 0-4°C UW solution to reduce liver size under cold conditions. Livers were then transplanted without veno-venous bypass. Amounts of bile secretion for the NMP groups were recorded hourly. The serological indices were measured. Expressions of cytochrome C, caspase 3, and NF-κB p65 in liver tissue were observed. RESULTS The levels of bile secretions were gradually diminished from 16.50±2.66 mL/h before splitting to 6.35±1.24 mL/h after splitting. With the exception of TNF-α on postoperative day 2, overall, levels of TNF-α, IL-1, IL-6, and MDA were significantly lower in the NMP group versus CS group for all 5 days postoperatively. Finally, cytochrome C, caspase 3, and NF-κB p65 expressions were all significantly suppressed in the NMP group as compared with the CS group. CONCLUSIONS MP preservation is superior to cold preservation in protecting against liver IRI during RSLT in pigs.

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What this paper is about

BACKGROUND Normothermic machine perfusion (NMP) preservation is superior to cold preservation during reduced-size liver transplantation (RSLT) in pigs. However, the mechanism of this protective effect has not been explained. We aimed to compare the effects of NMP preservation with that of cold preservation (CS) in protecting against ischemia-reperfusion injury (IRI) during RSLT in pigs. MATERIAL AND METHODS Twenty-four healthy Bama miniature pigs were randomized into 2 groups: 1) the NMP group in which donor livers harvested without warm ischemia time and cardiac activity were connected to the NMP system to reduce liver size under normothermic conditions, and 2) the CS group in which donor livers harvested without warm ischemia time and cardiac activity were perfused using the University of Wisconsin (UW) solution and then preserved in the 0-4°C UW solution to reduce liver size under cold conditions. Livers were then transplanted without veno-venous bypass. Amounts of bile secretion for the NMP groups were recorded hourly. The serological indices were measured. Expressions of cytochrome C, caspase 3, and NF-κB p65 in liver tissue were observed. RESULTS The levels of bile secretions were gradually diminished from 16.50±2.66 mL/h before splitting to 6.35±1.24 mL/h after splitting. With the exception of TNF-α on postoperative day 2, overall, levels of TNF-α, IL-1, IL-6, and MDA were significantly lower in the NMP group versus CS group for all 5 days postoperatively. Finally, cytochrome C, caspase 3, and NF-κB p65 expressions were all significantly suppressed in the NMP group as compared with the CS group. CONCLUSIONS MP preservation is superior to cold preservation in protecting against liver IRI during RSLT in pigs.

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Available abstract

BACKGROUND Normothermic machine perfusion (NMP) preservation is superior to cold preservation during reduced-size liver transplantation (RSLT) in pigs. However, the mechanism of this protective effect has not been explained. We aimed to compare the effects of NMP preservation with that of cold preservation (CS) in protecting against ischemia-reperfusion injury (IRI) during RSLT in pigs. MATERIAL AND METHODS Twenty-four healthy Bama miniature pigs were randomized into 2 groups: 1) the NMP group in which donor livers harvested without warm ischemia time and cardiac activity were connected to the NMP system to reduce liver size under normothermic conditions, and 2) the CS group in which donor livers harvested without warm ischemia time and cardiac activity were perfused using the University of Wisconsin (UW) solution and then preserved in the 0-4°C UW solution to reduce liver size under cold conditions. Livers were then transplanted without veno-venous bypass. Amounts of bile secretion for the NMP groups were recorded hourly. The serological indices were measured. Expressions of cytochrome C, caspase 3, and NF-κB p65 in liver tissue were observed. RESULTS The levels of bile secretions were gradually diminished from 16.50±2.66 mL/h before splitting to 6.35±1.24 mL/h after splitting. With the exception of TNF-α on postoperative day 2, overall, levels of TNF-α, IL-1, IL-6, and MDA were significantly lower in the NMP group versus CS group for all 5 days postoperatively. Finally, cytochrome C, caspase 3, and NF-κB p65 expressions were all significantly suppressed in the NMP group as compared with the CS group. CONCLUSIONS MP preservation is superior to cold preservation in protecting against liver IRI during RSLT in pigs.

Key concepts: Medicine, Viaspan, Perfusion, Reperfusion injury, Liver transplantation, Ischemia, Transplantation, Cold storage

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