Decreased survival in rat liver transplantation with extended cold preservation: Role of portal vein clamping time

Urata, Koichi; Nguyen, Bich; Brault, Antoine; Lavoie, Jean-Claude; Rocheleau, Bernard; Huet, Pierre‐Michel

doi:10.1002/hep.510280211

Cited by 44 publications

(49 citation statements)

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“…But in the course of cold storage, cells remained to be injured in different degrees with the extension of preservation time. In the period of liver cold storage, hepatocytes and SECs were all injured, especially the latter [18,19] . During warm ischemia hepatocytes were the most vulnerable cells whereas SECs were less sensitive [20] .…”

Section: Discussionmentioning

confidence: 99%

“…Male Sprague-Dawley rats weighing 200-300 g were purchased from Sino-British Sippr/BK Lab Animal Ltd. All rats were kept in animal quarters with controlled temperature (18)(19)(20)(21)(22)(23)(24)(25) and light (light on from 7 a.m. to 7 p.m.) and were fed with a standard laboratory chow and water in accordance with institutional animal care policies. Prior to the experimental procedure, the rats were fasted for 12 hours but allowed free access to water.…”

Section: Animalsmentioning

confidence: 99%

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Protective effect of doxorubicin induced heat shock protein 72 on cold preservation injury of rat livers

Chen

Yu²,

Zhang³

et al. 2004

WJG

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AIM:To observe the protective effect of heat shock protein 72 (HSP 72) induced by pretreatment of doxorubicin (DXR) on long-term cold preservation injury of rat livers. METHODS:Sprague-Dawley rats were administered intravenously DXR at a dose of 1 mg/kg body mass in DXR group and saline in control group. After 48 h, the rat liver was perfused with cold Linger's and University of Wisconsin (UW) solutions and then was preserved in UW solution at 4 for 24, 36 and 48 h. AST, ALT, LDH and hyaluronic acid in preservative solution were determined. Routine HE, immunohistochemical staining for HSP 72 and electron microscopic examination of hepatic tissues were performed. RESULTS:After 24, 36 and 48 h, the levels of AST, ALT and hyaluronic acid in preservative solution were significantly higher in control group than in DXR group (P<0.05), while LDH level was not significantly different between the 2 groups (P>0.05). Hepatic tissues in DXR group were morphologically normal and significantly injured in control group. HSP 72 was expressed in hepatocytes and sinusoidal endothelial cells in DXR group but not in control group.CONCLUSION: Pretreatment of DXR may extend the time of rat liver cold preservation and keep liver alive. The expression of HSP 72 in liver can prevent hepatocytes and sinusoidal endothelial cells from long-term cold preservation injury.

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Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Protective effect of doxorubicin induced heat shock protein 72 on cold preservation injury of rat livers

Chen

Yu²,

Zhang³

et al. 2004

WJG

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“…TNF-␣ is produced early after liver transplantation, and TNF-␣ production is increased in liver grafts failing from storage-reperfusion injury. 42,43 Anti-TNF-␣ antibodies reduce liver injury in models of warm and cold ischemia and reperfusion. 44,45 A variety of agents that suppress lipopolysaccharide-stimulated TNF-␣ formation by Kupffer cells also decrease graft failure from storage-reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

Ischemic preconditioning of rat livers against cold storage-reperfusion injury: Role of nonparenchymal cells and the phenomenon of heterologous preconditioning

2001

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Brief periods of ischemia followed by reperfusion render tissues resistant against subsequent prolonged ischemia, a phenomenon called ischemic preconditioning. The effect of ischemic preconditioning on liver transplantation was investigated in relation to sinusoidal endothelial cell injury and Kupffer-cell activation, which are prominent features of storage and reperfusion injury leading to liver graft failure. Rat livers were preconditioned by 5 or 10 minutes of ischemia and 5 minutes of reperfusion and stored in University of Wisconsin (UW) solution for 30 hours. Livers were then reperfused for 15 minutes with physiological buffer containing trypan blue. Under these conditions, injury occurs predominantly to sinusoidal endothelial cells, reflected by trypan blue staining of nonparenchymal cells in histological sections. Ischemic preconditioning decreased nonparenchymal cell killing by more than 50%. When half the liver was preconditioned, sinusoidal endothelial cells were also protected in the contralateral half. Other stored livers were reperfused with nitroblue tetrazolium, which is converted to insoluble formazan by superoxide radicals. Ischemic preconditioning decreased the intensity of formazan deposition over Kupffer cells. Finally, stored livers were transplanted into nontreated rats. Ischemic preconditioning improved recipient long-term survival after 30 hours of cold ischemic storage in UW solution from 30% to 80% and decreased serum tumor necrosis factor-␣ levels in posthepatic blood 4 hours postoperatively from 98 to 54 pg/mL. In conclusion, ischemic preconditioning protects sinusoidal endothelial cells and suppresses Kupffer-cell activation after storage and reperfusion. As a result, graft survival improves after liver transplantation. Moreover, ischemia to half the liver confers protection to the other half. Such heterologous preconditioning provides a new means to protect liver tissue against ischemia-reperfusion injury without imposing ischemia on the target tissue. (Liver Transpl 2001;7:292-299.)

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“…11 Indeed, in a recent study evaluating the precise time course and mechanism of SEC and hepatocyte death, it has been clearly shown that an early SEC necrosis followed by a limited and delayed hepatocyte apoptosis occurred under both viable [24-hour preservation in cold University of Wisconsin (UW) solution] and lethal conditions (42-hour preservation in cold UW solution). 12 The main pathologic difference between these 2 preservation conditions was the marked alteration of the hepatic microcirculation associated with a loss of extracellular matrix (ECM) and interruption of flow through sinusoids, leading to extensive hepatocyte necrosis.…”

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confidence: 99%

Matrix metalloproteinase inhibition protects rat livers from prolonged cold ischemia-warm reperfusion injury

et al. 2007

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Matrix metalloproteinases (MMPs) have been implicated in the hepatic injury induced after cold ischemia-warm reperfusion (CI-WR), by altering the extracellular matrix (ECM), but their precise role remains unknown. The hepatic MMP expression was evaluated after 2 conditions of CI (4°C for 24 and 42 hours: viable and nonviable livers) followed by different periods of WR, using isolated perfused rat livers. CI-WR induced moderate changes in hepatic MMP transcript levels not influenced by CI duration, whereas gelatinase activities accumulated in liver effluents. Therefore, the protective effect of a new phosphinic MMP inhibitor, RXP409, was tested after prolonged CI. RXP409 (10 M) was added to the University of Wisconsin solution, and livers were preserved for 42 hours (4°C), then reperfused for 1 hour in Krebs solution (37°C), containing 20% erythrocytes. Liver viability parameters were recorded, and the extent of cell necrosis was evaluated on liver biopsies, using trypan blue nuclear uptake. Treatment with RXP409 significantly improved liver function (transaminase release and bile secretion) and liver injury. In particular, the MMP inhibitor significantly modified the extent of cell death from large clusters of necrotic hepatocytes as found in control livers (2%-60% of liver biopsies; mean, 26% ؎ 9%) to isolated necrotic hepatocytes as found in treated livers (0.2%-12%; mean, 3% ؎ 2%) (P < 0.05). Conclusion: These data demonstrate that MMPs, by altering the ECM, play a major role in liver CI-WR injury leading to extensive hepatocyte necrosis and that their inhibition might prove to be a new strategy in improving preservation solutions. (HEPATOLOGY 2008;47:177-185.) See Editorial on Page 14 T he underlying mechanism of hepatic cold ischemia-warm reperfusion (CI-WR) injury, occurring during liver transplantation interventions, is not fully understood and has been the subject of many investigations during the past few years. 1-3 Numerous investigations have shown that sinusoidal endothelial cells (SECs) are the primary targets after CI preservation, 4-6 although the mechanism of their death, necrosis versus apoptosis, still remains controversial. [7][8][9] SECs die early during WR, whereas hepatocytes appear to be relatively unscathed after short periods of CI From the

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Decreased survival in rat liver transplantation with extended cold preservation: Role of portal vein clamping time

Cited by 44 publications

References 45 publications

Protective effect of doxorubicin induced heat shock protein 72 on cold preservation injury of rat livers

Protective effect of doxorubicin induced heat shock protein 72 on cold preservation injury of rat livers

Ischemic preconditioning of rat livers against cold storage-reperfusion injury: Role of nonparenchymal cells and the phenomenon of heterologous preconditioning

Matrix metalloproteinase inhibition protects rat livers from prolonged cold ischemia-warm reperfusion injury

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