Orthotopic Rat Liver Transplantation After Long-Term Preservation by Continuous Perfusion With Fluorocarbon Emulsion

Kamada, Nanao; Calne, R. Y.; Wight, D. G. D.; Lines, J. G.

doi:10.1097/00007890-198007000-00009

Cited by 63 publications

(28 citation statements)

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“…Bile production has been used as a reliable and accurate measure (19)(20)(21)(22) of cellular ATP in both donor liver preservation and in experimental liver perfusion (23)(24)(25)(26). Using bile production as an index of ATP generation, we observed that the rate was indeed related to the length of ischemia and could be predicted accurately by the PNP profile (Fig.…”

Section: Discussionmentioning

confidence: 84%

Purine nucleoside phosphorylase: A new marker for free oxygen radical injury to the endothelial cell

et al. 1990

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The effect of ischemia and reperfusion on purine nucleoside phosphorylase was studied in an isolated perfused rat liver model. This enzyme is localized primarily in the cytoplasm of the endothelial and Kupffer cells; some activity is associated with the parenchymal cells. Levels of this enzyme accurately predicted the extent of ischemia and reperfusion damage to the microvascular endothelial cell of the liver. Livers from Lewis rats were subjected to 30, 45 and 60 min of warm (37° C) no flow ischemia that was followed by a standard reperfusion period lasting 45 min. Purine nucleoside phosphorylase was measured at the end of the no flow ischemia and reperfusion periods as was superoxide generation (O 2 − ). Bile production was monitored throughout the no flow ischemia and reperfusion periods. Control perfusions were carried out for 120 min. A significant rise in purine nucleoside phosphorylase levels as compared with controls was observed at the end of ischemia in all the three groups. The highest level, 203.5 ± 29.2 mU/ml, was observed after 60 min of ischemia. After the reperfusion period, levels of purine nucleoside phosphorylase decreased in the 30-and 45-min groups 58.17 ± 9.66 mU/ml and 67.5 ± 17.1 mU/ml, respectively. These levels were equal to control perfusions. In contrast, after 60 min of ischemia, levels of purine nucleoside phosphorylase decreased early in the reperfusion period and then rose to 127.8 ± 14.8 mU/ml by the end of reperfusion (p < 0.0001). Superoxide generation at the beginning of reperfusion was higher than in controls with similar values observed at the end of 30, 45 and 60 min of ischemia. During reperfusion, production of superoxide continued. Bile production was significantly lower at the end of 30 min (0.044 ± 0.026 µl/min/gm), 45 min (0.029 ± 0.022 µl/min/gm) and 60 min of ischemia (0.022 ± 0.008 µl/min/gm) when compared with bile production by control livers during the corresponding time (0.680 ± 0.195, 0.562 ± 0.133 and 0.480 ± 0.100 µl/min/gm respectively; p < 0.001). During reperfusion, rates of bile production were normal after 30 and 45 min of ischemia. In contrast, significantly lower rates of bile production, 0.046 ± 0.36 µl/min/gm (p < 0.001) occurred during reperfusion after 60 min of ischemia. Control livers during the same period produced 0.330 ± 0.056 µl/min/gm of bile. The results indicate that purine nucleoside phosphorylase levels may be a good index of oxidative injury to the liver in ischemia reperfusion and reliably predict the functional state of the organ after reperfusion.Liver transplantation is now the therapy of choice for end-stage liver disease (1). Procurement, preservation and subsequent transplantation of solid organs involve a period of ischemia followed by reperfusion. Ischemia results in the breakdown of ATP to hypoxanthine, which is the substrate for xanthine oxidase-mediated conversion to xanthine (2). During the reperfusion, this reaction produces superoxide and other reactive oxygen species, which have been implicated in the reperfusio...

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Section: Discussionmentioning

confidence: 84%

Purine nucleoside phosphorylase: A new marker for free oxygen radical injury to the endothelial cell

et al. 1990

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“…Rat orthotopic liver cold perfusion was used according to the method described by Kamada and Calne [14] . Under ether anesthesia, 2 mL of heparinized saline solution (250 units/mL) was injected intravenously.…”

Section: Liver Procurement and Cold Storagementioning

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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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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“…The perfusion system previously described 42 was modified and the temperature was thermostatically maintained between 36.5-37.5°C. Culture supernatant and culture medium without retroviruses were used as perfusate, in two independent perfusion systems.…”

Section: Surgical Proceduresmentioning

confidence: 99%

A preclinical model of hepatocyte gene transfer: the in vivo, in situ perfused rat liver

Godoy

Malafosse

Fabrè³

et al. 2000

Gene Ther

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Orthotopic Rat Liver Transplantation After Long-Term Preservation by Continuous Perfusion With Fluorocarbon Emulsion

Cited by 63 publications

References 0 publications

Purine nucleoside phosphorylase: A new marker for free oxygen radical injury to the endothelial cell

Purine nucleoside phosphorylase: A new marker for free oxygen radical injury to the endothelial cell

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

A preclinical model of hepatocyte gene transfer: the in vivo, in situ perfused rat liver

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