Hepatic Microcirculatory Changes After Reperfusion In Fatty And Normal Liver TrANSPLANTATION IN THE RAT

Teramoto, Koji; Bowers, John Waite; Kruskal, Jonathan B.; Clouse, Melvin E.

doi:10.1097/00007890-199311000-00005

Cited by 172 publications

(136 citation statements)

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“…However, further studies of livers with severe macroveet al showed that failure of steatotic liver transplantation is associated with greater-than-normal hepatic cord width and sicular steatosis are needed to clarify the mechanisms of action of NAC and anti-ICAM-1 monoclonal antibody in I/ lower-than-normal sinusoidal blood flow. 5 Therefore, the possibility that NAC is a microcirculatory relaxant in the R injury of the steatotic liver. sinusoidal space is an attractive hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…In the first experiment, compared with normal non-tion of steatotic liver grafts has also been confirmed in animal steatotic liver, steatotic livers showed significantly greater in-models. [4][5][6] Furthermore, emergency liver transplantation is jury, as assessed by amounts of hepatic enzymes released into often required because liver failure may develop postoperathe perfusate, bile production, the concentrations of reduced tively when a steatotic liver has been partially resected and glutathione (GSH) in the perfusate, as well as in the livers Pringle's maneuver has been performed for 60 minutes or themselves, and electron microscopic findings of sinusoidal more. 7 The vulnerability of steatotic liver to normothermic microcirculatory injury.…”

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confidence: 99%

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The effects of N -acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet

et al. 1997

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tory injury is involved in hypothermic I/R injury, that oxidaAbundant fat in the liver has been implicated in poor outtive stress produced by PMNLs is involved in normothermic come after liver transplantation or liver surgery, but the rea-I/R injury, and that NAC and anti-rat ICAM-1 monoclonal sons for this association are still unclear. The aim of the antibody restore liver integrity in I/R injury. (HEPATOLOGY present study was to examine mechanisms that may be in-1997;26:670-678.) volved in hepatic dysfunction after ischemia-reperfusion (I/R) of the steatotic rat liver. Steatosis was produced by a cholinemethionine-deficient (CMDD) diet. In the first experiment,In clinical liver transplantation, donor livers may be subisolated perfused rat livers, subjected to 24-hour cold storage jected to various types of stress, such as ischemia caused by followed by 120-minute reperfusion, were used to investigate hypotension or drug-induced liver dysfunction. Steatotic hypothermic I/R injury of the steatotic rat liver. In the second liver grafts have recently been directly implicated in primary experiment, livers were subjected to 60-minute partial left graft nonfunction or dysfunction after orthotopic liver translobar vascular clamping to allow study of normothermic I/R plantation in humans. [1][2][3] The poor outcome of transplantainjury. In the first experiment, compared with normal non-tion of steatotic liver grafts has also been confirmed in animal steatotic liver, steatotic livers showed significantly greater in-models. [4][5][6] Furthermore, emergency liver transplantation is jury, as assessed by amounts of hepatic enzymes released into often required because liver failure may develop postoperathe perfusate, bile production, the concentrations of reduced tively when a steatotic liver has been partially resected and glutathione (GSH) in the perfusate, as well as in the livers Pringle's maneuver has been performed for 60 minutes or themselves, and electron microscopic findings of sinusoidal more. 7 The vulnerability of steatotic liver to normothermic microcirculatory injury. The addition of N-acetylcysteine ischemia-reperfusion (I/R) has also been shown experimen-(NAC), a precursor of glutathione, to the liver before cold tally. 8 However, mechanisms of I/R injury in the steatotic storage significantly improved these parameters in steatotic liver have not been fully clarified. Elucidation of these mechlivers. The second experiment showed that, compared with anisms and development of appropriate treatments are more nonsteatotic livers, steatotic livers had lower concentrations important than ever because of the severe shortage of donor of GSH and impaired rates of bile production. There was also organs. evidence of increased oxidative stress in polymorphonuclear N-Acetylcysteine (NAC) is a precursor of glutathione, leukocytes (PMNLs) in liver or peripheral blood of rats with which has been shown to be effective for the treatment of fatty livers. An anti-rat intercellular adhesion molecule-1 fulminant liver failure aft...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The effects of N -acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet

et al. 1997

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“…Abnormalities in sinusoidal microcirculation, 3,4 mitochondrial oxidative phosphorylation including a decrease in adenosine triphosphate production, 5,6 and dysregulation of cytokine production 7 are some of the mechanisms that have been associated with the increased injury to fatty livers in both rodents and humans. Oxidative stress has recently been postulated to be a common feature in fatty livers of diverse etiologies.…”

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confidence: 99%

Oxidative Stress in Fatty Livers of Obese Zucker Rats: Rapid Amelioration and Improved Tolerance to Warm Ischemia With Tocopherol

2001

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Fatty livers in humans and rats are less tolerant of ischemia, endotoxin, and alcohol. We hypothesized that fatty livers of obese (Ob) Zucker rats are oxidatively stressed and oxidative stress could be relieved by antioxidant treatment, leading to improved tolerance to ischemia. Total glutathione (GSH), tocopherol (TOC), ascorbic acid (AA), catalase (CAT), superoxide dismutase (SOD), and selenium-glutathione peroxidase (Se-GPx) were measured in the livers of Ob and lean (Ln) Zucker rats before and after treatment with high-dose TOC and ascorbate. Also, survival in treated Ob rats following a lethal 90 minutes of partial in vivo warm ischemia was examined. Fatty livers of Ob rats contained significantly less GSH, TOC, and CAT, in comparison with livers of Ln rats. Immunoblotting showed significantly decreased CAT protein without changes in mRNA in fatty livers. There were no significant differences in AA, SOD, and Se-GPx between the 2 groups. Pretreatment with TOC and ascorbate over 48 hours completely corrected the decreases in GSH, TOC, and CAT. Most importantly, TOC with or without ascorbate pretreatment significantly improved survival in Ob rats following ischemia in a dosedependent manner. Fatty livers in humans and experimental animals are more prone to a variety of insults such as ischemia/reperfusion (I/ RP), endotoxin, and alcohol. Nonalcoholic steatohepatitis and its progression to cirrhosis are well-defined clinical entities. 1 Recipients of human donor livers with moderate or severe steatosis have decreased graft and patient survival. 2 Although exact figures are not available, it is believed that as many as 30% of donor livers have varying degrees of steatosis on routine microscopic examination. About 10% of donor livers are not used for transplantation because of moderate to severe steatosis, and this worsens the current shortage of livers. 2 Treatment regimens that will improve tolerance of fatty livers to the aforementioned insults are needed, and would benefit a diverse group of patients.Two rodent models of fatty liver, the genetically obese (Ob) and lipotrope-deficient diet models, are used in the laboratory to further investigate the problems associated with fatty livers. Abnormalities in sinusoidal microcirculation, 3,4 mitochondrial oxidative phosphorylation including a decrease in adenosine triphosphate production, 5,6 and dysregulation of cytokine production 7 are some of the mechanisms that have been associated with the increased injury to fatty livers in both rodents and humans. Oxidative stress has recently been postulated to be a common feature in fatty livers of diverse etiologies. 1 Lipid peroxidation products in the liver are increased in both models of rat fatty liver. 8,9 Reactive oxygen intermediates are key mediators of I/RP injury in solid organs. Thus, a 2-step oxidative injury comprised of a chronic oxidative stress before and an additional acute oxidative stress following I/RP may explain the increased injury sustained by fatty livers following both cold and warm ischemia.To...

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“…11 Still, previous studies have shown that postoperative survival after rat liver transplantation, after 24 hours cold storage in UW solution and portal vein clamping time exceeding 20 minutes, is almost zero. 25 In addition, a brief exposure of rat livers to Ringer's lactate, before cold storage, reduced considerably the protective effects of UW solution. 26 Consistent with these observations, we did not observe any survivals in the non-hyaluronidase-treated grafts, as opposed to 40% survival of grafts preserved in UW solution containing hyaluronidase.…”

Section: Discussionmentioning

confidence: 99%

Improvement of rat liver graft function after storage in University of Wisconsin solution containing testicular hyaluronidase

et al. 2002

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Hyaluronan accumulates at sites of inflammation, which affects the organization of matrix and thereby the proliferation, migration, and adherence of cells. In this study we investigated possible beneficial effects of the hyaluronandegrading enzyme hyaluronidase on rat liver graft viability. Orthotopic rat liver transplantation was performed using a cuff technique in Wistar AL Bacharach Glaxo (WAG) rats grafted with WAG livers, which had been stored in the University of Wisconsin (UW) solution or in UW solution enriched with testicular hyaluronidase. Liver tissue architecture, as well as tissue and serum hyaluronan levels, were determined using immunohistochemistry and biochemical assays. Addition of testicular hyaluronidase (0.4 mg/mL) to livers preserved for 24 hours in cold UW solution followed by brief exposure to Ringer's lactate both prolonged the function of the grafted livers and improved their viability (4 of 10 grafts survived, compared with 0 of 10 in the control group). Hyaluronidase treatment did not damage the liver tissue architecture, and a reduced edema was observed in the survivors. Furthermore, 10 minutes after restoration of circulation, higher serum hyaluronan levels were observed in nonsuccessful compared with successful transplantations, whereas no differences in the levels of other serum viability markers were detected. We conclude that addition of testicular hyaluronidase to storage UW solution limits liver cell damage and considerably improves graft function. Furthermore, our data suggest that serum hyaluronan level is a better marker than other serum markers for early evaluation of postoperative graft function. (Liver

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Hepatic Microcirculatory Changes After Reperfusion In Fatty And Normal Liver TrANSPLANTATION IN THE RAT

Cited by 172 publications

References 0 publications

The effects of N -acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet

The effects of N -acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet

Oxidative Stress in Fatty Livers of Obese Zucker Rats: Rapid Amelioration and Improved Tolerance to Warm Ischemia With Tocopherol

Improvement of rat liver graft function after storage in University of Wisconsin solution containing testicular hyaluronidase

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