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  • 1
    ISSN: 1432-2277
    Keywords: Key words Organ retrieval ; Reperfusion injury ; Gadolinium chloride ; Glycine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Kupffer cell-dependent injury in livers gently manipulated during harvest develops upon reperfusion. The purpose of this study was to characterize this injury and to detect underlying mechanisms. Livers from female Sprague-Dawley rats were harvested for transplantation within 25 min. Minimal dissection was performed during the first 12 min, including freeing the liver from ligaments. After this, for further 13 min, livers were either left alone or manipulated gently. The livers were then cold-stored for 24 h in University of Wisconsin (UW) solution and perfused with oxygen-saturated Krebs-Henseleit buffer at 37 °C. Trypan blue in the buffer was used to index microcirculation. Cell damage was assessed with histology. Initial dissection during harvest and cold storage had minimal effects on sinusoidal lining cells; in contrast, the subsequent gentle organ manipulation dramatically increased cell death 6.5-fold, while the time for complete trypan blue distribution increased 2.3-fold (P 〈 0.05). Manipulation increased proteolysis 2-fold (P 〈 0.05). At harvest, manipulation increased portal venous pressure significantly by 68 %. Treatment of donors with gadolinium chloride, a selective Kupffer cell toxicant, or with dietary glycine, an inhibitor of Kupffer cell activation, prevented effects of organ manipulation on all parameters studied. These findings demonstrate Kupffer cell-dependent reperfusion injury of sinusoidal lining cells caused by manipulation of the liver during its recovery. The mechanisms are those of proteolysis and impaired hepatic microcirculation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Dans cet article, on décrit comment un score de facteurs de risques, aide à décider si un patient présentant des signes d'insuffisance hépatique après transplantation hépatique doit être traité ou si on doit envisager une retransplantation immédiate. Sur 78 patients ayant subi une première transplantation hépatique, 25 ont présenté des signes de rejet du transplant et ont demandé des explorations complémentaires. Neuf patients présentaient un problème initial irréversible; deux sont morts avant qu'une deuxième greffe soit envisagée; sept ont subi une retransplantation avec trois survivants à long terme. Chez les 16 autres patients, les lésions initiales étaient réversibles et ils ont survécu sans réopération. Puisque la retransplantation en case de non fonctionnement initial est couronnée de succès seulement si elle est pratiquée dans les premiers jours postopératoires, il est urgent de savoir si les lésions sévères sont irréversibles. Nous avons élaboré un système de score qui identifie et mesure les facteurs susceptibles de laisser prévoir si les lésions sont irréversibles. Les paramètres importants sont les transaminases, le volume de bile recueilli au drainage, la pente des enzymes LDH, la quantité de sang et de plasma frais nécessaire le jour de l'opération et le lendemain. L'analyse de régression logistique a donné un score numérique qui s'applique à un arbre décisionnel apportant des probabilités et des indications sur la reprise opératoire. Nous utilisons le système de score et nous pensons qu'il aide à prendre des décisions dans la période post-transplantation.
    Abstract: Resumen Este artículo describe como un sistema de calificación de factures de riesgo contribuye a la toma de decisión sobre si un paciente con signos de falla hepática en el período inmediato posttrasplante de hígado debe ser tratado en forma expectativa o debe ser sometido a retrasplante urgente. De 78 adultos receptores de un primer trasplante hepático, 25 presentaron evidencia de severa alteración, por lo cual fueron investigados más a fondo. Nueve presentaron ausencia de función inicial de tipo irreversible y 2 murieron antes de poder lograr un segundo trasplante; 7 fueron retrasplantados, con 3 sobrevivientes a largo plazo. Los otros 16 pacientes exhibieron severa alteración, pero reversible, y pudieron sobrevivir sin retrasplante. Puesto que el retrasplante por ausencia de función inicial es exitoso sólo cuando se realiza en los primeros días postoperatorios, surge una necesidad urgente de identificar si el daño hepático es de severidad irreversible. Hemos ideado un sistema de calificación que logró identificar y evaluar aquellos factores que permiten predecir la irreversibilidad. Las determinaciones de mayor pertinencia son las transaminasas, el volumen de bilis, la curva del nivel de la enzima GLDH, y las cantidades de sangre fresca y plasma fresco congelado requeridas como soporte en el día de la operación y en el día siguiente. El análisis logístico de regresión produjo una calificación numérica que aplicada a un esquema o árbol de flujo para la toma de decisiones indica probabilidades y utilidades sobre qué tan aconsejable es la reoperación. Hemos utilizado este sistema de calificación y creemos que es de ayuda para la toma de decisiones en el período inmediato posttrasplante.
    Notes: Abstract This article describes how a system of scoring risk factors contributes to deciding whether a patient showing signs of liver failure soon after hepatic transplantation should be treated expectedly or should undergo immediate retransplantation. Of 78 adult patients receiving a first liver graft, 25 had evidence of severe damage of the graft and were further investigated. Nine had failure due to irreversible initial nonfunction, and 2 of the 9 died before a second graft was available. Seven were retransplanted with 3 long-term survivors. The other 16 patients showed reversible severe damage and survived without retransplantation. Since retransplantation for irreversible initial nonfunction is successful only in the first postoperative days, there is an urgent need to identify the degree of the observed damage. We devised a scoring system which identified and weighted factors that were predictable in determining irreversibility. Measurements of highest relevance are transaminases, bile volume, the slope of the enzyme GLDH, and the amount of fresh blood and fresh-frozen plasma required for support on the day of operation and the following day. Logistic regressional analysis produced a numerical score which was applied to a decision tree and produced probabilities and utilities to indicate whether reoperation is advisable. We use this scoring system and believe it assists our decisions in the early posttransplant period.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Survival ; Amino acids ; Organ preservation ; Primary nonfunction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There are too few reliable markers by which one can predict future function of a liver before implantation. Consequently, the purpose of this study was to test the hypothesis that amino acids in rinse–effluents could predict transplant outcome in marginal fatty livers from rats. Amino acids were measured in the rinse effluent from the livers immediately after harvest and graft preparation or cold storage. Amino acids in the effluent were twice as high in ethanol-treated animals compared to those in nonfatty controls. Ethanol-treated fatty livers survived for no longer than 7 days after transplantation while 83 % of nonfatty controls survived (P 〈 0.05). In subsequent studies, the cold-storage time was decreased to 6 h to determine whether failing fatty livers released more amino acid than grafts that would function normally. There was a significant increase in amino acids in the effluent of fatty grafts compared to controls. Moreover, the sum of the four selected amino acids (alanine, valine, histidine, leucine) was lower than 23 nmol/g liver in functional livers, whereas failing grafts had totals significantly higher than 25 nmol/g liver. The sum of the four amino acids correlated well with 24 h post-transplant serum AST levels (r = 0.78, P 〈 0.0001). So we can conclude that amino acid release can serve as a useful marker of graft viability and reliably predicts survival.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Organ harvest ; Kupffer cells ; Ethanol ; Gadolinium chloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both in situ organ manipulation during harvest and steatosis reduce survival after liver transplantation via mechanisms involving Kupffer cells; thus, their effect on survival was compared here. Moderate steatosis was induced by a single dose of ethanol to Lewis rats, while long-term administration of ethanol yielded severe steatosis in donor animals. After minimal dissection during the first 12 min, livers were either manipulated gently or left alone for 13 min subsequently. Orthotopic liver transplantation was performed after 1 h of cold storage in UW solution. Ethanol increased hepatic lipid content to a level of moderate or severe steatosis that reduced survival after transplantation from 100 % to approximately 70 % (P 〈 0.05). However, gentle manipulation decreased survival to approximately 30 % (P 〈 0.05) in livers from normal, saline-treated rats and in livers from rats fed a high-fat control diet. Moreover, after short- or long-term ethanol administration, manipulation of fatty livers decreased survival from 70 % to approximately 13 % (P 〈 0.05). Further, manipulation elevated serum transaminases, total bilirubin, and necrosis significantly about 2- to 20-fold in fatty grafts after transplantation. At the end of harvest, trypan blue distribution time and hypoxia assessed from 2-nitroimidazole binding were elevated significantly about two- to fourfold by manipulation of fatty grafts. Gadolinium chloride, a Kupffer cell toxicant, blocked the detrimental effects of manipulation. These data demonstrate for the first time that, while steatosis is detrimental for survival, organ manipulation plays a much greater role than fat in mechanisms of primary nonfunction.
    Type of Medium: Electronic Resource
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