L-carnitine ameliorates abnormal vulnerability of steatotic rat livers to cold ischemic preservation
作者:
Rene´ Tolba,
Uwe Pütz,
Dorothee Decker,
Frank Dombrowski,
Holger Lauschke,
期刊:
Transplantation
(OVID Available online 2003)
卷期:
Volume 76,
issue 12
页码: 1681-1686
ISSN:0041-1337
年代: 2003
出版商: OVID
数据来源: OVID
摘要:
Background.Up to 30% of all livers retrieved for organ transplantation exhibit steatotic transformations. Chronic organ-donor shortage has led to the acceptance of these organs for transplantation, although a higher risk of graft nonfunction is associated with the preservation of steatotic livers.Methods.A dietary steatosis was induced in Wistar rats by fasting them for 2 days and feeding them with a fat-free diet. Fatty livers (n=14) were retrieved and flushed with 60 mL of histidine, tryptophane, alpha-ketoglutarate (HTK) solution. In half of the experiments, L-carnitine (5 mM) was added to the HTK. Functional integrity of the livers was evaluated by isolated reperfusion with KHB in a recirculating system at 37°C for 45 minutes.Results.Addition of L-carnitine to the HTK promoted a significant reduction of the enzyme leakage from the livers upon reperfusion. Release of alanine-aminotransferase was reduced to one third (127±22 vs. 423±61 U/L), and the loss of glutamate dehydrogenase in the perfusate could be reduced significantly (42±7 vs. 542±134 U/L) when compared with livers stored without additional medication. Morphologic corroboration of these data was obtained by electron microscopy. Although normal appearance of liver mitochondria was preserved at the end of the cold ischemic storage, reperfusion of cold-stored fatty livers entailed massive alterations and frequent destruction of hepatic mitochondria. However, these morphologic impairments were remarkably mitigated in the carnitine-treated group.Conclusions.L-carnitine represents a feasible metabolic adjunct for a safe and more successful preservation of ischemia–reperfusion-sensitive steatotic livers.
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