Lignocaine Metabolite Formation as a Measure of Pre-Transplant Liver Function

Oellerich, Michael; Ringe, Burckhardt; Gubernatis, G.; Pichlmayr, R.; Burdelski, M.; Lamesch, P.; Bunzendahl, H.; Herrmann, Heinz

doi:10.1016/s0140-6736(89)92144-2

Cited by 166 publications

(73 citation statements)

References 10 publications

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“…39 Standard biochemical parameters of liver function in the donor are unreliable as a guide to subsequent graft function, 40 as is the histology of the donor organ. 41 Oellerich et al 42 report a rapid assessment method for in situ donor hepatic function that relies on the conversion of an administered lignocaine bolus to monoethylglycinexylidide (MEGX). They correlated graft survival with plasma MEGX levels greater than 90 µg/L.…”

Section: Current Methods Of Assessing Donor Liver Damage and Viabilitymentioning

confidence: 99%

“…Levels of less than 90 µg/L were associated with poorer outcomes. 42 The formation of MEGX depends on hepatic blood flow, hepatocyte function, and the integrity of the cytochrome p450 system. 43 However, Rosenlof et al 19 could not distinguish histological differences in livers with high or low MEGX values and suggested that the MEGX test should not be used as the sole discriminatory factor for deciding whether to accept a donor liver for transplantation.…”

Section: Current Methods Of Assessing Donor Liver Damage and Viabilitymentioning

confidence: 99%

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Liver transplantation: Current and potential applications of magnetic resonance spectroscopy

Davidson

1997

Liver Transplantation

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Magnetic resonance spectroscopy (MRS) allows the noninvasive measurement of whole organ metabolism due to the presence of the MRsensitive nucleus phosphorus 31 in adenosine triphosphate (ATP), its precursors, and breakdown products. In small animal liver transplant studies it has been used to analyze the metabolic effects of cold and warm ischemia, hypothermic reperfusion, and the relative efficacy of different organ preservation solutions. In recent large animal studies MRS has been developed to provide continuous dynamic information on ATP metabolism during graft reperfusion and the bioenergetic consequences of altering preservation solutions. These basic experimental data need to be critically evaluated in human liver transplantation. Encouraging preliminary data on many possible clinical applications have already been obtained, such as the assessment of human donor liver viability and posttransplant graft function. At present, the cost and technically demanding nature of MRS may restrict its application to research units.

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Section: Current Methods Of Assessing Donor Liver Damage and Viabilitymentioning

confidence: 99%

Section: Current Methods Of Assessing Donor Liver Damage and Viabilitymentioning

confidence: 99%

Liver transplantation: Current and potential applications of magnetic resonance spectroscopy

Davidson

1997

Liver Transplantation

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“…[1][2][3]17 Liver graft microsomes were used to study the effects of treprostinil on CYP3A, CYP2E1, and CYP2C11 activity at 1, 3, and 48 h post-OLT. CYP3A activity was determined using the formation rate of 1-OH MDZ from MDZ and 6b-OH TST from TST as substrates.…”

Section: Treprostinil Improves Microsomal Cytochrome P450 Activity Inmentioning

confidence: 99%

“…[1][2][3] Considering that the liver is the most important site of drug metabolism and clearance, changes in CYP450 activity can directly alter the hepatic clearance of drugs. Consequences of reduced drug clearance include drug toxicity and sub-therapeutic plasma drug concentrations, which could precipitate hepatic dysfunction or lead to graft failure.…”

mentioning

confidence: 99%

Treprostinil Improves Hepatic Cytochrome P450 Activity during Rat Liver Transplantation

Ghonem

Yoshida²,

Murase³

et al. 2012

Journal of Clinical and Experimental Hepatology

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Background: Cytochrome P450 (CYP450) activity is an important indicator of liver graft function. CYP450 activity is altered by pro-inflammatory cytokines, which are associated with ischemia-reperfusion (I/R) injury during orthotopic liver transplantation (OLT). Treprostinil, an FDA-approved prostacyclin analog, ameliorated cold I/R injury during rat OLT. We hypothesized that treprostinil would improve CYP450 activity in liver graft during cold I/R injury post-OLT. Methods: OLT was performed in syngeneic male Lewis rats with 18 h graft preservation in cold UW solution. Donor and recipients received treprostinil (100 ng/kg/min) or matching placebo for 24 h before and up to 48 h post-OLT. Liver graft mRNA and protein expression of CYP450 isoforms were analyzed by qRT-PCR and Western blot analysis, respectively. The formation rates of 1-hydroxymidazolam and 6b-hydroxytestosterone, 6-hydroxychlorzoxazone, 2a-and 16a-hydroxytestosterone in liver graft microsomes served as markers for CYP3A, CYP2E1, and CYP2C11 activity, respectively, and were measured by LC-MS. Results: Treprostinil significantly decreased serum ALT and AST levels at 6-48 h after OLT, compared to placebo. The expressions of TNFa and IFNg mRNA in the liver graft were significantly inhibited in the treprostinil-treated group at 1 h post-reperfusion. Treprostinil restored CYP2E1 protein expression to that of normal liver and significantly improved CYP3A activity to more than two-fold of placebo early post-OLT. Conclusions: Treprostinil significantly ameliorated hepatic injury, reduced expression of pro-inflammatory cytokines, and improved CYP450 activity in liver graft early post-OLT. These findings suggest that treprostinil has the potential to serve as a therapeutic option to protect liver graft function against I/R injury during clinical OLT. ( J CLIN EXP HEPATOL 2012;2:323-332)

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“…These tests have been advocated as useful in determining the prognosis of patients with liver cirrhosis [7] or primary biliary cirrhosis [lo]. In addition, the MEGX formation test has been suggested as helpful in the selection of suitable donor organs for transplantation, although some groups have reported the test efficacy to be low [8,14,161.…”

Section: Introductionmentioning

confidence: 99%

Conventional and quantitative liver function tests after hepatic transplantation: a prospective long term follow-up

Schönfeld¹,

Beste²,

Mahl³

et al. 1997

Transplant Int

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In long-term survivors of liver transplantation, hepatic function is obviously of vital importance. Therefore, we prospectively performed conventional and quantitative liver function tests in patients who had survived a first transplantation for at least 4 years. Compared to 6 months after transplantation, serum bilirubin concentration and yGT activity were significantly lower after 3,4, and 5 years (bilirubin 1.2 f 0.2 mg/dl at 6 months vs 1.0 k 0.1,l.O +_ 0.2, and 0.8 f 0.1 mg/ dl respectively; yGT 106 f 33 U/1 at 6 months vs 56 f 17,67 * 35, 39 f 10 U/1 respectively). At these points in time, blood levels of cyclosporin A were also significantly lower. Other parameters of liver cell function and liver cell integrity (AP, AST, ALT, GLDH, total protein, thromboplastin time, partial thromboplastin time) were unchanged over time. Serial quantitative liver function tests (indocyanine green half-life, galactose elimination capacity, lidocaine half-life, and MEGX formation) also remained stable. Thus, we conclude that hepatic function remains stable in long-term survivors of liver transplantation for at least several years.

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Lignocaine Metabolite Formation as a Measure of Pre-Transplant Liver Function

Cited by 166 publications

References 10 publications

Liver transplantation: Current and potential applications of magnetic resonance spectroscopy

Liver transplantation: Current and potential applications of magnetic resonance spectroscopy

Treprostinil Improves Hepatic Cytochrome P450 Activity during Rat Liver Transplantation

Conventional and quantitative liver function tests after hepatic transplantation: a prospective long term follow-up

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