The aminopyrine breath test predicts the outcome of hepatic transplantation in pigs

Oakland, C. D. H.; Hickman, Rosemary; Terblanche, J.

doi:10.1002/hep.1840090415

Cited by 15 publications

(6 citation statements)

References 20 publications

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“…Among these, some studies [25] showed that the ABT was able to predict the outcome of liver transplantation in the pig and to diagnose acute allograft rejection [26] better than other laboratory test in humans. Moreover, a decrease in cytochrome P450 activity was demonstrated after ischaemia in rats [27].…”

Section: Discussionmentioning

confidence: 99%

Quantitative evaluation of liver function by the methionine and aminopyrine breath tests in the early stages of liver transplantation

Campli

Angelini²,

Armuzzi³

et al. 2003

European Journal of Gastroenterology & Hepatology

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Objective The early phase after liver transplant is considered the period of greatest risk for graft failure. In recent years breath tests have been proposed as a noninvasive method to assess liver function. In particular, the aminopyrine breath test is useful for evaluating the liver viable mass, and the methionine breath test could be used to evaluate oxidative capacity of liver mitochondria. We aimed to perform these tests in the early phase following liver transplant in order to correlate the time course of these tests to the outcome of transplantation.Methods Twenty-three patients undergoing liver transplant were enrolled. The methionine and aminopyrine breath tests were performed on the days 1, 3 and 5, and 2, 4 and 6, respectively, after transplant. Results were expressed as the percentage of administered 13 C recovered per hour and as the cumulative percentage of the 13 C dose recovered over the test period.Results All but two transplants were successful in the short term and the cumulative percentage of the dose of 13 C progressively increased after transplantation, reaching values not significantly different from controls (methionine at day 5). In two patients, primary non-function occurred: in these patients the cumulative percentage of the 13 C dose did not increase after orthotopic liver transplant and the results of both breath tests indicated that it always remained significantly lower compared to that of other patients.Conclusions A combination of breath tests, exploring both mitochondrial and microsomal function, could be useful in the early phase after liver transplant in order to evaluate the graft outcome. Eur J Gastroenterol Hepatol

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Section: Discussionmentioning

confidence: 99%

Quantitative evaluation of liver function by the methionine and aminopyrine breath tests in the early stages of liver transplantation

Campli

Angelini²,

Armuzzi³

et al. 2003

European Journal of Gastroenterology & Hepatology

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“…Such drug-metabolizing activity can be compromised after liver transplantation, and several studies sug-gest that it may serve as a good index of early graft function. [11][12][13] This may have an important impact on the health of the transplant recipient as evidenced, for instance, by an increased toxicity of immunosuppressants caused by decreased metabolism. 14 Alterations in the activity of the hepatic cytochrome P-450-dependent mono-oxygenase system would also be expected to perturb the metabolism of several other xenobiotics, as well as such endogenous substrates as bile acids and certain steroid hormones.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have indicated that drug-metabolizing capacity is a suitable indicator of hepatic functional integrity after liver transplantation. [11][12][13] Observed disturbances in liver metabolic integrity after cold preservation may further result in clinically relevant disturbances in drug handling, as seen particularly for immunosuppressive therapy. 14 It is therefore important to improve cold storage conditions to maintain not only a proper hepatocellular viability, but also near-normal functions, such as cytochrome P-450-dependent drug metabolism.…”

confidence: 99%

Cytochrome P-450 content and activity after cold storage of rat hepatocytes in university of wisconsin and sodium-lactobionate-sucrose solutions

et al. 1999

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We compared the capacity of University of Wisconsin (UW) and of sodium-lactobionate-sucrose (SLS) hypothermic preservation solutions to maintain the integrity of the hepatic cytochrome P-450-dependent mono-oxygenase system. Isolated rat hepatocytes were stored for 0, 10, 24, and 48 hours in UW or SLS solution and were subsequently cultured shortly at 37°C. Cell viability declined slightly but significantly in a timedependent manner during cold preservation in either UW or SLS solution, and warm culture exacerbated this effect. Total cytochrome P-450 declined gradually after cold preservation and warm culture to reach values of 70% and 52% of unstored controls in cells preserved for 24 and 48 hours in cold UW solution, respectively. Storage in cold SLS solution yielded a similar decrease to 79% and 59% of unstored controls for the equivalent preservation times. Cytochrome P-450 activity was assessed by the metabolism of theophylline after various cold preservation times in UW or SLS solutions. Production of the major metabolite 1,3-dimethyluric acid was not significantly affected by extended cold preservation periods in either UW or SLS solutions. Similarly, the amount of residual theophylline remained stable in all groups, suggesting that alternative metabolic routes were not modified. These studies show that cold preservation in SLS solution is as effective as that in UW solution in terms of cell viability, cytochrome P-450 content, and activity toward theophylline. In addition, the significant reduction in cytochrome P-450 in conjunction with unaffected theophylline disposition suggests that certain cytochrome P-450 isoforms are specifically damaged by cold preservation and rewarming.

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“…The functions of the liver can broadly be broken down into seven main areas: catabolic and anabolic functions with respect to carbohydrate, fat, and protein metabolism; production of bile; production and excretion of bilirubin; immunological functions involving the production and release of cytokines and interferons; scavenging and ®ltration of endotoxins and bacteria; storage of vitamin B 12 and glycogen; and the biotransformation and elimination of drugs and xenobiotics.…”

Section: Assessment Of Liver Function: Its Application To Outcome Fromentioning

confidence: 99%

“…11 Aminopyrine (assessed as the 14 CO 2 aminopyrine breath test) is also negligibly protein bound, and like antipyrine assesses hepatic metabolizing capacity rather than liver blood¯ow. Although it has been used in the pig to assess the outcome of transplantation, 12 the aminopyrine test has a number of limitations to its use in man. For instance, reduction in the test output can occur in patients with sepsis and viral infections; there is administration of radioactivity; endogenous carbon dioxide production may interfere with the results; and the drug can induce agranulocytosis in patients sensitized previously by pyrazolone derivatives.…”

Section: Capacity-limited Binding-insensitive Hepatic Eliminationmentioning

confidence: 99%

Editorial II

Sear

2002

British Journal of Anaesthesia

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The aminopyrine breath test predicts the outcome of hepatic transplantation in pigs

Cited by 15 publications

References 20 publications

Quantitative evaluation of liver function by the methionine and aminopyrine breath tests in the early stages of liver transplantation

Quantitative evaluation of liver function by the methionine and aminopyrine breath tests in the early stages of liver transplantation

Cytochrome P-450 content and activity after cold storage of rat hepatocytes in university of wisconsin and sodium-lactobionate-sucrose solutions

Editorial II

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