Combined compression and elongation experiments and non-linear modelling of liver tissue for surgical simulation

Chui, Chee-Kong; Kobayashi, Etsuko; Chen, X.; Hisada, Toshiaki; Sakuma, Ichiro

doi:10.1007/bf02345212

Cited by 130 publications

(131 citation statements)

References 27 publications

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“…An average mass density for porcine liver of 1.064 g/ml was used to convert the concentrations of ximelagatran, the two intermediates, and melagatran in the liver samples into molar amounts per volume unit of porcine liver (Chui et al, 2004). Statistical Analysis.…”

Section: Bile ϭmentioning

confidence: 99%

Intestinal and Hepatobiliary Transport of Ximelagatran and Its Metabolites in Pigs

Sjödin¹,

Fritsch²,

Eriksson³

et al. 2008

Drug Metab Dispos

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ABSTRACT:The direct thrombin inhibitor melagatran is formed from ximelagatran via two intermediate metabolites, OH-melagatran and ethylmelagatran. The biotransformation of ximelagatran does not involve cytochrome P450 isoenzymes, and it has been suggested that a reported interaction with erythromycin may instead be mediated by transport proteins. A pig model that simultaneously enables bile collection, sampling from three blood vessels and perfusion of a jejunal segment, was used to investigate the biotransformation of ximelagatran and the effect of erythromycin on the intestinal and hepatobiliary transport of ximelagatran and its metabolites. The pigs received enteral ximelagatran (n ‫؍‬ 6), enteral ximelagatran together with erythromycin (n ‫؍‬ 6), i.v. ximelagatran (n ‫؍‬ 4), or i.v. melagatran (n ‫؍‬ 4). The plasma exposure of the intermediates was found to depend on the route of ximelagatran administration. Erythromycin increased the area under the plasma concentration-time curve (AUC) of melagatran by 45% and reduced its biliary clearance from 3.0 ؎ 1.3 to 1.5 ؎ 1.1 ml/min/kg. Extensive biliary exposure of melagatran and ethylmelagatran, mediated by active transport, was evident from the 100-and 1000-fold greater AUC, respectively, in bile than in plasma. Intestinal efflux transporters seemed to be of minor importance for the disposition of ximelagatran and its metabolites considering the high estimated f abs of ximelagatran (80 ؎ 20%) and the negligible amount of the compounds excreted in the perfused intestinal segment. These findings suggest that transporters located at the sinusoidal and/or canalicular membranes of hepatocytes determine the hepatic disposition of ximelagatran and its metabolites, and are likely to mediate the ximelagatran-erythromycin pharmacokinetic interaction.Ximelagatran was the first oral direct thrombin inhibitor to reach the market. As an oral anticoagulant, it had the potential to become an alternative to warfarin and other vitamin K antagonists; however, because of safety concerns involving hepatotoxicity, ximelagatran was withdrawn in 2006. Warfarin currently has an important role in the prevention and treatment of thromboembolic events but is unfortunately also associated with a variable pharmacokinetic and pharmacodynamic response, delayed onset and offset of action, numerous drug-drug interactions, and serious safety issues (Hawkins, 2004;Greenblatt and von Moltke, 2005). The narrow therapeutic index of warfarin and the many sources of variability require monitoring of the anticoagulant effect to maintain blood levels within the therapeutic range. Because of these difficulties and the severe consequences of thrombosis, it is clear that there is a need for new oral anticoagulants. Ximelagatran was developed to improve the low and highly variable bioavailability of the reversible, direct thrombin inhibitor melagatran (Gustafsson et al., 2001). The hydrophilic carboxylic acid and amidine functions of melagatran were protected by introducing an ethylester residue and the less ...

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Section: Bile ϭmentioning

confidence: 99%

Intestinal and Hepatobiliary Transport of Ximelagatran and Its Metabolites in Pigs

Sjödin¹,

Fritsch²,

Eriksson³

et al. 2008

Drug Metab Dispos

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“…The Poisson's ratio of elastic cartilage in newborns is taken to be 0.475. This value has been widely used in soft-tissue modeling ͑Torres- Moreno et al, 1999;Cheung et al, 2004;Chui et al, 2004͒. The soft tissue is also assumed to be hyperelastic, as discussed in Sec.…”

Section: B Materials Propertiesmentioning

confidence: 99%

A nonlinear finite-element model of the newborn ear canal

Liu

Lutfy

et al. 2006

The Journal of the Acoustical Society of America

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A three-dimensional nonlinear finite-element model of a 22-day-old newborn ear canal is presented. The geometry is based on a clinical x-ray CT scan. A nonlinear hyperelastic constitutive law is applied to model large deformations. The Young's modulus of the soft tissue is found to have a significant effect on the ear-canal volume change, which ranges from approximately 27% to 75% over the static-pressure range of ±3kPa. The effects of Poisson's ratio and of the ratio C 10 : C 01 in the hyperelastic model are found to be small. The volume changes do not reach a plateau at high pressures, which implies that the newborn ear-canal wall would not be rigid in tympanometric measurements. The displacements and volume changes calculated from the model are compared with available experimental data.

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“…Next, the stress-strain relationship was modeled using the cubic function described in Eq. (14). Figure 4 also displays the nonlinear properties of the model.…”

Section: Resultsmentioning

confidence: 99%

“…(13) and (14) is sufficient to express nonlinear characteristics. (14) where G o is the linear shear modulus with low strain; γ 0 is the strain in which the characteristics of the liver change to show nonlinearity, and a γ is the coefficient deciding the change in stiffness. …”

Section: Resultsmentioning

confidence: 99%

“…Liu et al (12) developed a nonlinear viscoelastic model to represent the material properties based on a stress relaxation test. Sakuma et al (13) (14) derived an equation that combines both logarithmic and polynomial strain energy forms of pig liver from combined compression and elongation tests. Additionally, Kerdok et al (15) used a generalized Voigt model for perfused ex vivo porcine liver.…”

Section: Introductionmentioning

confidence: 99%

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Modeling of Viscoelastic and Nonlinear Material Properties of Liver Tissue using Fractional Calculations

Kobayashi

Kato

Watanabe

et al. 2012

JBSE

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We present a material model to represent the viscoelastic and material, nonlinear properties of liver tissue for needle insertion simulation. Material properties of liver tissue were measured using a rheometer and modeled from the measured data. The liver viscoelastic characteristics were represented by differential equations, including the fractional derivative term. Next, nonlinearity with respect to the fractional derivative was measured, and the stress-strain relationship using a cubic function was modeled. The material properties of liver tissue were represented by a simple equation with only a few parameters. We evaluated the variety of each stiffness parameter from measurements of 50 samples. The results showed a high degree of variation in each stiffness parameter, especially with respect to nonlinearity. Moreover, each parameter had a low correlation coefficient. We also modeled the probability of variation in material properties from these results to provide a basis for deformation simulations considering individual patient differences.

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Combined compression and elongation experiments and non-linear modelling of liver tissue for surgical simulation

Cited by 130 publications

References 27 publications

Intestinal and Hepatobiliary Transport of Ximelagatran and Its Metabolites in Pigs

Intestinal and Hepatobiliary Transport of Ximelagatran and Its Metabolites in Pigs

A nonlinear finite-element model of the newborn ear canal

Modeling of Viscoelastic and Nonlinear Material Properties of Liver Tissue using Fractional Calculations

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