Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: a computational study on glucosamine as a model solute
Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: a computational study on glucosamine as a model solute
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椎间盘尺寸显着影响椎间盘中静脉注射溶质的浓度分布：以葡萄糖胺作为模型溶质的计算研究
DOI：
10.1007/s00586-013-3142-5
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发表时间：
2014
影响因子：
2.8
通讯作者：
Jill P. G. Urban
中科院分区：
文献类型：
--
作者：
S. Motaghinasab;A. Shirazi;Mohamad Parnianpour;Jill P. G. Urban
目的椎间盘大小差异较大的不同物种动物的试验通常用于研究椎间盘内静脉注射溶质的治疗效果。我们假设，光盘的大小显着影响outcome.MethodsHere，使用一个小的非代谢分子，氨基葡萄糖（GL）作为模型溶质，我们计算的影响，光盘大小的GL运输到大鼠，兔，狗和人的光盘10小时后静脉注射。我们使用瞬态有限元模型，并认为一个相同的GL供应所有animal.ResultsHuge影响的光盘大小上GL浓度profile被发现。注射后GL浓度在大鼠光盘达到70%的血液浓度在15分钟内，但仍低于10%的人椎间盘核在整个。GL在注射后迅速渗透到较小的圆盘中，导致浓度均匀。相比之下，GL浓度，虽然在低得多的水平，随着时间的推移，在人类的光盘与一个小的向外通量在环周边在较长的periods.ConclusionsChanges在光盘大小的巨大影响GL浓度在整个光盘在所有地区和时间。增加给药剂量既不能纠正注射后早期较大人体椎间盘中心的极低浓度水平，也不能改变不同种属之间估计的浓度曲线的实质性差异。尺寸效应只会随着溶质分子量的增加和终板钙化而加剧。从动物椎间盘外推静脉给药溶质的有效性结果必须非常谨慎。
PurposeTests on animals of different species with large differences in intervertebral disc size are commonly used to investigate the therapeutic efficacy of intravenously injected solutes in the disc. We hypothesize that disc size markedly affects outcome.MethodsHere, using a small non-metabolized molecule, glucosamine (GL) as a model solute, we calculate the influence of disc size on transport of GL into rat, rabbit, dog and human discs for 10 h post intravenous-injection. We used transient finite element models and considered an identical GL supply for all animals.ResultsHuge effects of disc size on GL concentration profiles were found. Post-injection GL concentration in the rat disc reached 70 % blood concentration within 15 min but remained below 10 % in the human disc nucleus throughout. The GL rapidly penetrated post-injection into smaller discs resulting in homogeneous concentrations. In contrast, GL concentration, albeit at much lower levels, increased with time in the human disc with a small outward flux at the annulus periphery at longer periods.ConclusionsChanges in the disc size hugely influenced GL concentrations throughout the disc at all regions and times. Increases in administered dose can neither remedy the very low concentration levels in the disc center in larger human disc at early post-injection hours nor alter the substantial differences in concentration profiles estimated among various species. The size effect will only be exacerbated as molecular weight of the solute increases and as the endplate calcifies. Extrapolation of findings from animal to human discs on the efficacy of intravenously administered solutes must proceed with great caution.
影响因子：
2.4
作者：
Huang, Chun-Yuh;Gu, Wei Yong
通讯作者：
Gu, Wei Yong