Flexible versus rigid catheters for chronic administration of exogenous agents into central nervous system tissues
Flexible versus rigid catheters for chronic administration of exogenous agents into central nervous system tissues
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DOI：
10.1016/j.jneumeth.2004.10.019
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发表时间：
2005-06-15
影响因子：
3
通讯作者：
Jallo, GI
中科院分区：
文献类型：
--
作者：
Guarnieri, M;Carson, BS;Jallo, GI
引言：神经药理学研究依赖于药物输送的一致性。药物输注到中枢神经系统（CNS）组织中已被描述为不可靠。猜测集中在输液泵作为变异的来源。本报告证明导管可能是变异性的来源。的不一致性，可以显着减少导管design.Methods的变化：正常和肿瘤细胞的挑战（异常）Fischer大鼠的大脑注入了小和大分子量的细胞毒性药物，通过刚性和柔性导管直接放置到实质。分析输注点喙侧和尾侧的冠状组织切片的药物浓度。卡铂，估计通过原子吸收测定，和阿霉素和转铁蛋白结合的阿霉素，荧光光谱法测量，映射在连续的部分在不同的距离从infusion point.Results：预期的药物分布模式近似于一个钟形曲线的最大药物浓度附近的输液点和近似相等，下降的浓度吻和尾的输液。在17个正常大脑中只有10个发现了这种预期的分布，在28个用刚性导管灌注的异常大脑中只有15个发现了这种预期的分布。相比之下，10个正常大脑中的10个和16个异常大鼠大脑中的16个具有预期的分布模式。的分布模式是不相关的分子量的输注drug.Conclusion：更换刚性输液管与柔性管增加了当地中枢神经系统药物输注的可靠性。刚性导管可以允许输注的药物沿着导管的路径回流到硬膜下腔中。(c)2004 Elsevier B.V.保留所有权利。
Introduction: Neuropharmacology studies depend on consistency in drug delivery. Drug infusions into central nervous system (CNS) tissues have been described as unreliable. Speculation has focused on infusion pumps as the source of variation. This report demonstrates that the catheter may be a source of variability. The inconsistency can be significantly reduced by a change in catheter design.Methods: Normal and tumor cell-challenged (abnormal) brains of Fischer rats were infused with small and large molecular weight cytotoxic drugs via rigid and flexible catheters placed directly into the parenchyma. Coronal tissue sections rostral and caudal to the infusion point were analyzed for drug concentrations. Carboplatin, estimated through atomic absorption assays, and doxorubicin and transferrin-bound doxorubicin, measured by fluorescent spectroscopy, were mapped in serial sections at various distances from the infusion point.Results: The expected drug distribution pattern approximates a bell-shaped curve with a maximum drug concentration near the infusion point and approximately equal, declining concentrations rostral and caudal to the infusion. This expected distribution was found in only 10 of the 17 normal brains and 15 of the 28 abnormal brains infused with a rigid catheter. In contrast, 10 of the 10 normal brains and 16 of the 16 abnormal rat brains infused with a flexible catheter had the expected distribution pattern. The distribution pattern was not associated with the molecular weight of the infused drug.Conclusion: Replacement of rigid infusion tubes with flexible tubing increases the reliability of local CNS drug infusions. Rigid catheters may allow backflow of the infused drug along the path of the catheters into the subdural space. (c) 2004 Elsevier B.V. All rights reserved.