OSMOTIC PUMP IMPLANT FOR CHRONIC INFUSION OF DRUGS INTO THE INNER-EAR

OSMOTIC PUMP IMPLANT FOR CHRONIC INFUSION OF DRUGS INTO THE INNER-EAR
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DOI:
10.1016/0378-5955(93)90155-t
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发表时间:
1993-11-01
期刊:
影响因子:
2.8
通讯作者:
NUTTALL, AL
NUTTALL, AL
中科院分区:
医学1区
文献类型:
--
作者:
BROWN, JN;MILLER, JM;NUTTALL, AL

文献摘要

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将实验药物连续长期递送到小动物(例如年幼的豚鼠)的耳蜗存在几个技术问题。本文描述了一种放置和固定套管渗透泵系统的方法。豚鼠(225-410 g)单侧植入Alzet微型泵和插管,用于输送20 mM河豚毒素(mt)(六只动物)或盐水(三只动物)三天(1微升/小时)。在植入后第1天和第3天,在轻度麻醉下记录听觉脑干反应(ABR),并与植入前基线值进行比较。6个耳蜗灌注TTX后24 h内,多数频率的灵敏度下降30- 60 dB。生理盐水对照动物显示,大多数频率的敏感性较基线变化很小或无变化。在三只输注TTX的动物中,在第3天移除套管泵装置,并在恢复期间跟踪ABR。大多数频率在泵移除后恢复到或接近植入前水平,但恢复时间不同。到第6天,所有动物均恢复了术后体重减轻,并显示体重增加10-40 g。取出脑和耳蜗并进行切片处理。非恢复性TTX处理动物的耳蜗核的评估显示,处理侧的听觉神经活动区的平坦化与听力相关。
Continuous long-term delivery of experimental drugs to the cochlea of a small animal, such as a young guinea pig, presents several technical problems. A method of placing and securing a cannula-osmotic pump system is described in this paper. Guinea pigs (225-410 g) were unilaterally implanted with an Alzet micro-pump and cannula for delivery of 20 mM tetrodotoxin (mt) (six animals) or saline (three animals) for three days (1 mu l/h). Auditory brainstem responses (ABRs) were recorded under light anesthesia on post-implant day 1 and day 3 and compared with pre-implant baseline values. In all six cochleas infused with TTX, most frequencies showed a 30-60dB decrease in sensitivity within 24 h. Saline control animals showed little or no change from baseline sensitivity for most frequencies. In three TTX-infused animals, the cannula-pump unit was removed on day 3, and ABRs were followed during recovery. Most frequencies returned to, or near, pre-implant levels after pump removal but recovery times varied. By day 6, all animals had recovered post-surgical weight loss and showed a gain of 10-40 g. Brains and cochleas were removed and processed for sectioning. Assessment of the cochlear nucleus of non-recovery TTX-treated animals showed a deafness-related flattening of auditory nerve active zones on the treated side.