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建立通过麻痹颏舌肌致阻塞性睡眠呼吸暂停的兔模型。

Establishment of a rabbit model of obstructive sleep apnea by paralyzing the genioglossus.

机构信息

Department of Otorhinolaryngology, Korea Cancer Center Hospital, Seoul, South Korea.

出版信息

JAMA Otolaryngol Head Neck Surg. 2013 Aug 1;139(8):834-40. doi: 10.1001/jamaoto.2013.4001.

Abstract

IMPORTANCE

This study presents an innovative method for developing a neuromuscular model of obstructive sleep apnea (OSA).

OBJECTIVE

To establish a new OSA animal model simulating real upper airway conditions during sleep.

DESIGN AND SETTING

In vivo animal study at an academic tertiary referral center.

SUBJECTS

A total of 27 New Zealand white male rabbits were used.

INTERVENTION

Sleep was induced by intramuscular injection of 0.3 mL/kg of tiletamine hydrochloride plus zolazepam hydrochloride and 0.2 mL/kg of xylazine. Upper airway obstruction was induced by injecting botulinum toxin type A (2.5 U in 8 rabbits, 5.0 U in 10 rabbits, and 7.5 U in 1 rabbit) into the genioglossus. Eight rabbits were injected with normal saline as a control.

MAIN OUTCOMES AND MEASURES

Drug-induced sleep was evaluated using a portable polysomnography device for electroencephalography, electrooculography, chin electromyography, nasal airflow, breathing efforts, and pulse oxymetry. Respiratory events (apneas or hypopneas) during sleep were evaluated using a sleep-screening tool.

RESULTS

All the rabbits showed no apneas or hypopneas before injection of botulinum toxin type A. In the control rabbits injected with normal saline, apneas or hypopneas were not found. The respiratory events were observed in 5 of 8 rabbits injected with 2.5 U of botulinum toxin type A, whereas they were observed in 7 of 10 rabbits injected with 5.0 U of botulinum toxin type A. The median (interquartile range) apnea hypopnea index was 9.6 (5.3-14.8) per hour and 45.6 (21.5-70.5) per hour in the rabbits injected with 2.5 U and 5.0 U of botulinum toxin type A, respectively (P = .03).

CONCLUSIONS AND RELEVANCE

An animal model of OSA could be developed by paralyzing the genioglossus in rabbits. This model may contribute to identifying the pathogenesis of upper airway obstruction in OSA and to developing new diagnostic or treatment devices targeting specific obstruction sites.

摘要

重要性

本研究提出了一种开发阻塞性睡眠呼吸暂停(OSA)神经肌肉模型的创新方法。

目的

建立一种新的 OSA 动物模型,模拟睡眠期间真实的上呼吸道情况。

设计和设置

在学术三级转诊中心进行体内动物研究。

受试者

共使用了 27 只新西兰白雄性兔子。

干预措施

通过肌肉注射 0.3 毫升/千克盐酸替来他明加唑拉西泮和 0.2 毫升/千克二甲苯胺噻嗪诱导睡眠。通过向颏舌肌注射肉毒杆菌毒素 A(2.5U 在 8 只兔子中,5.0U 在 10 只兔子中,1 只兔子中 7.5U)诱导上气道阻塞。8 只兔子注射生理盐水作为对照。

主要结果和测量

使用便携式多导睡眠图设备评估药物诱导的睡眠,用于脑电图、眼电图、颏肌肌电图、鼻气流、呼吸努力和脉搏血氧测定。使用睡眠筛查工具评估睡眠期间的呼吸事件(呼吸暂停或低通气)。

结果

所有兔子在注射肉毒杆菌毒素 A 前均未出现呼吸暂停或低通气。在注射生理盐水的对照兔子中,未发现呼吸暂停或低通气。在注射 2.5U 肉毒杆菌毒素 A 的 8 只兔子中,有 5 只观察到呼吸事件,而在注射 5.0U 肉毒杆菌毒素 A 的 10 只兔子中,有 7 只观察到呼吸事件。注射 2.5U 和 5.0U 肉毒杆菌毒素 A 的兔子的中位(四分位间距)呼吸暂停低通气指数分别为 9.6(5.3-14.8)/小时和 45.6(21.5-70.5)/小时(P = .03)。

结论和相关性

通过麻痹兔子的颏舌肌,可以建立 OSA 的动物模型。该模型可能有助于确定 OSA 上气道阻塞的发病机制,并开发针对特定阻塞部位的新的诊断或治疗设备。

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