A new method to produce obstructive sleep apnoea in conscious unrestrained rats

Abstract

We developed a new method to produce obstructive apnoea in conscious rats. An inflatable balloon contained in a rigid Teflon tube was implanted in the trachea to allow the induction of apnoea without inducing pain. We also developed a balloon-tipped catheter that was advanced along the trachea into the mediastinum for the measurement of intrathoracic pressure. Rats recovered well from implantation of these balloons. The tracheal implant, while deflated, did not significantly impair normal breathing (thoracic pressure swing during rest was 4.5 ± 0.4 mmHg before implantation and 5.8 ± 0.5 mmHg 4 weeks after implantation; P > 0.2; n = 7). Apnoeas of up to 16 s could be made during rapid eye movement sleep without awakening the rat. During 15 s of balloon inflation, arterial O 2 saturation fell from 98 ± 0 to 80 ± 2% and partial pressure of CO 2 increased from 35 ± 1 to 44 ± 1 mmHg (n = 9; P < 0.001). Intrathoracic pressure changes during the respiratory cycle increased from 6.3 ± 0.2 to 38.5 ± 6.0 mmHg (P < 0.001; n = 4), indicating increased breathing effort. Heart rate fell from 373 ± 23 to 141 ± 18 beats min −1 (P < 0.001; n = 4), and the heart beat became irregular, with few beats during expiratory effort. These responses remained intact after 60 apnoea episodes. Responses developed slightly more slowly when apnoea started at the end than at the beginning of the respiratory cycle. As these balloons last for a long time, cause few complications, allow induction of apnoea during sleep, allow induction of apnoeas that start at a fixed point in the respiratory cycle and elicit cardiorespiratory responses similar to those observed in humans, these balloons may aid investigation of both acute apnoea and chronic intermittent sleep apnoea.

Evolution and physiology of neural oxygen sensing

“…However, since it produces consistent intermittent hypoxia, it is well accepted as an experimental model of sleep apnea. Novel methods, based on actual airway obstruction, have recently been developed and they may prove to be very useful for unraveling the full pathophysiology of OSA (Farre et al, 2007; Nacher et al, 2007; Schoorlemmer et al, 2011). …”

Cardiovascular Responses Induced by Obstructive Apnea Are Enhanced in Hypertensive Rats Due to Enhanced Chemoreceptor Responsivity

“…The syringe was driven by a solenoid, as described previously [19]. Because the balloon is contained in a rigid Teflon tube, balloon inflation does not cause stimulation of tracheal pain receptors.…”

“…Recently we developed a tracheal balloon to induce obstructive apnea in unanesthetized rats [19]. The balloon is contained in a rigid plastic tube, which permits induction of apnea without tracheal pain.…”

Cardiovascular Consequences of Sleep Apnea

“…They implanted an inflatable tracheal balloon that allows for the induction of obstructive apnea, along with a mediastinum balloon-tipped catheter for the measurement of intrathoracic pressure. Thus, combination of this method with procedures of sleep and respiratory cycle detection allows induction of sleep apnea that starts at a fixed point in the respiratory cycle, more closely imitating human obstructive sleep apnea, which typically occurs during early inspiration [153]. Even though no physical restraint is needed using this method, the animals do need to be tethered during the inflation period and this could be a matter of some concern.…”

“…Therefore, initiation of airway obstruction is closely coordinated with sleep onset [152]. Recent studies by Schoorlemmer et al [153] describe a new method for inducing obstructive sleep apnea in conscious rats. They implanted an inflatable tracheal balloon that allows for the induction of obstructive apnea, along with a mediastinum balloon-tipped catheter for the measurement of intrathoracic pressure.…”