Chronic apnea during REM sleep increases arterial pressure and sympathetic modulation in rats.

STUDY OBJECTIVES: Obstructive sleep apnea can induce hypertension. Apneas in REM may be particularly problematic: they are independently associated with hypertension. We examined the role of sleep stage and awakening on acute cardiovascular responses to apnea. In addition, we measured cardiovascular and sympathetic changes induced by chronic sleep apnea in REM sleep. METHODS: We used rats with tracheal balloons and electroencephalogram and electromyogram electrodes to induce obstructive apnea during wakefulness and sleep. We measured the electrocardiogram and arterial pressure by telemetry and breathing effort with a thoracic balloon. RESULTS: Apneas induced during wakefulness caused a pressor response, intense bradycardia, and breathing effort. On termination of apnea, arterial pressure, heart rate, and breathing effort returned to basal levels within 10 s. Responses to apnea were strongly blunted when apneas were made in sleep. Post-apnea changes were also blunted when rats did not awake from apnea. Chronic sleep apnea (15 days of apnea during REM sleep, 8 h/day, 13.8 ± 2 apneas/h, average duration 12 ± 0.7 s) reduced sleep time, increased awake arterial pressure from 111 ± 6 to 118 ± 5 mmHg (p < 0.05) and increased a marker for sympathetic activity. Chronic apnea failed to change spontaneous baroreceptor sensitivity. CONCLUSION: Our results suggest that sleep blunts the diving-like response induced by apnea and that acute post-apnea changes depend on awakening. In addition, our data confirm that 2 weeks of apnea during REM causes sleep disruption and increases blood pressure and sympathetic activity.

Cardiovascular responses induced by obstructive apnea are enhanced in hypertensive rats due to enhanced chemoreceptor responsivity.

Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n = 14/13). The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea.

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

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.

Cardiovascular adjustments induced by hypertonic saline in hemorrhagic rats: Involvement of carotid body chemoreceptors.

The peripheral hyperosmolarity elicited by intravenous infusion of hypertonic saline brings potential benefits to the treatment of hemorrhage. The neural mechanisms involved in these beneficial effects remain unknown. The present study examines the role of carotid chemoreceptors in cardiovascular responses induced by hypertonic saline after hypovolemic hemorrhage in rats. Male Wistar rats (300-400 g) were anesthetized with thiopental, and instrumented for recording of mean arterial pressure. Arterial pressure was reduced to 60 mm Hg by withdrawal of arterial blood over 10 min, and maintained at this level for 60 min by withdrawal or infusion of blood. In control rats (n = 8) with intact chemoreceptors, the subsequent intravenous infusion of hypertonic saline (3M NaCl, 1.8 ml kg(-1) body weight, in 2 min) restored blood pressure (pressure increased from 61 ± 4 to 118 ± 5 mm Hg). In experimental rats (n = 8), the carotid body arteries were tied, 30 min after the beginning of the hypotensive phase, leaving the carotid chemoreceptors ischemic. In these rats, hypertonic saline failed to restore blood pressure (pressure increased from 55 ± 1 to 70 ± 6 mm Hg). These findings suggest that the restoration of blood pressure after hypovolemic hemorrhage induced by hypertonic saline depends on intact carotid chemoreceptors.

Sleep perception in insomniacs, sleep-disordered breathing patients, and healthy volunteers--an important biologic parameter of sleep.

BACKGROUND: The mechanisms involved in sleep perception are not widely known. Therefore, we believe that investigating this phenomenon is the best way to understand some of the mechanisms involved in several sleep disturbances, particularly insomnias. OBJECTIVE: The objective of our study was to evaluate sleep perception in insomniacs, sleep-disordered breathing (SDB) patients, and healthy volunteers. Our hypothesis was that insomniacs have less sleep perception than healthy individuals and patients with sleep respiratory disorders. METHODS: We studied 199 individuals who were divided into the following four groups: (1) insomnia group; (2) patients with sleep-disordered breathing; (3) patients with insomnia complaints and an associated sleep respiratory disorder; and (4) healthy individuals with no sleep complaints. All patients were subjected to polysomnography (PSG) followed by a questionnaire addressing their perception about the previous night's sleep. In addition to analysis of all sleep parameters, we determined sleep perception as the percentage of the ratio between total sleep time perceived by the patient and the total sleep time obtained by PSG. RESULTS: Sleep perception was significantly lower in insomnia patients than in sleep-disordered breathing patients or the normal group. In addition, no significant differences across the four groups were observed in sleep efficiency and total sleep time. CONCLUSIONS: The results showed that the reported sleep perception of insomniacs is lower than that of sleep-disordered breathing patients or normal individuals. We believe that sleep perception is as important as other commonly measured parameters, such as sleep efficiency.