Effects of arousal and sleep state on systemic and pulmonary hemodynamics in obstructive apnea.

During obstructive sleep apnea (OSA), systemic (Psa) and pulmonary (Ppa) arterial pressures acutely increase after apnea termination, whereas left and right ventricular stroke volumes (SV) reach a nadir. In a canine model (n = 6), we examined the effects of arousal, parasympathetic blockade (atropine 1 mg/kg iv), and sleep state on cardiovascular responses to OSA. In the absence of arousal, SV remained constant after apnea termination, compared with a 4.4 +/- 1.7% decrease after apnea with arousal (P < 0.025). The rise in transmural Ppa was independent of arousal (4.5 +/- 1.0 vs. 4.1 +/- 1.2 mmHg with and without arousal, respectively), whereas Psa increased more after apnea termination in apneas with arousal compared with apneas without arousal. Parasympathetic blockade abolished the arousal-induced increase in Psa, indicating that arousal is associated with a vagal withdrawal of the parasympathetic tone to the heart. Rapid-eye-movement (REM) sleep blunted the increase in Psa (pre- to end-apnea: 5.6 +/- 2.3 mmHg vs. 10.3 +/- 1.6 mmHg, REM vs. non-REM, respectively, P < 0.025), but not transmural Ppa, during an obstructive apnea. We conclude that arousal and sleep state both have differential effects on the systemic and pulmonary circulation in OSA, indicating that, in patients with underlying cardiovascular disease, the hemodynamic consequences of OSA may be different for the right or the left side of the circulation.     

Cardiovascular changes associated with obstructive sleep apnea syndrome.

Five men free of lung or cardiovascular diseases and with severe obstructive sleep apnea participated in a study on the impact of sleep states on cardiovascular variables during sleep apneas. A total of 128 obstructive apneas [72 from stage 2 non-rapid-eye-movement (NREM) sleep and 56 from rapid-eye-movement (REM) sleep] were analyzed. Each apnea was comprised of an obstructive period (OP) followed by a hyperventilation period, which was normally associated with an arousal. Heart rate (HR), stroke volume (SV), cardiac output (CO) (determined with an electrical impedance system), radial artery blood pressures (BP), esophageal pressure nadir, and arterial O2 saturation during each OP and hyperventilation period were calculated for NREM and REM sleep. During stage 2 NREM sleep, the lowest HR always occurred during the first third of the OP, and the highest was always seen during the last third. In contrast, during REM sleep the lowest HR was always noted during the last third of the OP. There was an inverse correlation when the percentage of change in HR over the percentage of change in SV during an OP was considered. The HR and SV changes during NREM sleep allowed maintenance of a near-stable CO during OPs. During REM sleep, absence of a compensatory change in SV led to a significant drop in CO. Systolic, diastolic, and mean BP always increased during the studied OPs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stroke volume and cardiac output decrease at termination of obstructive apneas.

Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations of systemic arterial pressure that occur in association with changes in respiration and changes in sleep state. To investigate cardiac function during the cycle of obstruction (apnea) and resumption of ventilation (recovery), we continuously measured left ventricular stroke volume (LVSV) and mean arterial blood pressure (MAP) during non-rapid-eye-movement sleep in six males with severe OSA (apnea/hypopnea index > or = 30 events/h associated with oxygen saturation < 82%). LVSV was assessed continuously using an ambulatory ventricular function monitor (VEST; Capintec). The apnea-recovery cycle was divided into three phases: 1) early apnea (EA), 2) late apnea (LA), and 3) recovery (Rec). In all subjects recovery was associated with an abrupt decrease in LVSV [54.0 +/- 14.5 (SD) ml] compared with either EA (91.4 +/- 14.7 ml; P < 0.001) or LA (77.1 +/- 15.2 ml; P < 0.005). Although heart rate increased with recovery, the increase was not sufficient to compensate for the decrease in LVSV so that cardiac output (CO) fell (EA: 6,247 +/- 739 ml/min; LA: 5,741 +/- 1,094 ml/min; Rec: 4,601 +/- 1,249 ml/min; EA vs. Rec, P < 0.01; LA vs. Rec, P < 0.025). Recovery was also associated with a significant increase in MAP. We speculate that such abrupt decreases in LVSV and CO at apnea termination, occurring coincident with the nadir of oxygen saturation, may further compromise tissue oxygen delivery.     

Posthypoxic ventilatory decline during NREM sleep: influence of sleep apnea.

We wished to determine the severity of posthypoxic ventilatory decline in patients with sleep apnea relative to normal subjects during sleep. We studied 11 men with sleep apnea/hypopnea syndrome and 11 normal men during non-rapid eye movement sleep. We measured EEG, electrooculogram, arterial O(2) saturation, and end-tidal P(CO2). To maintain upper airway patency in patients with sleep apnea, nasal continuous positive pressure was applied at a level sufficient to eliminate apneas and hypopneas. We compared the prehypoxic control (C) with posthypoxic recovery breaths. Nadir minute ventilation in normal subjects was 6.3 +/- 0.5 l/min (83.8 +/- 5.7% of room air control) vs. 6.7 +/- 0.9 l/min, 69.1 +/- 8.5% of room air control in obstructive sleep apnea (OSA) patients; nadir minute ventilation (% of control) was lower in patients with OSA relative to normal subjects (P < 0.05). Nadir tidal volume was 0.55 +/- 0.05 liter (80.0 +/- 6.6% of room air control) in OSA patients vs. 0.42 +/- 0.03 liter, 86.5 +/- 5.2% of room air control in normal subjects. In addition, prolongation of expiratory time (Te) occurred in the recovery period. There was a significant difference in Te prolongation between normal subjects (2.61 +/- 0.3 s, 120 +/- 11.2% of C) and OSA patients (5.6 +/- 1.5 s, 292 +/- 127.6% of C) (P < 0.006). In conclusion, 1) posthypoxic ventilatory decline occurred after termination of hypocapnic hypoxia in normal subjects and patients with sleep apnea and manifested as decreased tidal volume and prolongation of Te; and 2) posthypoxic ventilatory prolongation of Te was more pronounced in patients with sleep apnea relative to normal subjects.     

Repetitive apneas induce periodic hypertension in normal subjects through hypoxia.

Periodic increases in blood pressure (BP) can occur in the sleep apnea syndrome (SAS) during recurrent apneas. To investigate the mechanisms causing this periodic hypertension, we simulated SAS by imposing a matching breathing pattern on seven healthy awake male volunteers. Continuous finger arterial BP, electrocardiogram, arterial O2 saturation (SaO2), end-tidal CO2, and tidal volume were measured. The role of hypoxia was studied by comparing apneas during depletion of O2 in the spirometer with those during 100% O2 breathing. In all subjects, BP periodically reached values greater than 150/95 mmHg in the hypoxic series. During the hyperoxic apnea series, however, BP remained stable. End-apneic mean BP was shown to be inversely correlated to SaO2 in six subjects in the SaO2 range from 60 to 100%. Although the hypoxic BP pattern closely mimicked that in SAS, the heart rate pattern in four of our subjects remained distinct from that in patients. Atropine could not prevent large BP swings in the hypoxic series. We conclude that SaO2 is a major determinant of periodic hypertension in recurrent apneas. Its effect probably results from chemoreflex modulation of peripheral resistance.     

Physiological determinants of nocturnal arterial oxygenation in patients with obstructive sleep apnea

Among patients with similar degrees of obstructive sleep apnea (OSA) there is considerable variability in the degree of associated nocturnal hypoxemia. The factors responsible for this variability have not been clearly defined. Therefore we studied 44 patients with OSA to identify the physiological determinants of nocturnal arterial O2 saturation (SaO2). All patients underwent pulmonary function testing, arterial blood gas analysis, and overnight polysomnography. Mean nocturnal SaO2 ranged from 96 to 66% and apnea-hypopnea index from 11 to 128 per hour of sleep. Several anthropometric, respiratory physiological, and polysomnographic variables that could be expected to influence nocturnal SaO2 were entered into a stepwise multiple linear regression analysis, with mean nocturnal SaO2 as the dependent variable. Three variables [awake supine arterial PO2 (PaO2), expiratory reserve volume, and percentage of sleep time spent in apnea] were found to correlate strongly with mean nocturnal SaO2 (multiple R, 0.854; P less than 0.0001) and accounted for 73% of its variability among patients. Body weight, other lung volumes, and airflow rates influenced awake PaO2 and expiratory reserve volume but had no independent influence on nocturnal SaO2. In a further group of 15 patients with OSA a high correlation was obtained between measured nocturnal SaO2 and that predicted by the model (r = 0.87; P less than 0.001). We conclude that derangements of pulmonary mechanics and awake PaO2 (generally attributable to obesity and diffuse airway obstruction) are of major importance in establishing the severity of nocturnal hypoxemia in patients with OSA.     

Diagnosis of obstructive sleep apnea syndrome]

Symptoms and signs in 12 patients with severe obstructive sleep apnea (OSA) syndrome have been presented. The most common symptoms were snoring , increased motor activity during sleep and excessive daytime somnolence. The factors predisposing to OSA syndrome were obesity and anatomic abnormalities of the upper airway structure. In some cases the signs of OSA syndrome included hypertension, right heart failure, chronic alveolar hypoventilation and polycythemia. Polysomnography showed sleep fragmentation and the prevalence of light sleep stages. Obstructive sleep apneas repeated 73 +/- 23 times per hour of sleep. The mean apnea duration was 19 +/- 8 s. The mean arterial oxygen saturation during apnea was 72 +/- 14%.     

Effects of nasal CPAP therapy on respiratory and spontaneous arousals in infants with OSA.

Obstructive sleep apnea (OSA) in infants has been shown to resolve frequently without a cortical arousal. It is unknown whether infants do not require arousal to terminate apneas or whether this is a consequence of the OSA. We studied the apnea and arousal patterns of eight infants with OSA before and after treatment with nasal continuous positive airway pressure (CPAP). These infants were age matched to eight untreated infants with OSA and eight normal infants. Polysomnographic studies were performed on each infant. We found that the majority of central and obstructive apneas were terminated without arousal in all OSA infants. After several weeks of nasal CPAP treatment, the proportion of apneas terminating with an arousal during rapid-eye-movement sleep increased in treated infants compared with untreated infants. Spontaneous arousals during rapid-eye-movement sleep were reduced in all OSA infants; however, during CPAP treatment, the spontaneous arousals increased to the normal control level. We conclude that OSA in infants possibly depresses the arousal response and treatment of these infants with nasal CPAP partially reverses this depression.     

Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia.

Patients with obstructive sleep apnea (OSA) have been reported to have an augmented pressor response to hypoxic rebreathing. To assess the contribution of the peripheral vasculature to this hemodynamic response, we measured heart rate, mean arterial pressure (MAP), and forearm blood flow by venous occlusion plethysmography in 13 patients with OSA and in 6 nonapneic control subjects at arterial oxygen saturations (Sa(O(2))) of 90, 85, and 80% during progressive isocapnic hypoxia. Measurements were also performed during recovery from 5 min of forearm ischemia induced with cuff occlusion. MAP increased similarly in both groups during hypoxia (mean increase at 80% Sa(O(2)): OSA patients, 9 +/- 11 mmHg; controls, 12 +/- 7 mmHg). Forearm vascular resistance, calculated from forearm blood flow and MAP, decreased in controls (mean change -37 +/- 19% at Sa(O(2)) 80%) but not in patients (mean change -4 +/- 16% at 80% Sa(O(2))). Both groups decreased forearm vascular resistance similarly after forearm ischemia (maximum change from baseline -85%). We conclude that OSA patients have an abnormal peripheral vascular response to isocapnic hypoxia.     

Atelectasis affects the rate of arterial desaturation during obstructive apnea

Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed.     

nCPAP improves abnormal autonomic function in at-risk-for-SIDS infants with OSA.

We evaluated cardiovascular autonomic control and arousability during sleep in infants with obstructive sleep apnea (OSA) before and after 10 +/- 4 (mean +/- SD) days of treatment with nasal continuous positive airway pressure (nCPAP). Six OSA infants and 12 age-matched control infants were studied with polygraphic sleep studies at the age of 13 +/- 4 wk. During the study, 45 degrees head-up tilt tests were performed in slow-wave and rapid eye movement sleep. Blood pressure (BP) and heart rate (HR) were continuously monitored. All OSA infants had decreased initial BP and HR responses, followed by hypotension in two and hypertension in two. OSA infants displayed higher arousal thresholds in response to the tilt in rapid eye movement sleep (P < 0.005) and higher baseline HR (P < 0.05) than controls. nCPAP treatment normalized BP and HR responses as well as arousal thresholds to tilting and stabilized HR levels. OSA in infants may be linked with cardiovascular autonomic control disturbances and decreased arousability during sleep. These defects are improved by control of OSA with nCPAP.     

Possible mechanisms of periodic breathing during sleep

To determine the effect of respiratory control system loop gain on periodic breathing during sleep, 10 volunteers were studied during stage 1-2 non-rapid-eye-movement (NREM) sleep while breathing room air (room air control), while hypoxic (hypoxia control), and while wearing a tight-fitting mask that augmented control system gain by mechanically increasing the effect of ventilation on arterial O2 saturation (SaO2) (hypoxia increased gain). Ventilatory responses to progressive hypoxia at two steady-state end-tidal PCO2 levels and to progressive hypercapnia at two levels of oxygenation were measured during wakefulness as indexes of controller gain. Under increased gain conditions, five male subjects developed periodic breathing with recurrent cycles of hyperventilation and apnea; the remaining subjects had nonperiodic patterns of hyperventilation. Periodic breathers had greater ventilatory response slopes to hypercapnia under either hyperoxic or hypoxic conditions than nonperiodic breathers (2.98 +/- 0.72 vs. 1.50 +/- 0.39 l.min-1.Torr-1; 4.39 +/- 2.05 vs. 1.72 +/- 0.86 l.min-1.Torr-1; for both, P less than 0.04) and greater ventilatory responsiveness to hypoxia at a PCO2 of 46.5 Torr (2.07 +/- 0.91 vs. 0.87 +/- 0.38 l.min-1.% fall in SaO2(-1); P less than 0.04). To assess whether spontaneous oscillations in ventilation contributed to periodic breathing, power spectrum analysis was used to detect significant cyclic patterns in ventilation during NREM sleep. Oscillations occurred more frequently in periodic breathers, and hypercapnic responses were higher in subjects with oscillations than those without. The results suggest that spontaneous oscillations in ventilation are common during sleep and can be converted to periodic breathing with apnea when loop gain is increased.     

Effects of aortic nerve on hemodynamic response to obstructive apnea in sedated pigs.

In this study we test the hypothesis that aortic nerve traffic is responsible for the pressor response to periodic apneas. In nine intubated, sedated chronically instrumented pigs, periodic obstructive apneas were caused by occlusion of the endotracheal tube for 30 s, followed by spontaneous breathing for 30 s. This was done under control (C) conditions, after section of the aortic nerve (ANS), and after bilateral cervical vagotomy (Vagot). Blood-gas tensions and airway pressure changed similarly under all conditions: PO(2) decreased to 50-60 Torr, PCO(2) increased to approximately 55 Torr, and airway pressure decreased by 40-50 mmHg during apnea. With C, mean arterial pressure (MAP) increased from 111 +/- 4 mmHg at baseline to 120 +/- 5 mmHg at late apnea (P < 0.01). After ANS and Vagot, there was no change in MAP with apneas compared with baseline. Relative to baseline, cardiac output and stroke volume decreased with C but not with ANS or Vagot during apneas. Increased MAP was due to increased systemic vascular resistance. Heart rate behaved similarly with C and ANS, being greater at early interapnea than late apnea. With Vagot, heart rate increased throughout the apnea-interapnea cycle relative to baseline. We conclude that, in sedated pigs, aortic nerve traffic mediates the increase in MAP and systemic vascular resistance observed during periodic apneas. Increase in MAP is responsible for decreased cardiac output and stroke volume. Additional vagal reflexes, most likely parasympathetic efferents, are responsible for interacting with sympathetic excitatory influences in modulating heart rate.     

A model of sleep-disordered breathing in the C57BL/6J mouse.

To investigate the pathophysiological sequelae of sleep-disordered breathing (SDB), we have developed a mouse model in which hypoxia was induced during periods of sleep and was removed in response to arousal or wakefulness. An on-line sleep-wake detection system, based on the frequency and amplitude of electroencephalograph and electromyograph recordings, served to trigger intermittent hypoxia during periods of sleep. In adult male C57BL/6J mice (n = 5), the sleep-wake detection system accurately assessed wakefulness (97.2 +/- 1.1%), non-rapid eye movement (NREM) sleep (96.0 +/- 0.9%) and rapid eye movement (REM) sleep (85.6 +/- 5.0%). After 5 consecutive days of SDB, 554 +/- 29 (SE) hypoxic events were recorded over a 24-h period at a rate of 63.6 +/- 2.6 events/h of sleep and with a duration of 28.2 +/- 0.7 s. The mean nadir of fraction of inspired O(2) (FI(O(2))) on day 5 was 13.2 +/- 0.1%, and 137.1 +/- 13.2 of the events had a nadir FI(O(2)) <10% O(2). Arterial blood gases confirmed that hypoxia of this magnitude lead to a significant degree of hypoxemia. Furthermore, 5 days of SDB were associated with decreases in both NREM and REM sleep during the light phase compared with the 24-h postintervention period. We conclude that our murine model of SDB mimics the rate and magnitude of sleep-induced hypoxia, sleep fragmentation, and reduction in total sleep time found in patients with moderate to severe SDB in the clinical setting.     

Impaired cerebral autoregulation in obstructive sleep apnea

Obstructive sleep apnea (OSA) increases the risk of stroke independent of known vascular and metabolic risk factors. Although patients with OSA have higher prevalence of hypertension and evidence of hypercoagulability, the mechanism of this increased risk is unknown. Obstructive apnea events are associated with surges in blood pressure, hypercapnia, and fluctuations in cerebral blood flow. These perturbations can adversely affect the cerebral circulation. We hypothesized that patients with OSA have impaired cerebral autoregulation, which may contribute to the increased risk of cerebral ischemia and stroke. We examined cerebral autoregulation in patients with and without OSA by measuring cerebral artery blood flow velocity (CBFV) by using transcranial Doppler ultrasound and arterial blood pressure using finger pulse photoplethysmography during orthostatic hypotension and recovery as well as during 5% CO(2) inhalation. Cerebral vascular conductance and reactivity were determined. Forty-eight subjects, 26 controls (age 41.0+/-2.3 yr) and 22 OSA (age 46.8+/-2.3 yr) free of cerebrovascular and active coronary artery disease participated in this study. OSA patients had a mean apnea-hypopnea index of 78.4+/-7.1 vs. 1.8+/-0.3 events/h in controls. The oxygen saturation during sleep was significantly lower in the OSA group (78+/-2%) vs. 91+/-1% in controls. The dynamic vascular analysis showed mean CBFV was significantly lower in OSA patients compared with controls (48+/-3 vs. 55+/-2 cm/s; P <0.05, respectively). The OSA group had a lower rate of recovery of cerebrovascular conductance for a given drop in blood pressure compared with controls (0.06+/-0.02 vs. 0.20+/-0.06 cm.s(-2).mmHg(-1); P <0.05). There was no difference in cerebrovascular vasodilatation in response to CO(2). The findings showed that patients with OSA have decreased CBFV at baseline and delayed cerebrovascular compensatory response to changes in blood pressure but not to CO(2). These perturbations may increase the risk of cerebral ischemia during obstructive apnea.     

Plasma adenosine and hypoxemia in patients with sleep apnea

Severe hypoxemia causes ATP depletion and increased adenosine production in many body tissues. Therefore we hypothesized that patients with sleep apnea and severe hypoxemia during sleep have higher adenosine production and higher plasma adenosine levels than patients without hypoxemia. Twelve patients with sleep apnea and six normal volunteers had plasma adenosine levels measured by high-performance liquid chromatography. Each patient with sleep apnea had a polysomnograph sleep study with oxyhemoglobin saturation continuously recorded. Five of 12 patients with sleep apnea had both sleep apnea and severe hypoxemia during sleep. These patients with severe nocturnal hypoxemia had significantly higher plasma adenosine levels (means +/- SD 9.7 +/- 5.5 X 10(-8) M) than either a group of six normal volunteers (3.5 +/- 0.7 X 10(-8) M) or a group of seven patients with sleep apnea without hypoxemia at night (3.1 +/- 1.5 X 10(-8) M) (P less than 0.01). In addition plasma adenosine levels were significantly correlated with two indexes of nocturnal hypoxemia (desaturation index rs = 0.79, and median oxyhemoglobin saturation during sleep rs = -0.75, P less than 0.01). Plasma adenosine markedly fell to a normal level in the only two patients with sleep apnea who had successful treatment of their multiple apneas and accompanying severe hypoxemia during sleep.     

Occlusion of the upper airway does not augment the cardiovascular response to arousal from sleep in humans.

The cardiovascular response to an arousal from sleep at the termination of an obstructive apnea is more than double that to a spontaneous arousal. We investigated the hypothesis that stimulation of respiratory mechanoreceptors, by inspiring against an occluded airway during an arousal from sleep, augments the accompanying cardiovascular response. Arousals (>10 s) from stage 2 sleep were induced by a 1-s auditory tone (85 dB) during a concomitant 1-s inspiratory occlusion (O) and without an occlusion [i.e., control arousal (C)] in 15 healthy men (mean +/- SE: age, 25 +/- 1 yr). Arousals were associated with a significant increase in mean arterial blood pressure (MAP) at 4 s (P < 0.001) and a significant decrease in R-R interval at 3 s (P < 0.001). However, the magnitude of the cardiovascular response was not different during C compared with O (MAP: C, 86 +/- 3 to 104 +/- 3 mmHg; O, 86 +/- 3 to 105 +/- 3 mmHg; P = 0.99. R-R interval: C, 1.12 +/- 0.03 to 0.89 +/- 0.04 s; O, 1.11 +/- 0.02 to 0.87 +/- 0.02 s, P = 0.99). Ventilation significantly increased during arousals under both conditions at the second breath (P < 0.001); this increase was not different between the two conditions (C: 4.40 +/- 0.29 to 6.76 +/- 0.61 l/min, O: 4.35 +/- 0.34 to 7.65 +/- 0.73 l/min; P = 0.31). We conclude that stimulation of the respiratory mechanoreceptors by transient upper airway occlusion is unlikely to interact with the arousal-related autonomic outflow to augment the cardiovascular response in healthy young men.     

Influence of sleep state on frequency of swallowing, apnea, and arousal in human infants.

Apnea and arousal are modulated with sleep stage, and swallowing may interfere with respiratory rhythm in infants. We hypothesized that swallowing itself would display interaction with sleep state. Concurrent polysomnography and measurement of swallowing allowed time-matched analysis of 3,092 swallows, 482 apneas, and 771 arousals in 17 infants aged 1-34 wk. The mean rates of swallowing, apnea, and arousal were significantly different, being 23.3 +/- 8.5, 9.4 +/- 8.8, and 15.5 +/- 10.6 h(-1), respectively (P < 0.001 ANOVA). Swallows occurred before 25.2 +/- 7.9% and during 74.8 +/- 6.3% of apneas and before 39.8 +/- 6.0% and during 60.2 +/- 6.0% of arousals. The frequencies of apneas and arousals were both strongly influenced by sleep state (active sleep > indeterminate > quiet sleep, P < 0.001), whether or not the events coincided with swallowing, but swallowing rate showed minimal independent interaction with sleep state. Interactions between swallowing and sleep state were predominantly influenced by the coincidence of swallowing with apnea or arousal.     

Mechanisms of acute cardiovascular response to periodic apneas in sedated pigs.

This study was designed to evaluate the importance of sympathoadrenal activation in the acute cardiovascular response to apneas and the role of hypoxemia in this response. In addition, we evaluated the contribution of the vagus nerve to apnea responses after chemical sympathectomy. In six pigs preinstrumented with an electromagnetic flow probe and five nonpreinstrumented pigs, effects of periodic nonobstructive apneas were tested under the following six conditions: room air breathing, 100% O2 supplementation, both repeated after administration of hexamethonium (Hex), and both repeated again after bilateral vagotomy in addition to Hex. With room air apneas, during the apnea cycle, there were increases in mean arterial pressure (MAP; from baseline of 108 +/- 4 to 124 +/- 6 Torr, P < 0.01), plasma norepinephrine (from 681 +/- 99 to 1,825 +/- 578 pg/ml, P < 0.05), and epinephrine (from 191 +/- 67 to 1,245 +/- 685 pg/ml, P < 0.05) but decreases in cardiac output (CO; from 3.3 +/- 0.6 to 2.4 +/- 0.3 l/min, P < 0.01) and cervical sympathetic nerve activity. With O2 supplementation relative to baseline, apneas were associated with small increases in MAP (from 112 +/- 4 to 118 +/- 3 Torr, P < 0.01) and norepinephrine (from 675 +/- 97 to 861 +/- 170 pg/ml, P < 0.05). After Hex, apneas with room air were associated with small increases in MAP (from 103 +/- 6 to 109 +/- 6 Torr, P < 0.05) and epinephrine (from 136 +/- 45 to 666 +/- 467 pg/ml, P < 0.05) and decreases in CO (from 3.6 +/- 0.4 to 3.2 +/- 0. 5 l/min, P < 0.05). After Hex, apneas with O2 supplementation were associated with decreased MAP (from 107 +/- 5 to 100 +/- 5 Torr, P < 0.05) and no other changes. After vagotomy + Hex, with room air and O2 supplementation, apneas were associated with decreased MAP (from 98 +/- 6 to 76 +/- 7 and from 103 +/- 7 to 95 +/- 6 Torr, respectively, both P < 0.01) but increased CO [from 2.7 +/- 0.3 to 3. 2 +/- 0.4 l/min (P < 0.05) and from 2.4 +/- 0.2 to 2.7 +/- 0.2 l/min (P < 0.01), respectively]. We conclude that sympathoadrenal activation is the major pressor mechanism during apneas. Cervical sympathetic nerve activity does not reflect overall sympathoadrenal activity during apneas. Hypoxemia is an important but not the sole trigger factor for sympathoadrenal activation. There is an important vagally mediated reflex that contributes to the pressor response to apneas.