Nonobstructive Apnea Research Articles

Intermittent hypoxia: keeping it real

in this issue of the Journal of Applied Physiology , Tamisier and colleagues ([20][1]) describe a novel method for studying the effects of chronic intermittent hypoxia (CIH) in healthy human subjects. To investigate the effects of CIH on sleep, ventilatory control, and blood pressure, the authors

Effects of vagotomy on cardiovascular response to periodic apneas in sedated pigs

There are few studies investigating the influence of vagally mediated reflexes on the cardiovascular response to apneas. In 12 sedated preinstrumented pigs, we studied the effects of vagotomy during apneas, controlling for apnea periodicity and thoracic mechanical effects. Nonobstructive apneas were produced by paralyzing and mechanically ventilating the animals, then turning the ventilator off and on every 30 s. Before vagotomy, relative to baseline, apnea caused increased mean arterial pressure (MAP; +19 +/- 25%, P < 0.05), systemic vascular resistance (SVR; +33 +/- 16%, P < 0.0005), and heart rate (HR; +5 +/- 6%, P < 0.05) and decreased cardiac output (CO) and stroke volume (SV; -16 +/- 10% P < 0.001). After vagotomy, no significant change occurred in MAP, SVR, and SV during apneas, but CO and HR increased relative to baseline. HR was always greater ( approximately 14%, P < 0.01) during the interapneic interval compared with during apnea. We conclude that vagally mediated reflexes are important mediators of the apneic pressor response. HR increases after apnea termination are related, at least in part, to nonvagally mediated reflexes.

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.

Role of hypoxemia and hypercapnia in acute cardiovascular response to periodic apneas in sedated pigs

The effects of hypoxemia and hypercapnia in acute cardiovascular response to periodic non-obstructive apneas were explored in seven preinstrumented, sedated paralyzed and ventilated pigs under three conditions: room air breathing (RA), O 2 supplementation (O2), and supplementation with O 2 and CO 2 (CO2). EEG monitoring showed no arousal under any conditions. RA apneas increased mean arterial pressure (MAP, from baseline 95.9±4.5 to late apnea 124.4±7.8 Torr, P<0.01), left ventricular end-diastolic pressure, end-diastolic and end-systolic myocardial fiber lengths and systemic vascular resistance, but decreased cardiac output (CO, 3.09±0.34–2.37±0.26 L/min, P<0.01), heart rate (HR, 115.1±7.5–102.0±7.8 bpm, P<0.01), and stroke volume (SV, 29.6±0.7–21.1±1.8 ml, P<0.01). O2 apneas produced similar decreases in HR (114.0±11.8–105.4±8.7 bpm, P<0.05) as with RA apneas, but smaller increases in MAP (94.5±1.8–103.4±2.8 Torr, P<0.01) and in the variables of pre- and after-load. CO and SV remained unchanged with O2 apneas. CO2 was associated with higher MAP, CO, and HR at baseline relative to RA, but similar cardiovascular response during apneas in direction and magnitude to those of O2 apneas. We conclude that in this model hypoxemia is a major but not the sole determinant of the pressor response during apneas. Hypercapnia cannot explain the pressor response seen when hypoxemia is abolished. The HR fall during apneas is independent of hypoxemia, hypercapnia and the pressor response.

Acute systemic blood pressure elevation in obstructive and nonobstructive breath hold in primates

Phasic blood pressure (BP) response during obstructive apnea (OA) in human sleep has been previously described as consisting of a slow incremental increase in BP to the point of apnea termination followed by a rapid rise and then fall in BP at the resumption of respiration. This rise in BP has been attributed to postapneic augmentation of cardiac output resulting after release of the marked negative intrathoracic pressure (NIP) of obstructed inspiration. Via an endotracheal tube, we created obstructed and nonobstructed breath hold (apnea) in chloralose-anesthesized baboons consisting of fixed-duration (30, 45, and 60 s) single OAs (mechanical obstruction) and nonobstructive (paralysis, ventilator cessation) apneas of matched duration and arterial desaturation. Systemic BP was measured before apnea (T0), during the last 5 s of apnea (T1), and during the first 5 s after resumption of respiration (T2). Despite wide fluctuations in NIP and BP during the T0 to T1 phase of OA, BP elevation in OA and nonobstructive apnea at T0, T1, or T2 did not differ for any duration apnea. At the release of obstruction, when resolution of NIP changes could theoretically increase cardiac output and accentuate BP, there was no difference in T1 and T2 pressures between the two conditions. We conclude that in this anesthesized animal model, mechanical (NIP) changes do not play a major role in overall maximum BP response to OA. Because of physiological differences between natural sleep in humans and the anesthetized state in animals, care must be taken in extrapolating these results to human sleep apnea.

Rate of Oxyhemoglobin Desaturation in Obstructive versus Nonobstructive Apnea

Preapneic thoracic gas volume (Vtg), arterial saturation (SaO2), and mixed venous oxygen saturation (SvO2), have been shown to influence the rate of SaO2 fall (dSaO2/dt) during apnea. We asked the following question: does tissue oxygen consumption (tVO2) affect the dSaO2/dt during apnea? We attempted to answer this question by comparing dSaO2/dt during obstructive apneas (high tVO2) with dSaO2/dt during nonobstructive apneas (low tVO2) in six adult baboons. Fiberoptic central venous and arterial catheters were used for continuous monitoring of SvO2, SaO2, and cardiac output. A sapphire-bearing turbine monitored minute ventilation and airflow cessation. A Respitrace and esophageal pressures were used to assess relative differences in Vtg. Obstructive apneas (30, 45, and 60-s) were created by clamping an indwelling cuffed endotracheal tube at end-expiration. Nonobstructive apneas were created by paralyzing the animals with atracurium and interrupting ventilation for periods equivalent to those of the obstructed apneas. The ventilator was adjusted to duplicate the respiratory rate, tidal volume, and relative Vtg of the spontaneously breathing animal. Mean tVO2 during spontaneous breathing was 110 ml/min (Fick method) and decreased to 90 ml/min during paralysis (p less than 0.05). The dSaO2/dt for the three apnea durations (mean, all animals), obstructive versus nonobstructed were: 0.85 and 0.74%/s (n = 6), 0.87 and 0.75%/s (n = 6), and 0.60 and 0.48%/s (n = 4), respectively. The dSaO2/dt was significantly lower during the nonobstructive apneas. We conclude that differences in VO2 during apnea may affect the dSaO2/dt and that for the same duration apnea, central apneas may show less desaturation than obstructive apneas where vigorous muscular efforts at overcoming obstruction are common.

Are Morning Headaches Part of Obstructive Sleep Apnea Syndrome?

To determine whether morning headaches are a consistent symptom in sleep apnea, we reviewed clinical and polysomnographic data of 304 patients with sleep apnea and compared the findings with normal control subjects and with three other groups of patients seen at a sleep disorders center. Eighteen percent of patients with sleep apnea had frequent morning headaches compared with 21% to 38% in the other groups of patients and 6% of control subjects. In patients with sleep apnea, morning headaches were most common in those with mild predominantly nonobstructive apnea. Polysomnographic characteristics of patients with moderate to severe sleep apnea did not significantly differ between patients with frequent headaches and those without such headaches. Frequent morning headaches are a nonspecific symptom in patients with sleep disorders and are not a consistent or reliable symptom of sleep apnea syndrome.

Continuous positive airway pressure selectively reduces obstructive apnea in preterm infants

Apnea in preterm infants has been classified as obstructive, central (nonobstructive), and mixed, based on the presence or absence of upper airway obstruction. Continuous positive airway pressure (CPAP) is widely used in apneic infants, although its mechanism of action is still unclear. To determine whether CPAP is equally effective in obstructive and nonobstructive apnea, we compared the types of apnea observed in 14 preterm infants during sequential 45-minute periods with and without CPAP. CPAP markedly decreased the incidence of both mixed and obstructive apnea episodes of greater than or equal to 5 seconds (P less than 0.01 and less than 0.03, respectively). In contrast, central apnea episodes of greater than or equal to 5 seconds were entirely unaffected by CPAP. Although minute ventilation was unchanged, transcutaneous PO2 increased by 11 +/- 11 mm Hg during CPAP whether or not apnea was present. We postulate that CPAP reduces apnea in preterm infants by relief of upper airway obstruction, possibly via splinting of the pharyngeal airway.

Oxygen Saturation during Breath-Holding and during Apneas in Sleep

The rate of fall in oxygen saturation is said to be greater during obstructive apneas than during breath-holding in wakefulness. Using an ear oximeter, a face mask and flowmeter, and measurements of thoracoabdominal motion, we determined in six healthy subjects the rate of fall in arterial oxygen saturation (SaO2) during breath-holding which simulated obstructive and nonobstructive apneas. Breath-holding maneuvers were performed during progressive isocapnic hypoxia and were initiated at the same end-expiratory thoracoabdominal configuration. We found that at any given initial SaO2 the rate of fall in SaO2 was similar during simulated obstructive (y = 5.5-0.06 x; r = 0.83) and nonobstructive (y = 6.8-0.07 x; r = 0.92) apneas. In two healthy subjects and 13 patients with obstructive and nonobstructive apneas during sleep, the rate of fall in SaO2 at any initial SaO2 was similar to that found in healthy subjects during breath-holding in wakefulness. We conclude that during wakefulness the presence or absence of respiratory efforts does not affect the rate of fall in SaO2 during breath-holding and that the rate of fall of SaO2 during sleep apnea is largely dependent on the initial SaO2 at the onset of apnea.