Evening and morning blood gases in patients with obstructive sleep apnea.

BACKGROUND AND PURPOSE: The purpose of this study was to see if blood oxygen levels deteriorate overnight during obstructive sleep apnea (OSA). Before and after sleep, arterial blood gases (ABGs) in OSA subjects and controls were drawn during a diagnostic night, as well as during a continuous positive airway pressure (CPAP) night for the OSA subjects. PATIENTS AND METHODS: Subjects, both male and female, were referred to our sleep laboratory for symptoms of daytime somnolence. Subjects consisted of a control group (N=13) with a mean apnea hypopnea index (AHI) of 3.3 events/h and a study group (N=22) with a mean baseline AHI of 57 events/h. RESULTS: With the subject supine, resting room air ABGs were drawn at 'lights out' on the evening before (PM) nocturnal polysomnography and in the morning (AM) at discontinuation ('lights on') of the sleep study. In controls, PM PaO(2) (79.4+/-9.7 mmHg) was not significantly different from AM PaO(2) (80.2+/-8.9 mmHg, P=0.5). In apneic subjects, the PM PaO(2) was 78.7+/-7.2 mmHg compared to an AM PaO(2) of 72.6+/-8.3 mmHg (P<0.05). The AM PaO(2) after a night of CPAP treatment in the OSA subjects was 77.5+/-10.2 mmHg compared to the PM PaO(2) of 76.0+/-6.0 mmHg (NS). The PM and AM PaCO(2)s were not different in controls or in study subjects under baseline conditions. However, during titration with nasal CPAP, the PaCO(2) was significantly higher in the morning after CPAP treatment [43.1+/-4.8 vs. 46.1+/-4.8 mmHg, respectively (P<0.05)]. CONCLUSIONS: OSA subjects showed a fall in overnight resting oxygenation. This could be accounted for by overnight deterioration of gas exchange and is ameliorated by CPAP.

Sympathetic over activity in the etiology of hypertension of obstructive sleep apnea.

Beginning with modest clinical observations in 1984, a picture has evolved suggesting that sympathetic nervous system over activity may be responsible in part for the elevated blood pressure seen in obstructive sleep apnea patients. Early studies of urinary and plasma catecholamines indirectly suggested sympathetic over activity carried to daytime, non-apneic conditions. Later intra-neuronal recordings of muscle sympathetic nerve activity directly demonstrated both acute and diumal (non-apneic) sympathetic over activity. Most importantly, diurnal sympathetic over activity has been shown to diminish with adequate treatment of apnea using nasal CPAP. Norepinephrine and angiotensin II are both released with increased peripheral sympathetic activity and are parallel vascular growth-promoting factors. Thus, one would expect alterations in vascular structure and function in a state of chronic sympathetic over activity. While changes in peripheral vascular structure have not been demonstrated in hypertension of sleep apnea, changes in peripheral vascular responsiveness have. There is reduced response to acetylcholine and isoproterenol vasodilation, and to norepinephrine and angiotensin vasoconstriction in humans with sleep apnea. Some of these vascular reactivity changes are shown to reversed with chronic nasal CPAP treatment. Finally, complimentary to the above evidence in humans, there is indirect evidence of sympathetic over activity as well as differences in vascular reactivity in intermittent hypoxia challenged rats. We have made significant strides in the past 15-20 years towards understanding systemic hypertension related to sleep apnea, especially the role of the sympathetic nervous system. Future research will need to look at exact mechanism of sympathetic nervous system over activity, particularly how central nervous system pathways may undergo facilitation, leading to daytime over activity. Furthermore, the mechanisms of sustained hypertension in sleep apnea patients is almost certainly of multiple etiologies. There is no marker for separating sleep apnea patients with hypertension derived solely from intermittent hypoxia from other secondary causes. Perhaps endothelial cell molecular markers could help to identify patients at risk for cardiovascular change associated with snoring and apnea, as well to guide treatment. Finally, studies demonstrating microvascular changes in blood vessels are extremely difficult to do, but promise to yield important knowledge about cellular mechanisms and results of long-term treatment of sleep apnea on cardiovascular disease.

Blood pressure response to chronic episodic hypoxia: the renin-angiotensin system.

By using an inspired oxygen fraction that produces oxyhemoglobin desaturation equivalent to that seen in human sleep apnea, we have demonstrated that 35 days of recurrent episodic hypoxia (every 30 s for 7 h/day) results in an 8-13 mmHg persistent increase in diurnal systemic mean arterial blood pressure (MAP) in rats. Blockade of angiotensin II receptors (AT(1a)) eliminates this response. Separate groups of male Sprague-Dawley rats were fed high-salt (8%), ad libitum-salt, or low-salt (0.1%) diets for 7 wk: 2 wk of wash-in for baseline blood pressure measurement and 5 wk of experimental conditions. Rats in each salt group were subjected to episodic hypoxia whereas controls remained unhandled under normoxic conditions. MAP remained at basal levels in all nonepisodic hypoxia controls as well as high-salt-diet episodic hypoxia-exposed rats. Ad lib and low-salt episodic hypoxia rats showed an increase in MAP from 106 and 104 mmHg at baseline to 112 and 113 mmHg, respectively (P < 0.05). Whole kidney renin mRNA was suppressed in high-salt controls and episodic hypoxia rats, whereas kidney AT(1a) mRNA showed opposite changes. Suppression of the renin-angiotensin system with a high-salt diet blocks the increase in MAP in episodic hypoxia-challenged rats, in part by suppressing local tissue renin levels. Upregulation of the tissue angiotensin II system appears to be necessary for the chronic blood pressure changes that occur from episodic hypoxia.