Impaired vascular regulation in patients with obstructive sleep apnea: effects of continuous positive airway pressure treatment

Abstract

Rationale: Impaired endothelium-dependent vasodilation has been documented in patients with sleep apnea. This impairment may result in blood flow dysregulation during apnea-induced fluctuations in arterial blood gases.

Objectives: To test the hypothesis that hypoxic and hypercapnic vasodilation in the forearm and cerebral circulation are impaired in patients with sleep apnea.

Methods: We exposed 20 patients with moderate to severe sleep apnea and 20 control subjects, to isocapnic hypoxia and hyperoxic hypercapnia. A subset of 14 patients was restudied after treatment with continuous positive airway pressure.

Measurements and main results: Cerebral flow velocity (transcranial Doppler), forearm blood flow (venous occlusion plethysmography), arterial pressure (automated sphygmomanometry), oxygen saturation (pulse oximetry), ventilation (pneumotachograph), and end-tidal oxygen and carbon dioxide tensions (expired gas analysis) were measured during three levels of hypoxia and two levels of hypercapnia. Cerebral vasodilator responses to hypoxia (-0.65 +/- 0.44 vs. -1.02 +/- 0.72 [mean +/- SD] units/% saturation; P = 0.03) and hypercapnia (2.01 +/- 0.88 vs. 2.57 +/- 0.89 units/mm Hg; P = 0.03) were smaller in patients versus control subjects. Hypoxic vasodilation in the forearm was also attenuated (-0.05 +/- 0.09 vs. -0.10 +/- 0.09 unit/% saturation; P = 0.04). Hypercapnia did not elicit forearm vasodilation in either group. Twelve weeks of continuous positive airway pressure treatment enhanced hypoxic vasodilation in the cerebral circulation (-0.83 +/- 0.32 vs. -0.46 +/- 0.29 units/% saturation; P = 0.01) and forearm (-0.19 +/- 0.15 vs. -0.02 +/- 0.08 units/% saturation; P = 0.003), and hypercapnic vasodilation in the brain showed a trend toward improvement (2.24 +/- 0.78 vs. 1.76 +/- 0.64 units/mm Hg; P = 0.06).

Conclusions: Vasodilator responses to chemical stimuli in the cerebral circulation and the forearm are impaired in many patients with obstructive sleep apnea. Some of these impairments can be improved with continuous positive airway pressure.

Figure 1.

Group mean values ± SE and individual subject vascular responses to isocapnic hypoxia in the brain (top) and forearm (bottom) in patients with obstructive sleep apnea (OSA) and control subjects (CON). In OSA, hypoxic vasodilation in both vascular beds was attenuated (P = 0.03 and 0.04).

Figure 2.

Individual subject values for the slope representing the stimulus–response relationship between arterial oxygen saturation (Sa_O2) and vascular conductance in the brain (left) and forearm (right). Note that although the means were significantly different, there was considerable overlap between the patient and control groups. *P < 0.05, obstructive sleep apnea (OSA) versus control subjects (CON).

Figure 3.

Group mean values ± SE and individual subject vascular responses to hyperoxic hypercapnia in the brain (top) and forearm (bottom) in patients with obstructive sleep apnea (OSA) and control subjects (CON). Hypercapnic vasodilation in the cerebral circulation was attenuated in OSA versus CON (P = 0.03), whereas in the forearm, the slopes were comparable (hypercapnia did not cause vasodilation in either group).

Figure 4.

Individual subject values for the slope representing the stimulus–response relationship between Pet_CO2 and vascular conductance in the brain (left) and forearm (right). Note that although the mean values for cerebrovascular responsiveness were significantly different, there was considerable overlap between the patient and control groups. In the forearm, the slopes were comparable in the two groups. *P < 0.05, OSA versus CON.

Figure 5.

Effects of continuous positive airway pressure (CPAP) on hypoxic and hypercapnic vasodilation in the brain and forearm (means ± SE; n = 12). CPAP elicited improvements in hypoxic vasodilation in both vascular beds that was evident after 6 weeks of treatment. No statistically significant changes in hypercapnic vasodilation were observed; however, there was a trend toward improvement in hypercapnic cerebral vasodilation (P = 0.06). *P < 0.05 versus pre-CPAP. Note that the negative slopes for hypoxic vasodilation have been changed to positive slopes to aid in visual comparison.