A new model of chronic intermittent hypoxia in humans: effect on ventilation, sleep, and blood pressure

Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas R, Levy P, Weiss JW. A new model of chronic intermittent hypoxia in humans: effect on ventilation, sleep, and blood pressure. J Appl Physiol 107: 17-24, 2009. First published February 19, 2009; doi: 10.1152/japplphysiol. 91165.2008.-Obstructive sleep apnea is characterized by repetitive nocturnal upper airway obstructions that are associated with sleep disruption and cyclic intermittent hypoxia (CIH) The cyclic oscillations in O-2 saturation are thought to contribute to cardiovascular and other morbidity, but animal and patient studies of the pathogenic link between CIH and these diseases have been complicated by species differences and by the effects of confounding factors such as obesity, hypertension, and impaired glucose metabolism. To minimize these limitations, we set up a model of nocturnal CIH in healthy humans. We delivered O-2 for 15 s every 2 min during sleep while subjects breathed 13% O-2 in a hypoxic tent to create 30 cycles/h of cyclic desaturation-reoxygenation [saturation of peripheral O-2 (SpO(2)) range: 95-85%]. We exposed subjects overnight for 8-9 h/day for 2 wk (10 subjects) and 4 wk (8 subjects). CIH exposure induced respiratory disturbances (central apnea hypopnea index: 3.0 +/- 1.9 to 31.1 +/- 9.6 events/h of sleep at 2 wk). Exposure to CIH for 14 days induced an increase in slopes of hypoxic and hypercapnic ventilatory responses (1.5 +/- 0.6 to 3.1 +/- 1.21.min(-1).% drop in Sp(O2) and 2.2 +/- 1.0 to 3.3 +/- 0.91.min(-1).mmHg CO2-1, respectively), consistent with hypoxic acclimatization. Waking normoxic arterial pressure increased significantly at 2 wk at systolic (114 +/- 2 to 122 +/- 2 mmHg) and for diastolic at 4 wk (71 +/- 1.3 to 74 +/- 1.7 mmHg). We propose this model as a new technique to study the cardiovascular and metabolic consequences of CIH in human volunteers.