Model-based stability assessment of ventilatory control in overweight adolescents with obstructive sleep apnea during NREM sleep.

Obstructive sleep apnea (OSA) involves the interplay of several different factors such as an unfavorable upper airway anatomy, deficiencies in pharyngeal muscle responsiveness, a low arousal threshold, and ventilatory control instability. Although the stability of ventilatory control has been extensively studied in adults, little is known about its characteristics in the pediatric population. In this study, we developed a novel experimental setup that allowed us to perturb the respiratory system during natural non-rapid eye movement (NREM) sleep conditions by manipulating the inspiratory pressure, provided by a bilevel pressure ventilator, to induce sighs after upper airway stabilization. Furthermore, we present a modeling framework that utilizes the noninvasively measured ventilatory responses to the induced sighs and spontaneous breathing data to obtain representations of the processes involved in the chemical regulation of respiration and extract their stability characteristics. After validation with simulated data, the modeling technique was applied to data collected experimentally from 11 OSA and 15 non-OSA overweight adolescents. Statistical analysis of the model-derived stability parameters revealed a significantly higher plant gain and lower controller gain in the OSA group (P = 0.046 and P = 0.007, respectively); however, no differences were found in loop gain (LG) and circulatory time delay between the groups. OSA severity and LG, within the 0.03-0.04-Hz frequency band, were significantly negatively associated (r = -0.434, P = 0.026). Contrary to what has been found in adults, our results suggest that in overweight adolescents, OSA is unlikely to be initiated through ventilatory instability resulting from elevated chemical loop gain.

Development of autonomic dysfunction with intermittent hypoxia in a lean murine model.

Intermittent hypoxia (IH) has been previously shown in a lean murine model to produce sustained hypertension and reverse the diurnal variation of blood glucose (BG). Concomitant glucose infusion attenuated the hypertension but exacerbated the BG fluctuations. In this study, cardiovascular variability analysis was employed to track the development of autonomic dysfunction in mice exposed to room air (IA) or IH, in combination with saline or glucose infusion. Baroreflex sensitivity was found to decrease in all animals, except in the control group. Low-frequency power of pulse interval spectrum, reflecting vagal activity, decreased more rapidly in glucose relative to saline while low-frequency power of blood pressure, reflecting sympathetic activity, decreased more slowly in IH relative to IA. Ultradian (≈ 12 h) rhythmicity was substantially suppressed in IH groups. These findings suggest that IH acted to increase sympathetic activity while glucose infusion led to reduced parasympathetic activity. The combination of IH and hyperglycemia leads to progressively adverse effects on autonomic control independent of obesity.