The effects of intermittent hypoxia and age on upper airway mechanics

Abstract

Obstructive sleep apnea (OSA) is correlated to obesity and increasing age. Occlusion of the airway is associated with decreased airflow and oxygen de-saturation. Hypoxia and aging impact the structure and function of skeletal muscle. The purpose of the following dissertation was to study the effects of intermittent hypoxia (IH) and aging on upper airway stability. Study 1 exposed lean Zucker rats to IH (Ln-RA, n=12, Ln-IH, n=11), study 2 investigated the effects of obesity (Ob-RA, n=10, Ob-IH, n=8), whereas study 3 investigated aging on upper airway stability in Fischer 344 rats (6 month old, n=8 vs. 30 month old, n=8). Animals were exposed to intermittent hypoxia for 90 seconds on/90 seconds off, 8 hours a day/6 days a week for 12 weeks. Fischer rats from study 3 were not exposed to long term IH. Blood pressure was recorded via the tail artery in freely moving rats. Rats were then anesthetized, mechanically ventilated, and the pharyngeal pressure associated with airflow limitation (Pcrit) was measured. Long term IH significantly increased Pcrit (more collapsible) (LnRA = -6.7 cmH 2 O ± 1.2 (SEM) vs. Ln-IH = -5.3 ± 0.9) and mean arterial blood pressure (Ln-RA = 96 mmHg ± 3.6 vs. Ln-IH = 109 ± 4.2) in lean Z. rats. However, airway collapsibility (Ob-RA = -3.0 cmH 2 O ± 0.8 vs. Ob-IH = -3.0 ± 0.3) and mean arterial pressure (Ob-RA =101 mmHg ± 4.3 vs. Ob-IH = 99 ± 6.0) were not altered following long term IH in obese Z. rats. In addition, older Fischer rats demonstrated a more collapsible UA compared to their young counterparts (-7.1 cmH 2 O ± 0.6 versus -9.5 ± 0.7, respectively, p=0.033). Upper airway muscle structure, measured by the expression of the myosin heavy chain isoforms was not significantly altered following exposure to long term IH or as a result of the aging process. In summary, structural changes to the UAM following long term IH or the aging process do not contribute to the decrease in airway stability. Therefore, we suggest alterations in the control of the upper airway muscles may contribute to the decrease in airway stability in patients with OSA.