Aging increases upper airway collapsibility in Fischer 344 rats.

The upper airway muscles play an important role in maintaining upper airway collapsibility, and the incidence of sleep-disordered breathing increases with age. We hypothesize that the increase in airway collapsibility with increasing age can be linked to changes in upper airway muscle mechanics and structure. Eight young (Y: 6 mo) and eight old (O: 30 mo) Fischer 344 rats were anesthetized and mechanically ventilated, and the pharyngeal pressure associated with flow limitation (Pcrit) was measured 1) with the hypoglossal (cnXII) nerve intact, 2) following bilateral cnXII denervation, and 3) during cnXII stimulation. With the cnXII intact, the upper airways of older rats were more collapsible compared with their younger counterparts [Pcrit = -7.1 +/- 0.6 (SE) vs. -9.5 +/- 0.7 cmH2O, respectively; P = 0.033]. CnXII denervation resulted in an increase in Pcrit such that Pcrit became similar in both groups (O: -4.2 +/- 0.5 cmH2O; Y: -5.4 +/- 0.5 cmH2O). In all rats, cnXII stimulation decreased Pcrit (less collapsible) in both groups (O: -11.3 +/- 1.0 cmH2O; Y: -10.2 +/- 1.0 cmH2O). The myosin heavy chain composition of the genioglossus muscle demonstrated a decrease in the percentage of the IIb isoform (38.3 +/- 2.5 vs. 21.7 +/- 1.7%; P < 0.001); in contrast, the sternohyoid muscle demonstrated an increase in the percentage of the IIb isoform (72.2 +/- 2.5 vs. 58.4 +/- 2.3%; P = 0.001) with age. We conclude that the upper airway becomes more collapsible with age and that the increase in upper airway collapsibility with age is likely related to altered neural control rather than to primary alterations in upper airway muscle structure and function.

Intermittent hypoxia reduces upper airway stability in lean but not obese Zucker rats.

Obstructive sleep apnea involves intermittent periods of airway occlusions that lead to repetitive oxygen desaturations. Exposure to chronic intermittent hypoxia (IH) in rats increases diurnal blood pressure and alters skeletal muscle physiology. The impact of IH on upper airway muscle function is unknown. We hypothesize that IH exposure increases upper airway collapsibility in rats due to alterations of the muscles surrounding the upper airway. Lean and obese rats were exposed to cyclic alterations in O(2) levels (20.6%-5%) every 90 s, 8 h/day for 6 days/wk for 12 wk. Following the exposure period, arterial pressure was recorded via the tail artery in conscious unrestrained rats. Mean arterial pressure was increased in lean IH but not in obese IH-exposed Zucker rats (P < 0.05). The pharyngeal pressure associated with airway collapse (P(crit)) was measured under anesthesia during baseline conditions and then during supramaximal stimulation of the hypoglossal nerve (cnXII). Baseline P(crit) was more positive (more collapsible) in lean but not obese rats following 12 wk of IH (P < 0.05), while supramaximal stimulation of cnXII increased airway stability (decreased P(crit)) in both lean and obese Zucker rats following IH to levels that were similar to their respective room air controls. The in vitro peak tension and the expression of the individual myosin heavy chain isoforms from the upper airway muscles were unaltered following IH. We conclude that IH leads to increases in baseline collapsibility in lean Zucker rats exposed to IH by nonmyogenic mechanisms.