Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC28
Chronic intermittent hypoxia does not affect upper airway dilator muscle function in aged male rats
R. Skelly1, A. Bradford2, K. O'Halloran1
1. School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. 2. Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Upper airway muscle dysfunction is implicated in obstructive sleep apnoea (OSA) - a common respiratory disorder. Chronic intermittent hypoxia (CIH), a central feature of OSA due to recurrent apnoea, causes oxidative stress which may well be the major culprit in the development of key morbidities associated with OSA. We have previously reported that CIH impairs upper airway muscle performance in adult male rats (1), an effect that is blocked by chronic antioxidant administration. Age is a major risk factor for the development of sleep-disordered breathing. As such, we sought to characterize the effects of CIH on pharyngeal dilator muscle function in aged male rats. We hypothesized that aged male rats would show increased susceptibility to CIH treatment. Aged (20 months) male Wistar rats were exposed to CIH (90s air/90s hypoxia - 5% O2 at the nadir resulting in arterial oxygen desaturation to ~80%) or sham (90s air/90s air) treatment for 8h/day for 9 days. Following treatments, isometric contractile and endurance properties of sternohyoid muscle bundles were examined at 35oC in vitro. Force-frequency relationship was assessed in response to electrical field stimulation across a range of stimulus frequencies (10-100Hz). Non-linear regression curve fitting was employed to determine the EF50 i.e. stimulus frequency producing 50% peak force. Performance was also assessed in response to repeated muscle stimulation in fatigue trials. Peak force was unaffacted by CIH treatment. Thus, specific force was 24±3 vs. 22±2 N/cm2, mean±SEM, sham (n=6) vs. CIH (n=7); P>0.05 (Student's t test). EF50 was not statistically different between the two groups (50±4Hz vs. 55±2Hz, sham vs. CIH). Furthermore, anoxic tolerance was equivalent in sham and CIH muscles. Performance during fatigue trials was similar in the two groups. In summary, CIH had no significant effect on sternohyoid muscle force in aged male rats, whereas respiratory muscle weakness occurs in response to this CIH paradigm in young adult rats (1). Thus, contrary to our hypothesis, aged muscle shows greater tolerance to hypoxia/re-oxygenation compared to young muscle. Upper airway collapsibility increases in aged rats (2) and CIH decreases airway stability in middle-aged rats (3). Taken together these studies support the notion that neurogenic, as opposed to myogenic, mechanisms contribute to age-related impairment in the control of upper airway patency.
Where applicable, experiments conform with Society ethical requirements