Proceedings of The Physiological Society
University College Dublin (2009) Proc Physiol Soc 15, PC56
Intermittent Hypoxia Impairs Rat Upper Airway Muscle Function: Protective Effects of a Superoxide Scavenger
S. Coyle-Rowan1, K. D. O'Halloran1
1. University College Dublin, Dublin, Ireland.
Upper airway muscle dysfunction is implicated in obstructive sleep apnoea, a debilitating respiratory disorder associated with cardiovascular and neurocognitive morbidities. Hypoxia-reoxygenation is a central feature of the disorder due to recurrent apnoea. We wished to characterize the effects of hypoxia (H), intermittent hypoxia (IH) and hypoxia-reoxygenation (HR) on pharyngeal dilator muscle function in adult male rats. As reactive oxygen species are implicated in skeletal muscle dysfunction, we hypothesized that antioxidant treatment would ameliorate the deleterious effects of (intermittent) hypoxia. Rats were killed humanely, under 5% isoflurane, by cervical spinal cord transection. Isometric contractile properties of isolated sternohyoid muscle strips were examined at 35OC under control (95%O2/5%CO2) or test conditions i.e. [H = 95%N2/5%CO2; IH = 3 cycles of 5 min control/5 min H; or HR = 15 min H/15 min control) in vitro in standard physiological salt solution with or without 10mM Tempol (a superoxide scavenger). All muscle strips were set to optimum length (i.e. length producing maximum isometric twitch force). After an equilibration period, peak tetanic force at 100Hz was determined under control conditions before drug or gas treatment. Next, muscles were randomly assigned to groups. After a 30 min incubation period, force-frequency relationship was determined by electrical field stimulation with stimulus frequencies ranging 10-100Hz. Forces in all trials were expressed relative to peak force measured at the beginning of each experiment (% of initial). All gas treatments caused significant decreases in sternohyoid muscle force compared to control (e.g. 89±9 vs. 28±4*, 61±7* and 60±8*, mean±SEM at 100Hz, % of initial, control (n=7) vs. H (n=8), IH (n=9) and HR (n=8), *p≤0.01 ANOVA). Likewise, muscle performance during repeated stimulation (40Hz, 300msec, every 2 sec for 150 sec), performed after force-frequency trials, was significantly impaired by all gas treatments. Antioxidant treatment with Tempol partly ameliorated the decline in muscle force in all groups (e.g. 86±9 vs. 44±7*, 70±5 and 69±13, mean±SEM at 100Hz, % of initial, control (n=7) vs. H (n=8), IH (n=9) and HR (n=8), *p<0.05 ANOVA). Additionally, Tempol rescued sternohyoid forces during the fatigue trial in IH and HR treated muscles such that they were not different from control values. Our results indicate that acute hypoxia and hypoxia/reoxygenation impairs pharyngeal dilator muscle function. Antioxidant treatment ameliorates these effects suggesting that reactive oxygen species-dependent mechanisms are implicated. As upper airway muscle dysfunction is implicated in OSA, we speculate that antioxidant supplementation might prove useful as an adjunct therapy in the treatment of the disorder.
Where applicable, experiments conform with Society ethical requirements