Proceedings of The Physiological Society
University College Dublin (2009) Proc Physiol Soc 15, PC57
Effects of Hypoxia on Geniohyoid Muscle Force and Endurance in Young Lean and Old Obese Male Rats
E. Lucking1, K. D. O'Halloran1
1. University College Dublin, Dublin, Ireland.
Age, obesity and male sex are independent risk factors for the development of obstructive sleep apnoea (OSA). Upper airway dilator muscle fatigue is implicated in the pathophysiology of OSA. As antioxidant capacity decreases with age, we speculated that old obese rats would show decreased endurance and hypoxic tolerance. Young (2-3 month old), lean (268±10g), male Wistar rats (n=14) and old (19-20 months), obese (822±41g), male Wistar rats (n=14) were used in this study. Rats were killed humanely, under 5% isoflurane, by high cervical spinal cord transection. Isometric contractile properties of isolated geniohyoid muscles were examined at 350C under control (95%O2/5%CO2) or hypoxic (95%N2/5%CO2) conditions. Force-frequency relationship was determined at stimulus frequencies ranging 10-100Hz. Curve-fitting analysis was employed allowing us to determine the values for min, max, slope and EF50 (i.e. stimulus frequency producing 50% of peak force). Fatigue was assessed by repeated stimulation of the muscle (40Hz, 300ms, every 2 sec for 3 min). Two-way analysis of variance (with Bonferroni correction) was employed to test for statistically significant effects of age and hypoxia. Geniohyoid muscle max force was 6.9±1.5 and 4.2±0.6 N/cm2, mean±SEM, control (n=7) and hypoxia (n=7). Corresponding values in young rats were 4.0±0.9 and 1.2±0.3 N/cm2 (p>0.05 ANOVA). The EF50 values were left-shifted in old compared to young animals (p<0.01 in hypoxia alone). Geniohyoid 3min fatigue index in old rats was 48±4% and 7±1%, [% of initial force, control (n=7) and hypoxia (n=7)]. Corresponding values in young rats were 78±6% and 24±4%. There was a statistically significant effect of age (p<0.001) and hypoxia (p<0.01), but no significant interaction. Force potentiation in the early phase of the fatigue trial was observed in all groups but was significantly greater in old compared to young animals in hyperoxia [186±9% vs. 146±8%, % of initial force, old (n=7) vs. young (n=7), p<0.01] but not hypoxia. Taken together, muscle performance (i.e. average force/initial force x 100) during repeated stimulation was not significantly different in old and young animals, though values were noticeably lower in hypoxia (62±6% vs. 79±2%, % of initial, old vs. young). This study illustrates that age (and/or) obesity causes plasticity in an upper airway dilator muscle. Though intrinsic fatigability of the geniohyoid decreased significantly with age both in hyperoxia and hypoxia, it should be noted that the muscles from old obese rats generated more force under hypoxic conditions than young animals, and this was largely maintained during repeated stimulation. We conclude that increased pharyngeal collapsibility associated with age and obesity relates more to neurogenic than myogenic impairment.
Where applicable, experiments conform with Society ethical requirements