Proceedings of The Physiological Society
University of Birmingham (2010) Proc Physiol Soc 20, C13 and PC13
Effects of chronic intermittent hypoxia on rat respiratory muscle structure and function
C. Shortt1, K. O'Halloran1, A. Bradford2
1. University College Dublin, Dublin, Ireland. 2. Royal College of Surgeons, Dublin, Ireland.
Chronic intermittent hypoxia (CIH) is a dominant feature of sleep-disordered breathing (SDB) due to recurrent apnoea (respiratory pauses). It is recognized that respiratory muscles have enormous capacity for remodelling. Respiratory muscle weakness and fatigue contributes to impaired respiratory homeostasis. Despite the clinical relevance, the effects of CIH on respiratory muscle function are relatively underexplored. Therefore, this study was designed to investigate the effect CIH on rat respiratory muscle structure and function. Adult male Wistar rats were exposed to CIH (90s normoxia/ 90s hypoxia [5% oxygen at the nadir; SaO2 ~ 80%], 8h/day) for two weeks. Sham treatments were conducted in separate animals in parallel as controls. Following exposure, the animals were anaesthetized with 5% isoflurane and killed by spinal transection. Sternohyoid and diaphragm muscle contractile and endurance properties were examined in vitro at 35°C under hyperoxic (95% O2/ 5% CO2) and anoxic (95% N2/ 5% CO2) conditions. Additionally, muscle was snap frozen and stored for structural analysis (immunofluorescence and enzymatic histochemistry). CIH decreased diaphragm force (18.1±1.7 vs. 14.5±1.9 N/cm2, sham (n=8) vs. treated (n=7) at 100 Hz, mean±SEM, P=0.0034, ANOVA) and decreased diaphragm endurance (52±5% vs 38±3%, sham (n=8) vs CIH (n=6), mean±SEM, % of initial force at 2 mins, P<0.0001, ANOVA). Anoxic tolerance was increased in CIH diaphragm. Areal density of fibres expressing SERCA 1 and SERCA 2 was similar in sham and CIH muscle. There was an increase in type 2B fibre density (5.4±1.5% vs. 13.7±3.8% areal density, sham (n=5) vs. treated (n=5), P=0.08). CIH did not alter the SDH or GPDH activity of the diaphragm. Sternohyoid muscle force was increased (11.8±1.3 vs. 15.3±1.5 N/cm2, sham (n=8) vs. treated (n=7) at 100 Hz, P<0.001, ANOVA) following CIH treatment, while sternohyoid muscle endurance was decreased (16.5±1.3% vs 11.1±1.6%, sham (n=8) vs CIH (n=7), P=0.08, ANOVA). Under anoxic conditions, CIH reduced muscle force but did not affect muscle endurance. There was no significant change in sternohyoid fibre-type, SDH or GPDH activity. We conclude that 2 weeks of CIH induces respiratory muscle remodelling. CIH had a differential effect on diaphragm and sternohyoid muscle force. We speculate that these opposing effects are due to the stark contrast in muscle composition, as diaphragm is predominantly a slow oxidative muscle, while sternohyoid is primarily a fast glycolytic muscle. CIH caused both respiratory muscles to become more fatigable. Respiratory muscle fatigue may have deleterious consequences for respiratory homeostasis in vivo. Our results may be relevant to respiratory disorders characterized by recurrent hypoxaemia such as the sleep apnoea syndrome.
Where applicable, experiments conform with Society ethical requirements