Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA086

Poster Communications

Effects of chronic intermittent hypoxia on breathing, metabolism and diaphragm muscle contractile properties in adult male mice

S. Drummond1, D. P. Burns1, K. D. O' Halloran1

1. Physiology, University College Cork, Cork, Cork, Ireland.


Chronic intermittent hypoxia (CIH), a dominant feature of sleep-disordered breathing in humans, is considered a major driving force in the development and elaboration of cardiorespiratory morbidity. Transgenic mouse models provide opportunity to explore fundamental mechanisms of CIH-induced aberrant plasticity, but at present data in mouse models is limited. We sought to investigate the effects of CIH on breathing, metabolism and diaphragm muscle contractile and endurance properties in a common laboratory mouse strain. Male C57/Bl6J mice (12 weeks) were exposed to normoxia (n=12) or 14 consecutive days of CIH (n=12) consisting of alternating cycles of normoxia (210s) and hypoxia (90s; 5% at the nadir), 12 times per hour, for 8 hours each day during light hours. Food and water were available ad libitum and mice were group housed in standard cages placed in custom environmental chambers with precise control of ambient O2 concentration. Following gas exposures, breathing was determined in unanesthetized, unrestrained mice by plethysmography. Ventilation, oxygen consumption and CO2 production were determined breathing air, hypoxia (FiO2=0.1) and hyperoxic hypercapnia (FiCO2=0.05 in oxygen). Diaphragm muscle isometric and isotonic contractile parameters were determined ex vivo. Body weight was decreased (p=0.01; unpaired t test) and haematocrit was increased (p=0.02) in animals exposed to CIH compared with normoxic controls. Ventilation (VE; 1.23 ± 0.13 versus 1.32 ± 0.12 ml/min/g) and metabolism (VCO2; 0.03 ± 0.01 versus 0.03 ± 0.01 ml/min/g) during air breathing was not different in control and CIH-exposed animals. Diaphragm twitch force (2.62 ± 0.89 versus 1.63 ± 0.31* N/cm2, n=8 per group), peak tetanic force (22.63 ± 5.55 versus 12.48 ± 2.32* N/cm2), peak work (1.57 ± 0.81 versus 0.58 ± 0.27* J/cm2), peak power (14.70 ± 8.13 versus 6.03 ± 3.15* W/cm2), peak shortening (0.35 ± 0.06 versus 0.30 ± 0.08 L/Lo), and peak shortening velocity (4.78 ± 1.57 versus 3.56 ± 1.21 Lo/s) were decreased (p<0.05*) in CIH-exposed animals compared with normoxic controls. Values are mean ± S.D. Our results reveal that exposure to CIH causes profound diaphragm muscle weakness without overt disruption to resting ventilation (including pattern of breathing) and metabolism. The striking muscle phenotype in the C57 mouse provides a robust platform for the study of mechanisms of hypoxia-related muscle dysfunction, which may have relevance to respiratory conditions characterised by CIH such as sleep apnoea.

Where applicable, experiments conform with Society ethical requirements