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Role of hypoxia in muscle function and muscular dystrophy
Author(s) -
Mosqueira Matias M,
Baby Santosh M,
Budak Murat,
Bogdanovich Sasha,
Willmann Gabriel,
Lahiri Sukhhamay,
Khurana Tejvir
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1224.12
Subject(s) - hypercapnia , hypoxia (environmental) , respiratory system , duchenne muscular dystrophy , hypoxic ventilatory response , peripheral chemoreceptors , mdx mouse , tidal volume , respiratory minute volume , medicine , ventilation (architecture) , control of respiration , respiration , muscular dystrophy , respiratory rate , physiology , biology , chemoreceptor , anatomy , chemistry , heart rate , dystrophin , blood pressure , mechanical engineering , receptor , organic chemistry , oxygen , engineering
Respiratory insufficiency contributes significantly to the morbidity and, is the commonest cause of mortality, in Duchene's muscular dystrophy (DMD). However, surprisingly little is known mechanistically about 1, basic respiratory physiology in the mdx (DMD‐mouse model) &, 2, effects of hypoxia (high altitude) on muscle function. To rigorously evaluate mdx respiration, we custom‐built a plethysmograph (with 1 microlitre sensitivity) and exposed awake adult mdx and control mice to graded levels of hypoxia and hypercapnia to determine respiratory rate (RR), tidal volume (V T ), and minute ventilation (V E ), HVR and HCVR. Additionally, phrenic nerve discharges were recorded from anesthetized mice to understand the integrated ventilatory response of central and peripheral chemoreceptors. Significant abnormalities were found in mdx mice respiratory parameters during normoxia as well as a blunting of the HVR reflex. Finally, we found anatomical, physiological and transcriptome‐level changes in muscle of animals exposed to hypoxia and high altitude (Mt. Marmolejo & Mt. McKinley). These observations support our hypotheses that dystrophic mice have respiratory abnormalities and that hypoxia itself may contribute as a ‘second‐hit’ to muscle patho‐physiology in DMD.