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Effects of Gestational and Postnatal Exposure to Chronic Intermittent Hypoxia on Diaphragm Muscle Contractile
Fiona B McDonald1, Eugene M Dempsey2, Ken D O'Halloran3
1Department of Physiology, School of Medicine and Medical Science, University College Dublin Dublin, Ireland.
Insights
Early life exposure to chronic intermittent hypoxia (CIH) did not impair diaphragm muscle function in rats. This suggests the diaphragm is relatively resilient to hypoxic stress, unlike upper airway muscles.
Area of Science:
- Physiology
- Respiratory Medicine
- Developmental Biology
Background:
- Early life oxygen supply alterations cause lasting physiological stress.
- Chronic intermittent hypoxia (CIH), seen in apnea and lung disease, impacts respiratory control.
- Limited data exists on CIH effects on respiratory muscles, particularly the diaphragm.
Purpose of the Study:
- To investigate the impact of gestational CIH (gCIH) and postnatal CIH (pCIH) on diaphragm muscle function in male and female rats.
- To assess diaphragm muscle contractile and endurance properties following early-life CIH exposure.
- To determine if early-life CIH affects diaphragm muscle tolerance to severe hypoxic stress.
Main Methods:
- Rats were exposed to CIH (90s hypoxia to 5% O2 every 5 min, 8h/day) during gestation (gCIH) or postnatally (pCIH).
- Diaphragm muscle function (force, endurance, hypoxic tolerance) was assessed ex vivo in adulthood (postnatal days 22 or 42).
- Sham groups exposed to normoxia served as controls.
Main Results:
- Neither gCIH nor pCIH affected diaphragm muscle force-generating capacity or endurance in either sex.
- Early-life CIH exposure did not alter diaphragm muscle tolerance to severe hypoxic stress ex vivo.
- These findings contrast with previous observations of upper airway dilator muscle weakness after pCIH.
Conclusions:
- The diaphragm muscle exhibits relative resilience to early-life chronic intermittent hypoxia.
- A potential mismatch in muscle capacity between the diaphragm and upper airway dilators could impact airway patency and respiratory homeostasis.
- Further research is needed to understand the implications of differential muscle responses to early-life hypoxia.
Abstract:
Alterations to the supply of oxygen during early life presents a profound stressor to physiological systems with aberrant remodeling that is often long-lasting. Chronic intermittent hypoxia (CIH) is a feature of apnea of prematurity, chronic lung disease, and sleep apnea. CIH affects respiratory control but there is a dearth of information concerning the effects of CIH on respiratory muscles, including the diaphragm-the major pump muscle of breathing. We investigated the effects of exposure to gestational CIH (gCIH) and postnatal CIH (pCIH) on diaphragm muscle function in male and female rats. CIH consisted of exposure in environmental chambers to 90 s of hypoxia reaching 5% O2 at nadir, once every 5 min, 8 h a day. Exposure to gCIH started within 24 h of identification of a copulation plug and continued until day 20 of gestation; animals were studied on postnatal day 22 or 42. For pCIH, pups were born in normoxia and within 24 h of delivery were exposed with dams to CIH for 3 weeks; animals were studied on postnatal day 22 or 42. Sham groups were exposed to normoxia in parallel. Following gas exposures, diaphragm muscle contractile, and endurance properties were examined ex vivo. Neither gCIH nor pCIH exposure had effects on diaphragm muscle force-generating capacity or endurance in either sex. Similarly, early life exposure to CIH did not affect muscle tolerance of severe hypoxic stress determined ex vivo. The findings contrast with our recent observation of upper airway dilator muscle weakness following exposure to pCIH. Thus, the present study suggests a relative resilience to hypoxic stress in diaphragm muscle. Co-ordinated activity of thoracic pump and upper airway dilator muscles is required for optimal control of upper airway caliber. A mismatch in the force-generating capacity of the complementary muscle groups could have adverse consequences for the control of airway patency and respiratory homeostasis.
