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Developmental changes in diaphragm muscle function in the preterm and postnatal lamb
1School of Anatomy, Physiology, and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia.
Insights
The preterm lamb diaphragm shows immature function, increasing fatigue susceptibility. Diaphragm development improves contractile force but initially heightens fatigue risk, impacting respiratory outcomes.
Area of Science:
- Physiology
- Developmental Biology
- Respiratory Medicine
Background:
- The preterm diaphragm's immaturity is linked to respiratory distress and failure.
- Understanding diaphragm development is crucial for preventing respiratory disorders.
Purpose of the Study:
- Investigate developmental changes in fetal lamb costal diaphragm contractile function.
- Assess diaphragm susceptibility to fatigue across different maturational stages.
Main Methods:
- Studied lambs at various postconceptional ages (75-200 days).
- Assessed muscle fiber contractile function.
- Analyzed myosin heavy chain (MHC) mRNA and protein expression.
Main Results:
- Maximal specific force increased with fetal development.
- Diaphragm susceptibility to fatigue increased during fetal development.
- Postnatal development showed decreased fatigue susceptibility and increased MHC I:II protein ratio.
Conclusions:
- Diaphragm functional capacity changes significantly with maturational age.
- These maturational changes are key determinants of preterm respiratory failure susceptibility.
Rationale:
The preterm diaphragm is structurally and functionally immature, potentially contributing to an increased risk of respiratory distress and failure. We investigated developmental changes in contractile function and susceptibility to fatigue of the costal diaphragm in the fetal lamb to understand factors contributing to the risk of developing diaphragm dysfunction and respiratory disorders. We hypothesized that the functional capacity of the diaphragm will vary with maturational stage as will its susceptibility to fatigue.
Methods:
Lambs were studied at 75, 100, 125, 145, 154, 168, and 200 days postconceptional age (term = 147 days). Lambs were euthanized (sodium pentobarbitone, 100 mg/kg) either at delivery or immediately prior to post-mortem for postnatal lambs. Contractile function was assessed on longitudinal strips of intact muscle fibers and the remaining tissue frozen in liquid nitrogen for analysis of myosin heavy chain (MHC) mRNA expression and protein content.
Results:
Fetal development of diaphragm function was characterized by a significant increase in maximum specific force, increased susceptibility to fatigue, reduced twitch contraction times, and a progressive increase in MHCI and MHCII protein content. Postnatally, there was a progressive decrease in the susceptibility to fatigue that coincided with an increase in the MHC I:II protein ratio.
Conclusion:
These data indicate that the functional capacity of the diaphragm varies with maturational age and may be an important determinant of the susceptibility to preterm respiratory failure.
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