This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abstract: Prenatal steroids are now routinely used in the care of women that show signs or have risk factors for giving birth to their fetuses prematurely. It is known that these prenatal steroids stimulate lung development and surfactant production and that the increased maturity of the lungs at birth is at least partially responsible for the decreased incidence of respiratory distress syndrome (RDS) in steroid-treated premature infants. However, studies of the effects of these steroids on fetal, juvenile, and adult skeletal muscle suggest that the maturation and function of the ventilatory muscles may be detrimentally affected by prenatal steroid exposure. Therefore, the purpose of this study is to determine the effects of prenatal steroid treatment on the development of guinea pig ventilatory muscles. We propose to test the hypotheses that prenatal steroids lead to changes in (1) the fiber type profiles, (2) myosin heavy chain (MHC) expression patterns, (3) fiber sizes, and (4) the functional abilities of guinea pig (Cavia porcellus) ventilatory muscles. Pregnant Hartley (Crl:(HA)BR) guinea pigs will be injected twice (24 hours apart) intramuscularly with betamethasone (0.5 mg/kg body weight) or saline at forty-seven days gestation. The fetuses will then be delivered 24 hours after the final injection. Histochemical and immunocytochemical methods will be used to compare the fiber type profiles and MHC isoform expression patterns of six ventilatory muscles in steroid treated and untreated infants to determine if prenatal steroid exposure leads to decreases in the percentages of fast-twitch fibers and in the expression of developmental myosins. Fiber diameters will be measured to determine if betamethasone leads to atrophy. To determine if the functional abilities of treated muscles are detrimentally affected, the maximum tetanic forces (per cross-sectional area) and maximal unloaded shortening velocities of the fibers making up these muscles will be measured. The treated ventilatory muscles of premature infants may not be able to adequately power breathing, and the decreases in functional abilities may lead to further respiratory complications in prenatal steroid exposed neonates. If this study demonstrates that there are morphological changes in the betamethasone-treated muscles and that these changes lead to decreases in the abilities of these muscles to contract quickly and produce force, these findings will have implications for the treatment and support of neonates after they are born.
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