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Low tidal volume ventilation as a strategy for inducing lung fluid absorption in the preterm guinea pig

Koshy, Shyny

Abstract Details

2009, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Respiratory distress syndrome (RDS) is one of many ailments that affect preterm infants. This disease is characterized by impaired breathing caused by insufficient surfactant in the lungs and ion transport deficiencies. The main hypothesis for this project is that maternal stress hormone release is important for the regulation of fetal lung fluid absorption near term and that supportive low tidal volume ventilation is beneficial in the outcome of preterm guinea pigs at risk of developing RDS. The primary experimental focus of this project was to determine if stress hormones i.e., cortisol and epinephrine, release lead to fetal lung fluid absorption via epithelial sodium channel (ENaC) induction by the serum and glucocorticoid-regulated kinase (SGK)/neural precursor cell expressed, developmentally down-regulated protein 4-2 (Nedd4-2) pathway. The second experimental focus was to determine if different tidal volume-ventilation strategies affected distal lung fluid absorption via this pathway. My thesis was thus divided into principal sections, referred to as the lung development study and the ventilation study. In the lung development study, my principal findings demonstrated that the lungs of fetal guinea pigs at a gestation of 61 days (GD61; term=GD69), were still at the fluid-secretory stage, and lungs of GD68 fetuses were at the fluid absorptive stage. This developmental increase in distal lung fluid absorption corresponded to a cortisol-dependent regulation of SGK, Nedd4-2, and αENaC expression. In the ventilation study, my principal finding was that ventilation with low tidal volume (6 ml/kg body wt) improved distal lung fluid absorption in GD65-68 guinea pig fetuses. This observed induction in distal lung fluid clearance corresponded to a MAP kinase-dependent regulation of distal lung fluid absorption, as well as an induction of SGK/Nedd4-2 regulation of αENaC expression. Thus, the principal observation in this thesis suggests that low tidal volume-ventilation of preterm infants may be useful as a therapy to induce lung maturation and absorption of fetal lung fluid.
Hans Folkesson, PhD (Advisor)

Recommended Citations

Citations

  • Koshy, S. (2009). Low tidal volume ventilation as a strategy for inducing lung fluid absorption in the preterm guinea pig [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1247949798

    APA Style (7th edition)

  • Koshy, Shyny. Low tidal volume ventilation as a strategy for inducing lung fluid absorption in the preterm guinea pig. 2009. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1247949798.

    MLA Style (8th edition)

  • Koshy, Shyny. "Low tidal volume ventilation as a strategy for inducing lung fluid absorption in the preterm guinea pig." Doctoral dissertation, Kent State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=kent1247949798

    Chicago Manual of Style (17th edition)