Impact of Antenatal Chorioamnionitis, Postnatal Steroids and Mechanical Ventilation on the Preterm Diaphragm
The diaphragm functions as a critical factor in determining successful establishment of unsupported self-ventilation. The preterm diaphragm is weak, and can be further compromised by antenatal and early postnatal exposures such as impaired nutrition, steroids, chorioamnionitis, or postnatal mechanical ventilation (MV). These injuries are frequently associated with preterm birth, and often occur clinically together. I aim to investigate how these combined injuries e.g. antenatal inflammation/postnatal steroid with postnatal MV affect immature diaphragm integrity, and explore the fundamental mechanisms underlying such dysfunction.
I will perform the physiological studies (skin fibre and muscle fibre typing) to observe the functional and phenotypic change in the preterm lamb diaphragm. Further I will employ a series of molecular and cellular techniques including qPCR, Western blot, ELISA, immunohistochemical assay and biochemical assays to analyse the major contractile protein distribution, inflammatory response, oxidative stress, protein signalling and intracellular protein degradation pathways.
Why my research is important
The incidence of respiratory failure is higher in preterm babies than at any other time of life. A number of preterm babies need minimal breathing support at birth, but appear unable to sustain their breathing efforts and subsequently develop respiratory failure in the first week of life. Successfully weaning extremely preterm infants from MV is a major clinical challenge.
In the presence of clinically relevant stressors that may disrupt the fragile diaphragm integrity, this study will provide unique information on the susceptibility of the preterm diaphragm to various injuries and the underlying mechanisms.