The purpose of this research project is to study the role of neuromuscular transmission failure in the diaphragm and determine how this role changes with maturation. In addition, I will determine how neuromuscular transmission is modulated by chronic loading. My hypothesis is that neuromuscular transmission failure plays a significant role in the development of diaphragmatic fatigue in adults, and even more so in newborns.
My specific aims are to: 1) determine whether neuromuscular transmission failure occurs in-vivo in chronically instrumented awake adult sheep during acute inspiratory flow resistive loaded breathing; 2) study the maturational changes in neuromuscular transmission during acute inspiratory flow resistive loaded breathing in awake lambs (ages <1 wk, 2 wk, 4 wk and 8 wk) ; 3) determine whether chronic inspiratory flow resistive loading improves neuromuscular transmission in the diaphragm in adult and newborn sheep, Measurements of indices of diaphragmatic function and neuromuscular transmission in-vivo (Pdi, EMG, single unit action potentials, phrenic neurogram, ventilation, blood gases) will be done using state-of-the-art techniques. Since this proposal presents an integrated approach to the study of neuromuscular transmission failure ad a function of age, it is highly likely to generate new information which will have direct relevance to our understanding of respiratory muscle function and failure in early life.
| Bhandari, A; Xia, Y; Cortright, R et al. (2000) Effect of respiratory muscle training on GLUT-4 in the sheep diaphragm. Med Sci Sports Exerc 32:1406-11 |
| Akiyama, Y; Garcia, R E; Bazzy, A R (1996) Effect of inspiratory training on mitochondrial DNA and cytochrome-c oxidase expression in the diaphragm. Am J Physiol 271:L320-5 |
| Akiyama, Y; Garcia, R E; Prochaska, L J et al. (1994) Effect of chronic respiratory loading on the subunit composition of cytochrome c oxidase in the diaphragm. Am J Physiol 267:L350-5 |
