SEMINAR: Diaphragm function during development and disease

The diaphragm is the major component of the respiratory muscle pump and is rhythmically active throughout life, from the moment of birth until our final breath. So the functional capacity of the diaphragm is critically important for achieving its life-sustaining role in ventilation. Appropriate in utero development of the diaphragm is essential for the establishment of spontaneous breathing at birth; respiratory capacity can be a limiting factor for exhaustive exercise; and respiratory muscle weakness is associated with increased morbidity and mortality in critically ill patients. In this seminar I will present an overview of our research investigating diaphragm contractile function during development and disease. Using an ovine model of preterm birth, and rodent models of diaphragm immaturity, we have identified unique activation properties of the neonatal diaphragm, characterized the rapid adaptation of the diaphragm immediately after birth, and established the impact of common, clinically relevant in utero exposures on the functional integrity of the diaphragm. I will also present some of our recent work characterising the vulnerability of the diaphragm to contractile dysfunction in several animal models of human diseases. These studies highlight the important contribution of diaphragm dysfunction to respiratory disorders and provide insight into potential treatment strategies that aim to preserve diaphragmatic function.