Clinical and experimental studies on the diaphragm during physiological and pathophysio-logical conditions

Abstract: The diaphragm is the most important respiratory muscle. It separates the thorax from the abdomen and it is innervated by phrenic nerve. The action of the diaphragm strongly depends on the combination of: the conductivity of the phrenic nerve; b) the developed force (pressure); c) the length at which it contracts; d) the velocity of short- ening and e) the level of activation.The general aim of this doctoral thesis is to study the diaphragm in different conditions in which different mechanical loads and/or different agents modified one or more of these factors in order to understand how the diaphragm copes with anesthesia, phrenic nerve injury, severe lung diseases and increasing abdominal load.In Study I, the movement induced by the diaphragm on tumor marker surrogate, being a source of noise while planning target volume during stereotactic body radiation ther- apy was quantified. High Frequency Jet Ventilation at a frequency of 200 min-1 seemed to be the best compromise between immobilization and gas exchange.In Study II, the role of the diaphragm during the emergence from anesthesia (namely, propofol) was investigated, finding no contribution because of active contraction of the expiratory muscles in this phase, presumably triggered by the resistance in the tracheal tube.In Study III, an animal model (porcine) of phrenic nerve damage was created and the compensatory mechanisms of non-diaphragmatic respiratory muscles studied. A 12- fold augmentation of the drive to ribcage muscles occurred during inspiration, while it almost doubled for abdominal muscles during expiration. Increasing level of pres- sure support ventilation masked these respiratory muscles strategy.Study IV described, within an integrated multidisciplinary longitudinal study, differ- ent functional aspects (geometry, weakness, force, mobility, contractility, electrical activity and kinematics) of the diaphragm before and after lung transplantation. A subclinical diaphragmatic dysfunction occurs after surgery, despite appropriate clini- cal course and respiratory outcome, induced by phrenic nerve neurapraxia secondary to surgical procedure.Study V was a non-invasive and longitudinal study of the progressive changes of the diaphragm during healthy pregnancy. During pregnancy, the diaphragm is condi- tioned to optimize its active role provided during parturition, as its co-contraction with abdominal muscles plays a fundamental role in the phase of baby expulsion.