Ultrasonography for the assessment of contractile properties of fresh and fatigued diaphragm muscle in healthy humans

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonContractile function of the diaphragm is characterised by its ability to shorten, generate force, produce power and perform work. Due to the diaphragm’s inaccessibility, these attributes are typically measured as the pressure difference across the diaphragm in response to twitch stimulation of phrenic nerves (i.e., twitch transdiaphragmatic pressure [ΔPdi,tw]). This technique, however, provides limited information concerning the muscle’s ability to shorten under load and to produce power. The overarching aim of this thesis was to determine whether ultrasound imaging could be used to elucidate the in vivo contractile properties of fresh and fatigued diaphragm muscle in healthy humans. Chapter 4 and 5 evaluated the feasibility, validity and intra-observer reliability of ultrasound-derived measures of crural diaphragm excursion, excursion velocity and power (i.e., kinetics) and costal diaphragm shortening in response to nerve stimulation, sniffs and hypercapnic hyperpnoea. Diaphragm kinetics and shortening exhibited good-to-excellent within-day reliability, with ultrasound acquisition during hyperpnoea unaffected by increasing tidal volume. Chapter 6 compared diaphragm contractile properties during CO2- vs. exercise-induced hyperpnoea, thereby elucidating the mechanisms that underpin postural-ventilatory modulation of the diaphragm. Compared to CO2-rebreathe, exercise evoked greater Pdi (17 ± 9 vs. 20 ± 8 cmH2O, p = 0.03; mean ± SD) but less diaphragm excursion (3.4 ± 1.1 vs. 2.5 ± 1.2 cm, p < 0.001), despite similar levels of ventilation. Thus, the diaphragm may be constrained during exercise due to quasi-isometric contractions required for modulating postural and ventilatory tasks. Chapter 7 assessed the effect of external loading (pressure and flow) on diaphragm kinetics and force to elucidate the mechanisms that underpin task-dependency of diaphragm fatigue. Pressure-loading, but not flow-loading, elicited a decline in ΔPdi,tw (–13%, p = 0.013) and excursion velocity (–39%; p = 0.043) with a subsequent decline in diaphragm power (–46%, p = 0.033). Chapter 8 was an exploratory study to assess the effect of external loading (pressure and flow) on costal diaphragm thickening. Despite a reduction in ΔPdi,tw (–11 ± 3%) after pressure loading, diaphragm thickening remained well-preserved in response to evoked contractions (fresh: 54 ± 27%; fatigued: 50 ± 33%), sniffs (fresh: 65 ± 25; fatigued: 78 ± 70%) and hypercapnic hyperpnoea (fresh: 130 ± 55%; fatigued: 86 ± 22%). Because measures of diaphragm thickening were highly variable, they may not be adequately sensitive to capture acute changes with fatigue. This body of work supports the use of subcostal ultrasonography in the assessment of in vivo diaphragm force-velocity-power relations, and suggests that ultrasound may be a useful tool to explore the effects of training interventions and healthy ageing on dynamic contractile properties of the human diaphragm