This thesis examines the importance of the length-force relationship and the three-dimensional shape of the diaphragm with regard to its inspiratory function. As well as it reports on the manner in which fatigue and aminophylline affect the length-force properties of the diaphragm. First, I studied the effect of fatigue on diaphragm contractility as a function of sarcomere length using an in vitro rat diaphragm strips. Results indicated that fatigue resulted in disproportionately greater reduction of tetanic force at short sarcomere lengths. Second, I reconstructed the three-dimensional shape of the diaphragm to determine if in vitro results are physiologically relevant in humans. I estimated the changes in fibre length and shape that occurs with lung inflation from residual volume to total lung capacity in normal subjects. Results suggested that the inspiratory function of the human diaphragm can be entirely attributed to its length-force relationship rather than changes in shape under conditions of twitch phrenic nerve stimulations. Finally, I confirmed that fatigue caused a greater percent reduction of transdiaphragmatic pressure at high lung volume in response to single supramaximal shocks delivered bilaterally to the phrenic nerves at high lung volume; and demonstrated that aminophylline potentiated human diaphragm contractility more at high than at low lung volumes, both under fresh and fatigue conditions. I propose an explanation for the effect of fatigue and aminophylline on diaphragm contractility at different sarcomere lengths based on known actions of these factors and muscle shortening on excitation-contraction coupling mechanisms of skeletal muscles.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41596 |
| Date | January 1993 |
| Creators | Gauthier, Alain P. |
| Contributors | Macklem, P. T. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001397566, proquestno: NN94623, Theses scanned by UMI/ProQuest. |
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