Recently, various proteoglycans (PGs) have been identified in the lung. The first objective of this thesis was to test the hypothesis that matrix glycosaminoglycans contribute to lung tissue viscoelasticity. Lung parenchymal strips were exposed to specific glycosaminoglycans-degradating enzymes to determine whether the mechanical properties of the tissue were affected. The degradation of heparan sulphate and chondroitin/dermatan sulphate glycosaminoglycans caused significant increases in energy dissipation and dynamic resistance relative to control strips. Hyaluronidase treatment did not alter any of the dynamic or static measures. Since PGs were found to be part of the stress bearing structure, the second part of the thesis aimed at examining whether subjecting the lung to excessive mechanical force can cause alteration in PG composition so as to adapt to the altered stress bearing requirement. To address this hypothesis, the effect of different ventilation regimes on lung tissue mechanics and PGs was examined in an in vivo rat model. After 2 h of mechanical ventilation, lung tissue elastance and resistance were significantly increased in rats ventilated with tidal volume of 30 ml/kg at 0 positive end-expiratory pressure (Vt30PEEP0) as compared to controls (Vt8PEEP1.5). Versican, a basement membrane heparan sulphate PG and biglycan, were all increased in rat lungs ventilated with Vt30PEEP0 as compared to control. These data demonstrated that alterations in lung tissue mechanics with excessive mechanical ventilation are accompanied by changes in all classes of ECM PGs. However, whether the alteration seen in PG composition resulted from excessive mechanical ventilation directly was unclear. In addition the cellular source of these PGs was not determined. Therefore, the aim of the third part of the thesis was to investigate and characterize the effect of mechanical strain on lung fibroblast PG production in vitro. We found cell layer associated versican protein in
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.37861 |
| Date | January 2001 |
| Creators | Al-Jamal, Rehab. |
| Contributors | Ludwig, Mara S. (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 (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001837501, proquestno: NQ75601, Theses scanned by UMI/ProQuest. |
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