The nature of shape change and aggregation of human and rabbit platelets was assessed by light transmission studies of stirred platelet suspensions and phase contrast microscopy. Platelet shape change and aggregation were differently affected by experimental conditions: pCO(,2), pH and anticoagulants, according to choice of aggregating agents. Optimal physiological conditions were established for functional studies. A new class of potent antithrombotic agents, BL-3459 and BL-4162A, were identified as selective low Km cyclic 3':5'-adenosine monophosphate (cAMP) phosphodiesterase inhibitors. These BL-compounds could block platelet shape change and aggregation for all aggregating agents tested. Dose-response studies with adenosine 5'-diphosphate demonstrated that these two consecutive events are separately and oppositely controlled by aggregating agent and inhibitor concentration. A model for the role of cAMP-calcium in regulating these changes is presented. Finally, we studied platelets from a distinct hereditary bleeding disorder, which we designated as the "Montreal Platelet Syndrome". These platelets showed abnormal shape change, low to absent thrombin-induced aggregation; and spontaneous aggregation leading to microaggregates of disc-shaped platelets.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.68521 |
| Date | January 1979 |
| Creators | Tang, Shiow-Shih. |
| 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: 000089963, proquestno: AAINK50576, Theses scanned by UMI/ProQuest. |
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