Mechanlcal RELATIONS in the DEVELOPING OVINE Thoraclc AORTA
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STRUCTURAL - MECHANlCAL RELATIONS IN THE DEVELOPING OVINE THORAClC AORTA Sarah Melissa Wells A thesis submitted in confonnity with the requirements for the degree of Ooctor of Philosophy Department of Metallurgy and Materials Science, University of Toronto O Copyright by Sarah Melissa Wells 9999 National Library Bibliottréque nationale l*l of Canada du Canada Acquisitions and Acquisitions et Bibliographie Services services bibliographiques 395 WeHingbn Street 395. rue Welligtm Ottawa ON K1A CIW Ottawa ON K1A O(J4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence ailowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sell reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/filrn, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be p~tedor otheMise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. STRUCTURAL - MECHANICAL RELATIONS IN THE DEVELOPING OVINE THORACIC AORTA Doctor of Philosophy, 1999 Sarah Melissa Wells Department of Metallurgy and Materials Science, University of Toronto Abstract During the perinatal period (interval surrounding birth), many cardiovascular tissues structurally remodel in preparation for, and adaptation to, postnatal hemodynarnic conditions. Changes occur in both the wall components and dimensions of large arteries such as the thoracic aorta. The effects of this remodelling on aortic mechanical properties are not known. Furthermore, how aortic structure and mechanics change with further postnatal maturation is poorly understood. The objective of this thesis was to assess the changes in the mechanical properties of the ovine thoracic aorta during perinatal and postnatal development, and to relate these changes to alterations in the main aortic wall components: elastin, collagen, and vascular smooth muscle cells. Aortic structure and mechanics were examined in fetal(119d gestation, term = 145d), newborn, and adult sheep. Aortic mechanics were assessed via: i) pressure wave propagation in vivo and ii) static/dynamic stress-strain relations in vitro. Biochemical structure was described by relative contents of elastin, collagen and DNA (representing smooth muscle cells). Collagen crosslinking was assessed using hydrothermal isometric tension (HIT) tests. These studies have demonstrated large developmental changes in the structure and mechanics of the thoracic aorta. The vesse1 becomes progressively stiffer and less viscous with development fiom fetal to adult life, and much of these changes occur perinataliy. Furthermore, key mechanical features were associated with specific stmctural changes. (1) A perinatal 89% increase in aortic low-stress incremental elastic modulus was associated with a 69% increase in relative elastin content. (2) A postnatal 88% increase in high-stress incremental elastic modulus paralleled a 75% increase in collagen crosslinking index. (3) Decreases in measures of wall viscosity (pressure wave attenuation coefficient and viscoelastic phase angle) from fetal to adult life followed a decrease in smooth muscle ce11 content. In summary, as the aorta becomes progressively less cellular fiom fetal to adult life, wall viscosity is concurrently reduced. A rapid perinatal accumulation of elastin may enhance the Windkessel function of the aorta, thereby accommodating the postnatal increases in blood pressure and stroke volume. Postnatal changes in vesse1 dimensions and blood pressure increase the physioiogical aortic wall stress which is resisted by an increased collagen crosslinking-not content. Acknowledgments 1 wish to express my gratitude to my supervisors: Dr. S. Lee Adamson, Dr. B. Lowe11 Langille, and Dr. J. Michael Lee for their guidance, support, patience, and encouragement throughout my graduate studies. 1 have found their expertise and interdisciplinary skills to be tmly inspiring. 1 would also Iike to express my appreciation to the other rnember of my advisory cornmittee, Dr. Fred W. Keeley, for his valuable advice and guidance. 1 would like to thank Dr. David Courtman for his advice and assistance in setting up the in vitro mechanical testing apparatus. 1 would also like to thank Chris Pereira for his technical help with the mechanical testing apparatus, HIT apparatus, and servo-hydraulic testing of the sonomicrometer crystals. 1 also wish to thank Chris Pereira for witing the various LabVIEW data acquisition programs as well as Damy Seto and Andrew Hi11 for providing the Viewdac data acquisition programs. 1 wish to extend my appreciation to Cathie Whitelely for her excellent technical assistance dunng the surgical procedures. 1 also wish to thank Doma Johnson, Paul Gratzer, and Cathie Bellingham for their guidance and patience in teaching me to perform the tissue bioc hemical assays. I wish to thank my fellow students past and present in the Perinatal Research lab: Tze- Chun Tai, Ann Chlorakos, Nancy Kninic, and Ian Copland for their support, encouragement and friendship. 1 wish to thank my parents: Donna and Lowe11 Wells and my sister and brother: Martha and Jonathan for their unwavenng support and encouragement-and for the countIess trips (which included a certain feline passenger) between Lucan and Toronto. 1 also wish to acknowledge Tooncies for bis entertaining Company. k 1 wish to gratefùlly acknowledge the studentship support fiom the Ontario Graduate Scholarship Program and the Medical Research Council of Canada. Publications of Thesis Work Journal Articles Wells, S.M., Langille, B.L.,and Adamson, S.L. In vivo and in vitro mechanical properties of the sheep thoracic aorta in the perinatal period and adulthood. American Journal of Physiology, 274 (43): H 1749-H 1760, 1998. Wells, S.M., Langille, B.L.,Adamson, S.L., and Lee, J.M. Thermomechanical characterization of collagen crosslinking in the developing ovine thoracic aorta. Biorheology 1 999 (in press). Wells, S.M., Lee, J.M, Langille, B.L. and Adamson, S.L. Determinants of mechanical properties of the developing ovine thoracic aorta. American Journal of Physiology (in press). B. Published Abstracts 1. Wells, S.M., Lee, J.M., Langille, B.L., and Adamson, S.L. Structural-mechanical relations in the developing thoracic aorta. Annals of biomedical Engineering, 26(Suppl. 1): S-67, 1998. 2. Wells, S.M., Lee, J.M., Langille, B.L., and Adamson, S.L. Thennomechanical characterization of collagen crosslinking in the developing thoracic aorta. Journal of Cardiovascular Diagnosis and Procedures, I 3(4): 299, 1996. 3. Wells, S.M., Langille, B.L., Lee, J.M., and Adamson, S.L. Mechanical properties and wall structure of the thoracic aorta in the pennatal period and adulthood. Annals of Biomedical Engineering, 23(Suppl. 1): S-44, 1995. Table of Contents .. ABSTRACT ........................................................................................................................... 11 ACKNOWLEDGMENTS .......................................................................................... iv PUBLICATIONS OF T HESlS WORK .............................................................................. v CHAPTER 1: Introduction 1. 1 Cardiovascular Physiology and the Role of the Thoracic Aorta ............................. 3 1.1.1 Cardiovascular System and its Mechanics .......................................... ..-7 1.1 -2 Developmental Cardiovascular Physiology ............................................ 3 1.1.2.1 The Fetal Circulation ......................................................... 3 1.1.2 -2 Cardiovascular Changes at Birth. ............................. .. ............ 3 1.1.2.3 Perinatal and Postnatal Arterial Remodelling .............................. 4 1 -2 Characterization of Arterial Mechanical Properties ..........................................- 5 1.3 Structural-Mechanical Relations and Remodelling in Arterial Tissue ........................ -7 1.3.1 The Composite Structure of the Aortic Wall ......................................... -7 1.3.1.1 Postnatal Development of the Aortic Media ............................... 8 1.3.2 Structure-Function Relationships in Arterial Wall Components.................... 9 1.3.2.1 Elastin ........................................................................... 9 1.3.2.2 Collagen ....................................................................... 13 1.3.2.3 Vascular Smooth Muscle Cells ............................................. 16 1.3.2.4 Proteoglycans ................................................................ -17 1.3.3 Structural-Mechanical Relations in Composite Arterial Tissue ................. -18 1.4 Age-Related Changes in Structure/Mechanics of Tissue ................................. -23 1 .4.1 Age-Related Changes in Arterial Mechanics ............................ ... ........-23 1 4.2 Developmental Changes in Arterial WalI Stmcture/Mechanics.................. -24 1.4.3 Assessing Structural-Mechanical Relations .......................................... 25 1 5 Rationale for this Thesis ...................................................................... -26 1.6 Objectives ........................................................................................