Numerical investigations of heat transfer in single and multiple thick-walled pipes and countercurrent pairs are used to deduce relationships between fluid and solid temperatures needed to develop more accurate thermal models of living tissue in the extremities. A structural model of heat transfer in living tissue is developed using currently available anatomical and physiological data for the extremities. In order to improve the heat transfer basis of thermal modeling under in vivo conditions, four heat transfer problems based on structures found in the extremities are solved using in vivo parameters-the thick-walled pipe and countercurrent pair, and the multiple thick-walled pipes and countercurrent pairs-are studied. Low resolution numerical models are devised to approximate the thick-walled pipe and the non-concentric thick-walled countercurrent pair in square geometries. A constant heat transfer coefficient at the fluid-solid interface adequately approximates the fluid and solid temperatures for moderate flow conditions (Peclet number of 10 < °Pe < 1000). In the thick-walled countercurrent pair, countercurrent exchange and fluid-solid thermal interaction are found to act simultaneously, giving rise to imperfect countercurrent exchange. Fluid and solid temperatures in the multiple thick-walled pipes and pairs near the outer boundary resemble those of the single thick-walled pipes and pairs. The countercurrent pairs near the center also exhibit imperfect countercurrent exchange. In cylinders with L* > 1 containing multiple countercurrent pairs, the shapes of the temperature profiles cannot be distinguished from the temperature profile shapes of cylinders containing multiple thick-walled pipes. Fluid and solid temperatures in multiple parallel pipes may be approximated with a field equation which has the same form as the Pennes' bioheat equation. Unlike Pennes' equation, the coefficients for the blood thermal energy term quantify the dependence of the amount of thermal energy transferred between blood and tissue with the geometry of the blood the flow rate through the dimensionless axial length L*, and the dimensionless axial coordinate x* . Comparisons of structural model temperatures with available in vivo temperature studies show that blood and tissue temperatures are consistent with fluid and solid temperatures of either multiple unpaired pipes or multiple countercurrent pairs embedded in a solid cylinder. Further improvements of the basis for in vivo heat transfer modeling are crucially dependent upon more extensive comparison with three-dimensional in vivo studies.

No description available.

No description available.

In vitro microphysiological system utilizes engineered tissue constructs from human cells to model functional activity of human tissues or organs in both healthy and diseased state, thereby providing a more accurate drug screening than animal models prior to clinical trials. One essential component of an in vitro microphysiological system is a tissue engineered blood vessel (TEBV) that can accurately recapitulate the functional vasculature in vivo. This thesis first explores two most important considerations to a successful TEBV generation, the cell source and the fabrication method. To engineer a vascular tissue construct, an ideal cell source should demonstrate high availability and accurate vessel functionality. Mesenchymal stem cells (MSC) were explored due to their high availability, proliferation capacity, and capability to deposit adequate extracellular matrix (ECM) for cell sheet formation. Vascular smooth muscle cells (SMC) are the cell components that comprise the medial layer of native blood vessel, and thus optimal for demonstrating equivalent biological functionality. However, SMC are much harder to acquire through biopsy, and they have limited proliferative capacity and quick senescence. Therefore, an alternative cell source for SMC was obtained through direct reprogramming approach involving the induced overexpression of myocardin in more readily available human cell sources. The resulting reprogrammed SMC demonstrated close resemblance to the native SMC in terms of its phenotype, related gene and protein expression levels, and contractile function. Two different fabrication methods, nanopatterned cell sheets and dense collagen hydrogel, were explored to engineer a 1 mm inner diameter blood vessel. The fabricated TEBVs were then compared to that of the native blood vessel and each other in terms of its structure, mechanical properties, and vasoactive function in response to stimuli. After selecting the most optimal cell source and fabrication method for developing a human cell-based TEBV for in vitro microphysiological system, the second part of this thesis assesses the capability of the designed TEBV to model a vascular disease for drug screening purposes. Marfan syndrome was selected as a model vascular disease due to its previous history of contradictory results from the animal models and human clinical trials using losartan, an angiotensin II receptor blocker, in terms of preventing aortic root dilation. TEBV fabricated using reprogrammed SMC from Marfan syndrome patient sample and dense collagen hydrogel showed reduced fibrillin deposition, increased vessel diameter and thickness, and reduced vasoconstriction levels when compared to the wild type TEBV, which is consistent with that observed in native vessels of Marfan syndrome patients. Losartan improved the function of Marfan syndrome TEBV, but still at reduced level when compared to that of the wild type. SB203580, a selective inhibitor of p53 MAPK that has been shown to be a better drug candidate than losartan in recent cell-based studies, showed improved TEBV function comparable to that of the wild type. In overall, this thesis presents a successful development of a highly robust, patient-specific in vitro vascular model. An accurate recapitulation of a drug-induced physiological response in humans can speed up the drug screening process with higher efficiency, and this will eventually increase the chances of successful treatment for patients.

Luk Wing Sze, Phoebe. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 173-190). / Abstracts in English and Chinese. / Abstract --- p.I / Acknowledgement --- p.XII / Publications Based on the Work in this Thesis --- p.XIII / Abbreviations --- p.IX / Table of Contents --- p.X / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1. --- Arthritis and Inflammation --- p.1 / Chapter 1.1.1. --- Tissue Reaction in Inflammation --- p.2 / Chapter 1.1.1.1. --- Mechanism of Vasodilatation --- p.2 / Chapter 1.1.1.2. --- Plasma Extravasation --- p.5 / Chapter 1.2. --- Neurogenic Inflammation --- p.8 / Chapter 1.2.1. --- Axon Reflex and Local Efferent Action of Primary Afferents --- p.9 / Chapter 1.2.2. --- Mediators of Neurogenic Inflammation --- p.10 / Chapter 1.2.3. --- Microvascular Effect of Substance P --- p.11 / Chapter 1.2.4. --- Microvascular Effect of Calcitonin Gene-Related Peptide --- p.13 / Chapter 1.3. --- Neurogenic Inflammation in the Joint --- p.16 / Chapter 1.3.1. --- Neuropeptides in Arthritic Knee --- p.16 / Chapter 1.3.2. --- Effects of Neuropeptides on Normal Knee --- p.16 / Chapter 1.3.3. --- Effects of Neuropeptides on Inflamed Knee --- p.17 / Chapter 1.3.4. --- Activation of Efferent Function of the Nerves --- p.19 / Chapter 1.4. --- Vanilloid Receptor --- p.20 / Chapter 1.4.1. --- The Use of Capsaicin as an Experimental Tool --- p.20 / Chapter 1.4.2. --- Identification of Vanilloid Receptor --- p.21 / Chapter 1.4.3. --- Molecular Biology of Vanilloid Receptor --- p.22 / Chapter 1.4.4. --- Electrophysiolgocial Properties of Vanilloid Receptors --- p.23 / Chapter 1.5. --- Activation of Vanilloid Receptors - A Detector of Physical Stimuli --- p.23 / Chapter 1.5.1. --- Exogenous Activators of Vanilloid Receptors --- p.25 / Chapter 1.5.2. --- Endogenous Activators of Vanilloid Receptors --- p.26 / Chapter 1.5.2.1. --- Anandamide as an Endovanilloid --- p.26 / Chapter 1.5.2.2. --- Other Possible Endovanilloid --- p.28 / Chapter 1.5.3. --- Biological Effects of Capsaicin --- p.29 / Chapter 1.5.3.1. --- Efferent Function: Neuropeptide Release --- p.29 / Chapter 1.5.3.2. --- Desensitization --- p.30 / Chapter 1.5.3.3. --- Neurotoxicity --- p.32 / Chapter 1.5.4. --- Biological Effects of Anandamide --- p.33 / Chapter 1.5.4.1. --- Vascular Effect of Anandamide --- p.33 / Chapter 1.5.4.2. --- Interaction of the Vanilloid and Cannabinoid System --- p.38 / Chapter 1.6. --- Aim of Study --- p.39 / Chapter Chapter 2 --- Methods --- p.40 / Chapter 2.1. --- Materials --- p.40 / Chapter 2.2. --- Protocols --- p.42 / Chapter 2.2.1. --- General Procedures --- p.42 / Chapter 2.2.2. --- Preparatory Procedure --- p.43 / Chapter 2.3. --- Measurement of Knee Joint Blood Flow --- p.46 / Chapter 2.3.1. --- Animal Preparation for Measuring Knee Joint Blood Flow --- p.48 / Chapter 2.3.2. --- Specific Procedures --- p.49 / Chapter 2.3.3. --- Image Analysis --- p.51 / Chapter 2.3.4. --- Data Analysis --- p.52 / Chapter 2.4. --- Quantification of Plasma Protein Extravasation --- p.52 / Chapter 2.4.1. --- Experimental Procedure --- p.53 / Chapter 2.4.2. --- Measurement of Evans Blue Content --- p.53 / Chapter 2.4.3. --- Measurement of Knee Joint Size --- p.54 / Chapter 2.5. --- Effect of Capsaicin on Acute Joint Inflammation --- p.54 / Chapter Chapter 3 --- Results --- p.55 / Chapter 3.1. --- Vanilloids on Knee Joint Blood Flow --- p.55 / Chapter 3.1.1. --- Capsaicin --- p.55 / Chapter 3.1.1.1. --- Cumulative Dosing of Capsaicin --- p.55 / Chapter 3.1.1.2. --- Time Course of Capsaicin-induced Vasodilatation --- p.55 / Chapter 3.1.1.3. --- VR1 Antagonists on Capsaicin-induced Vasodilatation --- p.57 / Chapter 3.1.1.4. --- NK1 Antagonists on Capsaicin-induced Vasodilatation --- p.58 / Chapter 3.1.1.5. --- CGRP Antagonist on Capsaicin-induced Vasodilatation --- p.60 / Chapter 3.1.1.6. --- Denervation on Capsaicin-induced Vasodilatation --- p.61 / Chapter 3.1.2. --- Anandamide --- p.62 / Chapter 3.1.2.1. --- Dose Responses of Anandamide --- p.62 / Chapter 3.1.2.2. --- Time Course of Anandamide-induced Vasodilatation --- p.63 / Chapter 3.1.2.3. --- VR1 Antagonist on Anandamide-induced Vasodilatation --- p.64 / Chapter 3.1.2.4. --- NK1 Receptor Antagonists on Anandamide-induced Vasodilatation --- p.65 / Chapter 3.1.2.5. --- CGRP Receptor Antagonist on Anandamide-induced Vasodilatation --- p.67 / Chapter 3.1.2.6. --- CB1 Receptor Antagonist on Anandamide-induced Vasodilatation --- p.67 / Chapter 3.1.2.7. --- CB2 Receptor Antagonist on Anandamide-induced Vasodilatation --- p.68 / Chapter 3.1.2.8. --- Anandamide Transporter Inhibitor on Anandamide-induced Vasodilatation --- p.69 / Chapter 3.1.2.9. --- Effects of Denervation on Anandamide-induced Vasodilatation --- p.70 / Chapter 3.2. --- Vanilloids on Plasma Extravasation --- p.71 / Chapter 3.2.1. --- Saline injection on Plasma Extravasation --- p.71 / Chapter 3.2.2. --- Capsaicin on Plasma Extravasation --- p.72 / Chapter 3.2.3. --- Capsaicin on Knee Joint Sizes --- p.73 / Chapter 3.2.4. --- Anandamide on Plasma Extravasation --- p.73 / Chapter 3.2.5. --- Anandamide on Knee Joint Size --- p.73 / Chapter 3.3. --- Effects of Vanilloid Agonists on Carrageenan-induced Acute Inflammation --- p.74 / Chapter 3.3.1. --- Capsaicin on Carrageenan-induced Plasma Extravasation --- p.74 / Chapter 3.3.2. --- Capsaicin on Carrageenan-induced Joint Swelling --- p.77 / Chapter 3.3.3. --- Anandamide on Carrageenan-induced Plasma Extravasation --- p.79 / Chapter 3.3.4. --- Anandamide on Carrageenan-induced Joint Swelling --- p.80 / Chapter Chapter 4 --- Discussion --- p.150 / Chapter 4.1. --- Capsaicin-induced Long Lasting Vasodilatation --- p.151 / Chapter 4.2. --- Capsaicin-induced Vasodilatation 一 a VR1 Mediated Effect? --- p.153 / Chapter 4.3. --- Substance P and CGRP in Capsaicin-induced Vasodilatation --- p.155 / Chapter 4.4. --- Anandamide-induced Vasodilatation --- p.157 / Chapter 4.5. --- VR1 in AEA-induced Vasodilatation --- p.159 / Chapter 4.6. --- Neuropeptides in AEA-induced Vasodilatation --- p.160 / Chapter 4.7. --- Cannabinoid Receptors in AEA-induced Vasodilatation --- p.161 / Chapter 4.8. --- Role of Anandamide Transporter in AEA-induced Vasodilatation --- p.163 / Chapter 4.9. --- A Neural Mechanism for Capsaicin- and AEA-induced Vasodilatation? --- p.164 / Chapter 4.10. --- Effects of Capsaicin and AEA on Plasma Extravasation --- p.167 / Chapter 4.11. --- Capsaicin and Anandamide in Acute Inflammation --- p.169 / Chapter 4.12. --- Conclusion --- p.170 / References --- p.173

No description available.

Abstract not available

x, 148 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1980) from the Dept. of Surgery, University of Adelaide

University of Macau / Institute of Chinese Medical Sciences

The mechanical environment influences vascular smooth muscle cell (VSMC) functions related to the vascular remodeling. However, the relationships are not appropriately addressed by most mechanical models of arteries assuming homogeneity. Accounting for the effects of heterogeneity is expected to be important to our understanding of VSMC functions. We hypothesized that local stresses computed using a heterogeneous mechanical model of arteries positively correlate to the levels of matrix metalloproteinase (MMP)-2 and -9 in situ. We developed a mathematical model of an arterial wall accounting for nonlinearity, residual strain, anisotropy, and structural heterogeneity. The distributions of elastin and collagen fibers, quantified using their optical properties, showed significant structural heterogeneity. Anisotropy was represented by the direction of collagen fibers, which was measured by the helical angle of VSMC nuclei. The recruiting points of collagen fibers were computed assuming a uniform strain of collagen fibers under physiological loading conditions; an assumption motivated by the morphology. This was supported by observed uniform length and orientation of VSMC nuclei under physiological loading. The distributions of circumferential stresses computed using both heterogeneous and corresponding homogeneous models were correlated to the distributions of expression and activation of MMP-2 and -9 in porcine common carotid arteries, which were incubated in an ex vivo perfusion organ culture system under either normotensive or hypertensive conditions for 48 hours. While strains computed using incompressibility were identical in both models, the heterogeneous model, unlike the homogeneous model, predicted higher circumferential stresses in the outer layer. The tissue levels of MMP-2 and -9 were positively correlated to circumferential stresses computed using the heterogeneous model, which implies that areas of high stress are expected to be sites of localized remodeling and agrees with results from cell culture studies. The results support the role of mechanical stress in vascular remodeling and suggest the importance of structural heterogeneity in studying mechanobiological responses.