Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / "May 2001." Typescript. Vita. Includes bibliographical references (leaves 122-137). Also available on the Internet.

Master of Science / Department of Food, Nutrition, Dietetics and Health / Mark Haub / The coronary microcirculation is the principle site of blood flow control and myocardium oxygen delivery within the coronary artery tree. Coronary arteriole tone is determined by three major endothelium derived vasoactive substances: endothelin, nitric oxide (NO), and reactive oxygen species (ROS). The effects of these substances change with aging and differ between sexes. Endothelin-1 (ET-1), the primary endothelin isoform in the coronary circulation, acts on smooth muscle receptors endothelin-A (ET[subscript A]) and endothelin-B (ET[subscript B]) to induce vascular smooth muscle (VSM) contraction and vasoconstriction. Whereas ET-1 activation of the ET[subscript B] receptor on the endothelium initiates a cascade of events leading to NO production via endothelium derived NO synthase (eNOS) enzyme activation and VSM relaxation. Aged males maintain ET[subscript A] receptor expression and higher levels of vasoconstriction than do age-matched females. High levels of ET[subscript A] receptor activity are associated with hypertension, myocardial infarction, coronary artery spasm, atherosclerosis, and finally heart failure (HF). Additionally, NO can displace ET-1 from the VSM ET[subscript A] and ET[subscript B] receptors. Thus, with reduced eNOS activity and decreased NO production, there is a simultaneous loss of vasodilatory capacity and increase in vasoconstrictive capacity. In both rodent and human models aged males and females ROS production increases with age. ROS, such as superoxide, scavenge NO, decreasing its bioavailability and producing peroxynitrite. Peroxynitrite is a potent reactive nitrogen species that leads to endothelial cell apoptosis and eNOS enzyme dissociation, potentiating superoxide production and NO reduction. It has been shown that the reduction in NO bioavailability may be a primary mechanism of coronary artery disease. However, the ROS hydrogen peroxide, also increased with aging, produces a potent vasodilatory effect in the coronary microcirculation and seems to be one mechanism that buffers the loss of NO-induced vasodilation. In postmenopausal women diminished estrogen levels further reduce eNOS production of NO. Males, however, tend to experience decrements in arteriole function a decade before women and estrogen may be one mechanism preserving vascular health into middle age that separates the chronology of coronary artery disease between sexes. Determining the mechanisms of disease onset that accompany the aging process will provide insight into potential therapies to preserve endothelium dependent dilation with aging such as exercise, dietary NO supplementation, and increased dietary anti-oxidant consumption.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 122-137). Also available on the Internet.

Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains xi, 87 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 71-79).

The purpose of this study was to identify the effects of a hemoglobin-based oxygen carrier, HBOC-201, on the cardiovascular system. Systemic cardiovascular parameters of mean arterial pressure (MAP), pulse pressure, heart rate, and oxygen saturation, as well as vascular resistance, were examined. A murine model of the cardiovascular system and microvasculature was employed. Sprague-Dawley rats (male; 230-530g; N = 13) were anaesthetised and surgically prepared for intravital microscopy of the spinotrapezius muscle. Increasing doses of HBOC-201 (2 mg/kg, 22 mg/kg, 230 mg/kg, and 780 mg/kg) and an iso-oncotic volume control were administered to assess for a dose-response relationship. MAP displayed a significant increase from baseline for both treatment groups, with no significant difference between the two. Arteriolar diameter displayed no changes from baseline, or between treatment groups or across doses. Based on these results, the noted changes in MAP were due to hypervolemia, and not a property of HBOC-201, itself.

Research into automatic retina image analysis has become increasingly important, not just in ophthalmology but also in other clinical specialities such as cardiology and neurology. In the retina, blood vessels can be directly visualised non-invasively in-vivo, and hence it serves as a "window" to cardiovascular and neurovascular complications. Biomarker research, i.e. investigating associations between the morphology of the retinal vasculature (as a means of revealing microvascular health or disease) and particular conditions affecting the body or brain could play an important role in detecting disease early enough to impact on patient treatment and care. A fundamental requirement of biomarker research is access to large datasets to achieve sufficient power and significance when ascertaining associations between retinal measures and clinical characterisation of disease. Crucially, the vascular changes that appear can affect arteries and veins differently. An essential part of automatic systems for retinal morphology quantification and biomarker extraction is, therefore, a computational method for classifying vessels into arteries and veins. Artery-vein classification enables the efficient extraction of biomarkers such as the Arteriolar to Venular Ratio, which is a well-established predictor of stroke and other cardiovascular events. While structural parameters of the retinal vasculature such as vessels calibre, branching angle, and tortuosity may individually convey some information regarding specific aspects of the health of the retinal vascular network, they do not convey a global summary of the branching pattern and its state or condition. The retinal vascular tree can be considered a fractal structure as it has a branching pattern that exhibits the property of self-similarity. Fractal analysis, therefore, provides an additional means for the quantitative study of changes to the retinal vascular network and may be of use in detecting abnormalities related to retinopathy and systemic diseases. In this thesis, new developments to fully automated retinal vessel classification and fractal analysis were explored in order to extract potential biomarkers. These novel processes were tested and validated on several datasets of retinal images acquired with fundus cameras. The major contributions of this thesis include: 1) developing a fully automated retinal blood vessel classification technique, 2) developing a fractal analysis technique that quantifies regional as well as global branching complexity, 3) validating the methods using multiple datasets, and 4) applying the proposed methods in multiple retinal vasculature analysis studies.

Thesis (Ph. D.)--West Virginia University, 2009. / Title from document title page. Document formatted into pages; contains xi, 78 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 59-67).

The involvement of the endothelial cell in the vasoconstriction induced by angiotensin I and II (AI, AII), and norepinephrine (NE) was studied in microvessels of the hamster cheek pouch before and after the following procedures: endothelial impairment by light-dye treatment, inhibition of angiotensin-converting enzyme (ACE), blockade of endothelium-derived relaxing factor (EDRF) and inhibiting prostaglandin (PG) synthesis. The results showed that in large 2nd-order arterioles, endothelial impairment did not affect the vasoconstrictor activity of AII and NE, nor did it alter ACE activity. However, in small 4th-order arterioles, endothelial impairment significantly reduced angiotensin conversion without altering the vasoconstrictor responses to either AII or NE. Thus, the endothelium plays differential roles in the modulation of local angiotensin conversion in these distinct segments of serial-arranged arterioles. Furthermore, it is unlikely that the vasoconstrictor response to AII in these arterioles is modulated by the endothelium through a pathway involving the release of EDRF or PGs.