Thesis (M.S.)--California Polytechnic State University, 2009. / Mode of access: Internet. Title from PDF title page; viewed on June 11, 2009. Major professor: Dr. Trevor Cardinal. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Biomedical Engineering." "March 2009." Includes bibliographical references (p. 76-83). Also available on microfiche.

Proefschrift van geaggregeerde-University catholique de Louvain. / Summary in Dutch. Bibliography: p. 147-160.

Proefschrift van geaggregeerde-University catholique de Louvain. / Summary in Dutch. Bibliography: p. 147-160.

Thesis (Ph. D.)--University of Missouri-Columbia, 2008. / "May 2008" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.

Clinical evidence indicates a higher incidence of peripheral arterial occlusive disease and associated likelihood of critical limb ischemia in women, as well as worse prognosis and decreased survival post myocardial infarction. Therefore, understanding the possible differences in underlying vascular compensation mechanisms is crucial. With arterial occlusions, necrosis and tissue injury can be naturally mitigated by the collateral circulation, improving patient prognosis. Previous sex-comparison studies describing differences in vascular remodeling are inconsistent. Therefore, the aim of this study was to describe the effect of arterial occlusion on collateral remodeling in healthy male and healthy reproductive-stage female mice. At 7 days following femoral artery ligation in C57Bl/6 and BALB/c mice, there were no sex-related differences in functional ambulatory recovery. There were no sex-related differences in mechanoadaption indicators in the collateral stem- vascular smooth muscle cell (VSMC) length and overlap, with the exception of longer smooth muscle cells in male C57Bl/6 mice, VSMC lengths 329 ± 19 verses 288 ± 13 μm, male and female. Collateral midzone luminal and abluminal diameters, as well as wall thicknesses were not different between sexes. As comprehensive sex-specific differences were not captured in our specific investigation of arteriogenesis, an evaluation of microvascular remodeling in the ischemic zone and collateral vasodilation would be of interest, as would evaluating arteriogenesis following oophorectomy with estrogen depletion. The determination of any underlying mechanistic sex-specific differences could be the foundation for which targeted therapeutics are developed, which will be crucial for closing the prognosis gap between men and women in the global treatment of peripheral arterial occlusive disease.

OBJECTIVE - Exercise training has been shown to restore vasodilation to nitric oxide synthase (NOS) activation in arterioles distal to coronary artery occlusion. Because reactive oxygen species are generated during NOS uncoupling and the production of vasodilator H2O2 is increased during exercise in patients with coronary disease, we proposed that H2O2 may contribute to the restoration of vasodilation in porcine coronary occlusion model. METHODS AND RESULTS - Left circumflex (LCX) coronary artery of miniature swine was progressively occluded for 8 weeks followed by exercise training (EX; 5 days/wk treadmill) or sedentary (SED) protocols for 12 weeks. Arterioles were isolated from distal LCX and nonoccluded left anterior descending (LAD) artery for in vitro study. Vasodilation to NOS activators adenosine and ionomycin was impaired in SED LCX, but not LAD, arterioles. This impairment was restored by L-arginine. NO production induced by adenosine was also reduced in SED LCX arterioles. EX had no effect on LAD arterioles but improved NO production and restored dilation of LCX arterioles. NOS blockade (L-NAME) inhibited vasodilation to NOS activators in LAD (SED & EX) arterioles but was ineffective in SED LCX arterioles. In EX LCX arterioles, vasodilation to NOS activators was slightly inhibited by L-NAME but abolished by catalase. H2O2 production was markedly increased by adenosine in EX LCX arterioles. CONCLUSIONS - This study demonstrates that endothelium-dependent NO-mediated dilation is impaired in SED LCX arterioles and that EX training restores the impaired function. It appears that H2O2, in addition to NO, contributes significantly to EX-induced restoration of endothelium-dependent dilation of coronary arterioles distal to occlusion.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13436号 / 論医博第2235号 / 新制||医||1054(附属図書館) / (主査)教授 花川 隆, 教授 YOUSSEFIAN Shohab, 教授 髙橋 良輔 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

The most frequent clinical presentation of peripheral arterial occlusive disease (PAOD) is intermittent claudication, which may be caused by impaired vasodilation. Patients demonstrate both local and systemic impairments in vasodilation, but as the collateral circulation is the primary site of resistance to the ischemic zone, impaired collateral vasodilation would have the greatest potential to induce claudication. Collateral function following arterial occlusion is not well defined, but immature collaterals may demonstrate impaired vasodilation in animal models, although this is potentially improved with exercise training. Furthermore, as females exhibit poorer physical function with ischemia and less improvement with therapeutic exercise, there appears to be a sexually dimorphic response to PAOD, warranting a comparison in collateral vasodilation between sexes. In this study, the femoral artery was ligated to induce chronic ischemia in sedentary and exercise-trained mice, and at 7 or 28 days post-surgery, the diameter of the gracilis collateral arteriole was measured at rest and after gracilis muscle contraction using intravital microscopy. No major sex differences were observed in any group. At day 7, both the resting and dilated diameters were increased, while vascular reactivity was minimal. By day 28, resting diameter decreased while maximal diameter was unchanged, causing an increase in functional vasodilation. Exercise training also improved vasodilation by decreasing collateral resting diameter. These results are consistent with reported trends in endothelium-dependent and smooth muscle-dependent vasodilation, which are impaired in immature vessels and improved with maturation and exercise, but the significance of the observed variations in resting diameter remains unclear. Large resting diameters at day 7 could be due to a loss of sympathetic tone or the proliferative and non-contractile state of smooth muscle cells, while decreased resting diameters at day 28 could indicate that a smooth muscle contractile phenotype has been restored, or that the gracilis collateral is no longer the primary collateral. However, the further research is required to determine the functional relevance of collateral resting diameter and its importance in the ischemic limb circulation.

Peripheral arterial occlusive disease (PAOD) often presents as intermittent claudication, which may be caused by impaired vasodilation. Impairment of resistance vessels may contribute to the pathogenesis of PAOD, and explain the poor correlation between resting blood flow and limb function. Collateral function following arterial occlusion is not well defined, however collaterals and arterialized collateral capillaries (ACCs) in male and female animal models exhibit impaired vasodilation following arterial occlusion, which can potentially be improved with exercise training. Furthermore, resistance vessels in the ischemic tree and stem are likely involved in the pathogenesis of PAOD, however the relative importance of each is unknown. Therefore, we measured functional vasodilation in pre-existing collaterals, ACCs, the ischemic tree, and the stem region, 7 and 21-days following spinotrapezius feed artery ligation in male and female BALB/c mice, and with exercise therapy. Vasodilation in ACCs was more impaired in female mice than in males. Generally, vasodilation was impaired at day-7, likely due to impaired endothelium-dependent and smooth muscle-dependent vasodilation in maturing collaterals, and recovered by day-21. Exercise training appears to enhance collateral reactivity, more in ACCs in males than in females, suggesting that its therapeutic benefits are linked not only to structural adaptation but also to vessel functionality. Therefore, future research is required to determine the cause of sex differences in exercise therapy to treat peripheral arterial occlusive disease.