CT is a powerful method for noninvasive assessment of the lung. Advancements to CT technology have guided the high-resolution structural and functional assessment of lung diseases. This has helped make the transition from characterizing the severity of lung disease to novel phenotyping of disease subtypes. Chronic obstructive pulmonary disease (COPD) is a spectrum of inflammatory lung disease affecting lung parenchyma, airways, and the pulmonary and systemic vasculature. Quantitative CT-based measures have largely focused on quantifying the extent of airway and parenchymal damage with disease. Recently perfusion CT method has been used to assess the pulmonary vascular bed. This technique was used to demonstrate a vascular etiology of smoking-associated centriacinar emphysema (CAE), a subtype of the COPD spectrum. However, technical challenges have limited the transition of this CT method to clinical studies to assess pulmonary vascular physiology. In this thesis, we introduce dual energy CT-perfused blood volume (DECT-PBV) as a novel image-based biomarker to assess peripheral pulmonary vascular dysfunction. Using this technique, we show that smoking-associated pulmonary perfusion heterogeneity, a marker of abnormal blood flow is a reversible process, in the midst of smoking-associated lung inflammation, and not a product of advanced lung disease. We demonstrate, via regional PBV measures and structural measures of the central pulmonary vessels, that the reversibility of pulmonary perfusion heterogeneity is a direct result of increased peripheral (downstream) parenchymal perfusion. We validate our quantitative imaging approach in a unique cohort of early CAE-susceptible smokers using a pharmaceutical intervention to dilate the pulmonary parenchymal vascular bed. The validated DECT approach and our novel DECT imaging findings extend our characterization of the vascular phenotype in inflammatory lung disease and provide a framework for future quantitative imaging studies of the lung to assess early intervention targeted to pulmonary vessels.

<p>The development of the avian embryo is dependent of heat provisioning from the parents. To increase the heat transfer to a cooled egg the Zebra finch females develop a brood patch. Mild cooling generally constricts the blood vessels but the Arterio-venous anastomoses (AVA) in the brood patch in birds dilate. This is called cold-induced vasodilation CIVD. The Zebra finches were anesthetized with isoflurane and the brood patch was stimulated with a cooling probe set at 20-21 °C. Differences in the vascular changes to cooling in broody and non- broody birds were studied by comparing males and broody females. The brood patch skin was cooled, but no cold-induced vasodilation (CIVD) was documented for the males or the broody females. Isoflurane anesthesia depresses the sympathetic nervous system activity and the results support that the mechanism for CIVD in the brood patch of Zebra finches depends on a neural pathway, but does not exclude a local non-neural mechanism.</p>

<p>Nitric oxide (NO) is an important chemical factor that controls vascular tone in the cardiovascular system. NO is a vasodilatory molecule that plays a role in blood pressure and blood flow regulation as well as vessel formation and tissue cell proliferation. NO influences the flow by which nutrients and other metabolites required for growth are transported to the tissues. The aim of this study was to investigate if NO, through mediation by the NO donors Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) affect growth and oxygen consumption of prenatal broiler chicken. The results indicate that, although the treatments did not have clear significant effects on the embryos or the organs examined, a slight delay in development can be observed in the GSNO treatment embryos. The study could not conclude, however, if this was due to effects of NO donors</p>

L-serine, a non-essential amino acid, plays a role in the biosynthesis of the amino acids, proteins, purine and pyrimidine nucleotides. It is important for the proper functioning of the nervous system. It has been considered in the treatment of patients with schizophrenia, depression, chronic fatigue syndrome and psychomotor retardation, and of the seizures encountered in patients with rare inborn errors of L-serine biosynthesis. However, there are no reports in the literature of the direct cardiovascular effects of L-serine. Using normotensive Sprague-Dawley rats, Sprague-Dawley rats rendered hypertensive by chronic treatment with the nitric oxide (NO) synthase inhibitior NG nitro L-arginine methyl ester (L-NAME) and spontaneously hypertensive rats (SHR), the present study examined the in vitro and in vivo effects of L-serine. In vitro studies focused on L-serine induced changes in phenylephrine constricted third order branches of rat mesenteric arterioles while the in vivo studies examined the effects of intravenous infusion of L-serine on mean arterial pressure (MAP) and heart rate (HR) in intact anaesthetized rats. L-serine (10 to 200 µmol/L) evoked concentration-dependent vasodilatation in phenylephrine constricted endothelium-intact, but not in endothelium-denuded, rat mesenteric arterioles. The vasodilator responses to L-serine were absent in the combined presence of apamin, a calcium activated small conductance potassium (SKCa) channel inhibitor, and TRAM-34, a calcium activated intermediate conductance potassium (IKCa) channel inhibitor, or ouabain, a sodium pump inhibitor and barium (Ba2+), an inward rectifying potassium (Kir) channel inhibitor, or when the vessels were depolarized by potassium chloride. The maximal vasodilatation response (Emax) to L-serine was higher in vessels from L-NAME treated rats (40%) than from control rats (20%). In anesthetized rats, L-serine evoked a rapid, reversible, dose-dependent fall in MAP (without a significant change in HR), which was more pronounced in L-NAME treated rats (> 60 mmHg) than in normotensive control rats (25 mmHg). The fall in MAP was inhibited (p<0.01) by apamin plus charybdotoxin pretreatment. Charybdotoxin was used in place of Tram-34 in in vivo studies since Tram-34 is not soluble in water or saline. In age matched Sprague-Dawley, Wistar-Kyoto (WKY) and SHR strains, D-serine had the same effects on MAP and HR as L-serine; however, L-serine evoked a greater maximal fall in MAP in all strains, and the effect was more pronounced in hypertensive rats. In contrast, the infusion of glycine, a metabolite of L-serine led to a dose-dependent fall in MAP in normotensive rats but a dose-dependent increase in MAP in both SHR and L-NAME treated hypertensive WKY rats. Both the depressor and pressor responses to glycine were abolished by pretreatment with the N-methyl D-aspartate receptor antagonist, MK-801. Regional hemodynamic studies performed using the fluorescent tagged microsphere distribution technique revealed that the fall in MAP and profound decrease in total peripheral resistance (TPR) evoked by acute L-serine infusion is due to increased blood flow in the splanchnic region and more particularly in the small intestinal vascular beds. This effect is blocked by the combined treatment with the KCa channel inhibitors, apamin plus charybdotoxin. Although resting MAP and TPR are higher, and cardiac output (CO) is lower both in SHR and in WKY rats rendered hypertensive by L-NAME treatment compared to normotensive WKY rats, L-serine infusion leads to a rapid fall in TPR and MAP, and an increase in CO in all models. This effect was more profound in the hypertensive rats. These findings suggest that L-serine could be helpful in overcoming splanchnic organ failure observed in patients with cardiopulmonary bypass. In addition, L-serine, either alone or in combination with other antihypertensive medications, could be considered in the management of endothelial dysfunctional states with reduced NO bioavailability such as hypertension and diabetes.

L-serine, a non-essential amino acid, plays a role in the biosynthesis of the amino acids, proteins, purine and pyrimidine nucleotides. It is important for the proper functioning of the nervous system. It has been considered in the treatment of patients with schizophrenia, depression, chronic fatigue syndrome and psychomotor retardation, and of the seizures encountered in patients with rare inborn errors of L-serine biosynthesis. However, there are no reports in the literature of the direct cardiovascular effects of L-serine. Using normotensive Sprague-Dawley rats, Sprague-Dawley rats rendered hypertensive by chronic treatment with the nitric oxide (NO) synthase inhibitior NG nitro L-arginine methyl ester (L-NAME) and spontaneously hypertensive rats (SHR), the present study examined the in vitro and in vivo effects of L-serine. In vitro studies focused on L-serine induced changes in phenylephrine constricted third order branches of rat mesenteric arterioles while the in vivo studies examined the effects of intravenous infusion of L-serine on mean arterial pressure (MAP) and heart rate (HR) in intact anaesthetized rats. L-serine (10 to 200 µmol/L) evoked concentration-dependent vasodilatation in phenylephrine constricted endothelium-intact, but not in endothelium-denuded, rat mesenteric arterioles. The vasodilator responses to L-serine were absent in the combined presence of apamin, a calcium activated small conductance potassium (SKCa) channel inhibitor, and TRAM-34, a calcium activated intermediate conductance potassium (IKCa) channel inhibitor, or ouabain, a sodium pump inhibitor and barium (Ba2+), an inward rectifying potassium (Kir) channel inhibitor, or when the vessels were depolarized by potassium chloride. The maximal vasodilatation response (Emax) to L-serine was higher in vessels from L-NAME treated rats (40%) than from control rats (20%). In anesthetized rats, L-serine evoked a rapid, reversible, dose-dependent fall in MAP (without a significant change in HR), which was more pronounced in L-NAME treated rats (> 60 mmHg) than in normotensive control rats (25 mmHg). The fall in MAP was inhibited (p<0.01) by apamin plus charybdotoxin pretreatment. Charybdotoxin was used in place of Tram-34 in in vivo studies since Tram-34 is not soluble in water or saline. In age matched Sprague-Dawley, Wistar-Kyoto (WKY) and SHR strains, D-serine had the same effects on MAP and HR as L-serine; however, L-serine evoked a greater maximal fall in MAP in all strains, and the effect was more pronounced in hypertensive rats. In contrast, the infusion of glycine, a metabolite of L-serine led to a dose-dependent fall in MAP in normotensive rats but a dose-dependent increase in MAP in both SHR and L-NAME treated hypertensive WKY rats. Both the depressor and pressor responses to glycine were abolished by pretreatment with the N-methyl D-aspartate receptor antagonist, MK-801. Regional hemodynamic studies performed using the fluorescent tagged microsphere distribution technique revealed that the fall in MAP and profound decrease in total peripheral resistance (TPR) evoked by acute L-serine infusion is due to increased blood flow in the splanchnic region and more particularly in the small intestinal vascular beds. This effect is blocked by the combined treatment with the KCa channel inhibitors, apamin plus charybdotoxin. Although resting MAP and TPR are higher, and cardiac output (CO) is lower both in SHR and in WKY rats rendered hypertensive by L-NAME treatment compared to normotensive WKY rats, L-serine infusion leads to a rapid fall in TPR and MAP, and an increase in CO in all models. This effect was more profound in the hypertensive rats. These findings suggest that L-serine could be helpful in overcoming splanchnic organ failure observed in patients with cardiopulmonary bypass. In addition, L-serine, either alone or in combination with other antihypertensive medications, could be considered in the management of endothelial dysfunctional states with reduced NO bioavailability such as hypertension and diabetes.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on Feb. 2, 2010). Includes bibliographical references.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Feb. 4, 2010). Includes bibliographical references (p. 120-131).

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Thesis (Ph. D.)--West Virginia University, 2009. / Title from document title page. Document formatted into pages; contains viii, 109 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.