Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1981. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 103-126).

A preparation is described utilizing a constant flow, right-heart bypass for perfusion of the isolated main pulmonary arteries at controlled pressures. It is demonstrated that stepwise increments of pressure in the pulmonary arteries are accompanied by increases in systemic vascular resistance and in hind-limb vascular resistance. These changes were demonstrated over the whole range of 5-120 cm H₂O pressure in the pulmonary arteries. In contrast there were no significant changes in renal vascular resistance or heart rate. It is .also shown that changing the temperature of the perfusate in the pulmonary artery from 37°C to 30°C is associated with a decrease in systemic vascular resistance. The effects of raising the pulmonary arterial pressure and of cooling the pulmonary artery were abolished by cervical vagotomy. It is suggested that there is a tonic reflex vasoconstrictor tone generated by activity of receptors lying in or close to the walls of the pulmonary artery. It is further suggested that the differential effects on systemic vascular resistance and renal resistance may distribute cardiac output preferentially to the kidney providing one mechanism by which changes in blood volume may lead to appropriate changes in renal solute excretion. The later hypothesis was put to test by collecting urine from the intact kidneys of animals with isolated pulmonary pouch preparation. A step increase in the pouch pressure evoked a corresponding rise in the urinary volume, osmolar clearance, sodium excretion rate, but not the free water clearance and the potassium excretion rate. The response may be caused by renal hemodynamic changes as a result of the reflex increase in systemic arterial pressure. The rise in sodium excretion rate continued even after the release of the pressure in the pulmonary artery pouch thus the role of a natriuretic hormone in the reflex was suspected. A series of animals with one kidney intact and one kidney isolated and perfused with constant pressure was used in attempt to demonstrate the natriuretic action. These results confirmed the hemodynamic effect on the urinary function of the intact kidney. In the isolated kidney there was no statistically significant increase in sodium excretion rate, therefore the role of a natriuretic agent in the reflex response to distension of the pulmonary artery is still uncertain. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 93-120).

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

Monocrotaline is a pyrrolizidine alkaloid found in plants implicated in livestock and human poisoning. Laboratory rats given monocrotaline develop pulmonary hypertension and right heart hypertrophy in the weeks following administration of the chemical. Lung weight increases and right heart hypertrophy correlate with increased pulmonary artery pressure. Rats which consumed monocrotaline drinking water (20 mg/l) for only 4 days developed significant increases in lung and heart weights 14 days after exposure began. This exposure was equivalent to a dose of 15 mg/kg. Other treatment combinations of time (0-10 days exposure) and monocrotaline concentration (5-60 mg/l in drinking water) were tested. The accumulative dose calculated for each of the treatment combinations which produced toxicity was in the range of 15 to 20 mg/kg. Monocrotaline injury appears to be cumulative, but organ weight increases reverse once exposure is stopped. As pulmonary hypertension develops and pulmonary arteries hypertrophy, the force with which isolated pulmonary artery segments contract decreases. This is a loss of efficacy rather than potency to the contracting agents KCl, norepinephrine, and 5-hydroxytryptamine. Relaxation of arteries under conditions of potassium-return (a measure of Na⁺/K⁺ ATPase activity) was also altered by monocrotaline treatment. In vivo monocrotaline treatment had little effect on the force of K⁺-return relaxation. However, the rate at which arteries relaxed was significantly decreased following 4 days ingestion of monocrotaline drinking water (20 mg/l). In vitro ouabain treatment and endothelial injury also decreased the rate of K⁺-return relaxation. Another Na⁺/K⁺ ATPase activity, ⁸⁶Rb⁺ uptake, was decreased following monocrotaline treatment only when 5-hydroxytryptamine was present and only uptake associated with the endothelium was affected. These studies utilized a very low exposure to monocrotaline (4 days ingestion of 20 mg/l monocrotaline drinking water or 15 mg/kg) to produce toxicity in rats. Monocrotaline-induced toxicity measured 20 days after treatment included right heart and lung hypertrophy and decreased contractions of isolated pulmonary arteries. Monocrotaline treatment decreased the rate of Na⁺/K⁺ ATPase-dependent relaxation of isolated pulmonary arteries 4 days after treatment began.

Pulmonary arterial hypertension (PAH) is a disease in which pulmonary vascular resistance increases. The cell membrane of pulmonary artery smooth muscle cells (PASMC) in PAH patients is depolarised, resulting in disrupted Ca2+ signalling leading to smooth muscle constriction and PASMC proliferation and migration. In rat pulmonary artery (PA) smooth muscle the KV7 K+ channels, encoded by the KCNQ genes, have been proposed to contribute to the resting K+ current, promoting low resting tone by maintaining a negative membrane potential and low intracellular Ca2+. KV7 channel activating drugs have the potential to counteract the dysfunctional signalling during PAH by causing hyperpolarisation. This study set out to determine if the KV7 channels are expressed in human PA and if so whether they can alter vascular tone, PASMC proliferation and/or migration due to their ability to reduce intracellular Ca2+ indirectly. The effects of KV7 K+ channel modulators on human PA tone were measured using myography, while KCNQ gene expression was examined with quantitative PCR. Markers of proliferation (5-bromo-2'-deoxy-uridine (BrdU) and Ki67 antigen), were used to measure PASMC proliferation, while migration was assessed using the scratch-wound assay. Human PASMCs express all KCNQ genes, except KCNQ2. The KV7 channel blockers XE991, linopirdine and (-)chromanol 293B, constricted PAs. The KV7 channel activators retigabine and zinc pyrithione (ZnPy) relaxed PAs pre-constricted with agonists. The retigabine response was enhanced in PAs constricted with Bay K 8644, abolished in ionomycin constricted PAs and reduced in the presence of 90 mM K+, suggesting inhibition of voltage-gated Ca2+ influx. Similar experiments on rat PAs suggest that only part of the ZnPy-induced relaxation can be attributed to KV7 channel activation. The KCNQ5 gene remained in cultured PASMCs while no KV7 channel modulator altered proliferation or migration. Thus KV7.5 channels could possibly be a marker of differentiated PASMCs and/or be involved in the regulation of cell phenotype. The results imply that KV7 channels play a role in regulating PA tone and Ca2+ signalling in PA smooth. It is concluded that although KCNQ5 transcripts are preserved in proliferating PASMC, it is unlikely they play a role in PASMC proliferation or migration. In summary, KV7 channel activators may be useful in the treatment of PAH since they can prevent vasoconstriction.

Pulmonary artery hypertension (PAH), which is diagnosed by an abnormal increase of blood pressure in the pulmonary artery, can be a severe disease, leading to heart failure. In recent years, medical imaging, such as echocardiography, magnetic resonance imaging (MRI), and computed tomography (CT), has been widely used due to its non-invasive property. Right pulmonary artery (RPA) wall distensibility derived from CT angiography was reported to serve as a reliabile marker for the diagnosis of PAH. This study presented a robust method for automatic segmentation of artery based on CT angiography. The algorithm can be divided into two steps: generation of initial contour and refinement of edge. In the first step, a series of original images at different cardiac phases were thresholded to retrieve appropriate intensity window of vessels, followed by the determination of initial contours by a series of morphological image processing on the binary images with two simple manual initializations. Initial contours without touching can be taken as the final results of segmentation, when others need further refinement of edge. In the second step, the center of vessel was automatically located by an ellipse fitting method and then the ray casting algorithm was applied to search for possible edge. Disconnected segments of edge will be linked to complete the vessel segmentation. Furthermore, cross-sectional areas of arteries at different cardiac phases can be measured and used to obtain distensibility. In this study, artery wall distensibility of patients and healthy subjects was evaluated on four vessels, including aorta, main pulmonary artery, right and left pulmonary artery. In addition, segmentation results of five subjects were compared with those obtained by manual selection to evaluate the reliability of the proposed method.

Thesis--University of Kentucky (M.S.), 2003. / Title from document title page. Document formatted into pages; contains viii, 86 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 82-85).

published_or_final_version / abstract / toc / Physiology / Doctoral / Doctor of Philosophy