Foram utilizadas vinte tartarugas da espécie Trachemys scripta elegans, sendo duas fêmeas jovens, quatro fêmeas adultas, oito machos jovens e seis machos adultos. Inicialmente, retiramos o plastrão, isolamos o coração e, já na aorta descendente, introduzimos uma cânula antes da bifurcação da aorta para injeção de solução de látex corado com pigmento vermelho para identificarmos as artérias com maior precisão. Após a injeção, os animais foram colocados em solução aquosa de formaldeído 20% por período não inferior a 72 horas e, após esse período, dissecamos as artérias responsáveis pela irrigação do baço. Observamos em 30% dos casos, o baço posicionado caudalmente ao cólon transverso e, em 70%, cranialmente ao mesmo, mas sempre apoiado neste segmento intestinal. Com relação à irrigação do baço, observamos que em 95% dos casos, o maior aporte sangüíneo era proveniente da artéria mesentérica cranial, onde apenas 30% dos animais apresentavam irrigação somente pela artéria lienal; já em 40% apresentavam irrigação pela artéria lienal e pequenos ramos da artéria cólica esquerda. Em 5% dos casos era irrigado pela artéria lienal e por um único ramo emitido por uma das artérias jejunais, 5% eram irrigados pela artéria lienal e por um ramo da artéria pancreaticaduodenal cranial e por uma artéria que tinha origem no tronco comum das artérias jejunais; 15% dos animais tinham seu baço irrigado pela artéria lienal e por ramos da artéria pancreaticaduodenal cranial. Em 5% dos animais observamos o baço sendo irrigado apenas por ramificações da artéria cólica esquerda. / This study was conduct using 20 turtles specie Trachemys scripta elegans, which 2 young females, 4 adults females, 8 young males and 6 adults males. Initially, it was took the hoof belly and, isolating the heart to identify more precisely the arteries was injected latex solution with red pigment through aorta descendens with one thin tube before aorta\'s bifurcation. After the latex injection, all the animals were submerged in 20% formaldeid water solution by a period of more than 72 hours. After that period, the arteries responsible by spleen irrigation were dissected. It was found in 30% of the cases the spleen was positioned behind colon transversum; and in 70% in front of colon transversum. Regarding the spleen irrigation, it was observed in 100% of the cases that arteria lienalis had its origin in arteria mesenterica cranialis. Which 30% had irrigation only by arteria lienalis. In 40% the irrigation was done by arteria lienalis and small branches of arteria colica sinistra. In 5% of the cases it was irrigated by arteria lienalis and by na unique branch sent by one of arteriae jejunales. In 5% of the cases the irrigation through arteria lienalis and by one branch of arteria pancreaticaduodenalis cranialis, and also by one artery with origin in the common trunk from arteriae jejunales. In 15% from the animals, irrigation was done by arteria lienalis and by branches from arteria pancreaticaduodenalis cranialis. In 5% of the cases the spleen was irrigated just by ramifications of arteria colica sinistra.

Peripheral arterial disease (PAD) affects approximately 200 million individuals worldwide. It is characterized by a reduction in blood flow to the lower extremities due to atherosclerosis. This can result in leg pain, tissue loss, and ultimately amputation. Revascularization procedures aim to restore blood flow, but up to 50% of patients require another intervention within a year. Revascularization monitoring and early detection of failure are crucial in preventing limb loss and adverse cardiovascular events. However, current evaluation methods do not directly measure perfusion and are limited in a significant segment of PAD patients, such as those with diabetes and renal insufficiency. Diffuse optical imaging (DOI) techniques are promising tools to overcome these limitations. Employing near-infrared light, they are non-invasive, non-ionizing, contrast-free, and cost-effective methods that are sensitive to hemodynamic parameters such as changes in oxy-, deoxy-, and total hemoglobin concentration, making DOI ideal for revascularization monitoring. In this dissertation, I investigate and develop DOI systems for the purpose of monitoring lower extremity revascularization procedures in PAD patients. We utilize a contact-based diffuse optical spectroscopy (DOS) system to monitor localized foot perfusion in an ongoing clinical study of 100 patients undergoing lower extremity angiography. I demonstrate the utility of DOS measurements to provide valuable insights into revascularization related hemodynamic remodeling and to predict revascularization success. Furthermore, I also develop a clinic friendly contact-free diffuse optical tomography (DOT) system that is better-suited for PAD patients with ulcers. I show that this system can provide spatial maps of perfusion within the foot. Collectively, this work establishes diffuse optical imaging as a valuable imaging modality for the evaluation of lower extremity perfusion.

Orientador: João Luiz Amaro / Banca: Sidney Glina / Banca: Humberto Elias Lopes / Banca: Eliney Ferreira Faria / Banca: Paulo Kawano / Resumo: O presente estudo tem como objetivo avaliar o impacto no corpo cavernoso causado pela lesão isolada do nervo e artéria cavernosa, assim como determinar o efeito da tadalafila (IPDE-5) na remodelação tecidual, utilizando um modelo experimental de ratos. 50 ratos machos, da raça Whistar, pesando entre 250 e 350 gramas, foram aleatoriamente divididos, de forma randomizada em cinco grupos. Grupo 1 (G1): controle cirúrgico - CCir (n=10), submetidos apenas a exposição do feixe vásculo nervoso peri prostático. Grupo 2 (G2): Lesão Nervosa Isolada - LNI (n=10), os animais foram submetidos a lesão seletiva do nervo cavernoso bilateralmente. Grupo 3 (G3): Lesão Vascular Isolada - LVI (n=10), os animais foram submetidos a lesão seletiva da artéria cavernosa bilateralmente. Grupo 4 (G4): Lesão Nervosa Isolada + Tadalafila - LNI+T (n=10), os animais foram submetidos a lesão do nervo cavernoso bilateralmente e receberam tadalafila na dose de 5mg/Kg/dia. Grupo 5 (G5): Lesão Vascular Isolada + Tadalafila - LVI+T (n=10), os animais foram submetidos a lesão seletiva da artéria cavernosa bilateralmente e receberam tadalafila na dose de 5mg/Kg/dia. A tadalafila foi administrada pelo período de 45 dias, quando os animais foram sacrificados e o corpo cavernoso foi removido em bloco para análise histomorfométrica. A organização e composição microestrutural do corpo cavernoso foram avaliadas por histomorfometria, imunohostoquímica e métodos bioquímicos. A análise estatística foi realizada pelo teste de comparações múltiplas de Bonferroni. Entre os grupos avaliados não houve diferença entra as áreas de secção peniana, demonstrando homogeneidade entre os mesmos. O volume de músculo liso diminuiu significativamente no grupo com lesão neural (G2), quando comparado ao controle (12,87±1,90 vs 21,78±1,81 p< 0,05), o que não ocorreu no grupo com lesão neural tratado com ... / Abstract: This study aims to evaluate the impact on the corpus cavernosum caused by isolated injury of the cavernous nerve and artery, as well as determine the effect of tadalafil (IPDE-5) on tissue remodeling, using a rat experimental model. Fifty (50) male Whistar rats, weighing between 250 and 350 grams, were divided randomly into five groups. Group 1 (G1): surgical control - SCon (n=10) having undergone only exposure of the periprostatic neurovascular bundle. Group 2 (G2): Isolated Nerve Lesion - INL (n=10), the animals were subjected to selective cavernous nerve injury, bilaterally. Group 3 (G3): Isolated Vascular Lesion - IVL (n=10), the animals were subjected to selective cavernous artery injury, bilaterally. Group 4 (G4): Isolated Nerve Lesion + Tadalafil - INL+T (n=10), the animals were subjected to cavernous nerve injury, bilaterally, and received tadalafil in a dosage of 5mg/kg/day. Group 5 (G5): Isolated Vascular Lesion + Tadalafil - IVL+T (n=10), the animals were subjected to selective cavernous artery injury, bilaterally, and received tadalafil in a dosage of 5mg/kg/day. The tadalafil was administered for a 45 day period, then the animals were sacrificed and the corpus cavernosum was removed en bloc for histomorphometric analysis. The organization and microstructural composition of the corpus cavernosum were assessed through histomorphometry, immunohistochemistry, and biochemical methods. Statistical analysis was performed using the Bonferroni multiple comparisons test. RESULTS: Among the groups evaluated, there was no difference between the penile section areas, demonstrating their consistency. The volume of smooth muscle decreased significantly in the group with nerve injury (G2) when compared with the control (12.87±1.90 vs 21.78±1.81 p<0.05), which did not occur in the group with nerve injury treated with tadalafil (G4). Sinusoidal space volume decreased both in the group with vascular injury ... / Doutor

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Includes bibliographical references. / 3 v. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / A selection of research papers, reviews, books and book chapters ... considered representative of the works by the author over the years 1958-1993. / Thesis (D.Sc.)--University of Adelaide, Dept. of Pathology, 1995

The overall goals of this project were to develop microstructurally based constitutive models to characterize the mechanical behavior of arteries and to investigate the effects of HIV proteins and antiretroviral drugs on the microstructure and mechanical behavior. To this end we created several constitutive models in aim 1 using a rule of mixtures approach, investigated the role of viral proteins in aim 2 through the use a transgenic mouse model, and studied the effects of the antiretroviral drug AZT administered to mice in aim 3. It is well known that the local mechanical environment which cells experience mediates growth and remodeling and that subsequent growth and remodeling can change that mechanical environment. This remodeling includes changes in the content and organization of the constituents of arteries (collagen, elastin, and smooth muscle cells). The first aim thus created models that incorporated the content and organization of these constituents using a rule-of-mixtures approach. The models we developed were able to capture the mechanical behavior of the arteries as well as previously developed phenomenological models while providing more physical meaning to the parameters, some which can be measured experimentally for incorporation into future models. Aims 2 and 3 investigated the mechanical and microstructural changes to murine arteries in response to HIV proteins or the drug AZT. While the development of antiretroviral therapy has greatly increased the life expectancy of patients with HIV, a number of other complications and co-morbidities including cardiovascular disease have become apparent. While clinical data has implicated both the virus and the antiretroviral drugs as playing roles, this work addressed the need of investigating these effects in a controlled manner. Specifically we used mouse models and focused on the two subclinical markers of increased intima-media thickness and arterial stiffening. Aim 2 used a transgenic mouse that expressed most of the human HIV proteins. We observed both intima-media thickening and arterial stiffening in alignment with clinical data. Other changes that also support a proatherogenic phenotype included decreased elastin content and changes in cathepsin activity. Aim 3 administered the antiretroviral drug AZT to healthy mice and we also observed the same subclinical markers of atherosclerosis including intima-media thickening and arterial stiffening as well as the other proatherogenic changes of decreased elastin and changes in cathepsin activity. Several other parameters including axial behavior, opening angles, collagen content, and collagen fiber angles were also quantified. These were important to fully characterize the vessel and may also be incorporated in the future into the constitutive models developed in aim1. In conclusion, in aim 1 we developed a microstructurally based constitutive model of arteries that effectively captures the mechanical behavior and includes parameters that have more physical meaning and some of which are experimentally tractable. Aims 2 and 3 both observed several subclinical markers of atherosclerosis in mice that express HIV proteins or were given AZT, providing a good model for future work and suggesting that both the HIV virus and antiretroviral drugs may play roles in the development of atherosclerosis in HIV.

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published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences