INTRODUÇÃO: A avaliação da morfologia das artérias coronárias é objeto de interesse dentro do desenvolvimento de uma melhor qualidade de imagem que possibilite um diagnóstico fidedigno das lesões coronárias. Para isso, estudos com ressonância magnética (RM) e ultra-som intravascular coronário (UIV) tem se desenvolvido na tentativa de mensurar e caracterizar melhor a doença coronária in vivo. OBJETIVO: Determinar a capacidade da ressonância magnética em detectar alterações na luz e na parede das artérias coronárias com aterosclerose, tendo como padrões o ultra-som intracoronário e a anatomia patológica.MÉTODOS: Estudamos 13 corações de pacientes, falecidos por infarto do miocárdio. Os corações foram fixados com solução de formol a 10% sob perfusão com pressão constante de 80 mmHg. Em seguida as artérias coronárias interventricular anterior, direita e circunflexa esquerda foram dissecadas, preservando-se a adventícia e parte da aorta. As seguintes medidas foram feitas: área total do vaso (ATV), área da luz (AL), maior (MaDV) e menor (MeDV) diâmetro do vaso, diâmetro mínimo (DminL) e máximo (DmaxL) da luz do vaso e espessura mínima (EminP) e máxima (EMaxP) da parede pelos seguintes métodos: UIV, RM e anatomia patológica (AP). Foram analisadas 38 artérias, correspondendo a 355 segmentos arteriais. Utilizamos em média os 3 primeiros centímetros de cada artéria, e em cada centímetro foram avaliados 3 segmentos: proximal, médio e distal. As medidas obtidas nos 3 métodos foram comparadas através do teste de correlação de Pearson e método de Bland Altman Plot. As comparações entre os 3 métodos, pelas suas respectivas médias e desvios padrão, foram realizadas pela análise de variância para medidas repetidas.RESULTADOS: As médias das variáveis na RM,UIV e AP foram respectivamente: ATV 15,46 ± 4,83, 13,86 ± 5,20 e 11,87 ± 4,57; MaDV 4,75 ± 0,84, 4,40 ± 0,87 e 4,18 ± 0,87; MeDV 4,23 ± 0,73, 3,75 ± 0,72 e 3,48 ± 0,70; AL 5,59 ± 2,93, 6,86 ± 3,18 e 5,57 ± 2,46; DmiL 2,54 ± 0,64, 2,55 ± 0,57 e 2,32 ± 0,52; DmaxL 3,07 ± 0,65, 3,34 ± 0,76 e 3,04 ± 0,83; EminP 0,76 ± 0,25, 0,38 ± 0,18 e 0,34 ± 0,17; EmaxP 1,11 ± 0,39, 0,88 ± 0,37 e 0,90 ± 0,48. As correlações com maior significância foram: 1. APxRM: ATV e AL (r=0,767 e r=0,805); 2. RMxUIV ATV e AL (r=0,836 e r=0,770); 3. APxUIV ATV e MeDV (r=0,89 e r=0,692). As variáveis que tiveram melhor correlação foram a ATV, MaDV, MeDV e AL nos 3 métodos. A EminP e EmaxP tiveram fraca correlação. As médias das variáveis DminL e DmáxL nos 3 métodos foram muito próximas. Na variável ATV notamos que a média superestimou a medida do vaso. CONCLUSÃO: A RM correlacionou-se com o UIV para a maioria das medidas, em especial: ATV, MaDV, MeDV, AL e DmaxL. As medidas nesses 2 métodos se correlacionaram em menor intensidade com a AP, sendo nesta sempre com valores menores. Assim, a RM pode vir a ser método fidedigno para o diagnóstico e prognóstico na doença aterosclerótica coronariana, na dependência do desenvolvimento tecnológico permitindo maior rapidez na aquisição de imagens / INTRODUCTION: Numerous studies in the area of image have been conducted to evaluate the morphology of the coronary arteries. Major technical advances have provided better image quality that allows a reliable diagnosis of coronary lesions. For this, studies with cardiovascular magnetic resonance (CMR) and coronary intravascular ultrasound has been developed in an attempt to better measure and characterize coronary heart disease \"in vivo\". PURPOSE: To determine the capacity of CMR to detect changes in the lumen and the wall of the coronary arteries caused by atherosclerosis, using as references intravascular ultrasound (IVUS) and pathology measurements. METHODS: We examined 13 hearts of patients that died of myocardial infarction. The hearts were fixed with formalin solution to the 10% with constant pressure of 80 mmHg. Then the left anterior descending (LAD), left circumflex (LCx) and right coronary (RCA) arteries were dissected from the the aorta and epicardial fat and isolated as pathological specimens. The arteries were analyzed by CMR, IVUS and pathology and the images were subjected to analysis of the following parameters: total vessel area (TVA), lumen area (LA), major (MaVD) and minor vessel diameter (MiVD), minor (MiLD) and major lumen diameter (MaLD), minor (MiWT) and major wall thickness (MaWT). We analyzed the entire 355 arterial segments, using at least the first proximal 2 cm, in most cases 3 cm or more of each artery. In every centimeter we measured the parameters of the proximal, mid and distal segments. The measures obtained in the three methods were compared using Pearson correlation and the method of Bland and Altman plot. Comparisons among the three methods, by their respective averages and standard deviations, were carried out by analysis of variance with repeated measures. RESULTS: Measures in CMR,IVUS e PA were as follow respectively: TVA 15.46 ± 4.83, 13.86 ± 5.20 and 11.87 ± 4.57; MaVD 4.75 ± 0.84, 4.40 ± 0.87 and 4.18 ± 0.87; MeVD 4.23 ± 0.73, 3.75 ± 0.72 and 3.48 ± 0.70; LA 5.59 ± 2.93, 6.86 ± 3.18 and 5.57 ± 2.46; MiLD 2.54 ± 0.64, 2.55 ± 0.57 and 2.32 ± 0.52; MaLD 3.07 ± 0.65, 3.34 ± 0.76 and 3.04 ± 0.83; MiWT 0.76 ± 0.25, 0.38 ± 0.18 and 0.34 ± 0.17; MaWT 1.11 ± 0.39, 0.88 ± 0.37 and 0.90 ± 0.48.The best correlations were: 1. PAxCMR: TVA and LA (r=0.767 and r=0.805); 2. CMRxIVUS: TVA and LA (r=0.836 and r=0.770); 3. PAxIVUS: TVA and MiVD (r=0.89 and r=0.692). The variables that have shown the best correlations were TVA, MaVD, MiVD and LA in the 3 methods. The MiWT and MaWT had a weak correlation. The averages of variables MiLD and MaLD in the 3 three methods were very similar. CONCLUSION: CMR correlated well with IVUS for the majority of measures done and in especial for TVA, LA, MaVD, MiVD and MaLD. Measures in both methods had lower correlation with pathology that showed the lower values of all. As a perspective CMR may be a reliable method for measuring coronary artery dimensions, depending on new technical development for faster image acquirer

Trinta dias após a indução do diabetes, em aortas com endotélio (E+) de ratas diabéticas (DB), a Rmáx ao cloreto de potássio (KCl) foi reduzida e a resposta à noradrenalina (NA) foi semelhante as controles (CT). A retirada do endotélio (E-) potencializou a resposta ao KCl e NA, porém essa potencialização foi de menor magnitude em DB. A Rmáx à NA em aortas E+: não foi alterada após o seqüestro de ânion superóxido ou inibição da síntese de óxido nítrico (NO) em DB, nas CT esta resposta foi reduzida e aumentada, respectivamente, e foi reduzida apenas nas DB após o bloqueio dos receptores para endotelina (ET). A mobilização de cálcio (Ca2+) em resposta à NA foi reduzida em aorta E+ e E- de DB. Em aortas de ratas diabéticas, as alterações no aparato contrátil, como por exemplo. A redução da mobilização de Ca2+, podem ser responsáveis pela redução da resposta contrátil e a redução da modulação do NO sobre a resposta à NA ou o aumento da liberação de ET pelo endotélio podem ser os responsáveis pela manutenção da resposta à NA. / Thirty days after induction of diabetes, in aortas with endothelium (E+) of diabetic female rats (DB), the maximum response (Rmax) to potassium chloride (KCl) was reduced and the Rmax to noradrenaline (NE) was similar to controls (CT). The endothelium (E-) removal increased the response to KCl and NE, but this increase was of a lower magnitude in DB than in CT. In aortas E+, the Rmax to NA: was not altered by superoxide anion scavenger or nitric oxide (NO) synthesis inhibition in DB, whereas in CT this response is reduced or increased, respectively, and was reduced only in DB after endothelin (ET) receptor blockade. The mobilization of the calcium (Ca2+) in response to NE was reduced in aortas E+ and E- of the DB. In aortas of DB, the alterations in the contractile apparatus, for example, reduction of the Ca2+ mobilization may be responsible for the reduction of the vasoconstriction. The reduction of NO modulation upon the response to NE or the increase of the ET release can be the responsible for the maintenance of the contractile response to NE.

Introdução: Segmentos coronários com doença aterosclerótica manifesta podem coexistir no mesmo paciente com artérias normais à angiografia. Porém as características desses vasos angiograficamente normais permanecem pouco estudadas. O presente estudo visa a descrição in vivo, através do ultrassom intravascular com histologia virtual, da presença, grau de acometimento e composição da doença coronária aterosclerótica em artérias normais ou quase normais (irregularidades parietais) do ponto de vista angiográfico, em pacientes com doença coronária obstrutiva em outros territórios. Métodos: Pacientes com doença coronária obstrutiva foram selecionados de forma prospectiva e foram submetidos a estudo ultrassonográfico com histologia virtual de múltiplos vasos. Artérias epicárdicas principais foram classificadas em quatro grupos baseado na sua aparência angiográfica: 1) vasos completamente normais, 2) vasos com irregularidades parietais, 3) vasos com pelo menos uma estenose discreta, 4) vasos com pelo menos uma estenose moderada ou importante. Para os vasos com estenoses luminais (grupos 3 e 4 acima), apenas segmentos que não possuíam lesão maior ou igual a 30% (não obstrutivos) foram incluídos na análise. Resultados: Um total de 60 pacientes (154 vasos) foram incluídos no estudo. Vasos angiograficamente normais apresentaram menor carga de placa, menos componente necrótico, menor densidade de lesões e quase nenhuma placa com características de alto risco. Entretanto, em vasos com irregularidades parietais encontramos uma maior carga de placa com elevada densidade de lesões pelo ultrassom intravascular similar a segmentos \"não obstrutivos\" de vasos com estenoses luminais evidentes pela angiografia em outro ponto. Conclusão: Artérias coronárias completamente normais pela angiografia parecem apresentar pouca doença aterosclerótica. Entretanto, vasos com irregularidades parietais estão associados com um maior acometimento aterosclerótico e elevada densidade placas de alto risco, achado este que não pode ser rapidamente obtido com o uso apenas da angiografia coronária / Background: Extensively diseased arteries may co-exist, in the same patient, with coronary vessels with a normal appearance by angiography. Thus far, however, the characteristics of the latter remain poorly described. The present study aims to evaluate in vivo, using intravascular ultrasound (IVUS) with radiofrequency backscatter analysis (RF), the presence, degree, and composition of atherosclerosis in arteries with angiographically normal or near-normal appearance, in patients with diagnosed coronary disease in other territories. Methods: Patients with diagnosed obstructive coronary disease were prospectively selected and underwent protocol-mandated multi-vessel IVUS-RF. Major epicardial branches were classified into four groups based on their angiographic appearance: 1) completely normal-looking; 2) near-normal; 3) at least one mild stenosis; 4) at least one severe or moderate stenosis. For vessels with lumen stenosis (groups 3 and 4 above), only \"non-stenotic\" portions were included in the IVUS analysis. Results: A total of 60 patients (154 vessels) comprised the study population. Completely normal-looking vessels had lower plaque burden, lower necrotic component, lower density of lesions, and almost null high-risk plaques. Conversely, a nearnormal aspect, with only subtle lumen irregularities by angiography, was associated with increased disease burden, with an elevated density of plaques with high-risk features, similar to \"non-stenotic\" portions of vessels with obvious atherosclerosis elsewhere. Conclusions: Coronary vessels with a completely normal-looking appearance by angiography appear to have little atherosclerosis. Conversely, yet mild luminal irregularities by angiography are associated with increased disease burden and elevated density of high-risk plaques by IVUS, which cannot be readily assessable by angiography alone. Descriptors: angiography; atherosclerosis; coronary artery disease; plaque, atherosclerotic; ultrasonography, interventional; coronary vessels.Background: Extensively diseased arteries may co-exist, in the same patient, with coronary vessels with a normal appearance by angiography. Thus far, however, the characteristics of the latter remain poorly described. The present study aims to evaluate in vivo, using intravascular ultrasound (IVUS) with radiofrequency backscatter analysis (RF), the presence, degree, and composition of atherosclerosis in arteries with angiographically normal or near-normal appearance, in patients with diagnosed coronary disease in other territories. Methods: Patients with diagnosed obstructive coronary disease were prospectively selected and underwent protocol-mandated multi-vessel IVUS-RF. Major epicardial branches were classified into four groups based on their angiographic appearance: 1) completely normal-looking; 2) near-normal; 3) at least one mild stenosis; 4) at least one severe or moderate stenosis. For vessels with lumen stenosis (groups 3 and 4 above), only \"non-stenotic\" portions were included in the IVUS analysis. Results: A total of 60 patients (154 vessels) comprised the study population. Completely normal-looking vessels had lower plaque burden, lower necrotic component, lower density of lesions, and almost null high-risk plaques. Conversely, a nearnormal aspect, with only subtle lumen irregularities by angiography, was associated with increased disease burden, with an elevated density of plaques with high-risk features, similar to \"non-stenotic\" portions of vessels with obvious atherosclerosis elsewhere. Conclusions: Coronary vessels with a completely normal-looking appearance by angiography appear to have little atherosclerosis. Conversely, yet mild luminal irregularities by angiography are associated with increased disease burden and elevated density of high-risk plaques by IVUS, which cannot be readily assessable by angiography alone

Ca2+-activated potassium channels (KCa) and canonical transient receptor potential (TRPC) channels are essential to endothelial function. In ischemic heart disease, or in cardiac surgery, coronary endothelium is subjected to ischemia-reperfusion (I-R) / hypoxia-reoxygenation (H-R) injury. Hyperkalemic cardioplegic or organ preservation solutions used in cardiac surgery including heart transplantation also impair endothelial function. The present study was designed to mainly investigate whether endothelial dysfunction occurring in H-R or in hyperkalemic exposure is attributable to alterations of intermediate- and small-conductance KCa (IKCa and SKCa) channels, or TRPC channels, in particular, the TRPC3 channel. / Exposure to 60-min hypoxia followed by reoxygenation inhibited the vasorelaxant response of coronary arteries to IKCa / SKCa activator 1-EBIO. H-R reduced endothelial IKCa and SKCa currents and downregulated IKCa expression in PCECs. 1-EBIO enhanced endothelial K+ current that was blunted by H-R. / Exposure to hyperkalemic solutions decreased Ca2+ influx via TRPC3 in PCECs. The reduced Ca2+ influx in PCECs and the attenuated EDHF-mediated vasorelaxation in porcine coronary arteries, which were caused by hyperkalemic or cardioplegic / organ preservation solutions, were restored by OAG. / In PCECs, hypoxia for 60-min with reoxygenation reduced TRPC3 current and Ca2+ influx via TRPC3, which was accompanied by decreased NO release and endothelium-dependent vasorelaxation of porcine coronary arteries. The compromised endothelial function was restored by OAG. The translocation of TRPC3 to endothelial membrane was inhibited by H-R. / In TRPC3-overexpressing HEK293 cells, followed by reoxygenation, short-time hypoxia (10-min) enhanced, whereas prolonged hypoxia (60-min) reduced the current induced by TRPC3/6/7 activator OAG. / Our results indicate that: (1) Endothelial IKCa, SKCa and TRPC3 play an important role in regulating vascular tone; TRPC3 contributes to NO release from endothelial cells and is also involved in the function of EDHF. (2) H-R (60-30 min) reduces endothelial IKCa and SKCa currents with downregulation ofthe protein expression of IKCa. (3) H-R has dual effect on TRPC3 with short-time hypoxia (lO-min) enhancing whereas prolonged hypoxia (60-min) decreasing the electrophysiological activity of this channel. H-R (60-30 min) inhibits the translocation of TRPC3 to endothelial membrane. Furthermore, H-R inhibits Ca2+ influx via TRPC3 and such inhibition is associated with a decrease of NO production. (4) The activator of IKCa / SKCa or TRPC protects coronary endothelium against H-R injury. In coronary endothelium exposed to hyperkalemic or cardioplegic / organ preservation solutions, TRPC activator also exhibits protective effect. / The above findings are likely to have significant implications in ischemic heart disease and in modem cardiopulmonary surgery. / Whole-cell membrane currents of IKCa, SKCa, or TRPC3 were recorded by patch-clamp in primary cultured porcine coronary endothelial cells (PCECs). TRPC3 current was also studied in human embryonic kidney cells (HEK293 cells) transiently overexpressed with TRPC3 gene. Protein or mRNA expression of these channels was detected by Western blot or RT-PCR. Intracellular Ca2+ concentration was measured by Ca2+ imaging technique. Isometric force study was performed in a wire myograph and endothelial nitric oxide (NO) release was measured electrochemically by using a NO-specific microsensor in porcine coronary small arteries. / Huang, Junhao. / "December 2010." / Adviser: Qin Yang. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 138-165). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Wu Min. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 87-114). / Abstracts in English and Chinese. / Declaration --- p.i / Acknowledgement --- p.ii / Publication list --- p.iii / Abstract (English) --- p.xi / Abstract (Chinese) --- p.xiv / Abbreviations --- p.xvi / List of figures / tables --- p.xviii / Chapter Chapter 1. --- General Introduction --- p.1 / Chapter 1.1 --- Endothelial function in the regulation of vascular tone --- p.1 / Chapter 1.1.1 --- NO --- p.2 / Chapter 1.1.2 --- PGI2 --- p.5 / Chapter 1.1.3 --- EDHF --- p.6 / Chapter 1.2 --- Alteration of endothelial functions after preservation with cardioplegia /organ preservation solutions in the coronary and pulmonary microcirculations --- p.18 / Chapter 1.2.1 --- Cardioplegia/organ preservation solutions --- p.21 / Chapter 1.2.2 --- Effect of Cardioplegia/organ preservation solutions on endothelial function --- p.22 / Chapter 1.2.2.1 --- Effect of K+ on endothelial function --- p.23 / Chapter 1.2.2.2 --- Effect of other components on endothelial function --- p.24 / Chapter Chapter 2. --- Materials and Methods --- p.26 / Chapter 2.1 --- Isometric force study in coronary/pulmonary resistance arteries --- p.26 / Chapter 2.1.1 --- Preparation of vessels --- p.26 / Chapter 2.1.1.1 --- Preparation of porcine coronary small arteries --- p.26 / Chapter 2.1.1.2 --- Preparation of porcine pulmonary small arteries --- p.26 / Chapter 2.1.2 --- Technique of setting up --- p.29 / Chapter 2.1.2.1 --- Mounting of small vessels --- p.29 / Chapter 2.1.2.2 --- Normalization procedure for small vessels --- p.29 / Chapter 2.1.3 --- EDHF-mediated vasorelaxation --- p.30 / Chapter 2.1.3.1 --- Precontraction and stimuli of EDHF --- p.30 / Chapter 2.1.3.2 --- """True"" response of EDHF" --- p.31 / Chapter 2.1.4 --- Data acquisition and analysis --- p.32 / Chapter 2.2 --- Electrophysiological study --- p.32 / Chapter 2.2.1 --- Preparation of small porcine coronary/pulmonary arteries --- p.32 / Chapter 2.2.2 --- Preparation of microelectrode --- p.32 / Chapter 2.2.3 --- Impaling of microelectrode --- p.33 / Chapter 2.2.4 --- Recording of membrane potential --- p.33 / Chapter 2.3 --- Statistical analysis --- p.34 / Chapter 2.4 --- Chemicals --- p.34 / Chapter Chapter 3. --- Effects of Celsior Solution on Endothelial Function in Resistance Coronary Arteries Compared to St. Thomas' Hospital Solution --- p.37 / Chapter 3.1 --- Abstract --- p.37 / Chapter 3.2 --- Introduction --- p.38 / Chapter 3.3 --- Experimental design and analysis --- p.40 / Chapter 3.3.1 --- Vessel preparation --- p.40 / Chapter 3.3.2 --- Normalization --- p.40 / Chapter 3:3.3 --- "Relaxation study: BK-induced, EDHF-mediated relaxation" --- p.41 / Chapter 3.3.4 --- Cellular electrophysiological study: EDHF-mediated cellular hyperpolarization and associated relaxation --- p.41 / Chapter 3.3.5 --- Data analysis --- p.42 / Chapter 3.4 --- Results --- p.43 / Chapter 3.4.1 --- Relaxation study --- p.43 / Chapter 3.4.1.1 --- Resting force --- p.43 / Chapter 3.4.1.2 --- U46619-induced precontraction --- p.43 / Chapter 3.4.1.3 --- EDHF-mediated relaxation --- p.43 / Chapter 3.4.2 --- Electrophysiological studies --- p.44 / Chapter 3.4.2.1 --- Resting membrane potential --- p.44 / Chapter 3.4.2.2 --- EDHF-mediated cellular hyperpolarization --- p.45 / Chapter 3.4.2.3 --- Cellular hyperpolarization-associated relaxation --- p.45 / Chapter 3.5 --- Discussion --- p.46 / Chapter 3.5.1 --- Effects of Celsior solution on endothelial function --- p.47 / Chapter 3.5.2 --- Effects of ST solution on EDHF-mediated function --- p.48 / Chapter 3.5.3 --- Comparison between Celsior and ST solutions on EDHF-mediated function --- p.48 / Chapter 3.5.4 --- Clinical implications --- p.49 / Chapter Chapter 4. --- Effects of Perfadex and Celsior Solution on Endothelial Function in Resistance Pulmonary Arteries --- p.57 / Chapter 4.1 --- Abstract --- p.57 / Chapter 4.2 --- Introduction --- p.58 / Chapter 4.3 --- Experimental design and analysis --- p.59 / Chapter 4.3.1 --- Vessel Preparation --- p.59 / Chapter 4.3.2 --- Normalization --- p.60 / Chapter 4.3.3 --- Isometric force study --- p.60 / Chapter 4.3.4 --- Electrophysiological studies --- p.61 / Chapter 4.3.5 --- Data analysis --- p.61 / Chapter 4.4 --- Results --- p.62 / Chapter 4.4.1 --- Relaxation study: EDHF-mediated relaxation --- p.62 / Chapter 4.4.1.1 --- Resting force --- p.62 / Chapter 4.4.1.2 --- U46619-induced precontraction --- p.62 / Chapter 4.4.1.3 --- EDHF-mediated relaxation --- p.62 / Chapter 4.4.2 --- Electrophysiological studies --- p.63 / Chapter 4.4.2.1 --- Resting membrane potential --- p.63 / Chapter 4.4.2.2 --- EDHF-mediated cellular hyperpolarization --- p.64 / Chapter 4.4.2.3 --- Cellular hyperpolarization-associated relaxation --- p.64 / Chapter 4.5 --- Discussion --- p.65 / Chapter 4.5.1 --- Effects of Celsior solution on endothelial function during cardiopulmonary surgery --- p.65 / Chapter 4.5.2 --- Effects of Perfadex solution on EDHF-mediated endothelial function --- p.66 / Chapter 4.5.3 --- Comparison between Celsior and Perfadex solutions on EDHF-mediated function --- p.66 / Chapter 4.5.4 --- Clinical implications --- p.67 / Chapter Chapter 5. --- Exploration of the Nature of EDHF - the Effect of H2O2 on the Membrane Potential in the Rat Small Mesenteric Arteries --- p.73 / Chapter Chapter 6. --- General Discussion --- p.75 / Chapter 6.1 --- EDHF-mediated endothelial function in porcine coronary and pulmonary circulation --- p.75 / Chapter 6.1.1 --- Role of EDHF in the regulation of porcine coronary arterial tone --- p.75 / Chapter 6.1.2 --- Role of EDHF in the regulation of porcine pulmonary arterial tone --- p.76 / Chapter 6.2 --- Alteration of EDHF-mediated endothelial functions after exposure to organ preservation solutions --- p.77 / Chapter 6.2.1 --- Effects of hyperkalemic solution on EDHF-mediated endothelial function in coronary and pulmonary circulation --- p.78 / Chapter 6.2.2 --- Effects of low-potassium-based preservation solution on EDHF-mediated endothelial function in pulmonary circulation --- p.79 / Chapter 6.2.3 --- Comparison between hyperkalemic solution and low-potassium-based preservation solution on EDHF-mediated endothelial function --- p.80 / Chapter 6.2.4 --- Effects of other component of organ preservation solutions on EDHF-mediated endothelial function --- p.81 / Chapter 6.3 --- Clinical implications --- p.82 / Chapter 6.4 --- The effect of H202 on the membrane potential in rat small mesenteric arteries --- p.83 / Chapter 6.5 --- Limitation of the study --- p.84 / Chapter 6.6 --- Future investigations --- p.85 / Chapter 6.7 --- Conclusions --- p.85 / References --- p.87

O Proepicárdio (PE) é uma estrutura transitória que dá origem aos componentes dos vasos coronários. Para avaliar seu potencial vascular em sítio adulto, transplantamos um coração neonatal para o pavilhão auricular de um animal adulto. Duas semanas depois, 2 PEs de embriões GFP+ foram transferidos para a superfície deste coração. Em outro grupo, transferimos os PEs diretamente para o pavilhão auricular. Para avaliar a incorporação de células GFP, e investigar sua diferenciação realizamos ensaios de imunofluorescência (IF) para GFP em combinação com outros marcadores. A adição do PE em sítio adulto teve como resultado a participação deste em processos de vasculogênese, iniciando a formação de novos vasos sanguíneos via formação de ilhotas sanguíneas e em um processo angiogênico, diferenciando-se em células endoteliais que se incorporaram aos vasos já existentes. Baseados nisso podemos afirmar que o PE possui potencial vasculogênico/angiogênico em sítio adulto, podendo ser exploradas como modelo para revascularização cardíaca e recuperação de tecidos vasculares. / The Proepicárdio (PE) is a transient structure giving rise to all components of the coronary vessels. To evaluate the vasculogenic potential of the PE in an adult site, a neonatal heart was transplanted into the subcutaneous of an adult ear Later, two PE from GFP-transgenic mice were transferred to the surface of this heart. In another group, we transferred the PEs directly into the ear pinna. To evaluate the incorporation of GFP cells derived from the PE, and to investigate their possible differentiation, we performed immunofluorescence (IF) for GFP in combination with other markers. The addition of PE in an adult site resulted in its participation in a vasculogenic and in an angiogenic processes. Based on this we conclude that PE cells can differentiate and likely participate in a neovascularization process when transplanted to adult sites. These findings demonstrate that the vasculogenic potential of the PE cells is conserved in an adult site and our model is adequate to study the mechanisms involved in the development and regeneration of vasculature.

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 186-210). Also available on the Internet.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from PDF title page (viewed on July 16, 2010). Includes bibliographical references.

Objetivo: checar se poluentes do ar urbano de São Paulo induzem alterações sangüíneas e cardiopulmonares. MM: camundongos Balb/c foram expostos por 7, 14, 21, 30 e 45 dias em 3 câmaras: Limpa (controle), Intermediária (seletiva ao PM) e Suja (ar externo). Após exposição, os animais foram ventilados (FlexiVent) e coletados dados de mecânica pulmonar, sangue, coração e pulmão. Foram registrados PM, CO, SO2 e NO2 diários. Resultados: aos 21 e 45 dias coincidentes com picos de poluição houve aumento da resistência de via aérea (45d p=0,012), leucocitose (21d p < 0,001 e 45d p=0,039) e vasoconstricção pulmonar (21d p=0,034) nos animais da Câmara Suja, sem alteração de coronárias. Nenhum poluente excedeu limites de qualidade de ar / Objective: verify if air pollution of São Paulo city induces alterations in blood and cardiopulmonary systems. MM: Balb/c mice were exposed during 7, 14, 21, 30 and 45 days to 3 chambers: Clean (control), Intermediate (PM only) and Dirty (external air). After exposure, animals were ventilated (FlexiVent) and collected lung mechanics data and blood, heart and lung. PM, CO, SO2 e NO2 were measured daily. Results: on day 21 and 45, coincidently to peak of pollutions, there was proximal airway resistance increase (45d p=0.012), leukocytosis (21d p < 0.001 and 45d p=0.039) and vasoconstriction of peribronchiolar arterioles (21d p=0.034) in animals of Dirty Chamber with no alterations of coronaries. Neither pollutants exceeded the standard limits

Trinta dias após a indução do diabetes, em aortas com endotélio (E+) de ratas diabéticas (DB), a Rmáx ao cloreto de potássio (KCl) foi reduzida e a resposta à noradrenalina (NA) foi semelhante as controles (CT). A retirada do endotélio (E-) potencializou a resposta ao KCl e NA, porém essa potencialização foi de menor magnitude em DB. A Rmáx à NA em aortas E+: não foi alterada após o seqüestro de ânion superóxido ou inibição da síntese de óxido nítrico (NO) em DB, nas CT esta resposta foi reduzida e aumentada, respectivamente, e foi reduzida apenas nas DB após o bloqueio dos receptores para endotelina (ET). A mobilização de cálcio (Ca2+) em resposta à NA foi reduzida em aorta E+ e E- de DB. Em aortas de ratas diabéticas, as alterações no aparato contrátil, como por exemplo. A redução da mobilização de Ca2+, podem ser responsáveis pela redução da resposta contrátil e a redução da modulação do NO sobre a resposta à NA ou o aumento da liberação de ET pelo endotélio podem ser os responsáveis pela manutenção da resposta à NA. / Thirty days after induction of diabetes, in aortas with endothelium (E+) of diabetic female rats (DB), the maximum response (Rmax) to potassium chloride (KCl) was reduced and the Rmax to noradrenaline (NE) was similar to controls (CT). The endothelium (E-) removal increased the response to KCl and NE, but this increase was of a lower magnitude in DB than in CT. In aortas E+, the Rmax to NA: was not altered by superoxide anion scavenger or nitric oxide (NO) synthesis inhibition in DB, whereas in CT this response is reduced or increased, respectively, and was reduced only in DB after endothelin (ET) receptor blockade. The mobilization of the calcium (Ca2+) in response to NE was reduced in aortas E+ and E- of the DB. In aortas of DB, the alterations in the contractile apparatus, for example, reduction of the Ca2+ mobilization may be responsible for the reduction of the vasoconstriction. The reduction of NO modulation upon the response to NE or the increase of the ET release can be the responsible for the maintenance of the contractile response to NE.