Dissertation (Ph.D.)--University of Toledo, 2008. / Typescript. "Submitted as partial fulfillment of the requirements for The Doctor of Philosophy degree in Exercise Science." Bibliography: leaves 6-9, 39-46, 66-68, 90-94 and 111-115.

Thesis (D.P.E.)--Springfield College, 2004. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (D.P.E.)--Springfield College, 2004. / Includes bibliographical references.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (M.S.)--University of Delaware, 2008. / Principal faculty advisor: David G. Edwards, Dept. of Health, Nutrition, & Exercise Sciences. Includes bibliographical references.

Cell-derived microvesicles (MVs) are naturally released into the human circulation and an increase in the concentration of certain MV populations have been observed after exercise. However, the MV appearance dynamics, the exercise-related stimuli that induce their formation and physiological relevance are poorly understood. Hence, the overall objectives of this thesis were to: 1) characterise the circulating platelet (PMV) and endothelial-derived MVs (EMVs) responses during exercise and recovery, as well as their arteriovenous dynamics, 2) investigate the potential role of haemodynamic forces on MVs formation in vivo by vascular shear stress manipulations, and 3) explore the putative proliferative, chemotactic and angiogenic potential of exercise-derived MVs upon human vascular endothelial cells in vitro. Chapter 5 of this thesis describes the time-course of MV appearance in response to prolonged cycling, and demonstrates that intravascular [PMV] increases during and after exercise performed in the heavy intensity domain, whereas [EMV] remains unaltered. Moreover, [PMV] during exercise was related to estimates of vascular shear stress and plasma noradrenaline levels. Results from chapter 6 revealed that PMVs increased in the arterial circulation during passive heat stress, and in the arterial as well as venous circulation during short duration very heavy exercise engaging either a large or small muscle mass. The increases in [PMV] were not directly linked to local changes in vascular shear stress through heat stress and exercise, indicating a systemic PMV response. Finally, chapter 7 revealed that exercise-derived MVs supported endothelial proliferation and migration, while displaying pro-angiogenic potential in vitro. In conclusion, results of this thesis provide original information about MV dynamics, by demonstrating that PMV increase systemically in the circulation not only after but during exercise involving a small and large muscle mass. This MV response seems to be modulated by exercise intensity, and is only partially linked to levels of vascular shear stress. Moreover, circulating MVs produced during exercise present stimulatory angiogenic and mitogenic effects upon endothelial cells in vitro, suggesting a novel potential link between vascular adaptation and exercise training.

Introdução A poluição do ar é um fator de risco associado com descompensação e mortalidade em pacientes com insuficiência cardíaca (IC). Objetivo Avaliar o impacto de um filtro de polipropileno sobre desfechos cardiovasculares em pacientes com IC e voluntários saudáveis durante exposição controlada à poluição. Métodos Ensaio clínico duplocego, controlado e cruzado, incluindo 26 pacientes com IC e 15 voluntários saudáveis, expostos a três protocolos diferentes de inalação randomizados por ordem: Ar Limpo; Exposição à Partículas de Exaustão do Diesel (ED); e ED filtrada. Os desfechos estudados foram função endotelial por índice de hiperemia reativa (RHi) e índice de aumento (Aix), biomarcadores séricos, variáveis de teste cardiopulmonar submáximo (caminhada de seis-minutos [tc6m]; consumo de oxigênio [VO2]; equivalente ventilatório de gás carbônico [VE/VCO2 slope]; consumo de O2 por batida [PulsoO2]) e variabilidade da frequência cardíaca (VFC). Resultados No grupo IC, a ED piorou o RHi [de 2,17 (IQR: 1,8-2,5) para 1,72 (IQR: 1,5-2,2); p=0,002], reduziu o VO2 [de 11.0 ± 3.9 para 8.4±2.8ml/Kg/min; p < 0.001], o tc6m [de 243,3±13 para 220,8 ± 14m; p=0,030] e o PulsoO2 [de 8.9 ± 1.0 para 7.8±0.7ml/bpm; p < 0.001]; e aumentou o BNP [de 47,0pg/ml (IQR: 17,3-118,0) para 66,5pg/ml (IQR: 26,5-155,5); p=0,004]. O filtro foi capaz de reduzir a concentração de poluição de 325±31 para 25±6?g/m3 (p < 0,001 vs. ED). No grupo IC, o filtro foi associado com melhora no RHi [2,06 (IQR: 1,5-2,6); p=0,019 vs. ED); aumento no VO2 (10.4 ± 3.8ml/Kg/min; p < 0.001 vs. ED) e PulsoO2 (9.7±1.1ml/bpm; p < 0.001 vs. ED); e redução no BNP [44,0pg/ml (IQR: 20,0-110,0); p=0,015 vs. ED]. Em ambos os grupos, a ED reduziu o Aix, sem efeito do filtro. O uso do filtro foi associado com maior ventilação e reinalação de CO2. Outras variáveis pesquisadas como VE/VCO2 slope e VFC não sofreram influências entre os protocolos. Conclusão A poluição do ar afetou adversamente o desempenho cardiovascular de pacientes com IC. Este é o primeiro ensaio clínico demonstrando que um simples filtrorespiratório pode prevenir a disfunção endotelial, a intolerância ao exercício e o aumento do BNP associados à poluição em pacientes com IC. O uso de máscaras com filtro tem o potencial de reduzir a morbidade associada à IC. Identificador ClinicalTrials.gov: NCT01960920 / Background Air pollution is considered a risk factor for heart failure (HF) decompensation and mortality. The effects of respiratory filters on patients with HF exposed to air pollution have not been established. Objective To test the effects of a respiratory filter intervention (filter) during controlled pollution exposure Methods Double-blind, randomized to order and 3-way crossover study with 26 HF patients and 15 control volunteers. Participants were exposed in three separate sessions to: clean air, diesel exhaust exposure (DE) or filtered-DE. Endpoints were endothelial function via reactive hyperemia index (RHi), and arterial stiffness (Aix), serum biomarkers, variables from submaximal cardiopulmonary exercise test (sixminute walk test [6mwt]; oxygen uptake [VO2]; ventilation and carbon dioxide production ratio [VE/VCO2 slope]; oxygen uptake per heart beat [O2Pulse]), and heart rate variability (HRV). Results In patients with HF, DE was associated with a worsening in RHi [from 2.17 (IQR: 1.8-2.5) to 1.72 (IQR: 1.5-2.2); p=0.002]; a decline in VO2 [from 11.0±3.9 to 8.4±2.8ml/Kg/min; 0.001], 6mwt [from 243.3 +- 13.0 to 220.8±13.7m; p=0.030] and O2Pulse [from 8.9±1.0 to 7.8±0.7ml/beat; 0.001] and a rise in BNP [from 47.0pg/ml (IQR: 17.3-118.0) to 66.5pg/ml (IQR: 26.5-155.5); p=0.004]. Filtration reduced the particulate concentration (from 325±31 to 25±6?g/m3; 0.001 vs. DE). In the HF group, filter was associated with an improvement in RHi [2.06 (IQR: 1.5-2.6); p=0.019 vs. DE]; an increase in VO2 (10.4 ± 3.8ml/Kg/min; p < 0.001 vs. DE) and O2Pulse (9.7 ± 1.1ml/beat; p < 0.001 vs. DE); and also a decrease in BNP [44.0pg/ml (IQR: 20.0-110.0); p=0.015 vs. DE]. In both groups DE decreased Aix, however filtration did not change these responses. In both groups, filtration was associated with higher pulmonary ventilation and CO2 rebreathing. Other variables as VE/VCO2 slope and HRV did not differ between exposure protocols. Conclusion Air pollution adversely affects cardiovascular performance in HF patients. To our knowledge, this is the first trial demonstrating that a simple respiratory-filter can prevent endothelial dysfunction; exercise intolerance and BNP rise in patients with HF during DE. Given these potential benefits, the widespread use of filters in HF subjects exposed to traffic-derived air pollution may have beneficial public health impacts and reduce the burden of HF ClinicalTrials.gov Identifier: NCT01960920

Introdução A poluição do ar é um fator de risco associado com descompensação e mortalidade em pacientes com insuficiência cardíaca (IC). Objetivo Avaliar o impacto de um filtro de polipropileno sobre desfechos cardiovasculares em pacientes com IC e voluntários saudáveis durante exposição controlada à poluição. Métodos Ensaio clínico duplocego, controlado e cruzado, incluindo 26 pacientes com IC e 15 voluntários saudáveis, expostos a três protocolos diferentes de inalação randomizados por ordem: Ar Limpo; Exposição à Partículas de Exaustão do Diesel (ED); e ED filtrada. Os desfechos estudados foram função endotelial por índice de hiperemia reativa (RHi) e índice de aumento (Aix), biomarcadores séricos, variáveis de teste cardiopulmonar submáximo (caminhada de seis-minutos [tc6m]; consumo de oxigênio [VO2]; equivalente ventilatório de gás carbônico [VE/VCO2 slope]; consumo de O2 por batida [PulsoO2]) e variabilidade da frequência cardíaca (VFC). Resultados No grupo IC, a ED piorou o RHi [de 2,17 (IQR: 1,8-2,5) para 1,72 (IQR: 1,5-2,2); p=0,002], reduziu o VO2 [de 11.0 ± 3.9 para 8.4±2.8ml/Kg/min; p < 0.001], o tc6m [de 243,3±13 para 220,8 ± 14m; p=0,030] e o PulsoO2 [de 8.9 ± 1.0 para 7.8±0.7ml/bpm; p < 0.001]; e aumentou o BNP [de 47,0pg/ml (IQR: 17,3-118,0) para 66,5pg/ml (IQR: 26,5-155,5); p=0,004]. O filtro foi capaz de reduzir a concentração de poluição de 325±31 para 25±6?g/m3 (p < 0,001 vs. ED). No grupo IC, o filtro foi associado com melhora no RHi [2,06 (IQR: 1,5-2,6); p=0,019 vs. ED); aumento no VO2 (10.4 ± 3.8ml/Kg/min; p < 0.001 vs. ED) e PulsoO2 (9.7±1.1ml/bpm; p < 0.001 vs. ED); e redução no BNP [44,0pg/ml (IQR: 20,0-110,0); p=0,015 vs. ED]. Em ambos os grupos, a ED reduziu o Aix, sem efeito do filtro. O uso do filtro foi associado com maior ventilação e reinalação de CO2. Outras variáveis pesquisadas como VE/VCO2 slope e VFC não sofreram influências entre os protocolos. Conclusão A poluição do ar afetou adversamente o desempenho cardiovascular de pacientes com IC. Este é o primeiro ensaio clínico demonstrando que um simples filtrorespiratório pode prevenir a disfunção endotelial, a intolerância ao exercício e o aumento do BNP associados à poluição em pacientes com IC. O uso de máscaras com filtro tem o potencial de reduzir a morbidade associada à IC. Identificador ClinicalTrials.gov: NCT01960920 / Background Air pollution is considered a risk factor for heart failure (HF) decompensation and mortality. The effects of respiratory filters on patients with HF exposed to air pollution have not been established. Objective To test the effects of a respiratory filter intervention (filter) during controlled pollution exposure Methods Double-blind, randomized to order and 3-way crossover study with 26 HF patients and 15 control volunteers. Participants were exposed in three separate sessions to: clean air, diesel exhaust exposure (DE) or filtered-DE. Endpoints were endothelial function via reactive hyperemia index (RHi), and arterial stiffness (Aix), serum biomarkers, variables from submaximal cardiopulmonary exercise test (sixminute walk test [6mwt]; oxygen uptake [VO2]; ventilation and carbon dioxide production ratio [VE/VCO2 slope]; oxygen uptake per heart beat [O2Pulse]), and heart rate variability (HRV). Results In patients with HF, DE was associated with a worsening in RHi [from 2.17 (IQR: 1.8-2.5) to 1.72 (IQR: 1.5-2.2); p=0.002]; a decline in VO2 [from 11.0±3.9 to 8.4±2.8ml/Kg/min; 0.001], 6mwt [from 243.3 +- 13.0 to 220.8±13.7m; p=0.030] and O2Pulse [from 8.9±1.0 to 7.8±0.7ml/beat; 0.001] and a rise in BNP [from 47.0pg/ml (IQR: 17.3-118.0) to 66.5pg/ml (IQR: 26.5-155.5); p=0.004]. Filtration reduced the particulate concentration (from 325±31 to 25±6?g/m3; 0.001 vs. DE). In the HF group, filter was associated with an improvement in RHi [2.06 (IQR: 1.5-2.6); p=0.019 vs. DE]; an increase in VO2 (10.4 ± 3.8ml/Kg/min; p < 0.001 vs. DE) and O2Pulse (9.7 ± 1.1ml/beat; p < 0.001 vs. DE); and also a decrease in BNP [44.0pg/ml (IQR: 20.0-110.0); p=0.015 vs. DE]. In both groups DE decreased Aix, however filtration did not change these responses. In both groups, filtration was associated with higher pulmonary ventilation and CO2 rebreathing. Other variables as VE/VCO2 slope and HRV did not differ between exposure protocols. Conclusion Air pollution adversely affects cardiovascular performance in HF patients. To our knowledge, this is the first trial demonstrating that a simple respiratory-filter can prevent endothelial dysfunction; exercise intolerance and BNP rise in patients with HF during DE. Given these potential benefits, the widespread use of filters in HF subjects exposed to traffic-derived air pollution may have beneficial public health impacts and reduce the burden of HF ClinicalTrials.gov Identifier: NCT01960920