O objetivo do presente estudo foi avaliar as características de dinâmica ovariana, aspectos do processo de involução uterina e características da hemodinâmica uterina e ovariana em éguas durante o período pós-parto (n = 10). Para isso, o conteúdo apresentado nesta dissertação está dividido em dois capítulos. No primeiro capítulo, os aspectos do processo de involução uterina e características de vascularização endometrial e mesometrial foram avaliados. Uma drástica redução (P<0,05) no diâmetro uterino foi observada durante os primeiros 7 dias pós-parto, com subsequente diminuição nas taxas de involução uterina, sendo que este processo se completou em torno de 21 dias para o corno anteriormente não gravídico (CNG) e 24 dias para o corno anteriormente gravídico (CG). Em relação às quantidades de fluido intrauterino, foi observado aumento nas quantidades entre os dias 1 e 2 pós-parto (d1 e d2), com significativa redução entre o d4 e d7, sendo que nenhuma quantidade de fluido foi observada em nenhum animal após o d16, ou após o terceiro dia pós-ovulação (D3). Nenhuma diferença (P>0,05) foi observada entre os cornos uterinos (CG e CNG) em relação às características de vascularização. Neste contexto, foi observado aumento (P<0,05) nos escores de vascularização endometrial entre d1 e d4, permanecendo semelhante até o d13, assim como aumento (P<0,05) de vascularização mesometrial entre o d1 e d2. No entanto, houve redução (P<0,05) nos escores de vascularização mesometrial do d2 ao d10. Após a ovulação, foi observado aumento de vascularização endometrial do D0 ao D5, com redução dos escores do D5 ao D11 e um novo aumento entre o D11 e o D14. De forma semelhante, o padrão de vascularização mesometrial foi similar ao observado no endométrio. No segundo capítulo, foram avaliados os aspectos de desenvolvimento e vascularização folicular durante o primeiro estro pós-parto, assim como as características de desenvolvimento e vascularização do corpo lúteo (CL) e níveis séricos de progesterona (P4) durante os 16 dias após a primeira ovulação pós-parto. Adicionalmente, os animais foram divididos em dois grupos, sendo o grupo precoce (ovulação antes do d10) ou tardia (ovulação após o d10). Em relação ao desenvolvimento folicular, nenhuma diferença foi observada entre os grupos nos dias relativos à primeira ovulação pós-parto, no entanto, quando avaliados os dias relativos ao parto, diferenças foram observadas entre os grupos. Neste contexto, o grupo precoce apresentou maior diâmetro (P<0,05) do folículo dominante (F1) em todos os dias no período pós-parto inicial (d1-d7), assim como apresentou um maior número de folículos (P<0,05) na classe > 25 mm durante os primeiros dias pós-parto (d1-d3). Adicionalmente, os animais do grupo tardia apresentaram maior número de folículos (P<0,05) na classe de 20-25 mm durante período pós-parto inicial (d4-d7). Em relação às características de vascularização, nenhuma diferença (P>0,05) foi observada entre os grupos quanto a vascularização do F1, pedículo ovariano ipsilateral ao F1, área e vascularização do CL ou níveis séricos de P4. Portanto, no período pós-parto inicial, padrões distintos nas características de vascularização uterina foram observados, porém, após a primeira ovulação pós-parto, os padrões observados assemelham-se aos de éguas não prenhes, possivelmente refletindo um retorno às características uterinas pré-gestacionais. Em relação às características de desenvolvimento folicular, não foram observadas diferenças entre os grupos em relação aos dias precedendo a primeira ovulação pós-parto, assim como as características de dinâmica folicular se assemelham aos resultados obtidos em ciclos de éguas não gestantes. No entanto, quando avaliadas as características em relação ao pós-parto imediato, diferenças no perfil de desenvolvimento folicular foram observadas entre os grupos, devido ao maior desenvolvimento folicular no grupo precoce durante a primeira semana pós-parto. Portanto, apesar do número reduzido de animais, os resultados observados sugerem que eventos cruciais ocorrem antes do parto, levando ao maior desenvolvimento folicular em alguns animais, principalmente os que apresentam rápido desenvolvimento folicular e ovulação pós-parto. / The aim of this study was to evaluate the characteristics of ovarian dynamics, aspects of the uterine involution process and characteristics of uterine and ovarian hemodynamic during the postpartum period in mares (n = 10). Thus, the content presented in this thesis is divided into two chapters. In the first chapter, the aspects of the uterine involution process and characteristics of endometrial and mesometrial vascularization were evaluated. A rapid reduction (P<0,05) in uterine diameter was observed during the first 7 days postpartum, with subsequent decrease in the rate of uterine involution, and this process was completed in about 21 days for formerly nongravid horn (CNG) and 24 days for the formerly gravid horn (CG). For intrauterine fluid accumulations, an increase (P<0,05) was observed between days 1 and 2 postpartum (d1 and d2), with a significant reduction between d4 and d7, and no amount of fluid collections was observed in the animals after d16 or after the third day post-ovulation (D3). No differences (P>0,05) was observed between the uterine horns (CG and CNG) in relation to vascular perfusion characteristics. In this context, an increase (P<0,05) in the endometrial vascularity scores was observed between d1 and d4, remaining similar until d13, as well as an increase (P<0,05) in mesometrial vascularization occurred between d1 and d2. However, a reduction (P<0,05) in scores of mesometrial vasculature was observed from d2 to d10. After ovulation, an increase of endometrial vascularization was observed from D0 to D5, with reduction in scores from D5 to D11 and a further increase between D11 and D14. Similarly, the pattern of mesometrial vascularization was similar to that observed in the endometrium. In the second chapter, follicular development and vascularization were assessed during the first postpartum estrus, as well the characteristics of development and vascular perfusion of the corpus luteum (CL) and serum progesterone (P4) during the 16 days after the first postpartum ovulation. Additionally, the animals were divided into two groups: the group early (ovulation before the d10) or late (ovulation after d10). With regard to follicular development, no difference was observed between groups in days relative to the first postpartum ovulation, however, when evaluated on the day of parturition, differences were observed between groups. In this respect, the early group had a larger diameter (P<0,05) of the dominant follicle (F1) each day in the early postpartum period (d1-d7) and had a greater number of follicles (P<0,05) in the > 25 mm class during the first days postpartum (d1-d3). Additionally, the animals in the late group showed a greater number of follicles (P<0,05) in the 20-25 mm class during early postpartum period (d4-d7). Regarding the characteristics of vascular perfusion, no difference (P>0,05) was observed between groups regarding the vascularization of F1, ipsilateral ovarian pedicle blood flow, area and vascularization of the CL or serum P4. Therefore, in the initial postpartum period, distinct patterns in the characteristics of uterine vascularization was observed, however, after the first ovulation postpartum, the observed patterns resemble those observed in non-pregnant mares, possibly reflecting a return to nonpregnant uterine characteristics. Regarding the characteristics of follicular development, no differences were observed between groups in relation to the days prior to the first postpartum ovulation, as well the characteristics of follicular dynamics are similar to the results obtained in cycles of non-pregnant mares. However, when the characteristics were evaluated concerning the immediate postpartum period, differences in the profile of follicular development were observed between groups, due to increased follicular development in the early group during the first week postpartum. Therefore, although a small number of animals, the results suggest that critical events occur before foaling, leading to increased follicle development in some animals, particularly those with rapid follicular development and postpartum ovulation.

INTRODUÇÃO: Exercícios físicos são utilizados como terapia nãofarmacológica para o tratamento da hipertensão arterial e o treinamento físico (TF) por natação é reconhecido por produzir remodelamento cardíaco em animais experimentais. Entretanto, a ação vasodilatadora da adenosina (ado) resultante do exercício físico como prevenção e tratamento da hipertensão é pouco explorada. OBJETIVO: Avaliar remodelamento cardíaco e papel da adenosina na distribuição do fluxo sanguíneo para o miocárdio após treinamento físico em SHR. MÉTODO: 28 SHR machos babies e adultos foram submetidos ao TF aeróbio de natação, durante 10 semanas (5x/sem - 1h/dia). Foram utilizados protocolos de microesferas coloridas para avaliar fluxo sanguíneo, técnicas de morfologia para avaliar hipertrofia cardíaca e análises bioquímicas para verificar atividade de enzimas envolvidas na formação de adenosina. RESULTADOS: TF por natação atenuou a evolução da HA em SHR babies (S: 145±2; T: 140±2 mmHg), promoveu bradicardia de repouso em SHR adultos (S: 340±4; T: 321±6 bpm) e desenvolveu HC nos dois grupos (TB: 12%; TA: 10%). Na condição basal, o TF aumentou o FS coronário em SHR babies (S: 4745±2145; T: 6970±2374 mi/coração) e maior resposta vasodilatadora à infusão de adenosina foi observada (S: 18946±6685; T: 25045±7031 mi/coração). Nesse grupo o TF promoveu maior atividade da enzima 5-nucleotidase, levando à maior formação de adenosina (S: 0.45±0.09; T: 1.01±0.05). CONCLUSÃO: O TF de natação, além de desenvolver HC e apresentar maior hidrólise de AMP, promoveu aumento no FS coronário, sendo mostrado que desempenha um importante papel na regulação da hipertensão / ABSTRACT: Exercise training (ET) has been used as non-pharmacological therapy for hypertension treatment and the swimming physical training is recognized for yield cardiac remodeling in experiments. However, little is known on the effects of adenosine (Ado) resulting from ET as hypertension prevention and treatment. OBJECTIVE: To evaluate cardiac remodeling and the role of adenosine in cardiac blood flow distribution (BF) to the myocardium after aerobic ET on SHR. METHODS: 28 male SHR, babies and adults, were submitted to swimming training protocol during 10 weeks (5 times a week 1 h a day). Colored micro spheres protocols were used to evaluate blood flow, morphological techniques were used to evaluate cardiac hypertrophy and biochemical analysis were performed to verify enzyme activity in the adenosine formation. RESULTS: ET attenuated the evolution of hypertension in babies SHR group (S: 145±2; T: 140±2 mmHg), HR was lower in adults SHR (S: 340±4; T: 321±6 bpm) and CH increased in both groups (TB: 12%; TA: 10%). At basal condition, BF was increased in trained babies (S: 4745±2145; T: 6970±2374 mi/heart) and higher vasodilatation response were observed due to adenosine infusion (S: 18946±6685; T: 25045±7031 mi/heart). In this group, the ET promoted a higher 5- nucleotidase enzyme activity leading to a higher adenosine formation (S: 0.45±0.09; T: 1.01±0.05). CONCLUSION: The swimming training developed CH as well as increased adenosine formation, leading to higher coronary blood flow, being demonstrated its important role in hypertension regulation

Foram analisados os efeitos da manobra de preensão manual (PM) na autorregulação encefálica (AE) dinâmica, através de um método não estacionário que utiliza o modelo de autorregressão de médias móveis. Doze indivíduos saudáveis foram orientados a realizar a manobra de PM durante 11 minutos com contração muscular constante e carga de 30% da força máxima. Registraram-se continuamente as medidas da velocidade do fluxo sanguíneo nas artérias cerebrais médias, pressão parcial de CO2 (PCO2) no ar expirado e pressão arterial (PA) não invasiva, durante o repouso (5 min), PM (3 min) e recuperação (3 min). A pressão crítica de fechamento (PCrF) e o produto área-resistência (PAR) foram obtidos empregando-se o método do primeiro harmônico. O índice de autorregulação encefálica (IAE) variável no tempo foi calculado através do modelo da autorregressão de médias móveis. As variáveis foram expressas em porcentagem de variação em relação aos valores obtidos no repouso (30 s previamente ao início da manobra de PM). Não houve alteração significativa da PCO2 do ar expirado durante MP. A PA aumentou continuamente durante a manobra (27% dos valores basais), enquanto que a velocidade do fluxo sanguíneo encefálico elevou-se inicialmente e alcançou um platô (15% dos valores basais). A elevação da PA aumentou o PAR, possivelmente devido à vasoconstricção arteriolar encefálica, o que refletiria a atuação do componente miogênico na regulação do fluxo sanguíneo encefálico; por outro lado, a PCrF reduziu-se, o que representa a ação do mecanismo metabólico. O IAE apresentou diminuição tanto no início quanto ao fim da manobra de PM; este achado pode estar relacionado à reação de alerta e/ou à diferença no tempo de resposta dos mecanismos envolvidos na adaptação neurovascular (mecanismos miogênico, metabólico e neurogênico). Conclui-se que o estudo da AE dinâmica com o modelo da autorregressão de médias móveis, durante a manobra de PM, pode ampliar os conhecimentos acerca das modificações hemodinâmicas encefálicas durante o exercício e elucidar aspectos ainda pouco conhecidos da resposta fisiológica do organismo / We investigated the effect of handgrip (HG) maneuver on time-varying estimates of dynamic cerebral autoregulation (CA), using the autoregressive moving average (ARMA) technique. Twelve healthy subjects were recruited to perform HG maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood flow velocity, end-tidal CO2 pressure (PETCO2), and noninvasive arterial blood pressure (ABP) were continuously recorded during baseline, HG and recovery. Critical closing pressure (CrCP), resistance areaproduct (RAP), and time-varying autoregulation index (ARI) were obtained. PETCO2 did not show significant changes during HG maneuver. Whilst ABP increased continuously during the maneuver, to reach 27% of its baseline value, CBFV raised to a plateau approximately 15% above baseline. This was sustained by a parallel increase in RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could be associated with metabolic vasodilation. The time-varying ARI index dropped at the beginning and end of the maneuver (p<0.005), which could be related to corresponding alert reactions or to different time constants of the myogenic, metabolic and/or neurogenic mechanisms. Changes in dynamic CA during HG suggest a complex interplay of regulatory mechanisms during static exercise that should be considered when assessing the determinants of cerebral blood flow and metabolism

Orientador: Mara Patrícia Traina Chacon Mikahil / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação Física / Made available in DSpace on 2018-08-23T03:14:09Z (GMT). No. of bitstreams: 1 Souza_LucianaCristinade_M.pdf: 3136861 bytes, checksum: 3f028a579a4869dd47ab258e4144ea85 (MD5) Previous issue date: 2013 / Resumo: A redução da Variabilidade da Frequência Cardíaca (VFC) está associada com o alto risco de eventos cardiovasculares, e também ao processo de envelhecimento e ao grau de sedentarismo. A prática regular de exercícios físicos, destacadamente os aeróbios, reflete em um aumento da VFC, decorrente da reduzida atividade simpática quase sempre acompanhada do aumento da atividade parassimpática sobre o coração, tanto em condições de repouso, como após sessão de treinamento. A prescrição do treinamento de força no envelhecimento tem sido prescrito por gerar ganhos de força e hipertrofia diminuindo o risco de lesões e quedas. Nesse sentido, o exercício resistido (RE) associado com uma restrição do fluxo sanguíneo (RE-BFR) tem sido utilizado por proporcionar ganhos de força ou hipertrofia muscular similar ao treinamento tradicional, fazendo uso de intensidades reduzidas de treinamento. Entretanto, pouco se sabe sobre as respostas autonômicas cardiovasculares agudas associadas a este tipo de treinamento. Objetivo: Desta forma, o presente estudo se propôs a comparar as respostas agudas da VFC após sessões de RE tradicional e RE-BFR, utilizando um ou dois exercícios em membros inferiores. Métodos: Quinze homens (47,6±5,28 anos, 76,81±10,95 kg, 1,74±0,08m), saudáveis e não ativos participaram desse estudo. Os voluntários foram submetidos a quatro sessões randomizadas de treinamento, compostas pelos seguintes exercícios: Leg Press de alta intensidade (Leg-HI) (80% 1RM), Leg Press de baixa intensidade com restrição parcial do fluxo sanguíneo (Leg-BFR) (20% 1RM), Extensão do joelho e Flexão de joelho de alta intensidade (EF-HI) (80% 1RM) e Extensão do joelho e Flexão de joelhos de baixa intensidade com restrição parcial do fluxo sanguíneo (EF-BFR) (20% 1RM). Os dados de VFC foram coletados nos momentos pré durante 20min, e imediatamente após a sessão de treinamento durante 60min, na posição supina. A coleta foi feita utilizando monitor Polar® s810 e os dados foram analisados a partir do software Kubios HVR Analysis 1.1. Foi utilizada uma análise da curva de crescimento para expressar o comportamento das variáveis ao longo do período de recuperação, bem como a comparação entre as diferentes sessões de exercício. Foi utilizado o software SAS 9.2. Resultados: A análise da curva de crescimento identificou aumento no índice LFnu para o grupo Leg-HI comparado ao Leg-BFR(P = 0,0033) e EF-BFR(P = 0,0062). O grupo Leg-HI também mostrou maior redução de HFnu comparado ao Leg-BFR (P = 0,0033) e EF-BFR(P = 0,0062). Além disso, houve uma tendência para maior LF/HF para EF-HI comparado ao Leg-BFR(P = 0,0758). Houve efeito de tempo (P=0,0001; P=0,0001; P=0,0067) e efeito de grupo (P=0,001; P=0,0169; P=0,0001) para os índices iRR, SDNN e RMSSD, respectivamente. Entretanto, não houve efeito grupo x tempo para essas variáveis. Conclusões: Os resultados mostraram aumento da modulação simpática e diminuição na modulação parassimpática para Leg-HI quando comparado com ambos os protocolos de RE-BFR após a sessão de exercício. Esses resultados podem ser importantes especialmente para pessoas envelhecendo, visto que o RE-BFR pode ser um método interessante, pois somados aos benefícios neuromusculares já reportados, apresenta menor stress autonômico comparado ao RE de alta intensidade / Abstract: Reduced Heart Rate Variability (HRV) is associated with high risk of cardiovascular events, and also to the aging process and the degree of inactivity. The regular practice of physical exercise, the aerobic prominently, reflects an increase in HRV, due to reduced sympathetic activity almost always accompanied by an increase in parasympathetic activity on the heart, both at rest, and after the exercise session. The prescription of strength training in aging has been prescribed for generating gains in strength and hypertrophy decreasing the risk of injury and falls. Accordingly, the resistance exercise (RE) associated with a restriction of blood flow (RE-BFR) has been used for providing strength gains and muscle hypertrophy similar to traditional training with lower intensity training. However, studies about the acute cardiovascular autonomic responses associated with this type of training are scarce. Objective: Thus, the present study purposed to compare the acute responses of HRV after sessions of traditional RE and RE-BFR, using one or two exercises for lower limbs. Methods: Fifteen men (47.6 ± 5.28 years, 76.81 ± 10.95 kg, 1.74 ± 0.08m), healthy and non-active participated in this study. The volunteers were randomly assigned to four sessions of training, consist of the following exercises: Leg Press high intensity (Leg-HI) (80% 1RM), Leg Press low intensity with partial blood flow restriction (Leg-BFR) (20% 1RM), knee extension and knee flexion high intensity (EF-HI) (80% 1RM) and knee extension and knee flexion low intensity with partial restriction of blood flow (EF-BFR) (20% 1RM). HRV data were collected in pre session during 20min and immediately after session during 60min in the supine position. The collection was made using Polar ® S810 monitor and data were analyzed using the software Kubios HVR Analysis 1.1. Random coefficient growth curve analysis allowed comparison between slopes to express the behavior of variables over the period of recovery, as well as the comparison between different exercise sessions. We used SAS 9.2 software. Results: The analysis of the growth curve identified an increase in LFnu index to Leg-HI compared to Leg-BFR (P = 0.0033) and EF-BFR (P = 0.0062). The Leg-HI group also showed greater reduction in HFnu compared to Leg-BFR (P = 0.0033) and EF-BFR (P = 0.0062). In addition there was a tendency for higher LF/HF compared to EF-HI-Leg BFR (P = 0.0758). There was a time effect (P = 0.0001, P = 0.0001, P = 0.0067) and group effect (P = 0.001, P = 0.0169, P = 0.0001) to iRR, SDNN and RMSSD indices, respectively. However, no significant group vs time effect for these variables. Conclusions: The results showed increased sympathetic modulation and reduced parasympathetic modulation for Leg-HI when compared with both protocols RE-BFR after the exercise session. These results are especially important for aging people, since RE-BFR may be an interesting method because in addition to neuromuscular benefits reported, presented lower autonomic stress compared to RE high intensity / Mestrado / Atividade Fisica Adaptada / Mestra em Educação Física

Orientadores: Marcelo Ganzarolli de Oliveira, Lício Augusto Velloso / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-19T04:20:06Z (GMT). No. of bitstreams: 1 Souza_GabrielaFreitasPereirade_D.pdf: 2358320 bytes, checksum: 5cf57adeef1d3cfe0789e7a9320c4569 (MD5) Previous issue date: 2011 / Resumo: No presente estudo foram investigadas as ações fisiológicas associadas ao óxido nítrico (NO), obtidas topicamente na mucosa gástrica e sistemicamente nas administrações orais de dois S-nitrosotióis (RSNOs) doadores de NO, S-nitrosoglutationa (GSNO) e S-nitroso-N-acetilcisteína (SNAC) em modelos animais. A aplicação tópica ex-vivo de soluções de RSNOs na mucosa gástrica de ratos Sprague-Dawley levou ao aumento dose-dependente do fluxo sanguíneo gástrico (FSG), medido por fluxometria por laser-Doppler, com FSG máximo c.a. 5 x maior do que os obtidos pela aplicação de soluções equimolares de nitrito ou nitrato. A administração oral de soluções de GSNO e SNAC se refletiu em aumentos tempo e dose-dependentes do nível plasmático de nitrito+nitrato em camundongos Swiss. A administração de SNAC na doença hepática gordurosa não alcoólica (DHGNA) induzida em camundongos ob/ob ou Swiss não levou a alterações significativas na histologia hepática ou no padrão de aumento de massa dos animais. O acompanhamento cinético da estabilidade de soluções aquosas de GSNO e SNAC em função do pH e a identificação de seus produtos de decomposição, permitiram demonstrar que esses RSNOs se decompõem predominantemente através de mecanismos de hidrólise catalisada por ácido ou base com meias vidas máximas em torno do pH fisiológico. Observou-se que camundongos Swiss submetidos à dieta hiperlipídica apresentam um perfil heterogêneo de ganho de massa, que permite estabelecer uma correlação tempo-dependente da propensão e da resistência à obesidade com alterações nas expressões de neuropeptídios hipotalâmicos e na resistência à insulina e intolerância à glicose / Abstract: In the present study, the nitric oxide (NO)-associated physiological actions obtained topically on the gastric mucosa and systemically in oral administrations of two NO donors-S-nitrosothiols (RSNOs), S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) were investigated in animal models. The topical ex vivo administration of RSNOs solutions on the gastric mucosa of Sprague-Dawley rats led to a dose-dependent increase in the gastric blood flow (GBF), measured by laser-Doppler flowmetry, with maximum GBF value c.a. 5 x higher than those obtained by equimolar applications of nitrite and nitrate solutions. The oral administration of GSNO and SNAC solutions was reflected in a time and dose-dependent increases in the plasma nitrite+nitrate level in Swiss mice. SNAC administration on non alcoholic fatty liver disease (NAFLD) induced in ob/ob or Swiss mice did not lead to significant changes in liver histology or in the mass gain pattern of the animals. The kinetic monitoring of the stability of aqueous GSNO and SNAC solutions as a function of pH and the identification of their decomposition products allowed to demonstrate that these RSNOs decay predominantly through mechanisms of acid or base-catalyzed hydrolysis, with maximum half-lives around the physiological pH. It was observed that Swiss mice fed a high-fat diet show an heterogeneous mass gain profile, which allows establishing a time-dependent correlation of obesity propensity and resistance with changes in the expressions of hypothalamic neuropeptides and in insulin resistance and glucose tolerance / Doutorado / Físico-Química / Doutor em Ciências

Master of Science / Department of Kinesiology / Thomas J. Barstow / Limb blood flow increases linearly with exercise intensity; however, invasive measurements of microvascular muscle blood flow during incremental exercise have demonstrated submaximal plateaus. Diffuse correlation spectroscopy (DCS) noninvasively quantifies relative changes in microvascular blood flow at rest via a blood flow index (BFI). The purpose of this study was to quantify relative changes in tissue blood flow during exercise using DCS, compare the BFI of the flexor digitorum superficialis (BFI[subscript]FDS) muscle to brachial artery blood flow (Q̇[subscript]BA) measured via Doppler ultrasound, and employ near infrared spectroscopy (NIRS) alongside DCS to simultaneously measure perfusive and diffusive oxygen transport within a single volume of exercising skeletal muscle tissue. We hypothesized Q̇[subscript]BA would increase with increasing exercise intensity until task failure, BFI[subscript]FDS would plateau at a submaximal work rate, and muscle oxygenation characteristics (total-[heme], deoxy-[heme], and % saturation) measured with NIRS would demonstrate a plateau at a similar work rate as BFI[subscript]FDS. Sixteen subjects (23.3 ± 3.9 yrs; 170.8 ± 1.9 cm; 72.8 ± 3.4 kg) participated in this study. Peak power (P[subscript]peak) was determined for each subject (6.2 ± 1.4W) via an incremental handgrip exercise test to task failure. Measurements of Q̇[subscript]BA, BFI[subscript]FDS, total-[heme], deoxy-[heme], and % saturation were made during each stage of the incremental exercise test. Q̇[subscript]BA increased with exercise intensity until the final work rate transition (p < 0.05). No increases in BFI[subscript]FDS or muscle oxygenation characteristics were observed at exercise intensities greater than 51.5 ± 22.9% of P[subscript]peak and were measured simultaneously in a single volume of exercising skeletal muscle tissue. Differences in muscle recruitment amongst muscles of the whole limb may explain the discrepancies observed in Q̇[subscript]BA and BFI[subscript]FDS responses during incremental exercise and should be further investigated.

Doctor of Philosophy / Department of Anatomy and Physiology / Thomas J. Barstow / The interaction between dynamic muscle contractions and the associated muscle blood flow is very intriguing leading to questions regarding the net effect of these contractions on oxygen delivery and utilization by the working muscle. Study 1 examined the impact of contractions on muscle blood flow at the level of the femoral artery. We demonstrated that muscle contractions had either a facilitory, neutral, or net impedance effect during upright knee extension exercise as intensity increased from very light to ~70% peak work rate. This led to the question of what impact a change in contraction frequency might have on the coupling of blood flow to metabolic rate during cycling exercise. The blood flow/VO2 relationship has been shown to be linear and robust at both the central (i.e., cardiac output/pulmonary VO2) and peripheral (leg blood flow/leg VO2) levels. However, an increase in contraction frequency has been reported to either decrease, have no effect, or increase the blood flow response during exercise. Study 2 determined if the steady state coupling between muscle blood flow and metabolic rate (centrally and/or peripherally) would be altered by varying contraction frequency. Our results indicate that both central and peripheral blood flow/VO2 relationships are robust and remain tightly coupled regardless of changes in contraction frequency. Study 3 examined muscle microvascular hemoglobin concentration and oxygenation within the contraction/relaxation cycle to determine if microvascular RBC volume was preserved and if oxygen extraction occurred during contractions. We concluded that microvascular RBC volume was preserved during muscle contractions (i.e., RBCs remained in the capillaries), which could facilitate continued oxygen delivery. Further, there was a cyclic pattern of deoxygenation/oxygenation that corresponded with the contraction/relaxation phases of the contraction cycle, with deoxyhemoglobin increasing significantly during the contractile phase. These data suggest that oxygen extraction continues to occur during muscle contractions. Significant insight has been gained on the impact of muscle contractions on oxygen delivery to and exchange in active skeletal muscle. This series of studies forms a base of knowledge that furthers our understanding of the mechanisms which govern the control of skeletal muscle blood flow and its coupling to muscle metabolic rate.

Master of Science / Department of Kinesiology / Timothy I. Musch / Dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs) containing docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) has been demonstrated to produce advantageous effects on vascular function. Specifically, PUFA supplementation has resulted in enhanced brachial artery blood flow (Q), dilation, and vascular conductance (VC) during rhythmic handgrip exercise. The effects of fish oils (FO) on skeletal muscle blood flow (Qm) during dynamic whole body exercise, however, remain unknown. PURPOSE: To test our hypothesis that 6 weeks of dietary FO supplementation with DHA and EPA enhances regional Qm and VC to the hindlimb musculature during submaximal treadmill exercise. METHODS: Following 6 weeks of dietary supplementation with safflower oil (SO) (control; n = 9) or FO (n = 8), heart rate (HR), mean arterial pressure (MAP), and Q[subscript]m to the hindlimb were measured at rest and during submaximal treadmill exercise (20 m/min, 10%, ~65% VO[subscript]2max) via radiolabeled microspheres in adult male Sprague-Dawley rats. RESULTS: HR and MAP were not different between SO and FO at rest or exercise (P<0.05). Q[subscript]m and VC were not different between SO and FO at rest. During exercise, FO exhibited greater Q[subscript]m in 8 of the 28 muscle parts measured as well as greater VC in 11 of the 28 muscle parts measured. Additionally, FO exhibited greater (Q)[subscript] m (158[plus or minus]9) and VC (1.156[plus or minus]0.066) to the total hindlimb musculature than SO (128[plus or minus]10 ml/min/100g, 0.918[plus or minus]0.077 ml/min/100g/mmHg) (P<0.05). CONCLUSION: These results demonstrate that 6 weeks of dietary FO supplementation with DHA and EPA results in enhanced Q[subscript]m and VC to the hindlimb during submaximal exercise. Thus, supplementation with DHA and EPA may have therapeutic effects on oxygen delivery and vascular function in patients with impaired vascular function and exercise tolerance (i.e., congestive heart failure, diabetes).

Recent advances in retinal imaging have made it possible to take measurements of retinal oxygen saturation noninvasively in humans. This allows studying the supply of oxygen in healthy and diseased retinae, thereby advancing our understanding of both the normal functioning of the retina and of retinal pathologies. However, retinal oximetry is still a research tool only and requires further improvement before being used in a clinical setting. Here, a single-wavelength flickering light was used to increase retinal blood flow in healthy subjects. This increase is revealed by both vasodilation and an increase in retinal oxygen saturation. A flickering light stimulus provides the means to assess the sensitivity of any retinal oximetry system, as such systems should be able to pick up this increase in retinal blood flow. In addition, the flickering light allows for com- parison to be made within rather than between subjects and can be used to examine the activation of the eye. This reduces the influence of potential confounding factors between subjects including differences in fundus pigmentation and illumination. The most commonly used method to measure retinal oxygenation is the optical density ra- tio (ODR) approach. The standard approach is to compute the average ODR for each vessel segment by combining the hundreds of individual ODR readings and then to use the mean of these segment averages as a measure of oxygen saturation. Alternatively, it has been suggested that the peak location of Gaussian functions fitted to histograms of individual ODR readings can be used as an measure of retinal oxygenation. In response to a 10Hz flickering light, the venular diameter increased by 3.44% (SEM: ±0.53%) (n=16, p<0.05) and the arteriolar diameter by 1.87% (±0.72 %) (p<0.05). The optical density ratio, measured with the Gaussian fit, decreased in the venules from 0.713 (±0.015) to 0.694 (±0.015) (p<0.05). No changes in arteriolar optical density ratios were measured. The post-flicker measurement was computed as the average of up to four post-flicker datasets obtained at 10s, 20s, 30s and 40s after onset of flickering. These results suggest that the flickering light increased retinal blood flow. The mean absolute percentage error was lower in venules for the Gaussian fit method than for the gold standard method for datasets taken at 30s and 40s after onset of flickering. Thus, the Gaussian fit method was more robust. All measurements were taken with a custom-made retinal oximeter. The pixel intensity of the blood vessel and the intensity on either side of the vessel had to be extracted to compute the individual optical density ratios. This required the automatic extraction of the retinal vasculature. Two such algorithms were developed and applied to two databases of retinal fundus images: the DRIVE and the novel DR HAGIS database. One algorithm was purely based on the pixel intensities, while the other made use of oriented Gabor filters. These two algorithms segmented the images to a similar accuracy (DRIVE: 94.56% and 94.54%, DR HAGIS: 95.83% and 95.71% for the intensity and Gabor filter based algorithm, respectively) and performed as well as a human expert (DRIVE: 94.73%). These algorithms were of sufficient quality to extract individual segments for the oximetry study and to align fundus images.

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