PURPOSE: This study examined the effects of creatine (Cr) supplementation and blood flow restriction (BFR) on muscle strength, neuromuscular function, body composition, and endothelial health in women across 8 weeks of training. METHODS: Recreationally active women (n= 59) were randomized into one of five groups: BFR-Pl (BFR exercise and placebo), BFR-Cr (BFR exercise and creatine supplementation), Pl (low-load exercise without BFR and placebo), Cr (low-load exercise without BFR and creatine supplementation), or Control (no exercise, BFR, or supplementation). Assessments of isometric strength, concentric strength, neuromuscular responses, muscle size, body composition, and endothelial function were evaluated at baseline, post-loading (after 5 days of supplementation), 4 weeks, and 8 weeks. RESULTS: All groups experience similar increases in measures of isometric strength (6.5%), muscle thickness (2.9%), cross sectional area (4.1%), body mass (2.8%), and total body water (1.2%). There were no significant changes in neuromuscular parameters or endothelial function for any of the groups across the 8-week intervention. The BFR and Cr groups (10.6 – 15.7%), however, experienced larger increases in concentric strength compared to placebo and control groups (6%). CONCLUSION: The results of the present study indicated that BFR and creatine alone are potent stimulators for muscle strength and muscle growth but may not have additive benefits. Further, the supplementation of creatine throughout this 8-week training program did effect body mass or total body water. Overall, resistance exercise, BFR and Cr can be used independently or together to induce positive muscular adaptations among women.

Bakgrund: Styrka är en viktig faktor i självständighet och säkerhet, i synnerlighet hos äldre. Evidensen idag säger att högintensiv styrketräning är att föredra över lågintensiv i syfte att maximera styrkeökning. BFR-träning är en metod där blodflödet stryps åt för att snabbare åstadkomma en metabolisk stress vilket innebär att styrketräning kan utföras lågintensivt men sägs producera resultat jämförbara med högintensiv styrketräning. Syfte: Syftet med denna studie var att mäta effekt avseende styrka och hypertrofi av lågintensiv BFR-träning samt smärta och upplevd ansträngning hos två friska unga män. Metod: Två personer rekryterades till studien. De fick utföra en intervention med lågintensiv BFR-träning tre pass i veckan under fem veckor. Utfallsmåtten för studien är maxstyrka mätt i 1RM, peak torque mätt i Biodex Isokinetic Dynamometer, hypertrofi mätt med måttband runt låren, samt upplevelse av ansträngningsgrad samt smärta utifrån Borg-RPE och NRS. Resultat: Deltagare 1 visade en förändring av muskelstyrka i peak torque (-7,2% H., -2,4% V.), -9,4% i benpress (1RM), +35,4% i knäextension (1RM). Omkrets uppmättes till -0,5cm H. (-0,79%), +1cm V. (+1,61%). Borg-RPE var jämn under hela interventionen medan NRS värdena sjönk successivt. Deltagare 2 visade en förändring av muskelstyrka i peak torque (-3,1% H., -3,2% V.), +11,5% i benpress (1RM), +9,3% i knäextension (1RM). Omkrets uppmättes till -0,5cm H. (-0,86%), -0,5cm V. (-0,88%). Borg-RPE och NRS visade båda en successivt stigande trend. Slutsats: 5 veckors lågintensiv BFR-träning visar en potential för styrkeökning i 1RM. Ingen styrkeökning i peak torque observerades och ingen påtaglig skillnad uppmättes i omkrets. BFR-träning som metod bör således vara en lägre prioriterad träningsmetod och bör endast användas efter noggrann övervägelse och uppsyn, med tanke på de kontraindikationer som finns. Denna studie undersökte endast unga friska individer vilket också då gör denna metod särskild applicerbar på denna målgrupp.

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Distortion to hemodynamic, ischemic and metabolic stimuli during low load resistance exercise with blood flow restriction (BFR) may influence regional vascular adaptation. This thesis investigated the acute response and chronic adaptations of the peripheral vasculature to low load resistance exercise with BFR. The methodology utilised Doppler ultrasound, strain gauge plethysmography and muscle biopsy for insightful measures of the vasculature at different regions of the arterial tree. Short term (4-6 weeks) localised low load (30-40% 1RM) resistance exercise with BFR increased brachial (3.1%) and popliteal (3.3%) artery maximal diameter (in response to ischemic exercise), forearm (29%) and calf (24%) post-occlusive blood flow, and calf filtration capacity (14%). These findings indicate potential vascular remodelling at the conduit (chapters 3, 4) resistance (chapter 4) and capillary (chapter 4) level of the vascular tree. Regional, rather than systemic, factors are responsible for these adaptations as evidenced by an absent response in the contralateral control limb. Transient improvements in popliteal artery FMD% occurred at week 2 before increased maximal diameter at week 6, suggesting functional changes precede structural remodelling (chapter 4). Maximal brachial artery diameter and forearm post-occlusive blood flow returned to baseline values after a 2 week detraining period, signifying rapid structural normalisation after stimulus removal (chapter 3). Enhanced capillarity, despite low training loads, could be explained by augmentation of VEGF (~7 fold), PGC-1α (~6 fold) and eNOS (~5 fold) mRNA, and upregulation VEGFR-2 (~5 fold) and HIF-1α (~2.5 fold) mRNA with BFR (chapter 5). This indicates a targeted angiogenic response potentially mediated through enhanced metabolic, ischemic and shear stress stimuli. Large between subject variability in the level of BFR was observed during upper and lower limb cuff inflation protocols. Adipose tissue thickness and mean arterial pressure were the largest independent determinants of upper and lower limb BFR, respectively (Chapter 6). In conclusion, this thesis demonstrates that low load resistance exercise with BFR induces adaptation in the conduit, resistance and capillary vessels. The mediators of this response are likely to be the hemodynamic and chemical signals elicited by repeated bouts of BFR resistance exercise, although confirmation of these mechanisms is required. The functional significance of these adaptations is unknown and warrants further investigation.

Low load resistance training (LLRT) with blood flow restriction (BFR) is a novel form of exercise that has been demonstrated to increase muscle mass and strength. Combined with the fact that as individuals age they lose both of these parameters, LLRT with BFR has been put forward as a method to help reverse/prevent the associated sarcopenia of ageing. This research investigated the effect the effect of LLRT with BFR on muscle strength firstly in younger people and then an older population group following 4 weeks of training. Muscle function measurements of young and old people included dynamic strength, identified as one repetition maximum (1 RM), isometric strength and isokinetic torque at a range of velocities (0.52 2.09 rad.s-1). Vascular adaptations were also measured using venous occlusion plethysmography to assess rest blood flow (Rbf) and post occlusive reactive hyperemia (PObf). The mechanisms behind any adaptations were measured following acute responses of plasma hormones and growth factors (cortisol, growth hormone (GH), insulin like growth factor 1 (IGF-1), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF)) as well as local skeletal muscle gene expression (IGF-1Ea and MGF mRNA) to LLRT with BFR. LLRT with BFR increased (P < 0.05) all measurements of muscle strength by 13 30% in both young and older people. PObf was also increased (P < 0.05) following 4 weeks of LLRT with BFR in both population groups. Acute responses to LLRT with BFR identified an increase (P < 0.05) in GH and VEGF in older people. These are similar response to those seen in the young. Finally local gene expression of MGF mRNA was elevated (P < 0.05) 24 hours post LLRT with BFR in both young and older people. Any changes in muscle and blood flow adaptations may be as a result of increased hormones and growth factors at a circulation and local level. Key words: Blood flow restriction, blood flow, muscle strength, growth hormone, IGF-1

Functional magnetic resonance imaging (fMRI) can be used to track neural activation in the brain during functional activities. The purpose of this study was to investigate brain neural responses to blood flow restricted (BFR) versus control handgrip exercise. Using a randomized crossover design, 25 subjects (12 males, 13 females) completed handgrip exercises during two conditions: BFR vs. control. To familiarize participants with the exercise conditions, one week prior to MRI scanning participants completed each exercise condition once on separate days, with 72 hours between days. The following week fMRI scans were performed at the same time of day, separated by 72 hours. The exercise protocol consisted of five 30-second sets of squeezing a nonmetallic handgrip exerciser (a reported 13.6 kg resistance), doing as many repetitions as possible, with 20-second rest intervals between sets. We saw a significant main effect of exercise condition (BFR versus control) between premotor dorsal (PMd)(F = 5.71, p = 0.022), premotor ventral (PMv)(F = 8.21, p = 0.007), and right ventral striatum (VS_R)(F = 7.36, p = 0.01). When considering anatomical regions of interest, we did not find significant differences between exercise conditions in bilateral S1 (p > 0.82), primary motor cortex (M1)(p > 0.33), supplementary motor area (SMA)(p > 0.66), cerebellum (CB)(p > 0.70), insular cortex (INS)(p > 0.45), anterior cingulate cortex (ACC)(p > 0.24), or thalamus (TH)(p > 0.66). Bilateral ACC (ACC_B), right middle frontal gyrus (MFG_R), and the right primary sensory cortex (S1_R) showed significant linear trends (p = 0.001) over the five exercise sets. Finally, the S1_R, left primary sensory cortex (S1_L), and the right anterior cingulate cortex (ACC_R) showed a main effect of set (p < 0.02). These data demonstrate that acute training with BFR during handgrip exercise results in different neural activation patterns in select areas of the brain, compared to a control. These results show that while completing less work with BFR exercise, subjects can achieve a similar amount of brain neural activation as with a higher-volume exercise. Brain neural activation is important to overall patient health and these findings may be important for prescribing training with BFR in clinical and applied research settings.

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

Vascular disease is the leading cause of mortality and morbidity in the western world, and account for the 1 of every 3 death’s in the US, but a cure for vascular disease is yet to be realized. Hematopoietic stem progenitor cells (HSPCs) are mobilized from bone marrow and have the innate propensity to accelerate vascular repair by reendothelialization and revascularization of ischemic areas. The vasoreparative ability of HSPCs is largely due to their capacity to home to the areas of hypoxia and their sensitivity to hypoxia plays a critical role in the vasoreparative functions of these cells. The discovery of vasoreparative potential of HSPCs resulted in a breakthrough approach of cell-based therapies for the treatment of ischemic vascular diseases. However, success of this approach is essentially dependent on the number of cells that could be collected from an individual. Therefore, novel mechanism-based strategies are needed to enhance the outcomes of autologous cell-based therapies in poor mobilizers and older adults. Recent evidence of a potential role of the vasoprotective axis of the renin angiotensin system (RAS) in HSPCs functions offers a breakthrough. Angiotensin-(1-7), the primary mediator of the protective functions which acts on Mas receptor (MasR), is generated by angiotensin converting enzyme-2 (ACE2). In this study, we tested the effects of hypoxia on stimulation of vasoreparative potential of HSPCs and in upregulation of ACE2 and MasR. Importantly, we delineated the molecular mechanism of hypoxic exposure in regulation of ACE2 and MasR in a HIF1α- dependent manner and hypoxic exposure induced shedding of the membrane bound ACE2 in HSPCs. We used luciferase, a reporter assay, cell-based assays, gene/protein expression studies and pharmacological strategies in human and mouse HSPCs to test our hypotheses. To verify the biological significance of hypoxia, we performed in vivo studies in mice and humans, which recapitulated the in vitro observations on vascular protective axis of RAS in HSPCs. Collectively, these studies provided mechanistic insights into hypoxic regulation of vascular protective axis of RAS in HSPCs and also provided compelling evidence for the clinical use of hypoxia as a promising approach for enhancing the vasoreparative outcomes of cell-based therapies. / American Heart Association grant, 13SDG16960025 / National Institutes of Health, National institute of Aging (NIA), 1R01AG056881

PURPOSE: This study comparted arterial occlusion pressure (AOP) of the superficial femoral artery (SFA) between the dominant and nondominant legs and the relationship between blood flow and occlusion pressure at rest and during muscle contractions in males and females. METHODS: The AOP of the SFA was measured using Doppler ultrasound in the dominant and nondominant legs of 35 (16 males, 19 females) apparently healthy, normotensive young adults. Blood flow in the SFA was measured in the resting state (REST) and during plantar flexion exercise (EXC) at occlusion pressures ranging from 0% to 100% of AOP. ANOVA was used to compare AOP between the dominant and nondominant legs and between males and females. Regression analysis was used to evaluate the influence of relevant variables on AOP. A mixed model was used to evaluate the relationship between blood flow and occlusion pressure at REST and during EXC. RESULTS: There was a significant difference in the AOP between the dominant and nondominant legs in males (230 ± 41 vs 209 ± 37 mmHg) and females (191 ± 27 vs 178 ± 21 mmHg), respectively. There was also a significant sex difference in the AOP in the dominant (230 ± 41 vs 191 ± 27 mmHg; p = 0.002) and nondominant (209 ± 37 vs 178 ± 21 mmHg; p = 0.004) legs, respectively. Regression analysis revealed that after accounting for leg circumference, age, sex, blood pressure, and skinfold thickness were not independent predictors of AOP. At REST and during EXC, there was a linear relationship between relative blood flow and occlusion pressure. CONCLUSIONS: Differences in leg circumference contribute to a portion of the differences in AOP between the dominant and nondominant legs and between sexes. The linear relationship between relative blood flow and occlusion pressure suggests that occlusion pressures during blood flow restriction exercise should be chosen carefully. A large variance in blood flow measurements at different occlusion pressures suggests the need for evaluating the reliability of blood flow measurements and standardization of methods.

Orientador: Franciele Marques Vanderlei / Resumo: Estudos sobre o treinamento resistido de baixa intensidade associado à restrição de fluxo sanguíneo (RFS) atualmente tem ganhado destaque, porém ainda existem lacunas que podem ser exploradas em relação aos seus efeitos fisiológicos quando associado a treinamentos excêntricos, principalmente na força e hipertrofia muscular. Objetivo: Realizar uma revisão sistemática com metanálise e um estudo aleatorizado controlado a fim de esclarecer os reais efeitos do TRBI associado à RFS nos desfechos de força, hipertrofia muscular e desempenho funcional, e se a RFS quando associada a treinamentos excêntricos de baixa e alta intensidade é capaz de aumentar as respostas desses desfechos dos extensores de joelho em homens adultos saudáveis. Métodos: A revisão sistemática foi registrada no PROSPERO (número do registro #CRD42018104065). Os estudos foram selecionados por meio de sete bases de dados. Todos os estudos incluídos foram avaliados quanto à qualidade metodológica, utilizando a Escala PEDro, bem como foi avaliada a qualidade da evidência. Somente ensaios clínicos randomizados que avaliaram a eficácia do treinamento com RFS na força e hipertrofia muscular dos músculos extensores de joelho em adultos do sexo masculino, saudáveis e/ou fisicamente ativos, com idade de 18 a 35 anos, contra algum grupo de intervenção foram considerados elegíveis. Todas as metanálises foram conduzidas por meio do software Review Manager – RevMan e descritos como diferenças médias padronizadas (standardized ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Studies on low intensity resistance training associated with blood flow restriction (RFS) are currently gaining prominence, however there are still gaps that can be explored in relation to their physiological effects when associated with eccentric training, especially in muscle strength and hypertrophy. Objective: To carry out a systematic review with meta-analysis and a randomized controlled study in order to clarify the real effects of TRBI associated with RFS on the outcomes of strength, muscle hypertrophy and functional performance, and whether RFS when associated with low and high intensity eccentric training is able to increase the responses of these knee extensor outcomes in healthy adult men. Methods: The systematic review was registered in PROSPERO (registration number # CRD42018104065). The studies were selected through seven databases. All included studies were assessed for methodological quality, using the PEDro Scale, as well as the quality of evidence was assessed. Only randomized controlled trials that assessed the effectiveness of RFS training on muscle strength and hypertrophy of knee extensor muscles in healthy, male and / or physically active adults, aged 18 to 35, against any intervention group were considered eligible. All meta-analyzes were conducted using the Review Manager - RevMan software and described as standardized mean differences (SMD) or mean differences (mean difference - MD) with 95% confidence intervals (CI). The randomized controlled study ... (Complete abstract click electronic access below) / Mestre