It is well documented that engaging in resistance exercise can lead to further improvements in endurance performance. Whilst, not fully understood, it is speculated that increased motor unit recruitment, improved muscle coordination and enhanced utilisation of stored elastic energy after resistance-based exercise improves exercise economy. Nevertheless, while prolonged exposure to resistance training improves endurance performance in the long-term, a consequence of such training when unaccustomed is the appearance of exercise-induced muscle damage (EIMD). Exercise-induced muscle damage is well known to affect athletic performance requiring muscular strength and power; however, its effects on markers of endurance exercise are unclear. Therefore, the aim of this thesis was to investigate the effects of EIMD on endurance performance, with an emphasis on the physiological (oxygen uptake; , minute ventilation; ), metabolic (blood lactate; [La]), perceptual (rating of perceived exertion; RPE) and kinematic (stride length; SL, stride frequency; SF) responses during sub-maximal endurance exercise.

Introduction: A hallmark of the human aging process is the gradual loss of muscle mass and strength, a phenomenon commonly referred to as sarcopenia. Although sarcopenia is likely the result of both a reduction in fiber size and a loss of muscle fibers, it has become abundantly clear that sarcopenia is primarily characterized by the reduction in type II fiber size. The mechanism(s) driving this fiber type-specific loss still remain largely unknown, but it has become evident that the dysregulation of a muscle-specific stem cell population called satellite cells (SC) plays an important role in its progression. Luckily, older adults still retain the ability to activate and expand their SC in response to exercise; what remains unclear is which modality of exercise is optimal for promoting SC contribution to skeletal muscle remodelling. We sought to test the hypothesis that both resistance exercise (RE) and high-intensity interval training (HIIT) would stimulate greater expansion of SC when compared to traditional aerobic exercise (AE). Furthermore, we also sought to determine potential extrinsic/intrinsic factors that might contribute to regulating the differences in SC behavior across the different modalities of exercise Methods: Sedentary older men (n=22; 67 ± 4 yr; BMI: 27.0 ± 2.6 kg•m-2 [mean ± SEM]) were randomly assigned to complete an acute bout of either RE (3 sets of leg extensor and press, 95% 10RM, n = 7), HIIT (10 x 1min, 95% maximal heart rate [HRmax], n= 8) or AE (30min, 55-60% HRmax. n = 7). Muscle biopsies were obtained before and at 24h and 48h following each exercise bout, while blood samples were taken before and at 24h after exercise. The SC response was analyzed using immunofluorescent microscopy and whole-muscle mRNA analysis, while the variability in exercise-induced muscle damage (EIMD) was estimated by analyzing serum samples for creatine kinase (CK) concentration. Results: The muscle SC content increased 45% (p < 0.001) and 52% (p = 0.001) relative to baseline at 24h and 48h respectively following RE, while HIIT stimulated a significant increase of 33% (p = 0.007) at 48h. Fiber type-specific analysis further revealed that both RE and HIIT were capable of inducing significant increases in both type I and type II-specific SC by 48h post-exercise. Further analysis of individual SC responses also revealed a correlation (r = 0.737, p < 0.001) between the change in SC content across the acute time-course and the relative change in creatine kinase (CK) activity levels 24h post-exercise. The lack of any notable SC expansion following AE was to some degree explained by insufficient changes to cell cycle and myostatin (MSTN)-related genes. Conversely, RE produced the greatest reduction in MSTN mRNA over the 48h time-course while inducing a noticeable decrease of 124% in SMAD3 (a mediator of MSTN signaling) mRNA at 48 post-exercise. Conclusions: These data illustrate that RE is the most potent stimulator of acute SC activity in older men, while also showing for the first time that of HIIT can induce a SC response in the same population. The positive relationship between the changes in SC content in response to exercise and CK activity levels suggests that the level of muscle damage induced by an exercise type may influence the magnitude of the subsequent SC response. The magnitude of each SC response is also likely influenced by unique changes in MSTN signaling that follow each modality of exercise. / Thesis / Master of Science in Kinesiology

Thesis (MSc)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: This thesis aims to determine whether supplementation with a grape-seed derived antioxidant, oligomeric proanthocyanidin (PCO) or the glutathione precursor, N-acetylcysteine (NAC) may prove beneficial as treatment for exercise induced muscle damage (EIMD) in athletes. In this double-blind cohort study, 21 healthy, uninjured male rugby-players in mid-season training phase, aged between 18 and 25 years were randomly divided into three treatment groups. Participants received 210 mg PCO, NAC or placebo treatment for 9 consecutive days. The study comprised a 6-day wash-out period (protocol days: -12 to -7), followed by a 6-day supplement loading period (protocol days: -6 to -1) a plyometric exercise intervention (protocol day 0) and continued supplementation for 2 days (protocol days: 1 to 2). The exercise intervention comprised 15 sets of 10 near maximal, vertical plyometric squat jumps. Blood samples and delayed onset of muscle soreness (DOMS) scores were collected on protocol days: -6, 0, 1 and 2. Assessments included serum creatine kinase (CK) activity, oxygen radical absorbance capacity (ORAC), malondialdehyde (MDA) and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentrations over time as well as a differential circulating leukocyte count (neutrophils, lymphocytes, monocytes, eosinophils and basophils). Data analysis of CK activity revealed no significant differences between groups. However, PCO treatment prevented a significant peak in the CK response at 24 h (as seen in the placebo and NAC groups) when compared to baseline, pre and post readings (p<0.05). NAC supplementation significantly improved serum ORAC after the exercise intervention. By 48 h, serum ORAC had improved significantly from readings taken immediately post exercise (p<0.05) only in the NAC group. For all groups, absolute neutrophil counts peaked at 6 h post exercise from baseline or pre readings (p<0.05). In both NAC and placebo treated groups, neutrophil counts had decreased significantly in circulation by 24 h post exercise from the 6 h time-point (p<0.05). However, neutrophil counts only reached significantly lower levels by 48 h post exercise (p<0.05) in the group supplemented with PCO. The monocyte count also peaked significantly at 6 h post exercise when compared with other time-points before and after the exercise intervention (p<0.05) in all treatment groups. Neither antioxidant treatment significantly altered the responses of other leukocyte sub-populations, MDA or sVCAM-1 concentrations where main effects of plyometric exercise was evident. Although not statistically significant, a trend toward diminished sVCAM-1 expression with either antioxidant supplementation was apparent. These findings suggest that PCO supplementation (210mg/d) which includes a 7 day loading period may diminish plyometric EIMD by limiting (but not completely inhibiting) the neutrophil response. Secondary muscle damage may be prevented by partially blunting neutrophil infiltration, rather than only quenching free radicals released during the neutrophil oxidative burst. Furthermore, the finding that NAC supplementation improves serum ORAC only after exercise may provide added benefit when administered in combination with PCO. / AFRIKAANSE OPSOMMING: Hierde tesis is daarop gerig om vas te stel of aanvulling met ‘n druifsaadekstrak (DSE) gederiveerde antioksidant: pro-antosianiedoliese oligomeer (PSO), of die glutathione voorloopermolekule, N-asetielsistien (NAS) voordelig beskou kan word as behandeling vir atlete onderhewig aan spierskade veroorsaak deur oefening. Gedurende hierdie dubbelblinde kohort studie is 21 gesonde, manlike rugbyspelers sonder beserings tussen die ouderdom van 18 en 25 jaar in middel-seison fase ewekansig in drie behandelingsgroepe verdeel. Deelneemers het elk 210 mg PSO, NAS of placebo-aanvulling geneem vir nege agtereenvolgende dae. Die studie het bestaan uit ‘n 6-dag uitwasperiode (protokoldae: -12 tot -7), as ook ‘n 6-dag aanvullings periode (protokoldae: -6 tot -1), gevolg deur ‘n pliometriese oefeningsintervensie (protokol dag 0) en verdere aanvulling tot en met 2 dae na die oefening (protokol dae: 1 tot 2). Die oefeningsintervensie het 15 stelle van 10 naastenby maksimale, vertikale pliometriese hurkspronge behels. Bloedmonsters en vertraagde aanvang spierseerheid (VAS) tellings is op protokoldae: -6, 0, 1 en 2 geneem. Analiese het serum kreatien kinase (KK) aktiwiteit, suurstof radikaal absorpsie kapasiteit (SRAK), Malondialdahied (MDA) en oplospare vaskulêresel adhesie molekule-1 (oVAM-1) konsentrasie bepalings asook ‘n differentiële sirkulerende leukosiet seltelling ingesluit. KK aktiewiteit het geen merkwaardige verskil tussen groepe getoon nie. PSO aanvulling het wel gelei tot die voorkoming van ‘n merkwaardige piek in die KK response soos in die placebo en NAC behandelde groepe bevind is by die 24 h tydspunt in vergelyking met basislyn-, voor- en na-oefeningslesings (p<0.05). NAS het ‘n merkwaardige verbetering in serum SRAK getoon, maar eers teen 48 h na oefening. Slegs die NAS behandelde groep het op hierdie tydspunt ‘n betekenisvolle verbetering in SRAK getoon in vergelyking met lesings direk na oefening (p<0.05). Vir alle groepe is ‘n betekenisvolle toename in absolute neutrophiltellings waargeneem 6 h na oefening in vergelyking met basislyn- en vooroefeningslesings (p<0.05). Beide NAS en placebo-behandelde groepe het ‘n betekenisvolle afname in neutrophiltellings teen 24 h na oefening getoon in vergelyking met die 6 h tydspunt (p<0.05) maar met die PSO-behandelde groep word hierde afname eers teen 48 h waargeneem (p<0.05). Monosiettellings het in alle groepe 6 h na oefening ‘n betekinsvolle piek getoon (p<0.05). Waar slegs die hoofeffek van die pliometriese oefening betekenisvol was, het nie een van die twee antioksidant aanvullings ‘n merkwaardige verandering aan die respons van ander leukosiet sub-populasies, MDA of oVAM-1 konsentrasies getoon nie. Al kon statistiese beduidenheid nie bewys word nie, wil dit blyk dat ‘n verminderde oVAM-1 uitdrukking onstaan het in die geval van beide antioksidant-behandelde groepe. Tesame stel hierdie bevindinge voor dat PSO toediening (210mg/d) insluitende ‘n 7-dag aanvullingsperiode die vermoë verleen om die neutrophielrespons gedeeltelik te onderdruk (sonder om dit heeltemal te inhibeer) en sodoende spierskade verminder. Dus word verdere spierskade moontlik verlaag deur die voorkoming van neutrophil weefsel infiltrasie eerder as verwydering van reaktiewe spesies wat vrygestel word tydens oefening. Die bevinding dat NAS aanvulling serum SRAK eers na oefening merkwaardig verbeter, kan as voordelig beskou word, veral wanneer toegedien in samewerking met PSO om verdere spierskade te voorkom en herstelling vinniger te bewerkstellig.

The effectiveness of recovery interventions following prolonged multiple sprint team sports matches has rarely been studied despite the potential for exercise-induced muscle damage to adversely affect training in the days following games. The lack of research related to this topic is probably owing to the wide variability that exists in the movement demands of players between matches and the impact that this has on the subsequent rate and magnitude of recovery which makes it difficult to detect meaningful differences when conducting research with small sample sizes. Therefore, the purpose of this thesis was to develop a rugby league-specific match simulation protocol that replicates the movement demands, physiological responses and subsequent recovery from matches in order to study the effectiveness of recovery interventions. Hence, two time-motion analysis studies were conducted using a semi-automated image recognition system to inform the development of the rugby league match simulation protocol (RLMSP). Whilst mean total distance covered over the duration of the match was 8,503 m, ball in play and stoppage work-to-rest ratios were 1:6.9 and 1:87.4, respectively, for all players. Furthermore, a significant decline in high and very high intensity running locomotive rates were observed between the initial and final 20 min periods of the match. Thus a RLMSP was devised to replicate the overall movement demands, intra-match fatigue and recovery from a senior elite rugby league match. Not only was there a low level of variability in the movement demands during the RLMSP over consecutive trials, but with the exception of creatine kinase, the rate and magnitude of recovery following the RLMSP was similar to that that has been published following competitive matches. Therefore, the RLMSP devised in this thesis may be a more appropriate research tool for assessing the effectiveness of recovery interventions following match related exercise than following actual match play.

A dor muscular após a realização de exercícios intensos tem sido objeto de investigações científicas desde o início do século XX. O primeiro tópico da revisão de literatura contextualiza historicamente o estudo envolvendo a dor muscular e revisita as evidências que levaram ao conhecimento de que a dor muscular tardia é resultado de dano à estrutura muscular, associado a contrações excêntricas. O dano muscular induzido por contrações excêntricas é largamente abordado na literatura, no entanto, recentemente alguns estudos passaram a utilizar exercícios convencionais do treinamento de força para induzir dano muscular e estudar a manifestação e a recuperação de marcadores indiretos de dano muscular. Uma das principais variáveis do treino de força é a seleção dos exercícios, que podem ser divididos em multiarticulares e monoarticulares. O segundo tópico da revisão de literatura trata da definição desses tipos de exercícios e dos estudos que investigaram as diferenças entre eles. Foi constatado que não há consenso na literatura sobre o dano muscular após a execução de exercícios de força multiarticulares e monoarticulares. Portanto, o objetivo do estudo foi comparar o dano muscular induzido por um exercício multiarticular versus monoarticular em indivíduos destreinados. Vinte e quatro sujeitos saudáveis e destreinados foram divididos em dois grupos aleatoriamente: grupo multi (n=12), que realizou o exercício multiarticular Puxada pela Frente e grupo mono (n=12), que realizou o exercício monoarticular Rosca Scott. O protocolo de exercício consistiu de quatro séries de 10 repetições a 80% de uma repetição máxima (1RM). Os flexores do cotovelo foram avaliados nos momentos pré, 0, 24, 48, 72 e 96 h após o protocolo de exercício através do decréscimo na produção de força (CIVM), da dor muscular tardia (DMT) por palpação do braço e extensão do cotovelo, da espessura muscular (EM), do grau de ecogenicidade (ECO) dos músculos Braquial e Bíceps Braquial e da concentração plasmática de creatina cinase (CK). Todos os marcadores apresentaram diferenças significativas ao longo do tempo comparado com o pré. Houve diferença significativa entre os grupos apenas na DMT por palpação (DMT-p) em 24 e 48 h e na CK em 24 e 96 h. O grupo mono apresentou maior DMT-p, enquanto o grupo multi apresentou maior CK. Nenhum dos outros marcadores indireto de dano muscular apresentou diferença significativa entre os grupos. Houve variabilidade nas respostas ao dano muscular devido à responsividade dos sujeitos. Quando separados em responsivos (R) e não-responsivos (NR), grupos mais homogêneos foram formados, porém resultados semelhantes foram encontrados, exceto no ECO, o qual, nos NR, apresentou redução nos valores, o que não corrobora com o comportamento reportado na literatura para essa variável. Os achados sugerem que, em indivíduos destreinados, não há diferença no dano muscular induzido por exercícios de força multiarticulares e monoarticulares. / Muscle soreness after intense exercise has been investigated since the early twentieth century. The first topic of the literature review historically contextualizes the study of muscle soreness and revisits evidences that shed light on the fact that muscle soreness is a consequence of damage to muscle structure, associated with eccentric contractions. Eccentric-induced muscle damage is largely studied and reported on the literature. However studies recently began to use conventional strength training exercises to induce muscle damage and account for the manifestation and recovery of indirect markers of muscle damage. A major intervenient variable in strength training is exercise selection, which can be defined as multiple and single-joint exercises (MJ and SJ, respectively). The second topic of the literature review deals with these different exercise types and the investigation carried out in this field. It was found that there is no consensus concerning muscle damage after MJ and SJ exercises. Therefore, the aim of the study was to compare MJ and SJ exercises on muscle damage in untrained subjects. Twenty four healthy and untrained subjects were randomly assigned to one of two groups: MJ group (n=12), which performed a Front Pull-Down and SJ group (n=12), which performed an elbow flexion with a Scott bench. Exercise protocol consisted of four sets of 10 repetitions at 80% of one repetition maximum (1RM). Elbow flexors were evaluated at pre, 0, 24, 48, 72 and 96 h post-exercise through reduction in muscular force (CIVM), muscle soreness (DMT) by palpation and by elbow extension, muscle thickness (EM), echo intensity (ECO) of brachialis and bíceps brachii and plasma creatine kinase activity (CK). All markers of damage presented significant differences across time compared to pre-exercise. There was a statistically significant difference between groups in DMT by palpation (DMT-p) at 24 and 48 h and in CK at 24 and 96 h. SJ group presented larger DMT-p while MJ group presented higher CK. Neither of the other indirect markers of muscle damage showed stastistical differences between groups. A marked variability was demonstrated in muscle damage responses due to subjects’ responsiveness. When splitted in responders (R) and non-responders (NR), more homogenous groups were formed, yet similar trends were found, except for ECO, where a reduction in values were evident in NR, which do not corroborate with the literature. The findings of the present study suggest that there are no differences in muscle damage induced by MJ and SJ exercises in untrained individuals.

A dor muscular após a realização de exercícios intensos tem sido objeto de investigações científicas desde o início do século XX. O primeiro tópico da revisão de literatura contextualiza historicamente o estudo envolvendo a dor muscular e revisita as evidências que levaram ao conhecimento de que a dor muscular tardia é resultado de dano à estrutura muscular, associado a contrações excêntricas. O dano muscular induzido por contrações excêntricas é largamente abordado na literatura, no entanto, recentemente alguns estudos passaram a utilizar exercícios convencionais do treinamento de força para induzir dano muscular e estudar a manifestação e a recuperação de marcadores indiretos de dano muscular. Uma das principais variáveis do treino de força é a seleção dos exercícios, que podem ser divididos em multiarticulares e monoarticulares. O segundo tópico da revisão de literatura trata da definição desses tipos de exercícios e dos estudos que investigaram as diferenças entre eles. Foi constatado que não há consenso na literatura sobre o dano muscular após a execução de exercícios de força multiarticulares e monoarticulares. Portanto, o objetivo do estudo foi comparar o dano muscular induzido por um exercício multiarticular versus monoarticular em indivíduos destreinados. Vinte e quatro sujeitos saudáveis e destreinados foram divididos em dois grupos aleatoriamente: grupo multi (n=12), que realizou o exercício multiarticular Puxada pela Frente e grupo mono (n=12), que realizou o exercício monoarticular Rosca Scott. O protocolo de exercício consistiu de quatro séries de 10 repetições a 80% de uma repetição máxima (1RM). Os flexores do cotovelo foram avaliados nos momentos pré, 0, 24, 48, 72 e 96 h após o protocolo de exercício através do decréscimo na produção de força (CIVM), da dor muscular tardia (DMT) por palpação do braço e extensão do cotovelo, da espessura muscular (EM), do grau de ecogenicidade (ECO) dos músculos Braquial e Bíceps Braquial e da concentração plasmática de creatina cinase (CK). Todos os marcadores apresentaram diferenças significativas ao longo do tempo comparado com o pré. Houve diferença significativa entre os grupos apenas na DMT por palpação (DMT-p) em 24 e 48 h e na CK em 24 e 96 h. O grupo mono apresentou maior DMT-p, enquanto o grupo multi apresentou maior CK. Nenhum dos outros marcadores indireto de dano muscular apresentou diferença significativa entre os grupos. Houve variabilidade nas respostas ao dano muscular devido à responsividade dos sujeitos. Quando separados em responsivos (R) e não-responsivos (NR), grupos mais homogêneos foram formados, porém resultados semelhantes foram encontrados, exceto no ECO, o qual, nos NR, apresentou redução nos valores, o que não corrobora com o comportamento reportado na literatura para essa variável. Os achados sugerem que, em indivíduos destreinados, não há diferença no dano muscular induzido por exercícios de força multiarticulares e monoarticulares. / Muscle soreness after intense exercise has been investigated since the early twentieth century. The first topic of the literature review historically contextualizes the study of muscle soreness and revisits evidences that shed light on the fact that muscle soreness is a consequence of damage to muscle structure, associated with eccentric contractions. Eccentric-induced muscle damage is largely studied and reported on the literature. However studies recently began to use conventional strength training exercises to induce muscle damage and account for the manifestation and recovery of indirect markers of muscle damage. A major intervenient variable in strength training is exercise selection, which can be defined as multiple and single-joint exercises (MJ and SJ, respectively). The second topic of the literature review deals with these different exercise types and the investigation carried out in this field. It was found that there is no consensus concerning muscle damage after MJ and SJ exercises. Therefore, the aim of the study was to compare MJ and SJ exercises on muscle damage in untrained subjects. Twenty four healthy and untrained subjects were randomly assigned to one of two groups: MJ group (n=12), which performed a Front Pull-Down and SJ group (n=12), which performed an elbow flexion with a Scott bench. Exercise protocol consisted of four sets of 10 repetitions at 80% of one repetition maximum (1RM). Elbow flexors were evaluated at pre, 0, 24, 48, 72 and 96 h post-exercise through reduction in muscular force (CIVM), muscle soreness (DMT) by palpation and by elbow extension, muscle thickness (EM), echo intensity (ECO) of brachialis and bíceps brachii and plasma creatine kinase activity (CK). All markers of damage presented significant differences across time compared to pre-exercise. There was a statistically significant difference between groups in DMT by palpation (DMT-p) at 24 and 48 h and in CK at 24 and 96 h. SJ group presented larger DMT-p while MJ group presented higher CK. Neither of the other indirect markers of muscle damage showed stastistical differences between groups. A marked variability was demonstrated in muscle damage responses due to subjects’ responsiveness. When splitted in responders (R) and non-responders (NR), more homogenous groups were formed, yet similar trends were found, except for ECO, where a reduction in values were evident in NR, which do not corroborate with the literature. The findings of the present study suggest that there are no differences in muscle damage induced by MJ and SJ exercises in untrained individuals.

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Entretanto, outros modelos [p.ex., dano muscular (DM) induzido por corridas em declive (CrED)] mostram que a magnitude e a cinética de recuperação da EC e da força máxima medida em exercícios de cadeia cinética aberta [pico de torque isométrico de extensão do joelho (PTI)] podem ser diferentes. Fatores como o tipo de exercício usado para medir a força e a forma pela qual a força se manifesta (máxima e explosiva), podem explicar, pelo menos em parte, estes dados antagônicos. O objetivo geral deste estudo foi utilizar o modelo de DM induzido pela CrED para analisar a relação entre força máxima e explosiva e a EC. Método: Para isso, foram empregadas três intervenções para modular o DM induzido pela CrED e verificar seus efeitos sobre a força e a EC. Participaram do estudo 85 sujeitos ativos (22,3 ± 2,4 anos, 78 ± 9,4 kg, 176,9 ± 5 cm) que foram aleatoriamente separados em grupo controle (CON), placebo (PLA), suplementação (SUP), isométrico (ISO) e combinado (COMB). CON foi dividido em indivíduos com presença e ausência da α-actinina-3, resultante de polimorfismo do gene ACTN3. Todos os grupos realizaram uma CrED (-15%) por 30 min a 70% VO2max. SUP ingeriu um suplemento rico em compostos flavonoides antes e após a CrED, PLA ingeriu um placebo nos mesmos períodos, ISO realizou 10 contrações isométricas máximas (CIM) dois dias antes da CrED e COMB ingeriu o suplemento e realizou 10 CIM antes da CrED. Foram avaliados marcadores indiretos de DM (força, dor, amplitude de movimento e circunferência da coxa, e atividade sérica de CK) e EC antes e imediatamente, 24, 48, 72 e 96 horas após a CrED. Alterações ao longo do tempo e entre grupos foram analisadas por meio de ANOVA de dois caminhos com post-hoc de Bonferroni. Resultados: Os resultados obtidos demonstraram comprometimento significante da EC após a CrED, assim como alterações significantes em marcadores de DM. Foi identificado um efeito de aceleração da recuperação nas alterações no DM e EC para os grupos SUP e COMB (que apresentaram retorno do VO2 e PTI a níveis basais no dia seguinte e dois dias após a CrED, respectivamente) em relação ao grupo CON. Os grupos que consumiram o suco antioxidante também apresentaram atenuação significante da dor muscular após a CrED. Entretanto, a diferença de cinética de recuperação entre força e EC se manteve mesmo frente aos tratamentos. O grupo ISO apresentou aceleração da recuperação do PTI, mas não da EC, assim como atenuação da dor muscular em relação ao grupo CON. Alterações na altura de saltos foram significantes, sendo que os valores retornaram a níveis basais antes dos valores de PTI. Em relação aos polimorfismos do gene ACTN3, não houve influência do genótipo nas alterações na EC. Entretanto, como esperado, houve maior perda de força para indivíduos RR (que sintetizam a α-actinina-3). Conclusão: Em conjunto, os resultados obtidos sugerem que há, sim, uma relação entre aspectos neuromusculares e a EC. Entretanto, outros fatores, que não a capacidade de produção de força isoladamente, parecem contribuir para essa relação. Ademais, as estratégias de atenuação do DM investigadas no presente estudo parecem ser eficazes na aceleração da recuperação da EC e da força muscular e o polimorfismo do gene ACTN3 parece ser um dos fatores que explicam a susceptibilidade ao DM. / Introduction: Longitudinal studies have been showing that strength production capacity might influence running economy (RE). However, other study models [e.g., downhill running (DhR) induced muscle damage (MD)] show different magnitudes of change and recovery kinetics between strength measured with open kinetic chain exercises [knee extension isometric peak torque (IPT)] and RE might differ. Factors such as the type of exercised used to measures strength and its form of manifestation (maximal or explosive) might, at least in part, explain these differences. The aim of the present study was to analyze the association between strength production capacity and RE using an DhR induced MD model. Methods: To do so, three different prophylactic strategies were adopted to modulate MD induced by DhR and also analyze their effects on strength production capacity and RE. Eighty five active subjects (22.3 ± 2.4 years, 78 ± 9.4 kg, 176.9 ± 5 cm) participated in the study and were randomly allocated to control (CON), placebo (PLA), supplementation (SUP), isometric (ISO), and combined (COMB) groups. Participants in CON were separated based on their ACTN3 polymorphisms. All groups ran downhill (-15%) for 30 min at 70%VO2max. SUP ingested a flavonoid-rich supplement before and following DhR, PLA ingested an isocaloric placebo at the same time points, ISO performed 10 maximal isometric contractinons (MIC) two days prior to the DhR, and COMB ingested the supplement and performed the MIC before DhR. MD symptoms (strength, soreness, knee joint range of motion, thigh circumference, and serum CK activity) and RE were assessed before, immediately after, and 1-4 days following DhR. Changes over time and between groups were analyzed with two-way ANOVA followed by Bonferroni’s post hoc tests. Results: Results showed that RE was significantly compromised following DhR and MD markers were also affected. Faster recovery of RE and MD markers was identified for the SUP and COMB groups (which reached full recovery of VO2 and IPT 1 and 3 days following the DhR, respectively), as compared to CON. Both groups that consumed the antioxidant supplement also presented significant attenuation of muscle soreness following DhR. However, the difference in the recovery kinetics of strength and RE was maintained with this treatment. ISO presented faster recovery of IPT, but not RE, and attenuation and faster recovery of soreness, as compared to CON. Significant changes in jump height were found for all groups, with faster recovery when compared to IPT. No influence of the ACTN3 gene polymorphism was found for changes in RE. However, as expected, RR individuals presented significantly greater strength loss following DhR. Conclusion: When put together, our results suggest that there is, indeed, an association between neuromuscular aspects and RE. However, factors other than strength production per se seem to contribute to this association. Moreover, the prevention/recovery strategies investigated in the present study seem to be effective to promote faster recovery of RE and strength following DhR. Also, ACTN3 gene polymorphism seems to be one of the factors contributing to susceptibility to MD, but not changes in RE. / FAPESP: 2013/23585-4

A dor muscular após a realização de exercícios intensos tem sido objeto de investigações científicas desde o início do século XX. O primeiro tópico da revisão de literatura contextualiza historicamente o estudo envolvendo a dor muscular e revisita as evidências que levaram ao conhecimento de que a dor muscular tardia é resultado de dano à estrutura muscular, associado a contrações excêntricas. O dano muscular induzido por contrações excêntricas é largamente abordado na literatura, no entanto, recentemente alguns estudos passaram a utilizar exercícios convencionais do treinamento de força para induzir dano muscular e estudar a manifestação e a recuperação de marcadores indiretos de dano muscular. Uma das principais variáveis do treino de força é a seleção dos exercícios, que podem ser divididos em multiarticulares e monoarticulares. O segundo tópico da revisão de literatura trata da definição desses tipos de exercícios e dos estudos que investigaram as diferenças entre eles. Foi constatado que não há consenso na literatura sobre o dano muscular após a execução de exercícios de força multiarticulares e monoarticulares. Portanto, o objetivo do estudo foi comparar o dano muscular induzido por um exercício multiarticular versus monoarticular em indivíduos destreinados. Vinte e quatro sujeitos saudáveis e destreinados foram divididos em dois grupos aleatoriamente: grupo multi (n=12), que realizou o exercício multiarticular Puxada pela Frente e grupo mono (n=12), que realizou o exercício monoarticular Rosca Scott. O protocolo de exercício consistiu de quatro séries de 10 repetições a 80% de uma repetição máxima (1RM). Os flexores do cotovelo foram avaliados nos momentos pré, 0, 24, 48, 72 e 96 h após o protocolo de exercício através do decréscimo na produção de força (CIVM), da dor muscular tardia (DMT) por palpação do braço e extensão do cotovelo, da espessura muscular (EM), do grau de ecogenicidade (ECO) dos músculos Braquial e Bíceps Braquial e da concentração plasmática de creatina cinase (CK). Todos os marcadores apresentaram diferenças significativas ao longo do tempo comparado com o pré. Houve diferença significativa entre os grupos apenas na DMT por palpação (DMT-p) em 24 e 48 h e na CK em 24 e 96 h. O grupo mono apresentou maior DMT-p, enquanto o grupo multi apresentou maior CK. Nenhum dos outros marcadores indireto de dano muscular apresentou diferença significativa entre os grupos. Houve variabilidade nas respostas ao dano muscular devido à responsividade dos sujeitos. Quando separados em responsivos (R) e não-responsivos (NR), grupos mais homogêneos foram formados, porém resultados semelhantes foram encontrados, exceto no ECO, o qual, nos NR, apresentou redução nos valores, o que não corrobora com o comportamento reportado na literatura para essa variável. Os achados sugerem que, em indivíduos destreinados, não há diferença no dano muscular induzido por exercícios de força multiarticulares e monoarticulares. / Muscle soreness after intense exercise has been investigated since the early twentieth century. The first topic of the literature review historically contextualizes the study of muscle soreness and revisits evidences that shed light on the fact that muscle soreness is a consequence of damage to muscle structure, associated with eccentric contractions. Eccentric-induced muscle damage is largely studied and reported on the literature. However studies recently began to use conventional strength training exercises to induce muscle damage and account for the manifestation and recovery of indirect markers of muscle damage. A major intervenient variable in strength training is exercise selection, which can be defined as multiple and single-joint exercises (MJ and SJ, respectively). The second topic of the literature review deals with these different exercise types and the investigation carried out in this field. It was found that there is no consensus concerning muscle damage after MJ and SJ exercises. Therefore, the aim of the study was to compare MJ and SJ exercises on muscle damage in untrained subjects. Twenty four healthy and untrained subjects were randomly assigned to one of two groups: MJ group (n=12), which performed a Front Pull-Down and SJ group (n=12), which performed an elbow flexion with a Scott bench. Exercise protocol consisted of four sets of 10 repetitions at 80% of one repetition maximum (1RM). Elbow flexors were evaluated at pre, 0, 24, 48, 72 and 96 h post-exercise through reduction in muscular force (CIVM), muscle soreness (DMT) by palpation and by elbow extension, muscle thickness (EM), echo intensity (ECO) of brachialis and bíceps brachii and plasma creatine kinase activity (CK). All markers of damage presented significant differences across time compared to pre-exercise. There was a statistically significant difference between groups in DMT by palpation (DMT-p) at 24 and 48 h and in CK at 24 and 96 h. SJ group presented larger DMT-p while MJ group presented higher CK. Neither of the other indirect markers of muscle damage showed stastistical differences between groups. A marked variability was demonstrated in muscle damage responses due to subjects’ responsiveness. When splitted in responders (R) and non-responders (NR), more homogenous groups were formed, yet similar trends were found, except for ECO, where a reduction in values were evident in NR, which do not corroborate with the literature. The findings of the present study suggest that there are no differences in muscle damage induced by MJ and SJ exercises in untrained individuals.

The age-related loss of skeletal muscle mass and function is accompanied by a decline in regenerative capacity. The processes that facilitate healthy muscle repair are complex, involving several phases of degradation and rebuilding of muscle tissue and the surrounding microenvironment. Specifically, myogenic progenitor cells known as satellite cells are the most influential in repairing damaged muscle tissue. Following injury, satellite cells become activated and migrate, proliferate and fuse with mature skeletal muscle fibers to restore homeostasis to the tissue. However, satellite cells do not act in isolation, a robust inflammatory response is necessary to facilitate successful and rapid healing. Macrophages are one of the first and most abundant immune cells to infiltrate damaged skeletal muscle tissue. Primarily, macrophages adapt to a proinflammatory state to clear the area of cellular debris, promote degradation of the extracellular matrix and stimulate satellite cell activation and proliferation. Afterwards, a timely transition to an anti-inflammatory state directs rebuilding of the extracellular matrix and terminal differentiation of satellite cells. Indeed, the inhibition of macrophage activity leads to impaired healing and loss of skeletal muscle function. Little is known regarding the behavior of macrophages in aged skeletal muscle following injury in humans. Thus, the objective of this dissertation is to investigate the age-related response of macrophages in human skeletal muscle, and their role in muscle repair.

Skeletal muscle is prone to damage from a range of stimuli. The muscle repair process that ensues is complex, involving several phases and requiring the participation of many different cell types. Among the cells involved are various immune cells including neutrophils, macrophages, monocytes, and eosinophils. More recently, T cells were added to this list of immune cells known to participate in effective muscle repair from traumatic injuries in mice. We recently published data showing that T cells also accumulate in human muscle following contraction-induced damage. These data suggested that T cells might be involved an adaptation known as the repeated bout effect that renders muscle protected from future damage after an initial exposure. This document contains research on the role of the immune system, particularly T cells, in the "repeated bout effect."