Esta dissertação apresenta um estudo da caracterização numérica do comportamento mecânico de um músculo esquelético estriado sujeito à combinação de diferentes contrações. A partir dos mecânismos fisiológicos da contração do tecido muscular esquelético, são apresentadas as principais características da produção de força do músculo em diferentes tipos de contrações (isométrica, concêntrica, excêntrica) e suas combinações. A representação numérica da resposta mecânica do músculo esquelético foi investigada por diferentes autores. Dos diversos modelos encontrados na literatura, alguns foram escolhidos para a continuidade deste estudo, segundo sua capacidade representativa e facilidade de implementação em métodos numéricos de solução para grandes deformações. Os modelos disponíveis na literatura foram implementados e avaliados para diferentes sequências de contrações, sendo também realizado um ajuste de parâmetros para dados experimentais de contrações isométricas e isométricas-excêntricas-isométricas. Nenhuma das propostas avaliadas apresentou resultados satisfatórios. A principal deficiência dos modelos foi a incapacidade de reproduzir a dependência do histórico de carregamentos, ou seja, da combinação de contrações. Desta maneira, uma nova proposta de modelo constitutivo foi desenvolvida e implementada para testes uniaxiais e em um código de elementos finitos para testes tridimensionais. A partir destas implementações, foram executados testes numéricos para diferentes sequências de contrações, avaliando a capacidade representativa do modelo proposto neste trabalho. O modelo proposto apresentou bons resultados para contrações isométricas e a combinação de contrações com diferentes níveis de alongamento, ou encurtamento, a uma mesma velocidade. A principal contribuição deste modelo é a capacidade de representar a resposta associada à fadiga muscular e o ganho, ou perda de força, observados experimentalmente. / This work present a striated skeletal muscle numerical characterization subjected to different contractions. From the physiological contraction mechanism of the skeletal muscle tissue the force produced in different kinds of contraction (isometric, concentric and eccentric), and their combination, are presented. The numerical representation of these response was investigated by different authors. From the diverse models found in literature, some were selected to be studied according to their representation capability and the implementation ease in numerical methods for large strains. The models available in literature were implemented and evaluated for different contractions combinations and a parameter identification for experimental results of two isometric contraction and a isometric-eccentric-isometric contraction. None of the proposed models presented satisfactory results. The main deficiency of these models were the incapability of reproducing the loading history dependence, in other words, the contraction combination. In this way, a new material model was proposed and implemented to uniaxial and tridimensional finite element method tests. From these, different contractions sequences evaluated the proposed model representation capabilities. The proposed model present good results to isometric contraction, as well as contraction combination with different stretch, or shortening, level in the same speed. The main contribution of this model is the capability of represent the the response associated to the muscle fatigue and the force gain or loss, experimentally observed.

Doctorat en Sciences de la motricité / info:eu-repo/semantics/nonPublished

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.

This study analyzed an individual's ability to perceive levels of exertion of an isometric contraction. Two samples of college students were tested under magnitude production or magnitude estimation. A significant F was obtained for the magnitude production condition. An insignificant F was obtained for the magnitude estimation condition. This study concludes that subjects tested under magnitude production will perceive the 100 percent level with the least amount of error and that error will increase as the percentages descend from the 100 percent level. Subjects tested under magnitude estimation will be equally in error when perceiving percentages of a maximum contraction of the forearm flexors.

This thesis explains structure of skeletal muscles, generation of action potencial and principle of muscle contraction. Further it shows types of electromyographic signal recording and its usage in therapy. Technical aspects of EMG signal and components required for electromyograph assemblage are next topic of this thesis. Another part presents design of simple EMG module for therapeutical application with bluetooth 4.0 interface.

Regulation of smooth muscle contraction depends on the phosphorylated state of myosin light chain (MLC). Although there are many kinases responsible for phosphorylating MLC, the myosin phosphatase complex is solely accountable for its dephosphorylation. Myosin phosphatase, in turn, is tightly regulated by many proteins. One of them being the CPI-17 gene family, which inhibits myosin phosphatase. This family of proteins is composed of CPI-17 itself, PHI-1, KEPI, and GBPI. Zebrafish have two genes each of CPI-17 and PHI-1, which are expressed during early embryonic development. This study sets out to investigate whether the two isoforms of CPI-17 and PHI-1 have diverged in function or expression using zebrafish as a model organism. Through a series of biochemical tests and assays, we have determined that the two isoforms have diverged in their expression pattern from each other, however they have similar function.

Indiana University-Purdue University Indianapolis (IUPUI) / The contractile activation of airway smooth muscle tissues stimulates actin polymerization and the inhibition of actin polymerization inhibits tension development. Actin depolymerizing factor (ADF) and cofilin are members of a family of actin–binding proteins that mediate the severing of F–actin when activated by dephosphorylation at serine 3. The role of ADF/cofilin activation in the regulation of actin dynamics and tension development during the contractile activation of airway smooth was evaluated in intact canine tracheal smooth muscle tissues. Two–dimensional gel electrophoresis revealed that ADF and cofilin exist in similar proportions in the muscle tissues and that approximately 40% of the total ADF/cofilin in unstimulated tissues is phosphorylated (inactivated). Phospho–ADF/cofilin decreased concurrently with tension development in response to stimulation with acetylcholine (ACh) or potassium depolarization indicating the activation of ADF/cofilin. Expression of an inactive phospho–cofilin mimetic (cofilin S3E), but not WT cofilin in the smooth muscle tissues inhibited endogenous ADF/cofilin dephosphorylation and ACh–induced actin polymerization. Expression of cofilin S3E in the tissues depressed tension development in response to ACh, but it did not affect myosin light chain phosphorylation. The ACh–induced dephosphorylation of ADF/cofilin required the Ca2+–dependent activation of calcineurin (PP2B). Expression of Slingshot (SSH) inactive phosphatase (C393S) decreased force development and cofilin dephosphorylation. Activation of ADF/cofilin was also required for the relaxation of tracheal muscle tissues induced by forskolin and isoproterenol. Cofilin activation in response to forskolin was not Ca2+–dependent and was not inhibited by calcineurin inhibitors, suggesting it was regulated by a different mechanism. Cofilin activation is required for actin dynamics and tension development in response to the contractile stimulation of tracheal smooth muscle and is regulated by both contractile and relaxing stimuli. These concepts are critical to understanding the mechanisms of smooth muscle contraction and relaxation, which may provide novel targets for therapeutic intervention in the treatment of abnormal airway responsiveness.

Indiana University-Purdue University Indianapolis (IUPUI) / Asthma, a chronic inflammatory disease of the airways, affects nearly 25 million Americans. The vast majority of these patients suffer from exercise-induced bronchoconstriction (EIB), a complication of asthma. Although traditionally treated pharmacologically, nutritional strategies provide a promising alternative for managing EIB as the prevalence of asthma may be due in part to changes in diet. Our objective was to determine the effects of novel nutritional strategies on hyperpnea-induced bronchoconstriction (HIB) in asthmatic individuals. HIB uses rapid breathing to identify EIB in a research or clinical setting. Fish oil, a combination of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docsahexaenoic acid (DHA), has been shown to be effective in suppressing EIB. However, its use in combination with other nutritional supplements, the optimal fish oil formula, and its effect on smooth muscle contractility have not been fully explored. An in vivo study (study 1) was conducted in individuals with both asthma and HIB to determine whether a combination of fish oil and vitamin C was more effective than either one alone in alleviating HIB. Pulmonary function was significantly improved with both fish oil and the combination treatment but not with vitamin C alone. In study 2, individuals with both asthma and HIB were supplemented with DHA alone since the optimal formula for fish oil has yet to be ascertained; previous in vitro studies have suggested DHA may be the more potent omega-3 fatty acid in fish oil. However, no significant changes in pulmonary function or airway inflammation were seen with DHA supplementation. For study 3, canine airway smooth muscle tissue was treated with fish oil to determine the in vitro effect of fish oil on smooth muscle contractility. Acute treatment with fish oil relaxed smooth muscle strips that had been contracted with 5-hydroxytryptamine. These minor relaxations in smooth muscle tension with fish oil may represent significant changes at the level of the smaller airways. These studies have confirmed that fish oil represents a viable treatment modality for asthmatic individuals with EIB and suggest that fish oil may influence airway smooth muscle contractility.

Indiana University-Purdue University Indianapolis (IUPUI) / Voltage-gated sodium channels (VGSCs) are dynamic membrane spanning proteins which mediate the rapid influx of Na+ during the upstroke of the action potential (AP). In addition to the large inward Na+ currents responsible for the upstroke of the AP, some VGSC isoforms produce smaller, subthreshold Na+ currents, which can influence the excitable properties of neurons. An example of such a subthreshold current is resurgent Na+ current (INaR). These unusual currents are active during repolarization of the membrane potential, where the channel is normally refractory to activity. INaR exhibit slow gating kinetics and unusual voltage-dependence derived from a novel mechanism of channel inactivation which allows the channel to recover through an open configuration resulting in membrane depolarization early in the falling phase of the AP, ultra-fast re-priming of channels, and multiple AP spikes. Although originally identified in fast spiking central nervous system (CNS) neurons, INaR has recently been observed in a subpopulation of peripheral dorsal root ganglion (DRG) neurons. Because INaR is believed to contribute to spontaneous and high frequency firing of APs, I have hypothesized that increased INaR may contribute to ectopic AP firing associated with inherited and acquired disorders of excitability. Specifically, this dissertation explores the mechanisms which underlie the electrogenesis of INaR in DRG neurons and determines whether the biophysical properties of these unique currents were altered by mutations that cause inherited muscle and neuronal channelopathies or in an experimental model of nerve injury. The results demonstrate that (1) multiple Na+ channel isoforms are capable of producing INaR in DRG neurons, including NaV1.3, NaV1.6, and NaV1.7, (2) inherited muscle and neuronal channelopathIy mutations that slow the rate of channel inactivation increase INaR amplitude, (3) temperature sensitive INaR produced by select skeletal muscle channelopthy mutations may contribute to the triggering of cold-induced myotonia, and (4) INaR amplitude and distribution is significantly increased two weeks post contusive spinal cord injury (SCI). Taken together, results from this dissertation provide foundational knowledge of the properties and mechanism of INaR in DRG neurons and indicates that increased INaR likely contributes to the enhanced membrane excitability associated with multiple inherited and acquired disorders of excitability.

Evidence from various studies indicates that eccentric contractions produce more post-exercise changes in muscular function than do concentric contractions. Delayed muscular soreness, the pain and tenderness present 1 or 2 days after exercise, is negatively correlated with muscular performance and occurs particularly after eccentric work. The action of an analgesic, anti-inflammatory drug (Indocin) on muscular soreness indicates it may be effective in accelerating recovery of muscle function after eccentric work. In the study reported herein the effects of Indocin on muscular performance, as evaluated on the Cybex II isokinetic dynamometer, following prolonged concentric and eccentric work, were evaluated in 48 subjects who were randomly assigned to one of four drug groups. Subjects performed a 30 minute step test during which one limb led the stepping movement throughout (concentric contractions) and the contralateral limb trailed throughout (eccentric contractions). The muscular performance parameters of peak torque (PT), torque acceleration energy (TAE) and average power (AVP), evaluated at slow and high velocities, and the range of motion (ROM) at the knee joint were assessed prior to the step test and at five intervals thereafter. A non-significant decrease in PT and TAE at the contraction speed of 60 deg/sec were present in the eccentric limbs, greater reductions evidenced in the placebo group. Non-significant changes occurred in the concentric limbs, Non-significant changes in ROM and in muscular function parameters evaluated at 250 deg/sec were observed. / Master of Science