1,721,120 research outputs found

    Central and peripheral responses to exercise: the role of muscle synergy, central command and age.

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    Background and goals. In 1870, Fick, A. provided a mathematical means of oxygen uptake, arguing that cardiac output (CO) is equivalent to the oxygen consumed by aerobic metabolism divided by the arterial venous oxygen difference. In the last 140 years exercise-physiologists, being interested in the determinants of VO2 limiting factors. Physiology researches are commonly very specific, this cause lack of knowledge in translational studies, as for the interaction between neuromuscular coordination and cardiovascular, or metabolic exercise-factors. Moreover, is not clear the roles of central-command on the central and peripheral hemodynamic response. Exercise-physiologist usually describes physiological phenomena with models, because many influencing-factors can modify the result. This concept can be also applied to one of the most intriguing and ancestral question: what is the secret of longevity? The human-model of centenarians could be considered the best example of successful aging, however at this moment no studies have investigated maximal exercise capacity in centenarians. Therefore three different studies were performed to analyze these relationships reported above: I- the cardio-pulmonary responses during maximal exercise in centenarians; II- the contribution of muscular synergy to central and peripherals VO2 factors; III- the role of central command on hemodynamic response to passive-leg movement in subjects without afferent feedback. Methods: I- 8 centenarians (98 – 102yrs) and 8 young females (18 – 22yrs) were recruited for the 1st study. Subjects were evaluated for health history and physical evaluation, lung function, and anthropometric measures. Both groups performed oxygen uptake measurements by incremental maximal test on cycle ergometer at absolute and relative workloads. II- 8 right-legged healthy male participated at the 2nd study (26.4±5.1 yr; height 174.2±4.1 cm; weight 73.3±5.0 kg). After the practice sessions, each subject performed a constant workload exercise (20W ∼40% of maximal workload) in 2 different modalities: with dominant leg (1DL), non-dominant leg (1NDL). III- In 9 spinal cord injury humans (last study), we compared central and peripheral hemodynamic and ventilatory responses to one-leg passive knee extension with and without visual feedback, and with only the perception of movement. Ventilation, oxygen uptake, cardiac output, heart rate, stroke volume, mean arterial pressure, and leg arterial blood flow were evaluated during the 3 experimental protocols. Results: In the 1st study, instead of a sufficient health status, centenarians showed a dramatically reduction in lung function FEV1 (0.68±0.12 Vs 3.23±0.50l), and FVC (1.22±0.10 Vs 3.45±0.62l). The old women hypo-ventilate during exercise, VE was significantly lower at 45% of maximal exercise, and the strategy used to increase the ventilation was different compared to adult women. In the centenarians group the oxygen saturation decrease during the exercise (83±2 Vs 98±3%). At the same absolute exercise workload, centenarians showed an improved metabolic-efficiency, VO2max was significantly lower from 10 to 35w. However the heart rate response during the exercise at the same absolute workload was similar between the groups. The 2nd study showed that higher muscle synergy (quadriceps contraction/relaxation time) and mean leg force were associated to dominant limb, ∼30% and ∼50% of difference respectively, while similar limb work (p = 0.8) was maintained for all the modalities. At the same power output, the more coordinated limb showed better efficiency +25%, reduced cardiovascular responses -8%, higher blood flow (+0.45 l∙min-1) but reduced HHb (-38%), which explains the difference between a dominant and non-dominant limb. In the 3rd study VE was significantly increased from baseline to maximal response during movement with visual feedback (47 ± 12%); movement without visual feedback (34 ± 10%) and only the perception of passive movement (20 ± 9%). These increases were not different between protocols (p = 0.8), and were equally increased from baseline (∼33%; p < 0.05), but VE/VO2 was not different from baseline. Central hemodynamics (cardiac output ∼7%; heart rate ∼7%; stroke volume ∼4%; and mean arterial pressure ∼3%) were unchanged from baseline during the three different protocols. Leg blood flow increased significantly by 126 ± 18 ml⋅min-1, and 109 ± 23 ml⋅min-1 in movement with and without visual feedback, respectively, but was unchanged from baseline in the only perception of passive movement experiment (33 ± 21 ml⋅min-1; p = 0.8). The change in leg blood flow was significantly lower during this protocol compared to passive movement with and without visual feedback. Discussion: The overall results of these researches can facilitate in clarifying the role of different mechanisms, i.e. muscular synergy, central command and ageing, on central and peripheral oxygen uptake limiting factors. Especially these results demonstrate that the O2 delivery and utilization are clearly influenced by the intra and inter muscular synergies, in SCI individuals characterized by a complete spinal block, central command significantly contributes to the ventilatory response to passive movement, but has no effect on central or peripheral hemodynamics. Moreover, the cardio-pulmonary responses during exercise demonstrated that centenarians pulmonary function is very limited, but an incremented metabolic-efficiency, probably related to the markedly fibres type adaptation, maintain a sufficient maximal exercise capacity. Future development: Future developments for this study will be addressed to examine the molecular dimension of the above mentioned mechanism and it could be focused on the evaluation by a biopsy of the fibre type, capillarization, mitochondrial respiration in centenarian-quadriceps muscle, and on the analysis of the centenarians maximal exercise capacity during hyperoxia. Analyze the effect of different coordination pattern in specific “human-models”, (post-poliomyelitis subjects) on oxygen uptake central and peripheral factors, and evaluate on SCI subjects, the effect of passive leg movement on central and peripheral hemodynamic factors executed in different position: seated or supine.Background and goals. In 1870, Fick, A. provided a mathematical means of oxygen uptake, arguing that cardiac output (CO) is equivalent to the oxygen consumed by aerobic metabolism divided by the arterial venous oxygen difference. In the last 140 years exercise-physiologists, being interested in the determinants of VO2 limiting factors. Physiology researches are commonly very specific, this cause lack of knowledge in translational studies, as for the interaction between neuromuscular coordination and cardiovascular, or metabolic exercise-factors. Moreover, is not clear the roles of central-command on the central and peripheral hemodynamic response. Exercise-physiologist usually describes physiological phenomena with models, because many influencing-factors can modify the result. This concept can be also applied to one of the most intriguing and ancestral question: what is the secret of longevity? The human-model of centenarians could be considered the best example of successful aging, however at this moment no studies have investigated maximal exercise capacity in centenarians. Therefore three different studies were performed to analyze these relationships reported above: I- the cardio-pulmonary responses during maximal exercise in centenarians; II- the contribution of muscular synergy to central and peripherals VO2 factors; III- the role of central command on hemodynamic response to passive-leg movement in subjects without afferent feedback. Methods: I- 8 centenarians (98 – 102yrs) and 8 young females (18 – 22yrs) were recruited for the 1st study. Subjects were evaluated for health history and physical evaluation, lung function, and anthropometric measures. Both groups performed oxygen uptake measurements by incremental maximal test on cycle ergometer at absolute and relative workloads. II- 8 right-legged healthy male participated at the 2nd study (26.4±5.1 yr; height 174.2±4.1 cm; weight 73.3±5.0 kg). After the practice sessions, each subject performed a constant workload exercise (20W ∼40% of maximal workload) in 2 different modalities: with dominant leg (1DL), non-dominant leg (1NDL). III- In 9 spinal cord injury humans (last study), we compared central and peripheral hemodynamic and ventilatory responses to one-leg passive knee extension with and without visual feedback, and with only the perception of movement. Ventilation, oxygen uptake, cardiac output, heart rate, stroke volume, mean arterial pressure, and leg arterial blood flow were evaluated during the 3 experimental protocols. Results: In the 1st study, instead of a sufficient health status, centenarians showed a dramatically reduction in lung function FEV1 (0.68±0.12 Vs 3.23±0.50l), and FVC (1.22±0.10 Vs 3.45±0.62l). The old women hypo-ventilate during exercise, VE was significantly lower at 45% of maximal exercise, and the strategy used to increase the ventilation was different compared to adult women. In the centenarians group the oxygen saturation decrease during the exercise (83±2 Vs 98±3%). At the same absolute exercise workload, centenarians showed an improved metabolic-efficiency, VO2max was significantly lower from 10 to 35w. However the heart rate response during the exercise at the same absolute workload was similar between the groups. The 2nd study showed that higher muscle synergy (quadriceps contraction/relaxation time) and mean leg force were associated to dominant limb, ∼30% and ∼50% of difference respectively, while similar limb work (p = 0.8) was maintained for all the modalities. At the same power output, the more coordinated limb showed better efficiency +25%, reduced cardiovascular responses -8%, higher blood flow (+0.45 l∙min-1) but reduced HHb (-38%), which explains the difference between a dominant and non-dominant limb. In the 3rd study VE was significantly increased from baseline to maximal response during movement with visual feedback (47 ± 12%); movement without visual feedback (34 ± 10%) and only the perception of passive movement (20 ± 9%). These increases were not different between protocols (p = 0.8), and were equally increased from baseline (∼33%; p < 0.05), but VE/VO2 was not different from baseline. Central hemodynamics (cardiac output ∼7%; heart rate ∼7%; stroke volume ∼4%; and mean arterial pressure ∼3%) were unchanged from baseline during the three different protocols. Leg blood flow increased significantly by 126 ± 18 ml⋅min-1, and 109 ± 23 ml⋅min-1 in movement with and without visual feedback, respectively, but was unchanged from baseline in the only perception of passive movement experiment (33 ± 21 ml⋅min-1; p = 0.8). The change in leg blood flow was significantly lower during this protocol compared to passive movement with and without visual feedback. Discussion: The overall results of these researches can facilitate in clarifying the role of different mechanisms, i.e. muscular synergy, central command and ageing, on central and peripheral oxygen uptake limiting factors. Especially these results demonstrate that the O2 delivery and utilization are clearly influenced by the intra and inter muscular synergies, in SCI individuals characterized by a complete spinal block, central command significantly contributes to the ventilatory response to passive movement, but has no effect on central or peripheral hemodynamics. Moreover, the cardio-pulmonary responses during exercise demonstrated that centenarians pulmonary function is very limited, but an incremented metabolic-efficiency, probably related to the markedly fibres type adaptation, maintain a sufficient maximal exercise capacity. Future development: Future developments for this study will be addressed to examine the molecular dimension of the above mentioned mechanism and it could be focused on the evaluation by a biopsy of the fibre type, capillarization, mitochondrial respiration in centenarian-quadriceps muscle, and on the analysis of the centenarians maximal exercise capacity during hyperoxia. Analyze the effect of different coordination pattern in specific “human-models”, (post-poliomyelitis subjects) on oxygen uptake central and peripheral factors, and evaluate on SCI subjects, the effect of passive leg movement on central and peripheral hemodynamic factors executed in different position: seated or supine

    Shaping exercise performance and neuromuscular fatigue through neuromodulation: unleashing the power of brain-muscle connections

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    Neuromuscular fatigue represents a reduced ability of the muscle to express force during a motor task. The literature proposes protocols to limit the development of this physiological event by modulating the peripheral components (e.g., muscle). On the other hand, repetitive transcranial magnetic stimulation is a widespread tool for regulating neuronal networks and brain functions in clinical and research settings. However, theta burst stimulation (TBS) protocols, which are faster and equally effective, remain confined to the clinical sphere for treating neuropsychological disorders. To date, the still unclear physiological mechanisms, and the high variability of response to TBS limit its wide-ranging use and application. Instead, thanks to the induction of long-term excitatory (intermittent TBS) and inhibitory (continuous TBS) effects, TBS may be a valid approach for the modulation of the central components also in the field of neuromuscular fatigue. Therefore, this thesis aims to verify the effectiveness of excitatory and inhibitory TBS on the components of neuromuscular fatigue, and its adjustments during physical exercise in young and healthy subjects. Chapter 1 provides a brief introduction and a review of the literature with the necessary information to understand the phenomenon of neuromuscular fatigue, the tools for its verification, and the related physiological mechanisms. Subsequently, in Chapter 2 the objectives and hypotheses pursued in this thesis are presented. In Chapters 3, 4, and 5, you can find the results of original studies on the topic in question. Finally, Chapter 6 provides a summary and overview of the results, highlighting the strengths and limitations of the work, and providing ideas for future investigations

    Chapter 11: The role of nitric oxide on vascular dysfunction during aging and Alzheimer’s disease.

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    Nitric oxide (NO) is an endogenously synthesized free radical involved in a plethora of physiological phenomena affecting cardiovascular homeostasis and neural functions. Its unregulated bioavailability has been recognized as a key factor in neurodegenerative disorders, especially in relation to the mechanisms through which NO-mediated vascular impairment accentuates the effect of reactive oxygen species. Interestingly, the recent literature indicates the pivotal role of NO and oxidative stress to both early and advanced stages of neurodegenerative disorders, as well as promoting their progression. Alzheimer’s disease (AD) is the most common form of dementia, characterized by extracellular amyloid (Aβ) plaques and intracellular neurofibrillary tangles coupled with reactive microgliosis and the loss of neurons and synapses in the cortex. However, the recent research supports the hypothesis of the pivotal role of NO depletion in the reduction of extracranial blood flow and impairment of cortical and peripheral circulation with a consequent detriment of cognitive function in humans with AD. It is worth of mention that AD, the leading form of dementia, continues to elude the scientific “armada” devoted on fighting this disruptive neurodegenerative disease, particularly with respect to its multifaceted origin. Although research on the biological mechanisms underlying the cause and the progression of AD is advancing, we are far to discover effective therapeutics or disease-modifying approaches. Currently, there is no absolute cure for AD: the few drugs available simply lessen the clinical symptoms. Therefore, new therapeutic approaches, including NO homeostasis, should be considered and might be useful as therapeutic targets

    On the role of group III/IV muscle afferent feedback on endurance performance, neuromuscular fatigue, and autonomic adjustments to exercise

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    Afferent feedback mechanisms and reflex arcs represent fundamental regulatory systems for several processes such as motor control, proprioception, and autonomic adjustments to physiological stressors. Nowadays, compelling evidence exists that feedback mediated by group III/IV thin afferent fibers plays a quintessential role in contributing to maintain an appropriate locomotor muscle O2 delivery by facilitating cardiovascular and ventilatory responses to exercise and eventually delaying the onset of fatigue. Concurrently however, this feedback also inhibits neural drive to the muscle and facilitate central fatigue, which results in a negative effect on performance. Because of the ambivalent and “contradictory” nature of this feedback, the net effect on exercise performance and neuromuscular fatigue is still somewhat unclear. Throughout the years, many advancements have been done in this field through the discovery and optimization of the methods and tools apt to separate the influence of the different regulatory systems that contribute to the neurocirculatory adjustments to exercise. However, the redundancy existing in the regulation of physiological systems, make this endeavor challenging. In this dissertation, particular effort was put into separating the effects of group III/IV afferent feedback, from the potential effects played by the voluntary descending drive. Therefore, the purpose of this dissertation was to elucidate the role of group III/IV afferent feedback on exercise performance, neuromuscular fatigue, and autonomic adjustments to exercise in young healthy individuals. In Chapter 1, a brief introduction about the history of group III/IV afferent feedback is provided. In Chapter 2, a detailed literature review was performed in order to give a comprehensive background on the role of group III/IV afferent feedback on the autonomic adjustments to exercise, the neuromuscular fatigue processes, and exercise performance. In Chapter 3 the aims of the study are highlighted. Successively, Chapters 4, 5, and 6 include the results of the original investigations on this topic. Finally, Chapter 7 provides a summary and an ensemble view of our findings, highlighting strengths and weaknesses of our research, and providing future directions for further studies
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