Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation

Background and objectivesAge and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis. To overcome these confounding factors, alterations in skeletal muscle were analyzed in highly selected patients on long-term hemodialysis undergoing kidney transplantation.Design, setting, participants, & measurementsIn total, 22 patients on long-term hemodialysis scheduled for kidney transplantation with few comorbidities, but with a long-term uremic milieu exposure, and 22 age, sex, and physical activity level frequency-matched control participants were recruited. We compared biochemical, functional, and molecular characteristics of the skeletal muscle using maximal voluntary force and endurance of the quadriceps, 6-minute walking test, and muscle biopsy of vastus lateralis. For statistical analysis, mean comparison and multiple regression tests were used.ResultsIn patients on long-term hemodialysis, muscle endurance was lower, whereas maximal voluntary force was not significantly different. We observed a transition from type I (oxidative) to type II (glycolytic) muscle fibers, and an alteration of mitochondrial structure (swelling) without changes in DNA content, genome replication (peroxisome proliferator activator receptor γ coactivator-1α and mitochondrial transcription factor A), regulation of fusion (mitofusin and optic atrophy 1), or fission (dynamin-related protein 1). Notably, there were autophagosome structures containing glycogen along with mitochondrial debris, with a higher expression of light chain 3 (LC3) protein, indicating phagophore formation. This was associated with a greater conversion of LC3-I to LC3-II and the expression of Gabaralp1 and Bnip3l genes involved in mitophagy.ConclusionsIn this highly selected long-term hemodialysis population, a low oxidative phenotype could be defined by a poor endurance, a fiber-type switch, and an alteration of mitochondria structure, without evidence of sarcopenia. This phenotype could be related to uremia through the activation of autophagy/mitophagy.Clinical Trial registration numbers:NCT02794142 and NCT02040363.

Shouting strengthens maximal voluntary force and is associated with augmented pupillary dilation

Previous research has demonstrated that human maximal voluntary force is generally limited by neural inhibition. Producing a shout during maximal exertion effort enhances the force levels of maximal voluntary contraction. However, the mechanisms underlying this enhancement effect on force production remain unclear. We investigated the influence of producing a shout on the pupil-linked neuromodulatory system state by examining pupil size. We also examined its effects on the motor system state by examining motor evoked potentials in response to transcranial magnetic stimulation applied over the contralateral primary motor cortex, and by evaluating handgrip maximal voluntary force. Analysis revealed that producing a shout significantly increased handgrip maximal voluntary force, followed by an increase in pupil size and a reduction of the cortical silent period. Our results indicate that producing a shout increased handgrip maximal voluntary force through the enhancement of motor cortical excitability, possibly via the enhancement of noradrenergic system activity. This study provides evidence that the muscular force-enhancing effect of shouting during maximal force exertion is related to both the motor system state and the pupil-linked neuromodulatory system state.

Shouting Strengthens Maximal Voluntary Force with Pupillary Dilation

Previous research has demonstrated that human maximal voluntary force is generally limited by neural inhibition. Indeed, producing a shout during maximal exertion efforts enhances the force levels of maximum voluntary contractions. However, the mechanisms underlying this enhancing effect of force production remain unknown. We investigated the influence of a shout on the pupil-linked neuromodulatory system state by examining pupil size. We also examined its effect on the motor system state by examining motor evoked potentials in response to transcranial magnetic stimulation applied over the contralateral primary motor cortex, and by evaluating the handgrip maximal voluntary force. Analysis showed that a shout significantly increased the handgrip maximal voluntary force, followed by an increase in pupil size and a reduction of the cortical silent period. Our results indicate that a shout can increase handgrip maximal voluntary force through the enhancement of motor cortical excitability, possibly via the enhancement of noradrenergic system activity. This study provides evidence that the muscular force-enhancing effect of a shout during maximal force exertion is related to both the motor system state and the pupil-linked neuromodulatory system state.