In this Issue
September 2016; volume 121, issue 3
- Differential effects of respiratory and electrical stimulation-induced dilator muscle contraction on mechanical properties of the pharynx in the pig
Respiratory stimulation and electrical stimulation of the hypoglossus nerve differ in the mechanism by which they stabilize the pharynx in the isolated upper airway of the pig: respiratory stimulation reduces pharyngeal compliance, i.e., stiffens the area of collapse, whereas electrical stimulation lowers extrapharyngeal pressure, as calculated from the area-pressure curve. Tongue muscles, but not the neck muscles and thoracic forces, contributed to the respiratory stimulation-induced stiffening of the pharynx in this study.
- Evaluating the control: minipump implantation and breathing behavior in the neonatal rat
Accumulating evidence indicates that gestational and/or neonatal stress perturbs central nervous system (CNS) development and that fetal exposure to anesthetic agents or narcotics disrupts critical processes of axonal growth and synapse elimination. Here we focus on processes related to minipump implantation surgery and the potential impact of implant surgery on early postnatal respiratory control and function.
- Exercise physiological responses to drug treatments in chronic thromboembolic pulmonary hypertension
This is the first study using gas exchange during exercise to assess the response to pulmonary arterial hypertension drug therapy in patients with chronic thromboembolic pulmonary hypertension. We also for the first time compare patients with operable and inoperable chronic thromboembolic pulmonary hypertension.
- Prolonged adenosine triphosphate infusion and exercise hyperemia in humans
The novel and noteworthy findings are 1) in humans, the vasodilator response to infusion of exogenous ATP does not wane and 2) the magnitude of change in hyperemic responses to exercise during the ATP infusion is unaffected. The ability of ATP to evoke prolonged vasodilation shows it meets a key criterion of any putative dilator substance. The latter observation suggests a disconnect between the usual matching of blood flow and oxygen delivery during contractions.
- Maximal oxygen uptake is proportional to muscle fiber oxidative capacity, from chronic heart failure patients to professional cyclists
Maximal oxygen uptake during whole body exercise is presumably constrained by oxygen delivery to mitochondria rather than by mitochondria's ability to consume oxygen. However, mitochondrial oxidative overcapacity remains unclear due to complicated isolation and permeabilization procedures. In the present study, human maximal oxygen uptake attained during cycling exercise is related and ∼90% of mitochondrial oxidative capacity predicted from skeletal muscle succinate dehydrogenase activity. This mitochondrial oxidative overcapacity is substantially lower than previously reported from isolation and permeabilization procedures.
- Morphological and molecular aspects of immobilization-induced muscle atrophy in rats at different stages of postnatal development: the role of autophagy
Immobilization induces muscle maladaptations at different stages of postnatal development, but the cellular mechanisms involved in such effects are unclear. Our data show that the alterations in muscle proteostasis during immobilization occur in age-independent and -dependent manners and muscle disorders are aggravated by autophagy blockade with colchicine, inducing a myopathic profile. This understanding may help us optimize treatment outcomes in immobilized adults and infants and encourages the testing of different autophagy inhibitors in muscle atrophy.
- Dietary nitrate supplementation: impact on skeletal muscle vascular control in exercising rats with chronic heart failure
Chronic heart failure (CHF) impairs skeletal muscle vascular control and tolerance to exercise. Dietary nitrate supplementation elevates skeletal muscle blood flow and improves exercise performance in some populations. Here we demonstrate that nitrate supplementation via beetroot juice elevates skeletal muscle blood flow during exercise in rats with moderate CHF.
- Intermittent hypoxia induces murine macrophage foam cell formation by IKK-β-dependent NF-κB pathway activation
Intermittent hypoxia (IH)-induced inflammation increases the risk of atherosclerosis in obstructive sleep apnea (OSA) patients. However, the effect of IH on macrophage foam cell formation, a key player in atherosclerosis, has not been elucidated. We demonstrate for the first time that IH-induced foam cell formation is diminished by IKK-β deletion. Our findings highlight the importance of the IKK-β- dependent NF-κB pathway and the potential of this pathway as a therapeutic target.
- Home-based aerobic exercise training improves skeletal muscle oxidative metabolism in patients with metabolic myopathies
Twelve weeks of home-based moderate-intensity aerobic training in mitochondrial myopathies and McArdle's disease patients attenuated the impairments of skeletal muscle oxidative metabolism and improved variables associated with exercise tolerance. Despite this, 3-mo after the termination of the exercise training program the level of habitual physical activity was not increased vs. the baseline.
- Pregnancy at high altitude in the Andes leads to increased total vessel density in healthy newborns
The natural hypoxic environment at high altitude results in reduced oxygenation, especially in the growing human fetus. Our prospective observational study on healthy term newborns in Peru (Puno at 3,840 m) that included novel noninvasive visualization of microcirculation demonstrates that vessel density is elevated by 14% in neonates born to women living at high altitude compared with babies born at sea level, most likely revealing an early adaptive mechanism to a highly hypoxic antenatal environment.
- Passive heat therapy improves cutaneous microvascular function in sedentary humans via improved nitric oxide-dependent dilation
We showed for the first time that passive heat therapy improves cutaneous microvascular function in humans via improved nitric oxide (NO)-dependent dilation. This is the first study to investigate the mechanisms underlying improvements in vascular health associated with heat therapy. Our data add to the currently limited but strong evidence suggesting heat therapy could be a powerful novel tool for improving cardiovascular health, particularly in disease states characterized by impaired vascular function secondary to reduced NO bioavailability.
- No difference in exogenous carbohydrate oxidation during exercise in children with and without impaired glucose tolerance
This article is the first to report exogenous carbohydrate oxidative efficiency during exercise in children with impaired glucose tolerance using 13C-stable isotope methodology. The capacity to utilize exogenous carbohydrate was not impaired in children with impaired glucose tolerance compared with normal glucose tolerance, despite lower insulin sensitivity and beta-cell function. The findings suggest that exogenous carbohydrate oxidation was maintained during exercise, possibly via endocrine compensatory responses, such as increased insulin secretion, or via non-insulin-mediated mechanisms.
- Effect of betamethasone, surfactant, and positive end-expiratory pressures on lung aeration at birth in preterm rabbits
Antenatal betamethasone, surfactant therapy, and positive end-expiratory pressure (PEEP) ventilation are frequently used in combination to improve lung function in preterm newborns. However, it is unclear how these factors interact to enhance functional residual capacity (FRC) and dynamic lung compliance (CDL) at birth. Contrary to expectation, betamethasone hindered FRC development and abolished the benefit of low PEEP, yet improved CDL. However, surfactant administration counteracted the adverse effect of betamethasone on FRC recruitment at birth.
- Human motor control of landing from a drop in simulated microgravity
For the first time, the control of landing from a jump and from a drop is compared in weightlessness with different simulated gravity conditions (1–0.2 g). In these unusual conditions, humans adjust the landing command according to the amount of energy to be dissipated. Kinetic, kinematic, and electromyographic observations contribute to understanding the underlying mechanisms through which the central nervous system plans a complex motor task.
- Effects of pacing modality on noninvasive assessment of heart rate dependency of indices of large artery function
This was the first study to demonstrate significant differences in wave reflection indices with different cardiac pacing modalities. This has implications for future heart rate studies in wave reflections, and studies should either be designed to employ a single pacing modality for inducing heart rate changes, or to take pacing modality into account in the analysis.
- Membrane progesterone receptor-β, but not -α, in dorsal brain stem establishes sex-specific chemoreflex responses and reduces apnea frequency in adult mice
We tested the hypothesis that membrane progesterone receptors (mPR) contribute to respiratory control in adult male and female mice. The main results show that reduced expression of mPRβ (achieved by intracerebroventricular treatment with small interfering RNA) increases (3×) the frequency of apnea, suppresses the chemoreflex response to hypoxia, and reduces the response to hypercapnia. By contrast, mPRα had limited effects, slightly reducing the ventilatory response to hypercapnia.
- Combined effects of resistance training and calorie restriction on mitochondrial fusion and fission proteins in rat skeletal muscle
The original aim of this study was to examine the effects of resistance training with calorie restriction on skeletal muscle adaptation. We found that calorie restriction enhanced resistance training-induced increases in protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α, and in proteins involved in mitochondrial fusion (Opa1 and Mfn1) and oxidative phosphorylation.
- Lipopolysaccharide exposure during the early postnatal period adversely affects the structure and function of the developing rat carotid body
We have developed a newborn animal model of spontaneous intermittent hypoxia. Exposure to LPS during early postnatal development in rat pups significantly increases spontaneous intermittent desaturations and decreases the ventilatory and carotid sinus nerve responses to hypoxia that persist for 1 wk after exposure. Our model may simulate the chronic intermittent hypoxia that is often seen in premature infants with perinatal inflammation and help to further delineate mechanisms leading to disordered breathing in premature infants.
HIGHLIGHTED TOPIC | Molecular Adaptations to Exercise, Heat Acclimation, and Thermotolerance
- The role of Nrf2 in skeletal muscle contractile and mitochondrial function
Nrf2 is critical for mediating an antioxidant defense against oxidative insults. Emerging evidence has implicated Nrf2 in the regulation of mitochondrial function in some cell types, but no research has been devoted to understanding its contribution to exercise performance and mitochondrial biogenesis in muscle. Our work is the first to show that the presence of Nrf2 has an impact on muscle endurance performance and mitochondrial function in skeletal muscle.
- Transcriptional control, but not subcellular location, of PGC-1α is altered following exercise in a hot environment
This investigation explores the transcriptional control and subcellular location of proliferator-activated receptor-γ coactivator 1-α (PGC-1α) following exercise in a hot environment. It provides new evidence for decreased transcription of PGC-1α following an acute exercise bout in a hot environment, coinciding with decreased binding of cAMP response element-binding protein (CREB), myocyte enhancer factor 2 (MEF2), and forkhead box class-O1 (FoxO1) to the PGC-1α promoter region. However, translocation of PGC-1α protein from the cytosol into the nucleus following exercise appears to be unaffected by differences in environmental temperature.