In this Issue
April 2017; volume 122, issue 4
REVIEW | Cores of Reproducibility in Physiology
REVIEWS | Recovery from Exercise
RESEARCH ARTICLE | Hypoxia 2015
- β1-Blockade increases maximal apnea duration in elite breath-hold divers
The governing bodies for international apnea competition, the Association Internationale pour le Développment de l’Apnée and La Confédération Mondaile des Activités Subaquatiques, have banned the use of β-blockers based on anecdotal reports that they improve apnea duration. Using a randomized placebo-controlled trial, we are the first to empirically confirm that β-blockade improves apnea duration. This improvement in apnea duration coincided with a reduced myocardial oxygen consumption.
- How does passive lengthening change the architecture of the human medial gastrocnemius muscle?
Novel MRI and DTI techniques revealed changes in three-dimensional architecture of the human medial gastrocnemius during passive lengthening. Whole muscle belly width and depth decreased when the muscle lengthened. Fascicle length, pennation, and curvature changed uniformly or near uniformly along the muscle during passive lengthening. Diffusion of water molecules in muscle changes in the same direction as fascicle strains.
- Accelerated deflation promotes homogeneous airspace liquid distribution in the edematous lung
We introduce, in the isolated rat lung, a new model of pulmonary edema with elevated surface tension. We first generate hydrostatic edema and then ventilate gently to increase surface tension. We investigate the mechanical mechanisms through which 1) ventilation injures edematous lungs and 2) ventilation with accelerated deflation might lessen ventilation injury.
- Gene networks in skeletal muscle following endurance exercise are coexpressed in blood neutrophils and linked with blood inflammation markers
By using weighted gene coexpression network analysis, an advanced bioinformatics method, we have identified previously unknown, functional gene networks that are preserved between skeletal muscle and blood neutrophils during recovery from exercise. These novel preliminary data suggest that muscular gene networks are coexpressed in blood leukocytes following physiological stress. This is a step forward toward the development of blood neutrophil gene subnetworks as part of blood biomarker panels to assess muscle health and disease.
- Effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia in the frequently sampled intravenous glucose tolerance test
To our knowledge, this is the first study examining the role of adrenal catecholamines in glucose metabolism during intermittent hypoxia (IH) in unanesthetized unrestrained C57BL/6J mice. We report that IH did not affect fasting glucose and insulin levels nor insulin sensitivity and insulin secretion during, whereas glucose effectiveness was decreased. Adrenal medullectomy decreased fasting blood glucose and insulin levels in mice exposed to IH but had no effect on glucose metabolism, insulin secretion, and insulin sensitivity.
- Moderate-intensity resistance exercise alters skeletal muscle molecular and cellular structure and function in inactive older adults with knee osteoarthritis
Moderate-intensity resistance training causes sex-specific adaptations in skeletal muscle structure and function at the cellular and molecular levels in inactive older adult men and women with knee osteoarthritis. However, these responses were minimal compared with high-intensity resistance training. Thus adjuncts to moderate-intensity training need to be developed to correct underlying cellular and molecular structural and functional deficits that are at the root of impaired physical function in this mobility-limited population.
- Sleep during an Antarctic summer expedition: new light on “polar insomnia”
The present paper presents a rare body of work on sleep and sleep wake regulation in the extreme environment of an Antarctic expedition, documenting the effects of constant illumination on sleep, mood, and chronobiology. For applied research, these results suggest the potential efficiency of melatonin supplementation in similar deployments. For fundamental research, these results warrant further investigation of the potential link between melatonin secretion and the onset of slow-wave sleep.
- Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans
The signaling pathways that regulate human cerebral blood flow in hypoxia remain poorly understood. Using a randomized, double-blinded, and placebo-controlled study design, we determined that adenosine receptor-dependent signaling is not obligatory for the regulation of human cerebral blood flow at sea level; these findings also extend to high altitude.
- Contribution of rostral fluid shift to intrathoracic airway narrowing in asthma
In supine asthmatic subjects, application of positive pressure to the lower body caused appreciable increases in respiratory system resistance and stiffness. Moreover, these changes in respiratory mechanics correlated positively with increase in thoracic fluid volume. These findings suggest that fluid shifts from the lower body to the thorax may contribute to overnight intrathoracic airway narrowing and worsening of asthma symptoms.
- Exercise training decreases NADPH oxidase activity and restores skeletal muscle mass in heart failure rats
This study demonstrates, for the first time, the contribution of aerobic exercise training (AET) in decreasing muscle NADPH oxidase activity associated with reduced reactive oxygen species production and systemic inflammation, which diminish NF-κB overactivation, p38 phosphorylation, and ubiquitin proteasome system hyperactivity. These molecular changes counteract plantaris atrophy in trained myocardial infarction-induced heart failure rats. Our data provide new evidence into how AET may regulate protein degradation and thus prevent skeletal muscle atrophy.
- Contractile efficiency of dystrophic mdx mouse muscle: in vivo and ex vivo assessment of adaptation to exercise of functional end points
We focused on the adaptation/maladaptation of dystrophic mdx mouse muscles to a standard protocol of exercise to provide guidance in the development of more effective drug and physical therapies in Duchenne muscular dystrophy. The mdx muscles showed a modest functional adaptation to chronic exercise, but it was not sufficient to overcome the progressive in vivo weakness nor to counter signs of muscle damage. Therefore, a complex involvement of multiple systems underlies the maladaptive response of dystrophic muscle.
- Susceptibility to high-altitude pulmonary edema is associated with a more uniform distribution of regional specific ventilation
Uneven hypoxic pulmonary vasoconstriction (HPV) is thought to incite high-altitude pulmonary edema (HAPE). We evaluated whether greater heterogeneity of ventilation is also a feature of HAPE-susceptible subjects compared with HAPE-resistant subjects. Contrary to our hypothesis, ventilation heterogeneity was less in HAPE-susceptible subjects and unaffected by hypoxia, suggesting a vascular basis for uneven HPV.
- Coupling of EIT with computational lung modeling for predicting patient-specific ventilatory responses
In this work, we present a patient-specific computational lung model that is able to predict global and local ventilatory quantities for a given patient and any selected ventilation protocol. For the first time, such a predictive lung model is equipped with a virtual electrical impedance tomography module allowing real-time validation of the computed results with the patient measurements. First promising results obtained in an acute respiratory distress syndrome patient show the potential of this approach for personalized computationally guided optimization of mechanical ventilation in future.
- Carotid β-stiffness index is associated with slower processing speed but not working memory or white matter integrity in healthy middle-aged/older adults
Previously, studies investigating the relation between large elastic artery stiffness, cognition, and brain structure have focused mainly on aortic stiffness in aged individuals with cardiovascular disease risk factors and other comorbidities. This study adds to the field by demonstrating that the age-related increases in carotid artery stiffness, but not aortic stiffness, is independently and selectively associated with slower processing speed but not working memory among middle-aged/older adults with low cardiovascular disease risk factor burden.
- The cerebrovascular response to lower-body negative pressure vs. head-up tilt
Lower-body negative pressure has the potential to serve as a MRI-compatible surrogate of orthostatic stress, but a comparison with actual orthostasis was lacking. This study showed that the pronounced reduction in end-tidal Pco2 partial pressure together with gravitational effects on the brain circulation lead to a larger decline in cerebral blood flow velocity in response to head-up tilt than during lower-body negative pressure. This should be taken into account when employing lower-body negative pressure as an MRI-compatible alternative to orthostatic stress.
- Losartan reduces the immediate and sustained increases in muscle sympathetic nerve activity after hyperacute intermittent hypoxia
This study demonstrates for the first time in humans that losartan, an angiotensin receptor blocker (ARB), abrogates the acute and immediately persistent increases in muscle sympathetic nerve activity and arterial pressure in response to acute intermittent hypoxia. This investigation, along with others, provides important beginning translational evidence for using ARBs in treatment of the intermittent hypoxia observed in obstructive sleep apnea patients.
- Heart rate kinetics during exercise in patients with subclinical hypothyroidism
Subclinical hypothyroidism patients have slower heart rate kinetics in the transition from rest to exercise when performing a constant-load exercise at 50 W.
- Blood flow regulation and oxygen uptake during high-intensity forearm exercise
This study evaluated blood flow regulation and oxygen uptake during small muscle mass forearm exercise with high to maximal intensity. Despite utilizing only a fraction of cardiac output, blood flow reached a plateau at 80% of maximal work rate and regulated peak oxygen uptake. Furthermore, the results revealed that muscle contractions dictated bulk oxygen delivery and yielded three times higher peak blood flow in the relaxation phase compared with mean values.
- Respiratory muscle blood flow during exercise: Effects of sex and ovarian cycle
It has been proposed that sex and ovarian cycle modulate respiratory muscle blood flow control during exercise. We demonstrate herein that neither sex nor ovarian cycle influences respiratory muscle blood flow or vascular conductance at rest or during exercise in rats.
- Decreases in maximal oxygen uptake following long-duration spaceflight: Role of convective and diffusive O2 transport mechanisms
Long-duration spaceflight elicited a significant decrease in maximal oxygen uptake. Given the adverse physiological adaptations to microgravity along the O2 transport pathway that have been reported, an integrative approach to the determinants of post-flight maximal oxygen uptake is needed. We demonstrate that both convective and diffusive oxygen transport are decreased following ~6 mo International Space Station missions.
- Reduced prosthetic stiffness lowers the metabolic cost of running for athletes with bilateral transtibial amputations
We measured the metabolic rates and biomechanics of five athletes with bilateral transtibial amputations while running with different prosthetic configurations. The metabolic cost of running for these athletes is minimized by using an optimal prosthetic model and reducing prosthetic stiffness. The metabolic cost of running was independent of prosthetic height, suggesting that longer legs are not advantageous for distance running. Moreover, the in-series prosthetic stiffness governs the leg stiffness of athletes with bilateral leg amputations.
- Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial
The effects and prevalence of nonresponders (NR) to improve glucose control variables have predominately been reported by endurance training. A uniqueness of the present study was to examine the NR prevalence in women with insulin resistance after high-intensity interval (HIIT) and resistance training (RT). This study demonstrates that 12 wk of HIIT and RT have similar effects and NR prevalence to improve glucose control variables. However, significantly different NR prevalence were observed in other anthropometric, cardiovascular, strength, and endurance performance measurements.
- Melatonin protects against uric acid-induced mitochondrial dysfunction, oxidative stress, and triglyceride accumulation in C2C12 myotubes
Few studies have investigated the effects of uric acid on skeletal muscle. This study shows that hyperuricemia induces mitochondrial dysfunction and triglyceride accumulation in skeletal muscle. The findings may explain why hyperuricemia is an independent predictor of diabetes.
- Sublingual microcirculatory blood flow and vessel density in Sherpas at high altitude
Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitude, yet the physiological mechanisms underlying this tolerance remain unknown. In our prospective study, conducted on healthy volunteers ascending to Everest base camp (5,300 m), we demonstrated that Sherpas have a higher sublingual microcirculatory blood flow and greater capillary density at high altitude than lowlanders. These findings support the notion that the peripheral microcirculation plays a key role in the process of long-term adaptation to hypoxia.
- Assessment of cardiac fibrosis: a morphometric method comparison for collagen quantification
Direct comparison of frequently applied histological fibrosis assessment techniques revealed a distinct relation of measured collagen and utilized quantification method as well as section thickness. Besides electron microscopy-stereology, which was precise and sensitive, light microscopy-stereology and automated image analysis proved to be appropriate for collagen quantification. Moreover, consideration of collagen localization might be important in revealing minor fibrotic changes.
- Divergent endothelial function but similar platelet microvesicle responses following eccentric and concentric cycling at a similar aerobic power output
Continuous eccentric cycling exercise induces substantial skeletal muscle, tendon, and bone strain providing a potentially beneficial stimulus among clinical populations. This modality also induces temporary endothelial dysfunction but no apparent damage or activation of the endothelium indicated by microvesicle production, whereas proangiogenic platelet microvesicles are released similarly following both concentric and eccentric cycling and may relate to the shear stress and catecholamine response to exercise.
- A chronic physical activity treatment in obese rats normalizes the contributions of ET-1 and NO to insulin-mediated posterior cerebral artery vasodilation
The new and noteworthy findings are that 1) in rodents, obesity-related deficits in insulin-mediated vasodilation are associated with increased influence of insulin-stimulated ET-1 and depressed influence of insulin-stimulated NOS and 2) a physical activity intervention, initiated after the onset of disease, restores insulin-mediated vasodilation, likely by normalizing insulin-stimulated ET-1 and NOS balance. These data demonstrate that the treatment effects of chronic exercise on insulin-mediated vasodilation extend beyond active skeletal muscle vasculature and include the cerebrovasculature.
- DNA methylation assessment from human slow- and fast-twitch skeletal muscle fibers
This study validates a low-DNA input reduced representation bisulfite sequencing method for human muscle biopsy samples to investigate the methylation patterns at a fiber type-specific level. These are the first fiber type-specific methylation data reported from human skeletal muscle and thus provide initial insight into basal state differences in myosin heavy chain I and IIa muscle fibers among young, healthy men.