In this Issue
July 2016; volume 121, issue 1
- Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions
This work provides a direct comparison of commonly used positive inotropic medications, comparing contractility, heart rate, diastolic function, and myocardial oxygen consumption using a rodent isolated working heart model. When loading conditions were held constant, dobutamine and norepinephrine exhibited the most potent effects on systolic and diastolic function. In this model, milrinone and triiodothyronine exhibited minimal effects on contractility.
- Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity
Exercise oncology is a rapidly developing field; however, there is a paucity in our understanding of tumor blood flow responses during exercise and the potential dependence of tumor perfusion and outcomes upon host tissue type and location. This study is the first to demonstrate that blood flow responses to exercise are directionally opposed when the same tumor is grown in an ectopic or orthotopic manner and that host tissue vascular reactivity differs substantially in resistance vessels from different host tissues.
- Morphological dependency of cutaneous blood flow and sweating during compensable heat stress when heat-loss requirements are matched across participants
In this experiment, individuals of widely variable body size exercised in thermally compensable conditions under work loads that elicited equivalent heat-loss requirements and body temperature changes. This novel design yielded the first comprehensive evaluation of the morphological dependency of the resulting cutaneous vascular and sudomotor responses, explaining up to half of the interindividual, thermoeffector variability. This relationship provides a mechanism through which to explain thermoregulatory differences among men and women, and children and adults.
- Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes
Circulating endothelial progenitor cells contribute to vascular homeostasis and angiogenesis through engraftment and paracrine mechanisms. This study is the first to identify an impairment in acute exercise-induced CD34+/VEGFR2+ endothelial progenitor cell mobilization in older adults with either impaired glucose tolerance or type 2 diabetes mellitus. This impairment could play an underlying role in the link between diabetes, capillary rarefaction, and other vascular complications.
- A machine-learning approach for computation of fractional flow reserve from coronary computed tomography
We discuss a deep-learning-based approach for noninvasive computation of coronary fractional flow reserve (FFR) from computed tomography images. The deep-learning model is trained on a large database of synthetic vessel trees, followed by verification and validation against an existing physics-based model, as well as invasive measurements. The model exhibited high diagnostic accuracy when compared against invasively measured FFR. Average execution time was 2.4 ± 0.44 s, giving real-time assessment of FFR on standard workstations.
- Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness
Andean highlanders suffering from Chronic Mountain Sickness (CMS) show consistently lower levels of plasma soluble erythropoietin (Epo) receptor (sEpoR) and higher Epo-to-EpoR ratios (Epo/sEpoR) during sleep compared with their healthy counterparts. This indicates higher blood Epo availability in CMS patients and continuous nocturnal erythropoietic stimulus. Additionally, morning Epo/sEpoR and mean sleep-time SpO2 are independent main predictors of Hct. These findings support the role of the Epo system in the development of excessive erythrocytosis in CMS.
- Parasternal intercostal and diaphragm function during sleep
This study provides new insight into ventilation and respiratory muscles during rapid eye movement (REM)/dream sleep. Traditionally, it has been believed that during REM sleep, the diaphragm is spared as the preeminent inspiratory muscle while action of the chest wall muscles is globally diminished. Instead, this study confirms that the parasternal intercostal muscles, in the upper medial chest wall, which are primary muscles of inspiration during wakefulness, remain fully active during REM sleep, along with the diaphragm.
- Hyperoxia and hypergravity are independent risk factors of atelectasis in healthy sitting humans: a pulmonary ultrasound and SPECT/CT study
This paper reports the first-time use of pulmonary ultrasound and single-photon emission computed tomography combined with computed tomography (SPECT/CT) to study the influence of hyperoxia and sustained moderate hypergravity on lung tissue compression, and on ventilation and perfusion. Together with electrical impedance tomography measurements (reported separately), a functional and topographical imaging of lung function before, during, and after exposure to hyperoxia and hypergravity is obtained: zones with decreased ventilation are present above atelectatic areas and are prone to transient airway closure.
- Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature
Increases in total capillary length of the hippocampus occur linearly in response to increasing cyclical intermittent hypoxia (CIH) severity, but an increase in GLUT1 transporter along endothelial cells occurs only at very severe CIH. This highlights that there may be multiple mechanisms when exposed to different levels of CIH, providing a strong rationale for future CIH experiments to include multiple levels of CIH.
- No effect of elevated operating lung volumes on airway function during variable workrate exercise in asthmatic humans
We show that deliberate elevations in operating lung volumes during interval exercise do not prevent bronchoconstriction when workrate is reduced in asthmatic adults. In our subjects, exercise airway caliber fluctuated with changing workrate both when subjects ventilated spontaneously and when tidal volume and end-inspiratory lung volume were voluntarily and substantially increased at the lower of two exercise workloads. Thus exercise airway function behaved independently from lung stretch and oscillations in lung stretch.
- Mechanical and neural function of triceps surae in elite racewalking
In internationally competitive racewalkers, muscle-tendon unit length changes indicate a decrease in the spring-like function of the Achilles tendon compared with running at a given speed. For individual triceps surae muscles, cumulative muscle activity required to move a unit distance was also higher in racewalking than running. Thus racewalking is neurally and mechanically costly relative to running, which may lead to major energetic penalties in racewalking events, which are typically between 10 and 50 km.
- Predicting ventilator-induced lung injury using a lung injury cost function
This article describes a new computational model of lung mechanics that includes mechanisms for predicting the development of ventilator-induced lung injury (VILI) via the mechanisms of both volutrauma and atelectrauma. The model uses these predictions in two novel injury cost functions that potentially could be used to guide patient-specific mechanical ventilation in acute respiratory distress syndrome so that VILI is minimized.
- Morphometric differences between central vs. surface acini in A/J mice using high-resolution micro-computed tomography
Advanced high-resolution interior tomography has been used to explore the morphometric and geometric differences between surface and core alveoli within the intact mouse lung. Understanding of these differences is of importance when inferring global characteristics from limited sampling methodologies and may provide new insights into lung function and disease susceptibilities. The methodologies can be applied to an investigation of larger animals and humans.
- Comparison of high-intensity vs. high-volume resistance training on the BDNF response to exercise
There have been a number of investigations examining the BDNF response to exercise; however, our understanding of changes in the BDNF response to resistance training has been primarily limited to frail, older adults. This is the first study that has compared two different resistance training paradigms in experienced, resistance-trained adults and have demonstrated that training, independent of resistance training paradigm, can modify the BDNF response to an acute bout of resistance exercise.
- Neither load nor systemic hormones determine resistance training-mediated hypertrophy or strength gains in resistance-trained young men
We provide novel evidence of the effect of lifting markedly different (lighter vs. heavier) loads (mass per repetition) during whole-body resistance training on the development of muscle strength and hypertrophy in previously trained persons. Using a large sample size (n = 49), and contradicting dogma, we report that the relative load lifted per repetition does not determine skeletal muscle hypertrophy or, for the most part, strength development. In line with our previous work, acute postexercise systemic hormonal changes were unrelated to strength and hypertrophic gains.
- Voluntary physical activity abolishes the proliferative tumor growth microenvironment created by adipose tissue in animals fed a high fat diet
We hypothesized that voluntary physical activity (PA) would counteract the deleterious adipose-dependent growth microenvironment to which a breast cancer is exposed. We show that PA altered the adipokine secretion profile of adipose in a volume-dependent manner. This alteration resulted in growth inhibition of estrogen receptor positive breast cancer cells in culture. Furthermore, stabilizing adiponectin receptor 1 expression in the cancer cells made them resistant to the cell cycle entry effects that accompany obesity.
- Separate and combined effects of a 10-d exposure to hypoxia and inactivity on oxidative function in vivo and mitochondrial respiration ex vivo in humans
Superposition of 10 days of hypoxia on profound physical inactivity (bed rest) did not aggravate (and partially attenuated) impairment of oxidative function in vivo induced by bed rest alone. The main site(s) of impairment are presumably downstream of cardiovascular function but upstream of mitochondria. The findings add insights into the mechanisms of exercise limitations under environmental stressors such as microgravity/physical inactivity and hypoxic exposure, which characterize Moon and Mars environments as well as different pathological conditions.
- Role of histidyl dipeptides in contractile function of fast and slow motor units in rat skeletal muscle
To our knowledge, the current study is the first of its kind to apply the neurophysiological methodology of in vivo electrical stimulation of single motor units in rats, to decipher muscle fiber type-specific effects of ergogenic nutritional supplements. The data show that beta-alanine-induced muscle carnosine and anserine loading improves twitch force in fast fatigable units, increases maximum tetanic force in fast resistant units, and reduces force decline during repeated low-frequency stimulation in slow units.
- Effect of eccentric exercise with reduced muscle glycogen on plasma interleukin-6 and neuromuscular responses of musculus quadriceps femoris
Athletes may perform muscle-damaging exercise as part of training routines. Muscle-damaging eccentric exercise initiated with low muscle glycogen does not seem to exacerbate substantially the functional responses. In fact, voluntary force production and voluntary activation were not affected. In addition, muscle-damaging eccentric exercise with low muscle glycogen does not result in enhanced interleukin-6 levels.
- Model-based stability assessment of ventilatory control in overweight adolescents with obstructive sleep apnea during NREM sleep
Our finding of decreased loop gain in overweight adolescents with obstructive sleep apnea (OSA) suggests that ventilatory control instability is unlikely to be the primary underlying mechanism, contrary to what has been deduced from recent studies in adults. However, because of elevated plant gain in this population, ventilatory fluctuations, resulting from sleep-induced upper airway collapse and subsequent arousals, could lead to large swings in blood gases, increasing the likelihood of self-sustained oscillations in breathing.
- The relation between cardiac output kinetics and skeletal muscle oxygenation during moderate exercise in moderately impaired patients with chronic heart failure
This study extends current understanding of limitations of oxygen uptake kinetics during moderate exercise in patients with chronic heart failure (CHF) by using simultaneous measurements of cardiac output, skeletal muscle oxygenation, and pulmonary oxygen uptake. In our study, half of the patients showed slow Q̇ kinetics relative to the metabolic demands. In this group, Q̇ kinetics were related to the degree of skeletal muscle deoxygenation, suggesting that central hemodynamics may limit submaximal exercise performance in a substantial subset of moderately impaired CHF patients.
- Segmental extracellular and intracellular water distribution and muscle glycogen after 72-h carbohydrate loading using spectroscopic techniques
Total body water increases after carbohydrate loading due to binding of glycogen with water. Bioimpedance spectroscopy showed that intracellular water but not extracellular water increased after 72-h carbohydrate loading following glycogen depletion cycling. Additionally, increased intracellular water was observed in the leg segment only. Thus increased total body water after carbohydrate loading is caused by segment-specific increase in intracellular water.
- Exercise training reverses myocardial dysfunction induced by CaMKIIδC overexpression by restoring Ca2+ homeostasis
The novel finding in this study is that high-intensity endurance training turned the heart failure phenotype in CaMKIIδC-overexpressing mice toward a more healthy phenotype. We report improved cardiac and cardiomyocyte function and Ca2+ handling by reducing diastolic Ca2+ leak and restoring sarcoplasmic reticulum (SR) Ca2+ content through compensatory mechanisms of restored SR Ca2+-ATPase (SERCA2a) function and Na+/Ca2+-exchanger (NCX) function and increased L-type Ca2+ currents. The present data extend the basis for further understanding of cardiac adaptations to exercise training.
- Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall
Airway geometry, and the interplay between dynamic active and passive forces, give rise to large stress and compliance heterogeneities across the broncho-constricted intact airway wall that are absent in tissue strips with identical properties. These findings suggest a redesign of loading protocols in tissue-strip experiments to better mimic the dramatically different micromechanical conditions experienced by airway smooth muscle cells in the intact airway. Consequent cellular response could play an important role in airway hyperresponsiveness.
- Different effects of strength and endurance exercise training on COX-2 and mPGES expression in mouse brain are independent of peripheral inflammation
Both strength as well as endurance training induce COX-2 expression in the brain. The induction of cyclooxygenase (COX)-2 expression in the cortex/hippocampus and hypothalamus appears to be more pronounced following strength training. In the hypothalamus, strength training affected the COX-2 pathway including inflammatory signaling via nuclear factor (NF)κB. These signals seem to be independent from systemic inflammatory processes. A potential mediator of COX-2 expression after training might be the systemically released interleukin (IL)-6.
- The correlation between brain near-infrared spectroscopy and cerebral blood flow in piglets with intracranial hypertension
Near-infrared spectroscopy (NIRS) can noninvasively measure tissue oxygenation, but its usefulness in global cerebral ischemia has not been evaluated. By reducing cerebral perfusion pressure stepwise in an animal model, we found a strong correlation between NIRS and cerebral blood flow. This correlation was better than that between NIRS and cerebral perfusion pressure. Cerebral NIRS has great potential as a bedside monitor of brain blood flow in global cerebral hypertension.
- Airway mechanics and lung tissue viscoelasticity: effects of altered blood hematocrit in the pulmonary circulation
Additional insight into the participation of the pulmonary vascular capillary network in the elastic and dissipative properties of the lung tissue was revealed in the present study performed in isolated perfused rat lungs. Decreasing hematocrit in the pulmonary circulation below physiological level diminished the viscous and elastic parameters of the pulmonary tissues, therefore demonstrating that the energy dissipation and storage displayed by the red blood cells are significant contributing factors in the total lung viscoelasticity.
- Feed-forward and reciprocal inhibition for gain and phase timing control in a computational model of repetitive cough
This article proposes a complex inhibitory network of nucleus tractus solitarius (NTS) interneurons for the control of cough. This hypothesis has important implications in disease states, such as cough hyperresponsiveness. This may be largely a function of reduced inhibitory NTS control; thus reduced cough excitability may in part be due to enhanced inhibition. This hypothesis emphasizes that the levels of excitation and inhibition in a network determine sensory gating of afferent input.
- Effects of high-intensity interval training and moderate-intensity continuous training on endothelial function and cardiometabolic risk markers in obese adults
This study is the first to show that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) produce different vascular adaptations in adults with obesity. HIIT improved brachial artery flow-mediated dilation whereas MICT increased resting brachial artery diameter and enhanced low flow-mediated constriction. These vascular adaptations occurred without reductions in body weight, fat mass, or visceral adipose tissue. HIIT required 27.5% less total exercise time and ∼25% less energy expenditure than MICT.
- Aerobic training prevents oxidative profile and improves nitric oxide and vascular reactivity in rats with cardiometabolic alteration
We investigated whether aerobic training could alter the installation process of cardiometabolic changes induced by high-fructose diet in rats. Our data show that training prevented deleterious changes caused by fructose on local (aorta, heart, and muscle) and systemic oxidative stress, metabolic parameters, and endothelial nitric oxide synthase (eNOS) pathway, thus improving endothelial function and arterial contractility. Therefore aerobic training can avoid cardiometabolic disease progression, improving a number of parameters even in a model with continuous exposure to unhealthy diet.
- Effects of aging on mitochondrial function in skeletal muscle of American Quarter Horses
Skeletal muscle from aged (17–25 yr) compared with young (2 yr) American Quarter Horses was characterized by a change in fiber-type composition and a decline in mitochondrial density and cytochrome-c oxidase activity, without impairment of 3-hydroxyacyl-CoA dehydrogenase (3-HADH) and mitochondrial respiration. Our findings suggest that aged American Quarter Horses were either at a transition point of aging before overt decline in mitochondrial function, or, alternatively, display skeletal muscle aging different from traditional animal models and humans.
- Perfusion-related stimuli for compensatory lung growth following pneumonectomy
We demonstrate in a large animal model that altering the distribution of pulmonary artery (PA) perfusion by selective lobar PA banding impairs postpneumonectomy growth of gas exchange tissue while enhancing alveolar double-capillary formation in the remaining lobes. Divergent responses between tissue and capillaries indicate that perfusion-related signals play a major role in reinitiation of compensatory lung growth, acting independently from the major signals for extravascular tissue growth, i.e., mechanical stress and strain of the parenchyma.
- Physiological phenotyping of pediatric chronic obstructive airway diseases
Clustering signals from different single- and multiple-breath gas washout tests in children with various lung diseases (e.g., cystic fibrosis and primary ciliary dyskinesia) results in the identification of three different physiological phenotypes. This novel application of the hierarchical Ward's clustering method allows the characterization of lung disease independent of the underlying disease entity and thus seems a promising tool for personalized medicine.
- A functional tool to differentiate nasal valve collapse from other causes of nasal obstruction: the FRIED test
We propose for the first time an objective test to detect dynamic nasal valve collapse: the flow rate inspiratory-expiratory difference (FRIED) test. The FRIED test compares the absolute value of inspiratory and expiratory flow at the same pressure magnitude. This test, using rhinomanometry, is easy to perform in daily practice and showed a good sensitivity after validation in a prospective study in patients with nasal congestion.
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- Commentaries on Viewpoint: Time for a new metric for hypoxic dose?Commentaries on Viewpoint: Time for a new metric for hypoxic dose?Commentaries on Viewpoint: Time for a new metric for hypoxic dose?Commentaries on Viewpoint: Time for a new metric for hypoxic dose?Commentaries on Viewpoint: Time for a new metric for hypoxic dose?Commentaries on Viewpoint: Time for a new metric for hypoxic dose?Commentaries on Viewpoint: Time for a new metric for hypoxic dose?