bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative expansion of extracellular water in obese vs. normal children
Authors: Battistini N. , Virgili F. , Severi S. , Brambilla P. , Manzoni P. , Beccaria L. , Chiumello G.
Published: December 2017

This preliminary communication reports data regarding the distribution between intracellular (ICW) and extracellular (ECW) water compartments in a group of 21 prepubertal young obese children of both sexes in comparison with a group of 18 normal children weight matched for age. Our data indicate that obesity is associated with a highly significant relative expansion of extracellular water (ECW/ICW = 0.61 +/- 0.19 and 0.76 +/- 0.09 in control and obese subjects, respectively; P < 0.0015). This observation, which has been already reported in adult women, suggests that some disturbances of water homeostasis have an early onset and stress the need for an early control of energy imbalance in children. These findings are of great concern also in the field of human body composition, suggesting the opportunity for a critical reevaluation of the assumed constancy of some human body characteristics. Body composition methodologies developed for “normal” populations would require adjustment for use in the obese population, since a considerable error would be introduced.
Truncal vagotomy does not affect postabsorptive glucose metabolism in humans
Authors: Corssmit E. P. , Van Lanschot J. J. , Romijn J. A. , Endert E. , Sauerwein H. P.
Published: December 2017

To evaluate the effects of hepatic vagal denervation on the adaptation of glucose metabolism to short-term starvation (i.e., < 24 h), glucose metabolism was studied after 16 and again after 22 h of fasting in postsurgical patients with truncal vagotomy (n = 9; radical resection of esophageal carcinoma) and without truncal vagotomy (n = 5; partial resection of the large bowel for carcinoma). Glucose metabolism was studied 3–7.5 mo postoperatively by [3–3H]glucose turnover and by indirect calorimetry. Basal glucose production, plasma glucose concentration, glucose oxidation, serum free fatty acid concentration, and fat oxidation were not different between groups; neither were plasma concentrations of glucoregulatory hormones. The adaptation to prolongation of the fast by 6 h was not different for any of these parameters between both groups. In conclusion, truncal vagotomy does not affect the adaptation of glucose metabolism to the postabsorptive state (16–22 h of fasting).
Lung tissue distortion in response to methacholine in rats: effect of lung volume
Authors: Dolhnikoff M. , Dallaire M. , Ludwig M. S.
Published: December 2017

We have previously shown that, after induced constriction, there is substantial distortion of the parenchymal tissues. In this study we investigated whether differences in parenchymal morphology occurred when the lung was constricted at different lung volumes. We measured tracheal pressure and calculated lung resistance in mechanically ventilated rats under control conditions and after aerosol administration of methacholine (256 mg/ml) at different positive end-expiratory pressures (PEEP = 7, 5, and 3 cmH2O). The lungs were frozen with liquid nitrogen at different PEEP levels and processed via freeze substitution. We measured airway constriction as the ratio of the airway lumen to the ideally relaxed area, alveolar size by measuring the mean linear intercept between alveolar walls, and tissue distortion as the standard deviation of the number of intercepts in the 40 fields sampled per lung. The increase in lung resistance was largest at PEEP = 3 cmH2O. Whereas airway constriction decreased and alveolar size increased at higher lung volume (PEEP = 7 cmH2O), tissue distortion did not change. These data suggest that parenchymal distortion after induced constriction was not attributable to airway narrowing and/or closure.
Chronic prenatal cocaine retards maturation of state and of respiratory patterns in swine
Authors: Moss I. R. , Laferriere A.
Published: December 2017

This study assessed effects of prolonged prenatal cocaine exposure on respiratory pattern and sleep-wake states in a postnatal porcine model. Yucatan miniature sows received 2 mg/kg cocaine intravenously four times daily during 0.66–1.0 gestation. At birth, cocaine-exposed litters were fostered to unexposed paired sows and their litters. Chronically instrumented piglets were studied at 3–9 (young) and 21–31 days (older). Sleep-wake states were determined from electrocorticogram, eye movements, submental electromyogram, and behavior, and respiratory patterns were determined from diaphragmatic and posterior cricoarytenoid electromyograms (EMGdi and EMGpca, respectively). Under baseline conditions, prenatal cocaine 1) increased the number of apneas expressed by silence of EMGdi or EMGpca and prolonged the duration of EMGpca-related apneas at both ages; 2) increased the number of periodic breathing episodes at both ages; 3) increased percent time of active sleep and decreased that of wakefulness at both ages; and 4) increased time in quiet sleep in the older animals, producing in them a sleep-wake distribution similar to that of the young neonates. Whereas the findings in the youngest piglets may have been influenced by persistent systemic cocaine, those in the older preexposed piglets, devoid of systemic cocaine, imply that chronic prenatal cocaine retards the postnatal maturation of state and respiratory pattern.
L-arginine-related responses to pressure and vasoactive agents in monocrotaline-treated rat pulmonary arteries
Authors: Madden J. A. , Keller P. A. , Choy J. S. , Alvarez T. A. , Hacker A. D.
Published: December 2017

To determine whether altered NO production contributes to attenuated distensibility (alpha), vasoreactivity, and acetylcholine (ACh) dilation in pulmonary arteries from monocrotaline (MCT)-treated rats (J.A. Madden, P.A. Keller, R. M. Effrosa, C. Sequitte, J.S. Choy, and A.D. Hacker. J. Appl. Physiol. 76: 1589–1593, 1994), intralobar and sidebranch arteries from rats 21 days after MCT treatment were cannulated and pressurized and their diameter changes in response to KCl, norepinephrine, angiotensin II, and pressure were measured in the presence of N omega-nitro-L-arginine (NLA) and L-arginine. NLA treatment decreased MCT artery diameters more than normal arteries (P < 0.05) and abolished ACh dilation in both. Agonist responses were greater in normal but not MCT arteries. The alpha increased in NLA-treated normal (P < 0.05) but not MCT arteries. After L-arginine, normal and MCT arteries returned to control diameters and dilated to ACh. Agonist responses returned to control in normal but not MCT arteries. Normal but not MCT arteries dilated in calcium-free solution (P < 0.05). These results suggest that pulmonary arteries from rats with MCT-induced pulmonary hypertension produce more NO than do pulmonary arteries; inhibiting NO does not increase contractility; and decreased vasoreactivity and alpha values are not due to smooth muscle cell tone but may be due to abnormal vascular remodeling.
Determination of hemoglobin mass and blood volume with CO: evaluation and application of a method
Authors: Burge C. M. , Skinner S. L.
Published: December 2017

An improved protocol was applied to the use of carboxyhemoglobin (HbCO) saturation for the estimation of body hemoglobin (Hb) mass, red blood cell volume, and blood volume and was appraised in normal volunteers. A body size-related dose of CO (50–90 ml), estimated to change HbCO saturation by 6.5%, was introduced into a low-volume (2.8 liters) closed-circuit rebreathing system and allowed to equilibrate over 10 min. Plots of venous HbCO were characterized by a plateau after 8 min, which remained stable for at least 40 min. No loss of CO from the vascular space was evident. Three estimations of Hb mass at weekly intervals in seven subjects produced a coefficient of variation of 0.8% such that, in the absence of physiological influences, changes as little as 1.5% in Hb mass are detectable. Venesection [498 +/- 16 (SE) ml] in seven subjects was associated with a measured decrease in Hb mass after 1 wk equal to the calculated loss. Blood volume was, however, largely restored by plasma expansion. The method is sensitive and precise. It can be used safely and repeatedly in normal volunteers and hospital patients.
A mathematical model for measuring blood flow in skeletal muscle with the microdialysis ethanol technique
Authors: Wallgren F. , Amberg G. , Hickner R. C. , Ekelund U. , Jorfeldt L. , Henriksson J.
Published: December 2017

A theoretical analysis of the microdialysis ethanol technique in skeletal muscle is presented, and a model governing the transport of ethanol from the microdialysis probe to the capillaries in the muscle tissue is proposed. The model is derived under the assumption of a steady-state situation, and an analytical solution is found for the outflow-to-inflow ratio of ethanol in the perfusate. Theoretically calculated results are compared with experiments, and for at least one of the two probe types used good agreement is achieved in a wide range of blood flow and perfusate flow rates. The main uncertainty factor in the theoretical calculations is the diffusivity of ethanol in muscle tissue, and the value for best agreement between theory and experiments has been used. Error estimates show that for a constant relative error in the outflow-to-inflow ratio of ethanol in the perfusate, low perfusate flow rates give better predictions of the blood flow.
Indomethacin does not alter natural killer cell response to 2.5 h of running
Authors: Nieman D. C. , Ahle J. C. , Henson D. A. , Warren B. J. , Suttles J. , Davis J. M. , Buckley K. S. , Simandle S. , Butterworth D. E. , Fagoaga O. R. , et al.
Published: December 2017

The effect of 2.5 h of treadmill running at 75.6 +/- 0.9% maximal O2 uptake (VO2max) on natural killer (NK) cell cytotoxic activity (NKCA) was investigated in 22 experienced marathon runners (VO2max 57.9 +/- 1.1 ml.kg-1.min-1, age 38.7 +/- 1.5 yr). Blood samples were taken before (0715) and immediately after exercise (1000), with three more samples taken during 6 h of recovery (1130, 1300, and 1600). Ten sedentary controls (VO2max 34.7 +/- 1.0 ml.kg-1.min-1, age 45.3 +/- 2.3 yr) sat in the laboratory during testing and had their blood sampled at the same time points. The pattern of change in NKCA over time was significantly different between groups [F(4,27) = 6.53; P = 0.001], with the runner's NKCA dropping 51–61% below preexercise levels throughout 6 h of recovery. Preincubation of blood mononuclear cells in vitro with indomethacin had no effect on the difference in pattern of change in NKCA between groups [F(4,17) = 8.59; P = 0.001] and did not attenuate the postexercise reduction in the runners. When NKCA was adjusted on a per-NK cell basis, group differences and the postexercise decline in NKCA were eliminated [F(4,80) = 0.65; P = 0.63]. Serum cortisol and plasma epinephrine in the runners were elevated relative to control subjects during recovery from exercise, but no significant correlation with changes in NK cells or NKCA was found. These data indicate that NKCA is decreased significantly during recovery from 2.5 h of running due to a numerical redistribution of NK cells.
Hormonal changes in normal and polycythemic high-altitude natives
Authors: Antezana A. M. , Richalet J. P. , Noriega I. , Galarza M. , Antezana G.
Published: December 2017

Acute and chronic exposure to high-altitude (HA) hypoxia inhibits the renin-angiotensin-aldosterone system and may modify the release of atrial natriuretic peptide (ANP) in sea-level (SL) natives. In HA natives, the release of these hormones could be influenced by changes in blood volume or pulmonary arterial pressure. Twenty-four men residing in La Paz, Bolivia, at 3,600 m were separated into two groups: one normocythemic (HAN; with hematocrit < 57%; n = 13) and the other polycythemic (HAP; with hematocrit > 57%; n = 11). A control group of 9 SL residents was studied in normoxia (SLN) as well as after 4 days spent at 4,350 m (SLH). The groups were tested for plasma active renin (PAR), plasma aldosterone concentration, ANP, and potassium and norepineprine concentrations at rest and after a maximal exercise. Pulmonary arterial systolic pressure was assessed by a Doppler technique. It was observed that PAR and plasma aldosterone concentration at rest and after exercise were lower in the SLH than in the SLN group. PAR and norepineprine concentration were higher among highlanders than in the SLN group. Renin response to exercise was normal among the HAN group and slightly decreased among the HAP group, and an exercise-induced increase in aldosterone was attenuated in both HA groups. Aldosterone response to renin was maintained among the SLH group but was attenuated in the HA groups, possibly owing to a protective mechanism against salt and water retention. Resting and exercise ANP was lower in the HA groups than in the SLN group.
Lesser vagal withdrawal during isometric exercise with age
Authors: Taylor J. A. , Hayano J. , Seals D. R.
Published: December 2017

The tachycardia that accompanies isometric exercise decreases with age in humans; however, the mechanism of this decline is unknown. To determine whether less cardiac vagal withdrawal is associated with the age-related decrease in this response, we assessed high-frequency R-R interval variability (0.15–0.40 Hz), an index of cardiac vagal tone, before (control) and during isometric exercise to exhaustion in healthy young (21–29 yr; n = 12) and older (61–72 yr; n = 11) men. During control, the two groups did not differ in respiratory rate, mean arterial pressure, or heart rate, although the older subjects had a lower high-frequency amplitude (12.2 +/- 1.1 vs. 29.4 +/- 4.6 ms/Hz; P < 0.05). During isometric exercise, the respiratory rate and arterial pressure responses did not differ; however, the older men had a lower absolute heart rate and a smaller increase in heart rate, and only the young men demonstrated a significant decline in high-frequency amplitude. The heart rate responses to exercise were correlated with the declines in high-frequency amplitude (initial, r = -0.808; midpoint, r = -0.714; peak, r = -0.632; all P < 0.005), which were, in turn, correlated with the control high-frequency amplitude (initial, r = -0.727; midpoint, r = -0.643; peak, r = -0.610; all P < 0.01). Thus smaller declines in high-frequency amplitude, related to lower baseline amplitude, corresponded to smaller increases in heart rate throughout isometric exercise. Therefore, we conclude that the smaller tachycardiac response to isometric exercise in older humans is associated with an inability to decrease cardiac vagal tone below an already reduced baseline level.
Effects of maturation on cell water, protein, and DNA content in ovine cerebral arteries
Authors: Elliott C. F. , Pearce W. J.
Published: December 2017

The present study examined the effects of maturation on base-soluble protein, DNA content, and intracellular water volume in ovine cerebral arteries to evaluate these variables as references for normalization of levels of cellular constituents in studies of vascular maturation. With maturation, base-soluble protein per unit wet weight (measured by using the Bradford method) increased by 27% to 46%, and cell volume (estimated as the ratio of cell water to DNA) increased by 53% to 97%. However, intracellular water per unit wet weight (calculated as the difference between total water measured by dehydration and extracellular water measured by using the extracellular marker [57Co]EDTA) increased by only 1% to 16%, because of maturation-related hypertrophy (quantitated histologically) combined with decreased cell number per unit wet weight (DNA content, quantitated by using Hoechst dye, decreased by 32% to 41%). In addition, the effects of maturation were artery specific: maturational increases in cell water and volume were more pronounced in common carotid than in cerebral arteries. These findings demonstrate that different methods of normalization can produce quantitatively opposite results in maturation-related studies. For cellular constituents, the most physiologically relevant normalization is relative to intracellular water volume, which yields units of apparent intracellular concentration. Because the relative content of intracellular water per unit wet weight changes little with maturation, normalization of levels of cellular constituents relative to wet weight provides a reasonable index of intracellular concentration. Clearly, no single approach is optimal for all studies, and the method of normalization should be carefully considered with regard to effects of maturation on vascular composition.
Slow component of O2 uptake during heavy exercise: adaptation to endurance training
Authors: Womack C. J. , Davis S. E. , Blumer J. L. , Barrett E. , Weltman A. L. , Gaesser G. A.
Published: December 2017

Seven untrained male subjects [age 25.6 +/- 1.5 (SE) yr, peak O2 uptake (VO2) 3.20 +/- 0.19 l/min] trained on a cycle ergometer 4 days/wk for 6 wk, with the absolute training workload held constant for the duration of training. Before and at the end of each week of training, the subjects performed 20 min of constant-power exercise at a power designed to elicit a pronounced slow component of VO2 (end-exercise VO2-VO2 at minute 3 of exercise) in the pretraining session. An additional 20-min exercise bout was performed after training at this same absolute power output during which epinephrine (Epi) was infused at a rate of 100 ng.kg-1.min-1 between minutes 10 and 20. After 2 wk of training, significant decreases in VO2 slow component, end-exercise VO2, blood lactate ([La-] and glucose concentrations, plasma Epi ([Epi]) and norepinephrine concentrations, ventilation (VE), and heart rate (HR) were observed (P < 0.05). Although the rapid attenuation of the VO2 slow component coincided temporally with reductions in plasma [Epi], blood [La-], and VE, the infusion of Epi after training significantly increased plasma [Epi] (delta 2.22 ng/ml), blood [La-] (delta 2.4 mmol/l) and VE (delta 10.0 l/min) without any change in exercise VO2. We therefore conclude that diminution of the VO2 slow component with training is attributable to factors other than the reduction in plasma [Epi], blood [La-] and VE.
Effects of acute exercise on hepatic lipogenic enzymes in fasted and refed rats
Authors: Griffiths M. A. , Baker D. H. , Yu X. X. , Novakofski J. , Oscai L. , Ji L. L.
Published: December 2017

The effects of an acute bout of prolonged exhaustive exercise on the activities of hepatic lipogenic enzymes have been investigated. Male Sprague-Dawley rats were randomly divided into three groups: fasted for 48 h without refeeding (FA) and fasted for 48 h and refed a diet high in fructose (RF) or in cornstarch (RC). One-half of each group of rats exercised on a treadmill at 20 m/min, 5% grade, until exhaustion and the other half rested for the same amount of time without food. Dietary intakes during refeeding were kept equal between the exercised and rested control animals. Activities of all hepatic lipogenic enzymes measured, i.e., fatty acid synthase (FAS), L-type pyruvate kinase (L-PK), ATP citrate lyase, malic enzyme, and glucose-6-phosphate dehydrogenase, were induced dramatically by fasting-refeeding and were significantly higher in the RF than in the RC rats (P < 0.05). FAS activity was increased 19- and 39-fold, respectively, in the RC and RF rats compared with the FA rats. Exercise decreased FAS activity to approximately one-third of the resting control value in both RC and RF rats (P < 0.05) but not in FA rats. L-PK activity was elevated by 55% in RC and 100% in RF rats compared with FA rats (P < 0.05). FA and RF rats also showed a reduction of L-PK activity with exercise. No significant alteration of other lipogenic enzymes was observed after exercise.
Regulation of ventilatory capacity during exercise in asthmatics
Authors: Johnson B. D. , Scanlon P. D. , Beck K. C.
Published: December 2017

In asthmatic and control subjects, we examined the changes in ventilatory capacity (VECap), end-expiratory lung volume (EELV), and degree of flow limitation during three types of exercise: 1) incremental, 2) constant load (50% of maximal exercise capacity; 36 min), and 3) interval (alternating between 60 and 40% of maximal exercise capacity; 6-min workloads for 36 min). The VECap and degree of flow limitation at rest and during the various stages of exercise were estimated by aligning the tidal breathing flow-volume (F-V) loops within the maximal expiratory F-V (MEFV) envelope using the measured EELV. In contrast to more usual estimates of VECap (i.e., maximal voluntary ventilation and forced expiratory volume in 1 s x 40), the calculated VECap depended on the existing bronchomotor tone, the lung volume at which the subjects breathed (i.e., EELV), and the tidal volume. During interval and constant-load exercise, asthmatic subjects experienced reduced ventilatory reserve, higher degrees of flow limitation, and had higher EELVs compared with nonasthmatic subjects. During interval exercise, the VECap of the asthmatic subjects increased and decreased with variations in minute ventilation, due in part to alterations in their MEFV curve as exercise intensity varied between 60 and 49% of maximal capacity. In conclusion, asthmatic subjects have a more variable VECap and reduced ventilatory reserve during exercise compared with nonasthmatic subjects. The variations in VECap are due in part to a more labile MEFV curve secondary to changes in bronchomotor tone. Asthmatics defend VECap and minimize flow limitation by increasing EELV.
Metabolic responses of rat respiratory muscles to voluntary exercise training
Authors: Halseth A. E. , Fogt D. L. , Fregosi R. F. , Henriksen E. J.
Published: December 2017

Voluntary wheel running for 4 or 8 wk was used to assess whether a volitional training stimulus would induce adaptations in the oxidative capacity [citrate synthase activity (CS)], glucose phosphorylation capacity [hexokinase activity (HK)], and glucose transporter protein level (GLUT-4) of rat respiratory muscles. Running distances averaged approximately 10–13 km/day over the final 5 wk of training. Peak oxygen consumption by the trained animals was 17% greater (P < 0.05) than by age-matched sedentary control animals after 8 wk. CS, HK, and GLUT-4 in soleus and plantaris muscles all increased because of exercise training. CS increased in the rectus abdominis (+17%), external oblique (+28%), and internal oblique (+17%) but not in the costal or crural diaphragm after 4 wk of training. However, after 8 wk, CS in the costal diaphragm was 39% greater than control but was unchanged in the crural diaphragm. Whereas HK was significantly greater than control in the costal diaphragm (+18%) and rectus abdominis (+54%) after 4 wk, 8 wk of running were required for increases in HK in the external oblique (+17%) and internal oblique (+14%). HK in the crural diaphragm was not significantly altered by the exercise training. GLUT-4 did not change significantly in any of the respiratory muscles studied. These results indicate that significant adaptations in the glucose phosphorylation capacity and oxidative capacity of both inspiratory and expiratory muscles can take place in response to voluntary exercise. However, this same stimulus is not sufficient to cause an adaptive response in GLUT-4 protein level in these respiratory muscles.
Pulmonary capillaries are more resistant to stress failure in dogs than in rabbits
Authors: Mathieu-Costello O. , Willford D. C. , Fu Z. , Garden R. M. , West J. B.
Published: December 2017

We previously showed that stress failure of pulmonary capillaries occurs at transmural pressures of approximately 50 cmH2O (40 mmHg) and above in rabbit lung. In this study, we examined whether pulmonary capillaries are more resistant to failure in dogs than in rabbits. This might be expected because of the greater athletic ability of dogs and therefore their presumably greater tolerance to large cardiac outputs and higher pulmonary vascular pressures. The lungs of 12 anesthetized mongrel dogs [22.1 +/- 5.2 (SD) kg] were perfused in situ with autologous blood and then with saline-dextran (5 min) and glutaraldehyde solution (10 min), all three perfusions at the same preset transmural pressure of 32.5, 72.5, 92.5, or 112.5 cmH2O. In dogs, the stress failure curves relating break number per millimeter of epithelium and endothelium were right shifted by approximately 40 cmH2O compared with rabbits. Blood-gas barrier thickness was significantly greater than in rabbits at 32.5 cmH2O, and unlike in rabbits, neither total nor interstitial thickness increased significantly with increasing pressure. These results indicate that pulmonary capillaries are more resistant to stress failure in dogs than rabbits.
Stable VIP analogue Ro-24-9981 potentiates substance P-induced plasma exudation in hamster cheek pouch
Authors: Gao X. P. , Jaffe H. A. , Olopade C. O. , Rubinstein I.
Published: December 2017

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP; 300 nM) and a stable cyclic analogue of VIP, Ro-24–9981 (226 nM), modulated neurogenic plasma exudation in the oral cavity in situ and, if so, to determine the mechanisms that mediated these responses. With the use of intravital microscopy, we found that suffusion of substance P induced a significant concentration-dependent formation of fluorescein-isothiocyanate-dextran (mol wt 70 kDa) leaky sites in the hamster cheek pouch (P < 0.05). These effects were significantly and stereospecifically attenuated by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, and restored by L-arginine, the substrate for NO synthase (P < 0.05). Topical application of human VIP and Ro-24–9981 had no significant effects of leaky site formation. In addition, human VIP had no significant effects on substance P-induced responses. By contrast, Ro-24–9981 significantly potentiated substance P- and capsaicin-induced leaky site formation (P < 0.05). The effects of Ro-24–9981 on substance P-induced responses were significantly attenuated by NG-nitro-L-arginine methyl ester and restored by L-arginine (P < 0.05). Indomethacin had no significant effects on Ro-24–9981-induced responses. Ro-24–9981 had no significant effects on adenosine- and calcium ionophore A-23187-induced leaky site formation. Collectively, these data suggest that VIP plays no significant role in modulating neurogenic plasma exudation in the oral mucosa. By contrast, Ro-24–9981 amplified this response in a specific receptor-mediated fashion.
Effect of periodic thermal stimulus on heart rate in term newborn infant
Authors: Hathorn M. K. , Mannix P. A. , Costeloe K.
Published: December 2017

We studied heart rate changes in 25 term infants aged 1–7 days in quiet sleep during periodic thermal stimulation of one foot to widen the range of frequencies previously studied by others and to develop spectral analysis methods to quantify responses to thermal and other periodic sensory stimuli. The stimulation frequency was 0.10 Hz in all babies and ranged from 0.05 to 0.15 Hz in some. At 0.10 Hz, there was 1) an increase in spectral power at the frequency of stimulation (P < 0.001), 2) a tendency for overall low-frequency power to increase, 3) a reduction in respiratory sinus arrhythmia (P < 0.025), and 4) attenuation in the response between the first and second minute of stimulation (P < 0.01). At other frequencies of stimulation, essentially similar results were obtained. Respiration and other types of periodic sensory stimulation may also entrain the heart rate; we raise the question of whether low-frequency oscillations in heart rate are in fact related to thermoregulation or are a nonspecific feature of integrative processes in the brain stem.
Eccentric muscle damage transiently decreases rat skeletal muscle GLUT-4 protein
Authors: Asp S. , Kristiansen S. , Richter E. A.
Published: December 2017

The effects of concentric and muscle-damaging eccentric contractions on muscle glucose transporter GLUT-4 content were studied in rat muscles. Rats were anesthetized, the calf muscles on one side were stimulated electrically for concentric or eccentric contractions, and bilateral calf muscles were obtained in the postexercise period. Inflammatory and phagocytic cells accumulated in the eccentric white and red gastrocnemius muscles, whereas there were only discrete changes in the eccentric soleus. Glycogen was depleted to the same extent in the white and red gastrocnemius muscles after both types of stimulation, and it remained decreased > 2 days in eccentric muscles. The total GLUT-4 protein content was decreased in the eccentric white and red gastrocnemius muscles 1 and 2 days after the eccentric stimulation, whereas the maximal activity of glycogen synthase was unaffected at these time points. In conclusion, our one-legged stimulation model caused eccentric muscle damage in the white and red gastrocnemius, whereas only minor damage was observed in the soleus muscle. In damaged muscle, muscle glycogen and GLUT-4 protein content were decreased for > 2 days. These findings may suggest (but do not prove) that decreased muscle GLUT-4 protein is involved in the delayed glycogen resynthesis after eccentric exercise.
Measurement of airway mucosal blood flow with dimethylether: validation with microspheres
Authors: Scuri M. , McCaskill V. , Chediak A. D. , Abraham W. M. , Wanner A.
Published: December 2017

We have recently developed a noninvasive dimethylether (DME) uptake technique to estimate airway mucosal blood flow (Qaw) in humans (12). Because it was not feasible to validate the technique directly, we undertook the present study to compare Qaw as measured by DME (QDME) and by color-coded microspheres (QM) as a standard in seven anesthetized sheep prepared with a carotid and a left atrial catheter. QDME was determined by measuring DME uptake with multiple breath holds after passive inflation with a DME-helium gas mixture, simulating the technique used in humans. After the microspheres were injected into the left atrium, the sheep were killed and the tracheal segment corresponding to the dead space from which DME uptake was determined was removed, and its mucosa was stripped and processed for microsphere counts. Mean QDME was 35.6 ml.min-1.100 g-1 wet tissue (range 9.6–98.0 ml.min-1.100 g-1) and mean QM was 29.1 ml.min-1.100 g-1 (range 7.7–91.5 ml.min-1.100 g-1). There was a strong correlation between QDME and QM (r = 0.89; P = 0.01). Intravenous nitroglycerin and vasopressin caused comparable increases and/or decreases in QDME and QM (r = 0.87; P = 0.02). This suggests that the noninvasive DME uptake method measures Qaw accurately and supports its validity in human studies.
Differential responses of global airway, terminal airway, and tissue impedances to histamine
Authors: Hantos Z. , Petak F. , Adamicza A. , Daroczy B. , Fredberg J. J.
Published: December 2017

The forced oscillation and alveolar capsule techniques were applied to determine the input impedance of the lungs and the airway transfer impedances between 0.2 and 20 Hz in six open-chest dogs in the control state, during intravenous infusion of histamine at seven rates between 0.25 and 16 micrograms.kg-1.min-1, and after the infusion. In each condition, the input impedances seen from the alveolar capsules, i.e., terminal airway impedance (Zaw,ter), were measured by imposing 2- to 200-Hz oscillations from the capsules (B. L. K. Davey and J. H. T. Bates. Respir. Physiol. 91:165–182, 1993). Airway resistance (Raw) and inertance and tissue damping and elastance were derived from the lung impedance data. For all dogs, histamine progressively increased Raw and the real part of airway transfer impedance (airway transfer resistance), reaching, at 16 micrograms.kg-1.min-1, 241 +/- 109 (SD) and 370 +/- 186%, respectively, of the control value but caused greater, although locally highly variable, increases (769 +/- 716% of the control value) in the real part of Zaw,ter extrapolated to zero frequency (R0). With increasing doses of histamine, the changes in R0 always preceded those in Raw and airway transfer resistance implying that bronchoconstriction developed first in the lung periphery. It is therefore concluded that the measurement of Zaw,ter offers a sensitive method for the detection of early nonuniform responses to bronchoconstrictor stimuli that are not yet reflected by the values of the overall Raw. In one-half of the cases, significant increases in tissue damping and elastance occurred before any change in R0; this suggests that the mechanisms of airway and parenchymal constrictions may be unrelated.
Simultaneous 31P-NMR spectroscopy and EMG in exercising and recovering human skeletal muscle: a correlation study
Authors: Vestergaard-Poulsen P. , Thomsen C. , Sinkjaer T. , Henriksen O.
Published: December 2017

A large number of studies have shown amplitude and spectral changes of the electromyogram during exercise, leading to several theories of how these changes might be related to the underlying metabolic changes. The amplitude and spectral changes are generally interpreted as changes in motor unit recruitment and a reduction of the muscle fiber conduction velocity due to proton or lactate accumulation. This study focuses on the causality of spectral changes of the surface electromyogram and proton or lactate accumulation and how the changes in motor unit recruitment are related to the metabolic status of the muscle. Simultaneous 31P-nuclear magnetic resonance spectroscopy and surface electromyography were performed during sustained static exercise and recovery in healthy volunteers and a patient with McArdle's disease. A clear dissociation between the median power frequency of the surface electromyogram and pH was seen in the healthy volunteers during recovery and during exercise in the patient with McArdle's disease. The results indicate that proton or lactate accumulation is not primarily responsible for the spectral changes of the surface electromyogram as previously suggested. The motor unit recruitment (as judged by the root mean square of the surface electromyogram) increased hyperbolically during the submaximal static exercise, with decreasing phosphocreatine-to-P(i) ratio reaching maximum at 0.6 (exhaustion), and seems to constitute a consistent metabolic limit to the exercise. The increased myoelectrical activity seen after exercise is not caused by an incomplete recovery of phosphorous metabolism, pH, or lactate but could probably be an impairment of the excitation-contraction coupling.
Cerebral blood flow measured with intracerebral laser-Dopplerflow probes and radioactive microspheres
Authors: Kirkeby O. J. , Rise I. R. , Nordsletten L. , Skjeldal S. , Hall C. , Risoe C.
Published: December 2017

We have measured cerebral blood flow with intracerebral laser-Doppler microprobes in pentobarbital-anesthetized pigs. We compared the results with measurements from laser-Doppler probes placed on the surface of the brain and with blood flow estimation by the radioactive microsphere method. The cerebral blood flow was varied by alterations in inspired carbon dioxide, hemorrhagic hypotension, and high cerebrospinal fluid pressure. The intracerebral probes and the surface probes showed parallel responses to variations in cerebral blood flow. The correlation was closest between surface probes and the intracerebral probes measuring from the cerebral cortex (r = 0.46; P < 0.005). The r value between laser-Doppler flowmetry and radioactive microspheres was 0.41 (P < 0.0005) for all measurements. The correlation to microspheres was best for the probes located 3 or 10 mm into the brain and poorest for the surface probe. In conclusion, intracerebral laser-Doppler flow measurements reflect changes in blood flow, and the technique appears useful for continuous estimates of cerebral blood flow.
Acute hypoxic ventilation, carotid body cell division, and dopamine content during early hypoxia in rats
Authors: Bee D. , Pallot D. J.
Published: December 2017

In a previous study, we showed that the acute hypoxic ventilatory response was blunted in anesthetized chronically hypoxic rats and was restored by blockade of the dopamine D2 receptor with domperidone. We now report observations made during 1–8 days of exposure to 10% O2 on the acute hypoxic ventilatory response and the effect of domperidone and relate them to dopamine content and cellular proliferation in the carotid body. Hypoxic exposure caused a parallel shift in the hypoxic response curve to higher levels of ventilation and arterial oxygen saturation. The greatest response occurred on day 1 and was unaffected by domperidone: dopamine content diminished and mitotic activity increased. By 8 days, hypoxic ventilation approached normal and was significantly augmented by domperidone; in the carotid body, dopamine levels had risen above the control level and mitoses had diminished. Thus the increase in ventilation was inversely related to carotid body dopamine content, which was depressed. The possibility of a causal relationship is discussed.
Opioid pharmacodynamics in neonatal dogs: differences between morphine and fentanyl
Authors: Bragg P. , Zwass M. S. , Lau M. , Fisher D. M.
Published: December 2017

Clinical experience and laboratory studies suggest that neonates are more sensitive than adults to the ventilatory depressant effects of morphine. Similar sensitivity has been cited, but not demonstrated, for fentanyl. To examine this issue, we determined ventilatory pharmacodynamics of morphine and fentanyl in 28 dogs aged 2–35 days. During isohypercapnia, morphine or fentanyl was infused to depress minute ventilation by > 50% and arterial plasma opioid concentrations were measured. For each drug, an effect compartment pharmacodynamic model was fit to the values for minute ventilation to determine the steady-state opioid plasma concentration depressing ventilation by 50% (C50) and the rate constant for equilibration between plasma concentration and effect (keo). For morphine, there was a marked age-related increase in C50 but no change in keo. For fentanyl, there was a small maturational increase in C50 and no change in keo. We conclude that there are marked maturational changes in the ventilatory depressant effects of morphine resulting from maturational changes in sensitivity rather than in equilibration. Maturational changes in the ventilatory effects of fentanyl are much smaller in magnitude than those for morphine.
Phrenic motoneuron firing rates during brief inspiratory resistive loads
Authors: Road J. , Osborne S. , Cairns A.
Published: December 2017

The neural activation of the diaphragm during quiet and vigorously stimulated breathing has been hypothesized to be submaximal. In this study, we measured phrenic motoneuron firing rates during brief progressively increasing inspiratory resistive loads in anesthetized rabbits. We recorded activity in 68 phrenic motoneurons in 17 rabbits. We found that 40 of these axons were active during quiet breathing. Twenty-seven axons were silent during quiet breathing but began to fire as inspiratory loading progressed. The level of drive reflected by transdiaphragmatic pressure where silent phrenic motoneurons were recruited ranged from 5 to 45 cmH2O. Silent motoneurons showed significantly higher average rates of firing and significantly greater increases in firing rate as loading progressed (P < 0.01). The firing rate of both active and silent axons tended to plateau as rates approached 70–80 Hz. All motoneurons except for one, which may have been an afferent, were activated by inspiratory resistive loading. Inspiratory resistive loading activated phrenic motoneurons at high rates, and our results did not support the presence of significant numbers of unrecruited motoneurons.
Carotid arterial hemodynamics in response to LBNP in normal subjects: methodological aspects
Authors: Pannier B. , Slama M. A. , London G. M. , Safar M. E. , Cuche J. L.
Published: December 2017

Pulsatile changes in blood pressure and arterial diameter were studied noninvasively with applanation tonometry and echo-tracking techniques at the sites of the common carotid artery (CCA) and the carotid arterial bulb (CAB) in 12 healthy volunteers. Determinations were performed before and during application of -10 and -40 mmHg lower body negative pressure (LBNP) to investigate noninvasively the tensile forces acting on the CAB. Together with significantly decreased mean arterial pressure, increased heart rate, forearm vascular resistance, and plasma norepinephrine, the -40 mmHg LBNP stimulus produced the following significant changes in CCA and CAB hemodynamics: 1) for the same decrease in mean arterial pressure, a greater decrease in carotid than in brachial pulse pressure was observed (P < 0.01) due to a significant change in pressure wave transmission and in the timing of the carotid backward pressure wave; and 2) a highly significant decrease in pulsatile changes in diameter and tangential tension occurred, with a greater decrease in systolic than in diastolic tangential tension. Subsequently, cyclic tangential tension decreased more substantially than mean tangential tension. The cyclic changes in tension were quite significant after -40 mmHg LBNP but were already observed for mild -10 mmHg LBNP in which mean systemic blood pressure and heart rate were not modified. During -10 and -40 mmHg LBNP, CCA and CAB compliance and distensibility were unchanged. This study provides evidence that the autonomic nervous system activation produced by the LBNP procedure is associated with significant changes in pressure-wave amplification and in cyclic tensile forces acting on the CAB. These changes, which may occur even for mild LBNP, should be taken into account when interpreting results of the LBNP procedure in humans.
Superior laryngeal nerve blockade and inspiratory resistive load detection in normal subjects
Authors: Fitzpatrick M. F. , Zintel T. , Stockwell M. , Mink J. , Gallagher C. G.
Published: December 2017

The site for detection of added inspiratory resistive loads is unknown, but recent evidence suggests that the airways may play an important role. The aim of this study was to discern whether the larynx has an important independent role in conscious detection of added inspiratory resistive loads. A randomized double-blind placebo-controlled study of the effect of superior laryngeal nerve blockade on inspiratory resistive load-detection threshold was carried out in 12 normal subjects (7 women; mean age 27.5 yr; range 18–45 yr). Baseline (preinjection) detection thresholds were similar on the lidocaine [0.58 +/- 0.16 (SE) cmH2O.l-1.s] and saline (0.53 +/- 0.12 cmH2O.l-1.s; P = 0.28) days. There was no significant difference in load-detection thresholds after injection between lidocaine (0.60 +/- 0.15 cmH2O.l-1.s) and saline (0.55 +/- 0.10 cmH2O.l-1.s; P = 0.68). Thus, the larynx does not appear to be an important independent airway site for conscious inspiratory resistive load detection.
Cardiovascular responses at the onset of static exercise in patients with dual-chamber pacemakers
Authors: Williamson J. W. , Nobrega A. C. , Garcia J. A. , Friedman D. B. , Mitchell J. H.
Published: December 2017

Cardiac output (CO) responses to exercise can be altered by ventricular pacing in pacemaker-dependent patients. The relative contributions of CO and peripheral vascular resistance (PVR) toward the initial increase in blood pressure with the initiation of static exercise were investigated in eight otherwise healthy pacemaker-dependent subjects [age 24 +/- 2 yr (range 17–37 yr)]. Beat-by-beat measures of heart rate (HR; electrocardiography), mean arterial pressure (MAP), and CO derived from stroke volume (SV) (CO = HR.SV; 2-D echocardiography) were determined during the first 20 s of a one-legged static knee extension performed at 20% maximal voluntary effort by using three pacing modalities: dual pacing and sensing mode (DDD, i.e., normal physiological HR response), fixed at resting HR (DOO-R), and fixed at peak exercise HR (DOO-E), as previously achieved during 5 min of sustained contraction in the DDD mode. There were no differences in MAP, CO, or PVR (PVR = MAP/CO) between modes at rest (P > 0.05). With DOO-E pacing, SV was lower at rest compared with the other modes and increased with exercise (P < 0.05). Although there were no significant increase in MAP or CO during DOO-R pacing, both variables were elevated by leg contraction during DDD and DOO-E pacing (P < 0.05), with no significant change in PVR. Additionally, the CO and MAP increases were significantly greater with DOO-E pacing (P < 0.05). Thus the magnitude of the initial increase in arterial pressure at the onset of mild one-legged static exercise was dictated by the changes in CO as PVR remained unchanged.
Optimum gradient of mountain paths
Authors: Minetti A. E.
Published: December 2017

By combining the experiment results of R. Margaria (Atti Accad. Naz. Lincei Memorie 7: 299–368, 1938), regarding the metabolic cost of gradient locomotion, together with recent insights on gait biomechanics, a prediction about the most economical gradient of mountain paths (approximately 25%) is obtained and interpreted. The pendulum-like mechanism of walking produces a waste of mechanical work against gravity within the gradient range of up to 15% (the overall efficiency is dominated by the low transmission efficiency), whereas for steeper values only the muscular efficiency is responsible for the (slight) metabolic change (per meter of vertical displacement) with respect to gradient. The speeds at the optimum gradient turned out to be approximately 0.65 m/s (+0.16 m/s vertical) and 1.50 m/s (-0.36 m/s vertical), for uphill and downhill walking, respectively, and the ascensional energy expenditure was 0.4 and 2.0 ml O2.kg body mass-1.vertical m-1 climbed or descended. When the metabolic power becomes a burden, as in high-altitude mountaineering, the optimum gradient should be reduced. A sample of real mountain path gradients, experimentally measured, mimics the obtained predictions.
Effect of hindlimb unloading on rat soleus fiber force, stiffness, and calcium sensitivity
Authors: McDonald K. S. , Fitts R. H.
Published: December 2017

The purpose of this study was to examine the time course of change in soleus muscle fiber peak force (N), tension (Po, kN/m2), elastic modulus (Eo), and force-pCa and stiffness-pCa relationships. After 1, 2, or 3 wk of hindlimb unloading (HU), single fibers were isolated and placed between a motor arm and a transducer, and fiber diameter, peak absolute force, Po, Eo, and force-pCa and stiffness-pCa relationships were characterized. One week of HU resulted in a significant reduction in fiber diameter (68 +/- 2 vs 57 +/- 1 microns), force (3.59 +/- 0.15 vs. 2.19 +/- 0.12 x 10(-4) N), Po (102 +/- 4 vs. 85 +/- 2 kN/m2), and Eo (1.96 +/- 0.12 vs. 1.37 +/- 0.13 x 10(7) N/m2), and 2 wk of HU caused a further decline in fiber diameter (45 +/- 1 microns), force (1.31 +/- 0.06 x 10(-4) N), and Eo (0.96 +/- 0.09 x 10(7) N/m2). Although the mean fiber diameter and absolute force continued to decline through 3 wk of HU, Po recovered to values not significantly different from control. The Po/Eo ratio was significantly increased after 1 (5.5 +/- 0.3 to 7.1 +/- 0.6), 2, and 3 wk of HU, and the 2-wk (9.5 +/- 0.4) and 3-wk (9.4 +/- 0.8) values were significantly greater than the 1-wk values. The force-pCa and stiffness-pCa curves were shifted rightward after 1, 2, and 3 wk of HU. At 1 wk of HU, the Ca2+ sensitivity of isometric force, assessed by Ca2+ concentration required for half-maximal force, was increased from the control value of 1.83 +/- 0.12 to 2.30 +/- 0.10 microM. In conclusion, after HU, the decrease in soleus fiber Po can be explained by a reduction in the number of myofibrillar cross bridges per cross-sectional area. Our working hypothesis is that the loss of contractile protein reduces the number of cross bridges per cross-sectional area and increases the filament lattice spacing. The increased spacing reduces cross-bridge force and stiffness, but Po/Eo increases because of a quantitatively greater effect on stiffness.