bluuebunny/crossref_metadata_2025 huggingface dataset:
Eicosanoids and lipocortin-1 in BAL fluid in asthma: effects of smoking and inhaled glucocorticoids
Authors: Van Hal P. T. , Overbeek S. E. , Hoogsteden H. C. , Zijlstra F. J. , Murphy K. , Oosterhoff Y. , Postma D. S. , Guz A. , Smith S. F.
Published: December 2017

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.
Is respiratory sinus arrhythmia a good index of cardiac vagal tone in exercise?
Authors: Casadei B. , Moon J. , Johnston J. , Caiazza A. , Sleight P.
Published: December 2017

To assess the relative roles of neural and nonneural mechanisms in respiratory sinus arrhythmia (RSA) at rest and during exercise (steady-state supine cycle ergometry at 25% of peak oxygen uptake), we studied 10 healthy men (mean age 21 +/- 1 yr) before (control) and during ganglion blockade (GB) with trimetaphan camsylate (3–5 mg/min i.v.). GB was confirmed by the abolition of the reflex bradycardia in response to intravenous phenylephrine and of the blood pressure rise with the cold pressor test. RSA was calculated from the power of the spectral component of the R-R interval variability centered at the breathing frequency. GB decreased but did not abolish RSA. At rest, this nonneural component of RSA was negligible, accounting for < 1% of the control RSA. During GB, exercise did not affect RSA significantly. However, because control RSA was decreased by exercise, the proportion of nonneural RSA increased by 32% (range from 17 to 75%). These results indicate that as the vagal tone decreases with exercise, an increasing proportion of RSA is due to nonneural mechanisms.
Breathing during exercise in dogs--passive or active?
Authors: Ainsworth D. M. , Smith C. A. , Henderson K. S. , Dempsey J. A.
Published: December 2017

The activation patterns of the costal and crural diaphragm and transversus abdominis muscle and their relationship to esophageal pressure (Pes) changes and footplant were examined in five chronically instrumented dogs which breathed at high frequencies at rest and during exercise. In two tracheostomized dogs, measurements were made of diaphragmatic length via sonomicrometry and of airflow and were related to diaphragmatic electrical activity and Pes. Dogs exhibited either a high-frequency breathing pattern, characterized by Pes changes occurring at 2–6 Hz, or a mixed-frequency breathing pattern, characterized by low-amplitude Pes oscillations (4–6 Hz) superimposed on a slower breathing rate of 0.5–1 Hz. Regardless of the type of breathing pattern elected or of the various breathing-to-stride frequency ratios observed during exercise, decreases in Pes were always associated with phasic electromyographic activity of the costal and crural diaphragm and with phasic diaphragmatic muscle shortening. The transversus abdominis electromyographic activity coincided with an increasing Pes from peak negative values in resting dogs and exhibited both an expiratory and a locomotory modulation during exercise. Although footplant may have contributed to some airflow generation when dogs utilized the mixed-frequency pattern, these data demonstrate that the movement of air into and out of the lungs in stationary or exercising dogs requires phasic neural activation of the diaphragm and other respiratory muscles.
Hypoxia in vivo inhibits aldosterone synthesis and aldosterone synthase mRNA in rats
Authors: Raff H. , Jankowski B. M. , Engeland W. C. , Oaks M. K.
Published: December 2017

Hypoxia leads to a decrease in aldosterone that cannot be entirely explained by extrinsic controllers of adrenal function. We have shown that acute hypoxia attenuates aldosterone synthesis via a direct inhibition of the function of the aldosterone enzyme pathway. The mechanism of the sustained decrease in aldosterone during chronic hypoxia is unknown. The present study evaluated the hypothesis that chronic hypoxia leads to a decrease in the expression of the steroidogenic enzyme P-450c11AS unique to the aldosterone pathway. Rats were exposed to 3 days of normoxia, moderate hypoxia (12% O2), or severe hypoxia (10% O2). Adrenal glands were removed and prepared for biochemical analysis of steroidogenesis in vitro (dispersed capsular cells) and for measurement of steady-state enzyme mRNA levels by reverse-transcription competitive polymerase-chain reaction (RT-cPCR) and by in situ hybridization histochemistry (ISHH). Moderate hypoxia had no effect on steroidogenesis. Adrenal cells from rats exposed to severe hypoxia demonstrated a decreased conversion of corticosterone to aldosterone (late pathway catalyzed by P-450c11AS) without a change in the other mitochondrial cytochrome P-450 enzyme activities. Adrenal cells from rats exposed to hypoxia also demonstrated a three- to fourfold decrease in P-450c11AS mRNA without a change in the other mitochondrial cytochrome P-450 enzymes mRNAs, as determined by either RT-cPCR or ISHH. We conclude that relatively short-term chronic hypoxia in rats leads to a decrease in aldosteronogenesis by decreasing the expression of the gene for the late-pathway enzyme unique to the aldosterone pathway (P-450c11AS).
Breathing and brain blood flow during sleep in patients with chronic mountain sickness
Authors: Sun S. , Oliver-Pickett C. , Ping Y. , Micco A. J. , Droma T. , Zamudio S. , Zhuang J. , Huang S. Y. , McCullough R. G. , Cymerman A. , Moore L. G.
Published: December 2017

Chronic mountain sickness (CMS) patients have lower arterial O2 saturation (SaO2) during sleep compared with healthy high-altitude residents, but whether nocturnal arterial O2 content (CaO2) and brain O2 delivery are reduced is unknown. We measured SaO2, CaO2, sleep-disordered breathing (SDB), and internal carotid artery flow velocity in 8 CMS patients, 8 age-matched healthy CMS controls, 11 healthy younger-aged Han, and 11 healthy younger-aged Tibetan male residents of Lhasa, Tibet (3,658 m). CMS patients spent a greater portion of the night in SDB (total no. of episodes of apnea, hypopnea, and hypoventilation) than did the CMS controls, young Han, or young Tibetans (15% vs. 5, 1, and 1%, respectively; P < 0.05) because of more frequent apnea and hypoventilation episodes and longer duration of all types of episodes. SDB and unexplained arterial O2 desaturation caused nocturnal SaO2 to be lower and more variable in CMS patients than in CMS controls or in younger-aged Han or Tibetan men. Average CaO2 was similar, but the CMS patients spent 29%, whereas the other groups spent < 4%, of the night at values < 18 ml O2/100 ml whole blood. Internal carotid artery flow velocity during wakefulness was similar in CMS patients and CMS controls despite higher end-tidal PcO2 values in the CMS patients. When contiguous sleep stages are compared, flow velocity rose from stage 2 to rapid-eye-movement sleep in both groups. Whereas flow velocity remained elevated from awake to rapid-eye-movement sleep in the CMS controls, it fell in the CMS patients. During episodes of SDB, internal carotid flow velocity increased in CMS controls but did not change in the CMS patients such that values were lower in the CMS patients than in CMS controls at the end and after SDB episodes. We concluded that SDB and episodes of unexplained desaturation lowered nocturnal SaO2 and CaO2, which, together with a lack of compensatory increase in internal carotid artery flow velocity, likely decreased brain O2 delivery in CMS patients during a considerable portion of the night.
Electrical stimulation of the lingual musculature in obstructive sleep apnea
Authors: Schwartz A. R. , Eisele D. W. , Hari A. , Testerman R. , Erickson D. , Smith P. L.
Published: December 2017

The influence of lingual muscle activity on airflow dynamics in the upper airway was examined in nine patients with obstructive sleep apnea. Muscles that retract the tongue (hyoglossus and styloglossus) and protrude the tongue (genioglossus) were selectively stimulated electrically during sleep with fine wire electrodes placed intramuscularly transorally. We confirmed that stimulation with 50 Hz and 40-microseconds pulse duration did not elicit changes in electroencephalographic patterns or heart rate or alter airflow after the stimulation burst had ceased. The highest stimulus intensity that did not arouse patients from sleep was then utilized to examine the effect of lingual muscle recruitment on airflow dynamics during steady-state periods of inspiratory airflow limitation. When applying a stimulus burst during single inspirations, maximal inspiratory airflow decreased by 239 +/- 177 ml/s (P < 0.05) during retractor stimulation, whereas maximal inspiratory airflow increased by 217 +/- 93 ml/s during protrusor stimulation (P < 0.001) compared with breaths immediately before and after the stimulated breath. When consecutive inspirations were stimulated repeatedly, protrusor stimulation decreased the frequency of obstructive breathing episodes in four patients breathing at 3.9 +/- 3.4 (SD) cmH2O nasal pressure. The findings suggest that stimulation of the lingual muscles can increase or decrease airflow depending on the specific muscles stimulated without arousing patients from sleep.
Chemoreceptor nerve excitation may not be proportional to catecholamine secretion
Authors: Donnelly D. F.
Published: December 2017

Enhanced catecholamine secretion from the carotid body glomus cells is hypothesized to play an essential role in mediating the peripheral chemoreceptor response to hypoxia. To test aspects of this hypothesis, the relationship between catecholamine secretion and nerve activity was examined during repetitive hypoxia stimuli and after catecholamine depletion with reserpine. Single-fiber afferent serve activity was measured along with an estimate of free tissue catecholamine by using Nafion-coated carbon-fiber microelectrodes placed in rat carotid bodies in vitro. Baseline and stimulated nerve and catecholamine levels were quantified during repetitive stimulation (anoxia of 1-min duration; PO2 = 0 Torr at nadir, repeated each 200 s). Peak stimulated catecholamine progressively decreased from 26.4 +/- 2.6 microM for the first stimulus to 7.5 +/- 0.9 microM for the fifth stimulus (n = 15), but peak nerve activity was much less affected (23.0 +/- 1.9 Hz, first trial; 19.9 +/- 1.4 Hz, fifth trial). An exposure to moderate hypoxia (approximately 80 Torr) before the repetitive anoxia stimuli produced catecholamine levels comparable to those obtained during repetitive anoxia, but peak nerve activity was significantly less (22.5 +/- 3.4 vs. 12.7 +/- 2.1 Hz). Pretreatment with reserpine (1 mg/100 g) resulted in a large reduction in the average hypoxia-induced catecholamine response (1.4 +/- 0.3 microM, n = 9), but peak nerve activity was not different from nontreated controls. These results demonstrate an independence between carotid body catecholamine secretion and nerve activity, suggesting that nerve excitation is, at least, partially mediated through pathways independent of granule secretion.
Role of aerobic capacity and body mass index in the age-associated decline in heart rate variability
Authors: Byrne E. A. , Fleg J. L. , Vaitkevicius P. V. , Wright J. , Porges S. W.
Published: December 2017

The extent to which age-associated changes in aerobic capacity and body composition modulate the age-associated decline in heart rate variability (HRV) is unknown. We therefore measured HRV, peak O2 consumption (VO2peak) during treadmill testing, and relative weight (body mass index; BMI) in 164 healthy normotensive adults (75 men, age 20–87 yr) from the Baltimore Longitudinal Study on Aging. Two components of HRV, respiratory sinus arrhythmia (RSA; 0.12–0.40 Hz) and 0.10-Hz variability (0.06–0.10 Hz), were extracted from 8-min electrocardiogram recordings in the supine, seated, and standing postures. RSA, 0.10-Hz variability, and VO2peak varied inversely with age; BMI was unrelated to age. Age contributed 15.5–21.1% independent variance to RSA and 13.2–17.3% independent variance to 0.10-Hz HRV. VO2peak did not contribute significantly to RSA or 0.10-Hz HRV beyond the effect of age in any posture. There were no consistent independent contributions of BMI to HRV. Thus, in this population-based sample, age-associated changes in aerobic capacity and relative body weight do not provide the primary explanation for the decline in HRV observed with advancing age.
Diaphragmatic activity during REM sleep in the adult cat
Authors: Orem J. , Anderson C. A.
Published: December 2017

Diaphragmatic electromyograms from five adult cats were studied to determine whether diaphragmatic activity, like central respiratory activity, increases in rapid-eye-movement (REM) sleep. Breaths with inspiratory durations between 250 and 2,000 ms were analyzed. 1) There was a greater slope of the moving time average of diaphragmatic activity in REM than in non-REM (NREM) sleep. These greater slopes occurred whether the route of breathing was through the upper airways or through an endotracheal tube and may have resulted from early recruitment of motor units. 2) Mean diaphragmatic activity was also greater, but other variables (peak activity, the area under the curve of diaphragmatic activity, mean intratracheal pressures, inspiratory airflow rates, and tidal volumes) were not greater in REM than in NREM sleep. 3) Diaphragmatic activity was similar in REM sleep and active wakefulness. 4) Across states, slope of the moving time average varied with the duration of inspiration: greater slopes were associated with shorter breaths. These results are consistent with an increase in central respiratory drive in REM sleep that increases the rate of rise of diaphragmatic activity.
Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease
Authors: Hiatt W. R. , Regensteiner J. G. , Wolfel E. E. , Carry M. R. , Brass E. P.
Published: December 2017

Patients with symptomatic peripheral arterial occlusive disease have a claudication-limited peak exercise performance that is improved with exercise training. The effects of training on skeletal muscle metabolism were evaluated in 26 patients with claudication, randomized into a 12-wk program of treadmill training (enhances muscle metabolic activity in normal subjects), strength training (stimulates muscle hypertrophy in normal subjects), or a nonexercising control group. Gastrocnemius muscle biopsies were performed at rest and before and after training. After 12 wk, only treadmill training improved peak exercise performance and peak oxygen consumption. Treadmill training did not alter type I or type II fiber area and did not increase citrate synthase activity but was associated with an increase in the percentage of denervated fibers (from 7.6 +/- 5.4 to 15.6 +/- 7.5%, P < 0.05). Improvement in exercise performance with treadmill training was associated with a correlative decrease in the plasma (r = -0.67) and muscle (r = -0.59) short-chain acylcarnitine concentrations (intermediates of oxidative metabolism). Patients in the strength and control groups had no changes in muscle histology or carnitine metabolism, but strength-trained subjects had a decrease in citrate synthase activity. Thus treadmill training increased peak exercise performance, but this benefit was associated with skeletal muscle denervation and the absence of a "classic" mitochondrial training response (increase in citrate synthase activity). The present study confirms the relationship between skeletal muscle acylcarnitine content and function in peripheral arterial occlusive disease, demonstrating that the response to treadmill training was associated with parallel improvements in intermediary metabolism.
Angiotensin receptor 1 blockade does not prevent physiological cardiac hypertrophy in the adult rat
Authors: Geenen D. L. , Malhotra A. , Buttrick P. M.
Published: December 2017

The renin-angiotensin system has been implicated in the hypertrophic adaptation of the heart to exogenous pathological loads, such as hypertension and aortic stenosis; however, the role of this hormonal system in the cardiac adaptations to physiological loads, such as chronic exercise conditioning, has not been established. We therefore studied the effect of angiotensin receptor 1 (AT1) blockade on the chronic cardiac responses of rats subjected to an 8-wk swimming program. Compared with matched sedentary controls, untreated swimmers increased their left ventricular weights by 13%, and swimmers treated with the AT1 antagonist L-158809 increased their left ventricular weights by 11% (both P < 0.05 vs. sedentary controls). The incorporation of labeled amino acids into the heart at the time of death was unchanged in all groups, and therefore the increase in heart weight in both swim-conditioned groups appeared to reflect a decrease in the rate of protein degradation in the heart. Hearts from both swim-conditioned groups manifested an increase in the V1-predominant myosin isoform pattern but not an increase in atrial natriuretic factor mRNA expression or protein kinase C translocation. The fact that these patterns of adaptation are preserved in exercised conditioned animals treated with an AT1 antagonist suggests that the chronic hypertrophic response of the heart to physiological loads is not influenced by the renin-angiotensin system.
Effect of skin temperature on multifrequency bioelectrical impedance analysis
Authors: Gudivaka R. , Schoeller D. , Kushner R. F.
Published: December 2017

This study assessed the effects of changes in skin temperature on multifrequency bioimpedance analysis (MF-BIA) and on the prediction of body water compartments. Skin temperature (baseline 29.3 +/- 2.1 degrees C) of six healthy adults was raised over 50 min to 35.8 +/- 0.6 degrees C, followed by cooling for 20 min to 26.9 +/- 1.3 degrees C, by using an external heating and cooling blanket. MF-BIA was measured at both distal (conventional) and proximal electrode placements. Both distal and proximal impedance varied inversely with a change in skin temperature across all frequencies (5–500 kHz). The change in proximal impedance per degree centigrade change in skin surface temperature was approximately 60% of distal impedance. The change in measured impedance at 50 kHz erroneously increased predicted total body water (TBW) by 2.6 +/- 0.9 liters (P < 0.001) and underpredicted fat mass by 3.3 +/- 1.3 kg (P < 0.0001). Computer modeling of the MF-BIA data indicated changes in predicted water compartments with temperature modifications; however, the ratio of extracellular water (ECW) to TBW did not significantly change (P < 0.4). This change in impedance was not due to a change in the movement of water of the ECW compartment and thus probably represents a change in cutaneous impedance of the skin. Controlled ambient and skin temperatures should be included in the standardization of BIA measurements. The error in predicted TBW is < 1% within an ambient temperature range of 22.3 to 27.7 degrees C (72.1–81.9 degrees F).
Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: theory
Authors: Walley K. R.
Published: December 2017

The hypothesis that the distribution of oxygen demand in relation to oxygen supply (dO2/qO2) effects oxygen extraction in peripheral tissues was tested. By using a simple theoretical model, realistic biphasic oxygen consumption-delivery relationships were predicted from dO2/qO2 distributions. Increasing width (relative dispersion) of the dO2/qO2 distribution, indicating mismatch between oxygen demand and supply, nonlinearly decreased the critical oxygen extraction ratio (calculated by using dual-line regression). Skewed dO2/qO2 distributions had a lesser effect. Incomplete oxygen uptake, due to diffusion limitation or other causes of physiological arteriovenous shunt, linearly decreased the critical oxygen extraction ratio. Approximate dO2/qO2 distributions were then estimated from previously reported capillary transit-time distributions. Critical oxygen extraction ratios predicted from these estimated dO2/qO2 distributions match reported values. This theoretical approach also predicts the decrease in the critical oxygen extraction ratio in porcine gut after endotoxin infusion in the companion paper (M. F. Humer, P. T. Phang, B. P. Friesen, M. F. Allard, C. M. Goddard, and K. R. Walley. J. Appl. Physiol. 81: 895–904, 1996). Much as pulmonary ventilation-perfusion relationships account for pulmonary gas exchange, dO2/qO2 distributions quantitatively account for measured tissue oxygen extraction and predict novel features of the relationship between heterogeneity and oxygen extraction.
Heterogeneity of gut capillary transit times and impaired gut oxygen extraction in endotoxemic pigs
Authors: Humer M. F. , Phang P. T. , Friesen B. P. , Allard M. F. , Goddard C. M. , Walley K. R.
Published: December 2017

We tested the hypothesis that endotoxin increases the heterogeneity of gut capillary transit times and impairs oxygen extraction. The gut critical oxygen extraction ratio was determined by measuring multiple oxygen delivery-consumption points during progressive phlebotomy in eight control and eight endotoxin-infused anesthetized pigs. In multiple 1- to 2-g samples of small bowel, we measured blood volume (radiolabeled red blood cells) and flow (radiolabeled 15-microns microspheres) before and after critical oxygen extraction. Red blood cell transit time (= volume/flow) multiplied by morphologically determined capillary/total blood volume gave capillary transit time. During hemorrhage, capillary/total blood volume did not change in the endotoxin group (0.5 +/- 4.5%) but increased in the control group (17.6 +/- 2.5%; P < 0.05) due to a decrease in total gut blood volume. Flow decreased significantly in the endotoxin group (36 +/- 10%; P < 0.05) but not in the control group (12 +/- 10%). Capillary transit-time heterogeneity increased in the endotoxin group (12.3 +/- 4.9%) compared with the control group (-5.8 +/- 7.4%; P < 0.05), predicting a critical oxygen extraction ratio 0.14 lower in the endotoxin group than in the control group (K. R. Walley. J. Appl. Physiol. 81: 885–894, 1996). This matches the measured difference (endotoxin group, 0.60 +/- 0.04; control group, 0.74 +/- 0.03; P < 0.05). Increased heterogeneity of capillary transit times may be an important cause of impaired oxygen extraction.
Multiple-breath washout and washin experiments in steers
Authors: Rollin F. , Desmecht D. , Verbanck S. , Van Muylem A. , Lekeux P. , Paiva M.
Published: December 2017

Multiple-breath N2 washouts (WO) and washins (WI) were performed during regular tidal breathing in 11 unsedated healthy steers approaching pulmonary functional maturity (mean body weight = 271 kg). They inspired 20% O2 in 80% Ar during the WO and air during the WI. For each steer, we computed two indexes of ventilation inhomogeneity from the N2 WO curves: 1) the curvilinearity of the logarithm of end-tidal N2 concentrations as a function of cumulative expired volume reflected in the ratio of two slopes fitted between 100 and 50% and between 50 and 10%, respectively, of end-tidal N2 concentration of the first breath of the WO; and 2) the N2 phase III slope divided by the mean expired concentration (Sn) of each breath also plotted as a function of cumulative expired volume. Equivalent computation of both parameters was done on WI and WO curves, and similar results were obtained. The mean slope ratio was 0.812 +/- 0.119 (SD) for all the steers, which is consistent with topographic gravity-dependent specific ventilation distribution inhomogeneity. Sn was independent of the breath number both for WO and WI (mean Sn = 0.130 +/- 0.057 liters-1), suggesting that emptying between unequally ventilated units, is synchronous. This behavior resembles that observed in rats postmortem (S. Verbanck, E.R. Weibel, and M. Paiva. J. Appl Physiol. 71: 847–854, 1991) but contrasts with experiments in humans, in whom convection-dependent ventilation inhomogeneities generate a marked increase in Sn throughout the entire WO (A. B. H. Crawford, M. Makowska, M. Paiva, and L. A. Engel. J. Appl. Physiol. 59: 838–846, 1985). This is surprising because one would expect gravity-dependent sequential emptying in animals of this size.
Pulmonary blood flow distribution in standing horses is not dominated by gravity
Authors: Hlastala M. P. , Bernard S. L. , Erickson H. H. , Fedde M. R. , Gaughan E. M. , McMurphy R. , Emery M. J. , Polissar N. , Glenny R. W.
Published: December 2017

Recent studies using microspheres in dogs, pigs and goats have demonstrated considerable heterogeneity of pulmonary perfusion within isogravitational planes. These studies demonstrate a minimal role of gravity in determining pulmonary blood flow distribution. To test whether a gravitational gradient would be more apparent in an animal with large vertical lung height, we measured perfusion heterogeneity in horses (vertical lung height = approximately 55 cm). Four unanesthetized Thoroughbred geldings (422-500 kg) were studied awake in the standing position with fluorescent microspheres injected into a central vein. Between 1,621 and 2,503 pieces (1.3 cm3 in volume) were obtained from the lungs of each horse with spatial coordinates, and blood flow was determined for each piece. The coefficient of variation of blood flow throughout the lungs ranged between 22 and 57% among the horses. Considerable heterogeneity was seen in each isogravitational plane. The relationship between blood flow and vertical height up the lung was characterized by the slope and correlation coefficient of a least squares regression analysis. The slopes within each horse ranged from -0.052 to +0.021 relative flow units/cm height up the lung, and the correlation coefficients varied from 0.12 to 0.75. A positive slope, indicating that flow increased with vertical distance up the lung (opposite to gravity), was observed in three of the four horses. In addition, blood flow was uniformly low in three of the four horses in the most cranial portions of the lungs. We conclude that in lungs of resting unanesthetized horses, animals with a large lung height, there is no consistent vertical gradient to pulmonary blood flow and there is a considerable degree of perfusion heterogeneity, indicating that gravity alone does not play the major role in determining blood flow distribution.
Wet-cold exposure and hypothermia: thermal and metabolic responses to prolonged exercise in rain
Authors: Thompson R. L. , Hayward J. S.
Published: December 2017

Simulated conditions of hiking in rain, wind, and cold, without protective rainwear, were used to investigate wet-cold hypothermia in 18 male subjects. Thermal, metabolic, and motor responses were monitored during an attempted 5-h walk (5.1 km/h) at 5 degrees C, with continuous exposure to rain (7.4 cm/h) and wind (8.0 km/h) over the final 4 h. The majority of subjects (11) could not complete the protocol because of intolerance of wet-cold conditions during the last 2 h. Therefore, data from 5 subjects who completed the protocol in rain and control conditions were used to describe the general pattern of response. During the 1st h of walking, core temperature rose 1 degree C to 38.1 degrees C. The subsequent 2 h of rain caused substantial cold stress, indicated by a 40% increase in heat production due to shivering and significant loss of strength and manual dexterity. However, core temperature only decreased to 37.1 degrees C, merely eliminating the initial exercise hyperthermia. Over the last 2 h of rain, core temperature remained relatively stable at 36.8 degrees C, decreasing slightly to 36.4 degrees C by 5 h. Two other subjects developed significant hypothermia (35 degrees C). One demonstrated fatigue of shivering after 2.5 h of rain, confirming the exhaustion hypothesis of wet-cold hypothermia. The older cooled rapidly when he failed to maintain the walking pace. We conclude that if a person can tolerate the intense discomfort of prolonged wet-cold exposure, he or she has the potential to resist significant core hypothermia for at least 4 h of walking under the conditions of this experiment. Exceptions to this generalization occur, making exposure of < 4 h a hypothermia risk for some individuals. Exposures > 4 h would involve increasing probability of rapid decline into hypothermia, associated with exhaustion of shivering and exercise heat production.
Quantification of intensity of sensations during muscular work by normal subjects
Authors: Hamilton A. L. , Killian K. J. , Summers E. , Jones N. L.
Published: December 2017

Eleven subjects performed a series of 30-s work bouts on a cycle ergometer at power outputs ranging from 20-120% of the work capacity (Wcap) achieved during an incremental cycle to exhaustion and estimated the intensity of several sensations (leg effort, muscle tension, muscle discomfort, muscle pain, and breathing discomfort) by using Borg's category-ratio scale (range 0-10 units). Leg effort was perceived as "just noticeable" at 31 +/- 15% Wcap, muscle tension was just noticeable at 31 +/- 16% Wcap, muscle discomfort was just noticeable at 47 +/- 21% Wcap, breathing discomfort was just noticeable at 52 +/- 19% Wcap, and muscle pain was just noticeable at 58 +/- 33% Wcap. The intensity of all sensations increased in a positively accelerating manner with increases in power output (P < 0.001). Above 60% Wcap, the intensity of leg effort and muscle tension exceeded the intensity of muscle pain (P < 0.01), and above 100% Wcap the intensity of muscle discomfort also exceeded the intensity of muscle pain (P < 0.01). At 120% Wcap, leg effort, muscle tension, and muscle discomfort were rated between "severe" and "very severe" (6.1 +/- 2.2, 6.4 +/- 2.0, and 5.6 +/- 2.1 Borg units, respectively), whereas muscle pain and breathing discomfort were rated between "moderate" and "somewhat severe" (3.6 +/- 2.1 and 3.3 +/- 1.9 Borg units, respectively). These results suggest that subjects have a perception of muscle pain during muscular work that is distinct from perceptions of leg effort, muscle tension, and muscle discomfort.
Effects of acute exposure to simulated altitude on heart rate variability during exercise
Authors: Yamamoto Y. , Hoshikawa Y. , Miyashita M.
Published: December 2017

It has been shown that fluctuation of human heartbeat intervals [heart rate variability (HRV)] reflects variations in cardiac autonomic nervous system activity. The present study was designed to investigate whether the acute exposure to moderate levels of simulated altitude and the resultant hypoxia could modify HRV during exercise. Seven healthy men completed one resting measurement in the upright sitting position and two submaximal steady-state cycle ergometer exercises at intensities equivalent to 25 and 50% of their estimated maximal work rate. Experiments were conducted in random order at altitude equivalents of 500, 1,500, 2,500, and 3,500 m within 2 h of exposure to that altitude. Beat-to-beat HRV was measured continuously during the tests. HRV data were analyzed by "coarse-graining spectral analysis" (Y. Yamamoto and R.L. Hughson, Physica 68D: 250-264, 1993) to break down their total power (PT) into harmonic and nonharmonic (fractal) components. The harmonic component was further divided into low (0.0- to 0.15-Hz; PL)- and high (> 0.15-Hz; PH)-frequency components, and the indicators of relative sympathetic (SNS) and parasympathetic (PNS) nervous system activities were calculated by PL/PH and PH/PT, respectively. The fractal component was used to calculate the spectral exponent (beta) to evaluate the overall "irregularity" of HRV. The effects of exercise intensity (increase in heart rate, SNS indicator, and beta and decrease in PNS indicator) were significant (P < 0.05) at all altitude levels. The altitude effects (increase in heart rate and SNS indicator and decrease in PNS indicator) were found only during exercise at 3,500 m (P < 0.05). There was no significant effect of altitude on beta (P > 0.05). These data indicate that acute effects of altitude exposure on HRV were found 1) during exercise at moderate altitude (> 2,500 m) and 2) mainly for the harmonic components of HRV.
Alterations of diaphragm neuromuscular junctions with hypothyroidism
Authors: Prakash Y. S. , Gosselin L. E. , Zhan W. Z. , Sieck G. C.
Published: December 2017

Hypothyroidism (HYPO) often manifests as neuromuscular symptoms; however, little is known about its effects on the neuromuscular junction (NMJ). The present study examined changes in NMJ morphology and neuromuscular transmission failure (NTF) in the rat diaphragm muscle (Dimus) after 3 wk of HYPO. Three-color fluorescence immunocytochemistry and confocal microscopy were used to simultaneously visualize nerve terminals and axons, motor end plates, and myosin heavy chain isoform expression in Dimus fibers. NTF was assessed in vitro by comparing muscle fatigue induced by nerve with that induced by direct muscle stimulation. Diameters of axons innervating type I fibers were 30% smaller in the HYPO Dimus than in control (CTL). Planar areas of nerve terminals and end plates on type I and IIa fibers were 15-35% smaller in HYPO than in CTL. The extent of overlap between nerve terminals and end plates of type I fibers was 10% less in HYPO. Susceptibility to NTF during repetitive nerve stimulation was 20% greater in the CTL Dimus than in HYPO; however, changes in NMJ morphology could not fully account or the effect of HYPO on NTF.
Exercise hyperpnea and hyperthermia in humans
Authors: White M. D. , Cabanac M.
Published: December 2017

The problem of the relative hyperpnea occurring at high levels of exercise remains unresolved. This study examined whether the hyperpnea observed in humans during exercise at approximately 70% of maximal work capacity was related to cranial (tympanic) and thoracic (esophageal) temperatures. Six trained male subjects pedaled at approximately 60 revolutions/min on an electrically braked cycle ergometer in a climatic chamber at 25 degrees C and approximately 35% relative humidity in two sessions. The subjects pedaled until exhaustion in two sessions. In one session work rate was increased by 40 W every 2 min and in the other session by 20 W every 2 min. In both exercise sessions, core temperature thresholds for ventilation were evident and subsequently tympanic and esophageal temperatures diverged. This suggested that the hyperpnea in humans observed after approximately 70% of an individual's maximal work rate was determined, in part, by core temperatures and revealed supportive evidence for selective brain cooling in humans.
Eicosanoids modulate hyperpnea-induced bronchoconstriction in canine peripheral airways
Authors: Omori C. , Tagari P. , Freed A. N.
Published: December 2017

We examined the role of leukotrienes (LTs) in the development of dry air-induced bronchoconstriction (AIB) in canine peripheral airways. Airway reactivity to exogenous LTs was first tested by using an LTD4 aerosol challenge: peripheral airway resistance increased approximately 130 +/- 51% (n = 4) above baseline when compared with its vehicle control. AIB was then assessed by measuring peripheral airway resistance after, and airway wall temperature during, a dry air challenge (DAC). Treatment with a peptidoleukotriene biosynthesis inhibitor (MK-0591) attenuated AIB by approximately 65% without altering airway wall temperature. The fact that MK-0591 did not alter airway reactivity to aerosolized acetylcholine and completely inhibited Ca2+ ionophore-induced LTB4 generation in canine whole blood attests to the specificity of the drug. Treatment with MK-0591 did not affect the increased number of epithelial cells recovered in bronchoalveolar lavage fluid 5 min after DAC. Concentrations of LTs and other eicosanoids in bronchoalveolar lavage fluid from vehicle-treated DAC airways were increased above baseline values; only LTs were reduced by MK-0591. Before MK-0591, AIB was significantly correlated with the dry air-induced generation of LTC4, LTD4, and LTE4. After treatment with MK-0591, AIB was correlated with thromboxane B2, prostaglandin (PG) F2 alpha, and PGE2. We conclude that hyperpnea with dry air stimulates local production and release of LTs in canine bronchi and, alone with the generation of bronchoconstricting and bronchodilating PGs, plays a central role in the modulation of AIB.
Endogenous bradykinin in the thoracic spinal cord contributes to the exercise pressor reflex
Authors: Stebbins C. L. , Bonigut S.
Published: December 2017

This investigation tested the hypothesis that bradykinin causes excitatory effects in the thoracic spinal cord that augment the exercise pressor reflex. Thus we performed 30 s of electrically stimulated static contraction of the hindlimb in the anesthetized cat (alpha-chloralose) to provoke reflex-induced increases in mean arterial pressure, maximal rate of rise of left ventricular pressure (dP/dt), and heart rate (i.e., the exercise pressor reflex). These three responses were compared before and 15 min after intrathecal injection of 2 micrograms (n = 3), 10 micrograms (n = 6), or 50 micrograms (n = 3) of the selective bradykinin B2- receptor antagonist HOE-140 into the thoracic spinal cord or 10 micrograms of this antagonist into the lumbar (n = 3) spinal cord. In three of the six cats in which 10 micrograms of HOE-140 were injected into the thoracic spinal cord, an additional contraction was performed 60-90 min after treatment. The 2-microgram dose of HOE-140 had no effect on the exercise pressor reflex. Injection of 10 micrograms of this antagonist into the thoracic spinal cord reduced the contraction-evoked pressor, maximal dP/dt, and heart rate responses by 49 +/-7, 58 +/- 4, and 64 +/- 13%, respectively (P < 0.05). Fifty micrograms of HOE-140 failed to attenuate these responses further. In the three cats in which an additional contraction was performed 60-90 min after treatment with 10 micrograms of the antagonist, blood pressure and dP/dt responses had returned, in part, toward initial values. Neither intravenous (n = 3) nor intrathecal injection of 10 micrograms of HOE-140 into the lumbar spinal cord had any effect on the contraction-induced cardiovascular responses. Thoracic injection of 50-200 ng of bradykinin provoked a pressor response of 26 +/- 5 mmHg that was abolished by a similar injection of 10 micrograms of HOE-140. These data suggest that endogenous bradykinin contributes to the exercise pressor reflex by an excitatory action in the thoracic spinal cord.
Molybdenum metabolism in men with increasing molybdenum intakes: changes in kinetic parameters
Authors: Thompson K. H. , Scott K. C. , Turnlund J. R.
Published: December 2017

Molybdenum metabolism was studied in four young men to determine the effect of the amount of dietary molybdenum on molybdenum kinetics. A compartmental model, developed by using data from a study with low dietary molybdenum, was adapted to accommodate five levels of molybdenum. Each level, ranging from 22 to 1,470 micrograms molybdenum/day, was fed for 24 days. Kinetics of absorption and excretion were traced by using 97Mo (intravenous) and 100 Mo (oral) stable-isotope tracers at selected intervals. Urinary and fecal isotope excretion data for 6-day pooled collections were fit to a kinetic model by using SAAM/CONSAM software. Residence times for molybdenum were estimated at 2.4 days in the gastrointestinal tract, 40 min in plasma, from 3.3 to 0.3 days in fast-turnover tissue, and from 63 to 237 days in slow-turnover tissue. As dietary molybdenum increased, residence time decreased in fast-turnover tissue and increased in slow-turnover tissue. The model closely approximated the highly efficient homeostatic mechanisms of molybdenum metabolism over a wide range of intakes.
Muscle glycogen recovery after exercise during glucose and fructose intake monitored by13C-NMR
Authors: Van Den Bergh Adrianus J. , Houtman Sibrand , Heerschap Arend , Rehrer Nancy J. , Van Den Boogert Hendrikus J. , Oeseburg Berend , Hopman Maria T. E.
Published: December 2017

Van Den Bergh, Adrianus J., Sibrand Houtman, Arend Heerschap, Nancy J. Rehrer, Hendrikus J. Van Den Boogert, Berend Oeseburg, and Maria T. E. Hopman. Muscle glycogen recovery after exercise during glucose and fructose intake monitored by13C-NMR. J. Appl. Physiol. 81(4): 1495–1500, 1996.—The purpose of this study was to examine muscle glycogen recovery with glucose feeding (GF) compared with fructose feeding (FF) during the first 8 h after partial glycogen depletion by using13C-nuclear magnetic resonance (NMR) on a clinical 1.5-T NMR system. After measurement of the glycogen concentration of the vastus lateralis (VL) muscle in seven male subjects, glycogen stores of the VL were depleted by bicycle exercise. During 8 h after completion of exercise, subjects were orally given either GF or FF while the glycogen content of the VL was monitored by13C-NMR spectroscopy every second hour. The muscular glycogen concentration was expressed as a percentage of the glycogen concentration measured before exercise. The glycogen recovery rate during GF (4.2 ± 0.2%/h) was significantly higher ( P < 0.05) compared with values during FF (2.2 ± 0.3%/h). This study shows that 1) muscle glycogen levels are perceptible by13C-NMR spectroscopy at 1.5 T and 2) the glycogen restoration rate is higher after GF compared with after FF.
Fractal analysis of cytoskeleton rearrangement in cardiac muscle during head-down tilt
Authors: Thomason Donald B. , Anderson Otis , Menon Vandana
Published: December 2017

Thomason, Donald B., Otis Anderson III, and Vandana Menon.Fractal analysis of cytoskeleton rearrangement in cardiac muscle during head-down tilt. J. Appl. Physiol. 81(4): 1522–1527, 1996.—Head-down tilt by tail suspension of the rat produces a volume, but not pressure, load on the heart. One response of the heart is cytoskeleton rearrangement, a phenomenon commonly referred to as disruption. In these experiments, we used fractal analysis as a means to measure complexity of the microtubule structures at 8 and 18 h after imposition of head-down tilt. Microtubules in whole tissue cardiac myocytes were stained with fluorescein colchicine and were visualized by confocal microscopy. The fractal dimensions ( D) of the structures were calculated by the dilation method, which involves successively dilating the outline perimeter of the microtubule structures and measuring the area enclosed. The head-down tilt resulted in a progressive decrease in D(decreased complexity) when measured at small dilations of the perimeter, but the maximum D (maximum complexity) of the microtubule structures did not change with treatment. Analysis of the fold change in complexity as a function of the dilation indicates an almost twofold decrease in microtubule complexity at small kernel dilations. This decrease in complexity is associated with a more Gaussian distribution of microtubule diameters, indicating a less structured microtubule cytoskeleton. We interpret these data as a microtubule rearrangement, rather than erosion, because total tubulin fluorescence was not different between groups. This conclusion is supported by F-actin fluorescence data indicating a dispersed structure without loss of actin.
Effects of β2-agonist administration and exercise on contractile activation of skeletal muscle fibers
Authors: Lynch Gordon S. , Hayes Alan , Campbell Siun P. , Williams David A.
Published: December 2017

Lynch, Gordon S., Alan Hayes, Siun P. Campbell, and David A. Williams. Effects of β2-agonist administration and exercise on contractile activation of skeletal muscle fibers. J. Appl. Physiol. 81(4): 1610–1618, 1996.—Clenbuterol, a β2-adrenoceptor agonist, has therapeutic potential for the treatment of muscle-wasting diseases, yet its effects, especially at the single-fiber level, have not been fully characterized. Male C57BL/10 mice were allocated to three groups: Control-Treated mice were administered clenbuterol (2 mg ⋅ kg−1 ⋅ day−1) via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) in addition to receiving clenbuterol; and Control mice were sedentary and untreated. Contractile characteristics were determined on membrane-permeabilized fibers from the extensor digitorum longus (EDL) and soleus muscles. Fast fibers from the EDL and soleus muscles of Treated mice exhibited decreases in Ca2+ sensitivity. Endurance exercise offset clenbuterol’s effects, demonstrated by similar Ca2+ sensitivities in the Trained-Treated and Control groups. Long-term clenbuterol treatment did not affect the normalized maximal tension of fast or slow fibers but increased the proportion of fast fibers in the soleus muscle. Training increased the proportion of fibers with high and intermediate succinate dehydrogenase activity in the EDL and soleus muscles, respectively. If clenbuterol is to be used for treating muscle-wasting disorders, some form of low-intensity exercise might be encouraged such that potentially deleterious slow-to-fast fiber type transformations are minimized. Indeed, in the mouse, low-intensity exercise appears to prevent these effects.