bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevations in rat soleus muscle [Ca2+] with passive stretch
Authors: Armstrong R. B. , Duan C. , Delp M. D. , Hayes D. A. , Glenn G. M. , Allen G. D.
Published: December 2017

Previous work has demonstrated that muscular injury in rat soleus muscles resulting from eccentric contractions (downhill walking) is accompanied by elevations in mitochondrial [Ca2+] (MCC). Muscles are stretched during eccentric contractions, and there is evidence in the literature that stretch of the cell membrane induces Ca2+ influx in various tissues, including skeletal muscle. The purpose of this study was to determine if passive stretch of rat soleus muscles will induce increases in total muscle [Ca2+] (TCC) and MCC. Soleus muscles from female rats (51–122 g) were isolated and incubated in vitro for 2 h at resting length (Lo) or at the maximal in situ length (S). TCC (+62%) and MCC (+56%) were elevated in the S muscles. Also, there was a 63% reduction in maximal twitch tension in the S muscles. ATP concentration, phosphocreatine concentration, and lactate release between Lo and S muscles were the same, indicating that impaired metabolism was not responsible for the observed differences in [Ca2+] and force production between Lo and S muscles. Increases in TCC in the S condition indicate that stretch results in Ca2+ influx from the extracellular space, which is supported by the observation that when S muscles were incubated in Ca(2+)-free buffer, TCC and MCC did not increase. High concentrations of verapamil (0.25–0.75 mM) blocked the elevations in TCC and MCC in the S muscles, but the magnitude of the drug concentration required makes it questionable whether the effect resulted from specific blockade of slow voltage-sensitive Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac afferents attenuate the muscle metaboreflex in the rat
Authors: Collins H. L. , DiCarlo S. E.
Published: December 2017

The influence of cardiac afferents on the muscle metaboreflex was examined in 16 rats instrumented with a Silastic-tipped catheter in the pericardial space and right atrium, Doppler ultrasonic flow probe and a pneumatic vascular occluder around the terminal aorta, and a Teflon catheter in the thoracic aorta. In protocol I (cardiac efferent and afferent blockade), the muscle metaboreflex was examined under three experimental conditions: 1) control, 2) cardiac autonomic efferent blockade [intrapericardial methylscopolamine (10 micrograms/kg) and propranolol (50 micrograms/kg)], and 3) combined cardiac autonomic efferent and afferent blockade (intrapericardial procainamide, 2%). In protocol II (blood volume expansion), the muscle metaboreflex was examined before and after 15% blood volume expansion. Mild treadmill exercise (9 m/min, 10% grade) increased heart rate (71 +/- 9.4 beats/min), mean arterial pressure (12 +/- 2.0 mmHg), and terminal aortic blood flow velocity (6 +/- 1.0 kHz). During exercise, a reduction of terminal aortic blood flow velocity (10.5 +/- 1.1%) reduced mixed venous PO2 18 +/- 6%. The gain of the muscle metaboreflex in the control condition was 14.6 +/- 2.9 mmHg/kHz. Efferent blockade reduced the gain 51 +/- 7%. However, combined cardiac efferent and afferent blockade increased the gain 207 +/- 64% above the efferent blocked condition and restored the gain to levels above those obtained in the control condition (18.3 +/- 4.6 mmHg/kHz). In addition, 15% blood volume expansion reduced the gain of the muscle metaboreflex regulation of mean arterial pressure and heart rate (44 +/- 9.5% and 41 +/- 12.0%, respectively). Thus cardiac afferents tonically inhibit the pressor response to a reduction in terminal aortic blood flow velocity during exercise.
Influence of autonomic blockade on cardiovascular responses to exercise in rats
Authors: Overton J. M.
Published: December 2017

The purposes of this study were to determine the role of the sympathetic and parasympathetic nervous systems in producing the heart rate (HR) response to dynamic exercise in rats and to determine the effect of attenuation of the HR response to exercise on blood flow redistribution. Sprague-Dawley rats (n = 10) were instrumented with arterial and venous catheters and Doppler flow probes. Mean arterial pressure (MAP), HR, mesenteric blood flow (MBF), and iliac blood flow (IBF) were determined during four exercise tests. On 4 consecutive days, rats were treated with saline (SAL, 1 mg/kg iv), atropine methyl nitrate (ATR, 2 mg/kg), timolol maleate (TIM, 0.5 mg/kg), and combined timolol and atropine. One minute of mild exercise (10 m/min) produced an increase in HR of 90 +/- 6 beats/min after SAL treatment, which was significantly less than the increment after ATR (56 +/- 5 beats/min) or TIM (4 +/- 3 beats/min). For the remainder of graded exercise, ATR treatment produced a modest attenuation in the increment in HR and no effect on MAP, IBF, and MBF. At 30 m/min, TIM markedly blunted the exercise-induced increment in HR (SAL, 138 +/- 8 beats/min; TIM, 53 +/- 4 beats/min) and IBF (SAL, 324 +/- 33%; TIM, 197 +/- 33%) with no effect on MAP or MBF. The results suggest that 1) the sympathetic nervous system is an important mediator of exercise-induced tachycardia in rats and 2) exercised-induced hyperemia, but not MAP, is attenuated by nonselective beta-blockade during exercise in rats.
Regional lung mechanics and gas transport in lungs with inhomogeneous compliance
Authors: Tsuzaki K. , Hales C. A. , Strieder D. J. , Venegas J. G.
Published: December 2017

The effect of respiratory frequency (f) on the distributions of ventilation, regional gas transport, lung volume, and regional impedance was assessed with positron imaging in lungs with nonuniform lung mechanics after unilateral lung lavage. Supine dogs were studied during eucapnic oscillatory ventilation at f between 1 and 15 Hz and at a constant mean airway pressure of 5 cmH2O. Substantial differences in mean lung volume and tidal volume (VT) between lavaged and control lungs were found at all f values, but pendelluft never exceeded 2% of mouth flow. For f < or = 10 Hz, VT distributed in direct proportion to lung volume, whereas gas transport per unit of lung volume, measured from washout maneuvers, was reduced by 20% in the lavaged lung. At 15 Hz, however, the distributions of VT and gas transport approached equality between both lungs. Regional impedance was analyzed with a model that included a Newtonian resistance, an inertance, and Hildebrandt's model of tissue viscoelasticity. The data obtained from this work provide useful insights with respect to the mechanisms of gas transport during high-frequency ventilation and suggest the impact of operating frequency in clinical situations where substantial interregional heterogeneity in lung compliance could be expected.
Pulmonary vascular beta-adrenoreceptor activity in conscious dogs after left lung autotransplantation
Authors: Nishiwaki K. , Rock P. , Stuart R. S. , Nyhan D. P. , Peterson W. P. , Murray P. A.
Published: December 2017

Our objective was to determine whether chronic denervation associated with left lung autotransplantation (LLA) results in an alteration in sympathetic beta-adrenoreceptor regulation of the pulmonary circulation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 2–4 wk post-LLA and in sham-operated control conscious dogs. We tested the hypothesis that endogenous sympathetic beta-adrenoreceptor activation via circulating catecholamines acted to attenuate the chronic increase in pulmonary vascular resistance post-LLA. Administration of the sympathetic beta-adrenoreceptor antagonist propranolol had no significant effect on the LPQ relationship post-LLA. We also tested the hypothesis that pulmonary vascular reactivity to sympathetic beta-adrenoreceptor activation would be increased post-LLA. The thromboxane analogue U-46619 was used to acutely preconstrict (P < 0.01) the pulmonary circulation in control dogs; this preconstriction shifted the LPQ relationship to the same position measured post-LLA. Under these conditions, cumulative doses of the beta-adrenoreceptor agonist isoproterenol caused pulmonary vasodilation (P < 0.01) in the control group but had no effect post-LLA. However, after acute preconstriction with U-46619, the pulmonary vasodilator response (P < 0.01) to isoproterenol post-LLA was not significantly different from that in the control group. These differential responses to isoproterenol with and without acute preconstriction indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is mediated by passive nonvasoactive mechanisms. Moreover, sympathetic beta-adrenoreceptor reactivity of the pulmonary circulation is not enhanced by chronic denervation resulting from the LLA procedure.
Respiratory input impedance up to 256 Hz in healthy humans breathing foreign gases
Authors: Rotger M. , Farre R. , Navajas D. , Peslin R.
Published: December 2017

Currently available data concerning respiratory input impedance (Zrs) at frequencies up to 300 Hz indicate that Zrs is determined mainly by the airways and, in particular, the gas compressibility in the airways and the airway wall compliance. Hence, measurements of Zrs when breathing gases with different physical properties would be useful in investigating airway mechanics and the role of acoustic propagation. Zrs measured with a standard generator (Zst) and corrected for the upper airway shunt (Zrs*) were measured in nine healthy subjects breathing air or a gas mixture consisting of 20% O2 and 80% He or SF6. The frequency band was extended up to 256 Hz for air and He-O2 and up to 128 Hz for SF6-O2. Zrs exhibited a similar pattern for the three gases, with a shift toward low frequencies as the gas density increased. Moreover, the resonance peaks tended to be narrower and higher as the gas density increased. The second frequency of resonance for He-O2, air, and SF6-O2 were 220, 180, and 50 Hz, respectively, for Zrs* and were systematically higher for Zst. Zrs* and Zst data were interpreted in terms of a tricompartmental model that partitioned the airways into two segments: a central one featuring the acoustic propagation in the airways and a peripheral one that included bronchial wall elasticity (Farre et al. J. Appl. Physiol. 67: 1973–1981, 1989). The model was able to interpret the gas dependence of Zrs* but not that of Zst. The influence of the gas physical properties on both Zrs* and Zst confirms that total Zrs at high frequencies is basically that of the airways and that the second resonance is related mainly to the gas compressibility in the airways.
Fatigue-induced alterations in Ca2+ and caffeine sensitivities of skinned muscle fibers
Authors: Williams J. H. , Ward C. W. , Klug G. A.
Published: December 2017

The relative importance of laryngeal afferents in the cough reflex in humans is unknown. This study was designed to investigate the importance of superior laryngeal nerve afferents in the cough reflex induced by inhaled nebulized citric acid in awake humans. Nine healthy volunteers had their cough thresholds to inhaled nebulized citric acid measured after superior laryngeal nerve conduction blockade and after a sham nerve block. Of the nine subjects, four showed no change in cough threshold after superior laryngeal nerve anesthesia, three showed increased cough threshold after nerve block compared with no block, and two showed decreased cough threshold after nerve block. The geometric means of the cough thresholds for the nerve block vs. sham block tests were 16 +/- 13 (SD) and 15 +/- 8% citric acid, respectively. There was no statistically significant difference (Wilcoxon signed-rank test) between the cough thresholds with and without superior laryngeal nerve block (P > 0.05). We conclude that, in the awake human, superior laryngeal nerve afferents do not play a necessary role in initiation of citric acid-induced cough.
Detection of tracheal stenosis by frequency analysis of tracheal sounds
Authors: Yonemaru M. , Kikuchi K. , Mori M. , Kawai A. , Abe T. , Kawashiro T. , Ishihara T. , Yokoyama T.
Published: December 2017

To develop a simple noninvasive method for detecting tracheal stenosis, tracheal sounds were analyzed using fast-Fourier transform. The subjects were all female and included 5 normal volunteers and 13 patients with tracheal stenosis mostly secondary to thyroid cancer (11 extrathoracic and 2 intrathoracic lesions). Tracheal sounds were recorded during spontaneous breathing and were digitized with an analog-to-digital converter. Pulmonary functions, including forced expiratory volume in 1 s (FEV1) expressed as percentage of vital capacity, peak expiratory flow rate (PEFR), the ratio of FEV1 to PEFR (Empey's index), and the ratio of expiratory to inspiratory flow rates at 50% vital capacity, were measured. A computed tomography scan was used to obtain the tracheal minimum cross-sectional area. Whereas PEFR demonstrated a weak correlation with the stenotic area, FEV1%, Empey's index, and the ratio of expiratory to inspiratory flow rates at 50% vital capacity did not. The power of the fast-Fourier transform spectrum of normal tracheal sounds decreased as the frequency increased up to 500 Hz. A small spectral peak was observed at approximately 1 kHz. Patients with significant tracheal stenosis demonstrated an increase in the peak spectral power at approximately 1 kHz and in the mean spectral power from 600 to 1,300 Hz in their tracheal sounds. In patients with extrathoracic lesions, the peak and mean spectral powers correlated well with the area of the stenosis as defined by computed tomography scan. In patients with intrathoracic lesions, abnormalities in the pulmonary functions as well as tracheal sound spectra appeared more evident despite milder stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of sleep on alae nasi EMG and nasal resistance in normal men
Authors: Wheatley J. R. , Tangel D. J. , Mezzanotte W. S. , White D. P.
Published: December 2017

The influence of sleep on the upper airway musculature varies considerably, with some muscles maintaining their activity at waking levels and others falling substantially. The influence of sleep on the alae nasi (AN), a dilator muscle of the nasal airway, has been minimally studied to date. Thus we determined the effect of non-rapid-eye-movement (NREM) sleep on the AN electromyogram and its relationship to nasal resistance (Rn) in nine normal supine males. Phasic inspiratory AN activity decreased from 20 +/- 6 arbitrary units during wakefulness to 5 +/- 1 arbitrary units (P < 0.001) at the onset of stage 2 NREM sleep and remained unchanged for two subsequent hours of NREM sleep. However, the Rn at the onset of NREM sleep remained similar to awake values (5.7 +/- 0.9 cmH2O.l-1 x s) and increased only after 1 h of NREM sleep (8.6 +/- 1.7 cmH2O.l-1 x s, P < 0.05), thus demonstrating little relationship to AN activity. We conclude that Rn increases slightly after 1 h of sleep, whereas AN activity decreases at stage 2 sleep onset. Thus AN activity has little influence on Rn during sleep.
Effects of capsaicin desensitization on nasal mucosal secretion in guinea pigs in vivo
Authors: Gawin A. Z. , Baraniuk J. N. , Igarashi Y. , Kaliner M. A.
Published: December 2017

Capsaicin-sensitive mechanisms may contribute to histamine's effects on guinea pig nasal mucosal secretion in vivo. Histamine nasal provocations were performed, secretions were collected, and the following variables were measured: total protein (marker of all secretory processes), alkaline phosphatase (marker of glandular secretion), and albumin (marker of vascular permeability, epithelial permeability, and glandular transport). By challenging only one nostril (ipsilateral), the contralateral responses to these challenges were examined and the nature of "nasonasal" reflexes was determined. Histamine increased albumin and alkaline phosphatase concentrations in lavage fluid on the ipsilateral and contralateral sides. The alkaline phosphatase secretion was reduced by atropine. Capsaicin induced dose-dependent albumin exudation. To determine the roles of capsaicin-sensitive sensory nerves, one nostril was desensitized by topical application of capsaicin to one nostril in increasing doses daily for 5 wk. This led to 1) ablation of all secretory responses to capsaicin, 2) ablation of histamine-induced alkaline phosphatase and total protein secretion, 3) blunted histamine-induced albumin exudation on the desensitized side, and 4) ablation of histamine-induced contralateral reflex-mediated protein secretion. These results indicate that capsaicin stimulates vascular responses, probably by stimulating nociceptive nerve axon responses. Histamine induces vascular responses and albumin exudation by both capsaicin-sensitive sensory neuron axon responses and direct effects on vessels. Histamine stimulates glandular secretion through a capsaicin-sensitive afferent/cholinergic efferent reflex.
Bifurcations of the respiratory pattern produced with phasic vagal stimulation in the rat
Authors: Sammon M. , Romaniuk J. R. , Bruce E. N.
Published: December 2017

Geometric methods from nonlinear dynamics are employed to evaluate dynamic processing of vagal afferent information by the respiratory central pattern generator (RCPG). While measuring airflow and diaphragm EMG, we applied brief electrical stimuli (40- to 130-ms duration) to one afferent vagus of bilaterally vagotomized urethan-anesthetized rats during every breath at various phases of the respiratory cycle. Stimuli applied during early or late inspiration of every breath evoke highly predictable one-dimensional responses: reversible (graded inhibition) or irreversible (off-switching) inhibition of inspiratory activity, respectively. Stimulation during midinspiration produces higher-dimensional oscillations that wander unpredictably over a continuum of graded inhibition and off-switching; "spiral" attractors and "horseshoe" return maps at this phase are characteristic of Silnikov's bifurcation. Stimuli applied during early expiration always prolonged expiratory duration, but those delivered during midexpiration evoked unpredictable wandering between prolongations and shortening of expiratory duration. A narrow time window surrounds the expiratory-inspiratory (E-I) transition, where stimuli elicit either breaths of short duration and low amplitude (irreversible E-I transition, decreased total respiratory cycle duration) or transient bursts of inspiratory activity at the E-I transition followed by a prolonged breath (reversible E-I transition, increased total respiratory cycle duration). We conclude that RCPG "gating" of and adaptation to vagal feedback combine to produce complex breath-to-breath dynamics in the rat that are consistent with low-dimensional chaos.
Effect of temperature on alveolar liquid and protein clearance in an in situ perfused goat lung
Authors: Serikov V. B. , Grady M. , Matthay M. A.
Published: December 2017

To study the mechanisms of alveolar liquid and protein clearance, we investigated the effect of four different temperatures (7, 18, 30, and 38 degrees C) on the rate of liquid, [14C]mannitol, and 125I-labeled albumin (125I-albumin) transport from the air spaces of isolated perfused in situ goat lungs over 4 h under isogravimetric conditions. The concentrations of both native proteins and 125I-albumin in the alveolar fluid after 4 h were used to estimate alveolar liquid clearance. We instilled autologous serum (2 ml/kg) with 125I-albumin and [14C]mannitol into the distal air spaces of one lung and 131I-labeled albumin into the perfusate to measure the capillary-to-alveolar permeability to protein. Alveolar liquid clearance progressively declined from a control value of 24 +/- 6% at 38 degrees C to 12 +/- 7% at 30 degrees C, to 3 +/- 3% at 18 degrees C, and to -15 +/- 11% at 7 degrees C. 125I-albumin clearance into the perfusate was 0.3%/h of the instilled 125I-albumin at 38 degrees C. The clearance decreased abruptly to 0.06%/h at 30 degrees C and then slightly increased to 0.08%/h at 18 degrees C and to 0.15%/h at 7 degrees C. There were no changes in transport except for a twofold increase in mannitol at 7 degrees C. Increased permeability of the alveolar barrier to protein and small-molecular-weight tracers at 7 degrees C indicates that the barrier function of the alveolar epithelium is disrupted at this low temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of air embolism on sheep lung fluid volumes
Authors: Pou N. A. , Roselli R. J. , Parker R. E. , Clanton J. C.
Published: December 2017

Changes in lung fluid volumes and hyaluronan clearance were measured in six awake sheep during increased microvascular permeability induced by pulmonary air embolism (AE). After a 1- to 2-h baseline, filtered room air was infused through a proximal port of a Swan-Ganz catheter for 2 h at a rate sufficient to double pulmonary vascular resistance. The air infusion was discontinued, and the sheep were monitored for an additional 2 h (recovery). Lung lymph flow and protein flux increased during air infusion and continued to increase during recovery. During AE, lymph-to-plasma ratio for albumin decreased while lymph-to-plasma ratio for large protein remained the same. This would suggest that both microvascular pressure and microvascular permeability increase during AE. Protein clearance increased similarly for all protein sizes during AE and recovery. After 2 h of recovery, interstitial and extravascular volumes were elevated with no change in cellular volume. The volume of the interstitium available to albumin was more than twice control. The fraction of the interstitium that excludes albumin was calculated to be 0.32 +/- 0.04, with a 51% reduction in absolute excluded volume 2 h after AE. Clearance of hyaluronan by the lymphatics (normalized to baseline) increased 6- to 10-fold during and after AE. It was estimated that < 2% of the total hyaluronan in the lung would be cleared in 24 h under baseline conditions. This amount increased to approximately 11% under AE conditions and approximately 15% under recovery conditions. Changes in lung fluid volumes and protein clearance indicate increased microvascular permeability 2 h after AE.(ABSTRACT TRUNCATED AT 250 WORDS)
Laryngeal response to passively induced hypocapnia during NREM sleep in normal adult humans
Authors: Kuna S. T. , McCarthy M. P. , Smickley J. S.
Published: December 2017

Passively induced hypocapnia in animals activates vocal cord adductor muscles and decreases the glottic aperture. The purpose of this study was to determine if passively induced hypocapnia has similar effects in normal adult humans in stage 3/4 non-rapid-eye-movement (NREM) sleep. Hypocapnia was induced by hyperventilating the subjects with a positive-pressure ventilator via a nose mask. At hypocapnic levels below the CO2 apneic threshold, abrupt cessation of mechanical ventilation was followed by an apnea. In protocol 1, intramuscular electromyographic recordings of intrinsic laryngeal muscles were obtained in nine subjects. Activity of the posterior cricoarytenoid muscle, a vocal cord abductor, disappeared during passive hyperventilation. The muscle remained electrically silent during an apnea, but phasic inspiratory activity reappeared with the first respiratory effort. The thyroarytenoid and arytenoideus muscles, both vocal cord adductors, were electrically silent during spontaneous breathing in NREM sleep. Hypocapnia was frequently associated with activation of both adductor muscles. Once activated, the adductor muscles remained tonically active during an ensuring apnea. In protocol 2, a fiber-optic scope was advanced transnasally into the hypopharynx to determine glottic aperture size during passively induced hypocapnic apnea. In the seven subjects who achieved stable NREM sleep, the glottic aperture during an apnea was smaller than at any time throughout the respiratory cycle during spontaneous breathing just before positive-pressure ventilation. The results suggest that the decrease in glottic aperture observed during an induced hypocapnic apnea is due to suppression of the posterior cricoarytenoid muscle and/or activation of vocal cord adductor muscles.
Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage
Authors: West J. B. , Mathieu-Costello O. , Jones J. H. , Birks E. K. , Logemann R. B. , Pascoe J. R. , Tyler W. S.
Published: December 2017

Bleeding into the lungs in thoroughbreds is extremely common; there is evidence that it occurs in essentially all horses in training. However, the mechanism is unknown. We tested the hypothesis that exercise-induced pulmonary hemorrhage (EIPH) is caused by stress failure of pulmonary capillaries. Three thoroughbreds with known EIPH were galloped on a treadmill, and after the horses were killed with intravenous barbiturate the lungs were removed, inflated, and fixed for electron microscopy. Ultrastructural studies showed evidence of stress failure of pulmonary capillaries, including disruptions of the capillary endothelial and alveolar epithelial layers, extensive collections of red blood cells in the alveolar wall interstitium, proteinaceous fluid and red blood cells in the alveolar spaces, interstitial edema, and fluid-filled protrusions of the endothelium into the capillary lumen. The appearances were consistent with the ultrastructural changes we have previously described in rabbit lungs at high capillary transmural pressures. Actual breaks in the endothelium and epithelium were rather difficult to find, and they were frequently associated with platelets and leukocytes that appeared to be plugging the breaks. The paucity of breaks was ascribed to their reversibility when the pressure was lowered and to the fact that 60–70 min elapsed between the gallop and the beginning of lung fixation. Capillary wall stress was calculated from pulmonary vascular pressures measured in a companion study (Jones et al. FASEB J. 6: A2020, 1992) and from measurements of the thickness of the blood-gas barrier and the radius of curvature of the capillaries. The value was as high as 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2), which exceeds the breaking stress of most soft tissues. We conclude that stress failure of pulmonary capillaries is the mechanism of EIPH.
Effects of short-term and long-term androgen treatment on the diaphragm in male and female rats
Authors: Prezant D. J. , Valentine D. E. , Gentry E. I. , Richner B. , Cahill J. , Freeman K.
Published: December 2017

The effects of short-term (2.5 wk) and long-term (10 wk) testosterone propionate (2.5 mg/day; 5 days/wk) treatment on diaphragm contractility, fatigue resistance, and fiber type proportions were studied in male and female rats. Contractility and fatigue resistance indexes were measured in an in vitro diaphragm costal strip preparation by direct stimulation at 37 degrees C. The fatigue paradigm consisted of 30 trains/min at 5 Hz (50% duty cycle) for 10 min. Fatigue resistance indexes were calculated as postfatigue divided by baseline forces. In females but not males, testosterone treatment produced significant increases in body weight, costal diaphragm weight, and contractility and significant decreases in fatigue resistance indexes. The interaction between testosterone treatment and the duration of treatment was significant, with the increase in contractility (females) being significant after short-term but not long-term treatment. No significant difference in fiber type proportions or areas was observed, regardless of treatment duration or the preexperimental, basal circulating level of androgen.
Heart function after injection of small air bubbles in coronary artery of pigs
Authors: Van Blankenstein J. H. , Slager C. J. , Schuurbiers J. C. , Strikwerda S. , Verdouw P. D.
Published: December 2017

By its nature, vaporization of atherosclerotic plaques by laser irradiation or spark erosion may produce a substantial amount of gas. To evaluate the effect of gas embolism possibly caused by vaporization techniques, air bubbles with diameters of 75, 150, or 300 microns, each in a volume of 2 microliters/kg, were selectively injected subproximal in the left anterior descending coronary artery of seven anesthetized pigs (28 +/- 3 kg). Systemic hemodynamics such as heart rate, left ventricular pressure and its peak positive first derivative, and mean arterial pressure did not change after air injection, whereas there was a minor change in peak negative first derivative of left ventricular pressure. After injection of air bubbles there was a maximal relative reduction of systolic segment shortening (SS) in the myocardium supplied by the left anterior descending coronary artery of 27, 45, and 58% for 75-, 150-, and 300-microns bubbles, respectively, and a relative increase of postsystolic SS (PSS) of 148, 200, and 257% for 75-, 150-, and 300-microns bubbles, respectively. Recovery of SS and PSS started after 2 min and was completed after 10 min. A difference in SS and PSS changes between different bubble size injections could be demonstrated. From this study it is clear that depression of regional myocardial function after injection of air bubbles could pass unnoticed on the basis of global hemodynamic measurements.
In vivo antioxidant gene expression in human airway epithelium of normal individuals exposed to 100% O2
Authors: Erzurum S. C. , Danel C. , Gillissen A. , Chu C. S. , Trapnell B. C. , Crystal R. G.
Published: December 2017

Human bronchial epithelium is exquisitely sensitive to high O2 levels, with tracheobronchitis usually developing after 12 h of exposure to 100% O2. To evaluate whether this vulnerability results from inability of the bronchial epithelium to provide adequate antioxidant protection, we quantified antioxidant gene expression in bronchial epithelium of normal volunteers at baseline and after exposure to 100% O2 in vivo. After 14.8 +/- 0.2 h of 100% O2, 24 of 33 individuals had evidence of tracheobronchitis. Baseline gene expression of CuZn superoxide dismutase (SOD), MnSOD, and catalase in bronchial epithelium was very low (CuZnSOD 4.1 +/- 0.8 transcripts/cell, MnSOD 5.1 +/- 0.9, catalase 1.3 +/- 0.2), with control gamma-actin expression relatively abundant (50 +/- 6 transcripts/cell). Importantly, despite 100% O2 exposure sufficient to cause tracheobronchitis in most individuals, antioxidant mRNA transcripts/cell in bronchial epithelium did not increase (P > 0.5). Catalase activity in bronchial epithelium did not change after exposure to hyperoxia (P > 0.05). Total SOD activity increased mildly (P < 0.01) but not sufficiently to protect the epithelium. Together, the very low levels of expression of intracellular antioxidant enzymes and the inability to upregulate expression at the mRNA level with oxidant stress likely have a role in human airway epithelium susceptibility to hyperoxia.
Role of pulmonary surfactant in airway closure: a computational study
Authors: Otis D. R. , Johnson M. , Pedley T. J. , Kamm R. D.
Published: December 2017

A numerical model that simulates airway closure by liquid bridging during expiration has been developed. The effects of both surfactant and time-varying geometry have been included; the model determines the liquid layer flow resulting from a surface tension (Rayleigh) instability, and the computation traces the film's development to closure, yielding pressure, velocity, surface shape, and surfactant concentration distributions. It is found that surfactant is effective in retarding or eliminating liquid bridging through the reduction of the mean surface tension and the action of surface tension gradients. The former effect is also critical in minimizing the magnitude of the negative pressure in the liquid layer and thus presumably in reducing the tendency for airway compliant collapse.
Carbohydrate supplementation spares muscle glycogen during variable-intensity exercise
Authors: Yaspelkis B. B. , Patterson J. G. , Anderla P. A. , Ding Z. , Ivy J. L.
Published: December 2017

Effects of carbohydrate (CHO) supplementation on muscle glycogen utilization and endurance were evaluated in seven well-trained male cyclists during continuous cycling exercise that varied between low [45% maximal O2 uptake (VO2 max)] and moderate intensity (75% VO2 max). During each exercise bout the subjects received either artificially flavored placebo (P), 10% liquid CHO supplement (L; 3 x 18 g CHO/h), or solid CHO supplement (S; 2 x 25 g CHO/h). Muscle biopsies were taken from vastus lateralis during P and L trials immediately before exercise and after first (124 min) and second set (190 min) of intervals. Subjects then rode to fatigue at 80% VO2 max. Plasma glucose and insulin responses during L treatment reached levels of 6.7 +/- 0.7 mM and 70.6 +/- 17.2 microU/ml, respectively, and were significantly greater than those of P treatment (4.4 +/- 0.1 mM and 17.7 +/- 1.6 microU/ml) throughout the exercise bout. Plasma glucose and insulin responses of S treatment were intermediate to those of L and P treatments. Times to fatigue for S (223.9 +/- 3.5 min) and L (233.4 +/- 7.5 min) treatments did not differ but were significantly greater than that of P treatment (202.4 +/- 9.8 min). After the first 190 min of exercise, muscle glycogen was significantly greater during L (79 +/- 3.5 mumol/g wet wt) than during P treatment (58.5 +/- 7.2 mumol/g wet wt). Furthermore, differences in muscle glycogen concentrations between L and P treatments after 190 min of exercise and in time to fatigue for these treatments were positively related (r = 0.76, P < 0.05). These results suggest that CHO supplementation can enhance prolonged continuous variable-intensity exercise by reducing dependency on muscle glycogen as a fuel source.
Effect of fat emulsion infusion and fat feeding on muscle glycogen utilization during cycle exercise
Authors: Vukovich M. D. , Costill D. L. , Hickey M. S. , Trappe S. W. , Cole K. J. , Fink W. J.
Published: December 2017

Elevated plasma fatty acids have been shown to spare muscle glycogen during exercise. However, on the basis of recent findings, the saturation of fatty acids may influence this response. The purpose of this study was to determine whether saturated or unsaturated fatty acids affected muscle glycogenolysis to varying degrees during cycle exercise. Five healthy men completed three 60-min cycle ergometer trials (EX) at approximately 70% maximal O2 uptake (VO2max). Triglyceride levels were elevated by a fat feeding (FF) composed of 90% saturated fatty acids (heavy whipping cream, 90 g) or by the infusion of Intralipid (IL; Clintec Nutrition; 45 ml/h of 20% IL, 9.0 g), which was 85% unsaturated. A control trial (CON) consisted of a light breakfast (43 g carbohydrate and 1 g fat). Heparin (2,000 U) was administered 15 min before EX in FF and IL trials, resulting in one- and threefold increases in free fatty acid (FFA) levels in IL and FF, respectively. Pre-EX muscle glycogen did not differ. The utilization of muscle glycogen during 60 min of EX was less (P < 0.05) during the FF (60.0 +/- 5.2 mmol/kg wet wt) and IL (58.6 +/- 6.2 mmol/kg wet wt) compared with CON (81.8 +/- 7.5 mmol/kg wet wt). There was no difference between FF and IL in the amount of glycogen utilized. Serum triglyceride levels were greater (P < 0.05) at preheparin in FF (1.58 +/- 0.37 mmol/l) and IL (0.98 +/- 0.13 mmol/l) compared with CON (0.47 +/- 0.14 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
Neutral endopeptidase inhibition attenuates development of hypoxic pulmonary hypertension in rats
Authors: Klinger J. R. , Petit R. D. , Warburton R. R. , Wrenn D. S. , Arnal F. , Hill N. S.
Published: December 2017

Neutral endopeptidase (NEP) inhibition is thought to blunt hypoxic pulmonary hypertension by reducing atrial natriuretic peptide (ANP) metabolism, but this hypothesis has not been confirmed. We measured NEP activity, guanosine 3',5'-cyclic monophosphate (cGMP) production, plasma ANP levels, and cardiac ANP synthesis in rats given an orally active NEP inhibitor (SCH-34826) during 3 wk of hypoxia. Under normoxic conditions, SCH-34826 had no effect on plasma ANP levels but reduced pulmonary and renal NEP activity by 50% and increased urinary cGMP levels (60 +/- 6 vs. 22 +/- 4 pg/mg creatinine; P < 0.05). Under hypoxic conditions, SCH-34826-treated rats had lower plasma ANP levels (1,259 +/- 361 vs. 2,101 +/- 278 pg/ml; P < 0.05), lower right ventricular systolic pressure (53 +/- 5 vs. 73 +/- 2 mmHg; P < 0.05), lower right ventricle weight-to-left ventricle+septum weight ratio (0.47 +/- 0.04 vs. 0.53 +/- 0.03; P < 0.05), and less muscularization and percent medial wall thickness of peripheral pulmonary arteries (22 +/- 5 vs. 45 +/- 8% and 17 +/- 1 vs. 25 +/- 1%, respectively; P < 0.05 for all values) than did rats treated with vehicle alone. These values were not affected by SCH-34826 under normoxic conditions. SCH-34826 decreased right ventricular ANP tissue levels in hypoxic rats (27 +/- 10 vs. 8 +/- 1 ng/mg protein; P < 0.05) but did not affect steady-state ANP mRNA levels. We conclude that NEP inhibition blunts pulmonary hypertension without increasing plasma ANP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibitor sensitivity of pulmonary vascular carbonic anhydrase
Authors: Heming T. A. , Vanoye C. G. , Stabenau E. K. , Roush E. D. , Fierke C. A. , Bidani A.
Published: December 2017

The inhibitor sensitivity of pulmonary vascular carbonic anhydrase (CA) was examined in situ to identify the specific isozyme responsible for vascular activity and to study its distribution in the lung. Vascular CA activity was monitored in isolated rat lungs by measuring the rate of CO2 excretion and the magnitude of postcapillary CO2-HCO(3-)-H+ disequilibria. Lungs were perfused with isotonic salines containing gluconate, sulfate, Cl-, or I-, with or without sulfonamide derivatives. Effects of a CA inhibitor purified from porcine blood plasma were also determined. Vascular CA activity was unaffected by gluconate, sulfate, Cl-, and I- (< or = 100 mM). Sulfonamides with vastly different rates of membrane permeation (i.e., readily permeating ethoxzolamide, slowly permeating acetazolamide, and membrane-impermeant quaternary ammonium sulfanilamide) were capable of accessing all vascular CA with similar rates of access. The porcine inhibitor of CA (340 nM) produced a significant, but submaximal, inhibition of vascular CA activity. The data suggest that pulmonary vascular activity reflects a high-activity membrane-bound isozyme, CA IV, which is located on the extracellular luminal surface of capillary endothelial cells.
Expiratory airflow limitation and hyperinflation during methacholine-induced bronchoconstriction
Authors: Pellegrino R. , Violante B. , Nava S. , Rampulla C. , Brusasco V. , Rodarte J. R.
Published: December 2017

To investigate the role of airflow limitation on the increase of end-expiratory lung volume (EELV) during bronchoconstriction, nine stable asthmatic subjects and seven healthy subjects were challenged with inhaled methacholine (MCh). Changes in airway caliber were assessed by using forced expiratory volume in 1 s, partial forced expiratory flow at 50% of control forced vital capacity, and specific airway conductance. To detect airflow limitation, tidal flow-volume curves were superimposed on partial forced flow-volume curves at absolute lung volume. The electromyogram of the diaphragm was recorded by surface electrodes in four asthmatic and four healthy subjects, and the electrical diaphragmatic activity (DIA) during expiration was expressed as a percentage of the duration of expiratory time. In 10 subjects (9 asthmatic and 1 healthy) the partial forced expiratory flow recorded after some MCh dose impinged on tidal expiratory flow recorded before MCh. When this occurred it was associated with an increase in EELV by 0.54 +/- 0.07 (SE) liter (P < 0.001), which was larger than that occurring when lower MCh doses (0.11 +/- 0.04 liter, P < 0.05) were used, and with a moderate increase in DIA of 15 +/- 2.5% (P < 0.01). Six healthy subjects did not increase EELV after MCh despite a significant degree of bronchoconstriction; in these subjects tidal expiratory flow never impinged on forced expiratory flow, and DIA never increased. These results suggest that hyperinflation during MCh-induced bronchoconstriction is triggered by dynamic compression of the airways and is associated with moderate increase of DIA during expiration.
Estimating body composition of young children by using bioelectrical resistance
Authors: Goran M. I. , Kaskoun M. C. , Carpenter W. H. , Poehlman E. T. , Ravussin E. , Fontvieille A. M.
Published: December 2017

It is currently unclear whether age-specific equations should be used for assessing body composition from bioelectrical resistance. Kushner et al. (Am. J. Clin. Nutr. 56: 835#x2013;839, 1992) showed that the relationship between height2/resistance and total body water (TBW) is robust across a wide age range, although uncertainty remained over the relationship in preschool children. We therefore cross-validated the Kushner equation for predicting total body water in 4- to 6-yr-old children in two independent laboratories. TBW was measured from H2 18O dilution, and bioelectrical resistance and reactance were measured using an RJL 101A analyzer in 31 children (15 females, 16 males; 5 +/- 0.8 yr) studied in Burlington, Vermont, and 30 children (14 females, 16 males; 5 +/- 0.2 yr) studied in Phoenix, Arizona. There was no significant difference between TBW predicted from the Kushner equation and that measured in children in Burlington (11.76 +/- 2.00 vs. 11.91 +/- 2.46 kg; r = 0.94) or in Phoenix (11.53 +/- 1.64 vs. 11.66 +/- 1.90 kg; r = 0.94). The Kushner equation for TBW can be transformed into an equation for fat-free mass (FFM) by using published age- and gender-specific constants for the hydration of FFM: hydration of FFM = 76.9 - 0.25 age (yr) - 1.9 gender where female equals 0 and male equals 1. The intraclass reliability for estimates of fat mass and FFM with the use of bioelectrical resistance in an independent group of 26 children (5.0 +/- 0.8 yr, 20.2 +/- 3.0 kg) was > 0.99 for duplicate observations performed 2 wk apart.(ABSTRACT TRUNCATED AT 250 WORDS)
Superior fatigue resistance of elite black South African distance runners
Authors: Coetzer P. , Noakes T. D. , Sanders B. , Lambert M. I. , Bosch A. N. , Wiggins T. , Dennis S. C.
Published: December 2017

Black athletes currently dominate long-distance running events in South Africa. In an attempt to explain an apparently superior running ability of black South African athletes at distances > 3 km, we compared physiological measurements in the fastest 9 white and 11 black South African middle-to long-distance runners. Whereas both groups ran at a similar percentage of maximal O2 uptake (%VO2max) over 1.65#x2013;5 km, the %VO2max sustained by black athletes was greater than that of white athletes at distances > 5 km (P < 0.001). Although both groups had similar training volumes, black athletes reported that they completed more exercise at > 80% VO2max (36 +/- 18 vs. 14 +/- 7%: P < 0.005). When corrections were made for the black athletes' smaller body mass, their superior ability to sustain a high %VO2max could not be explained by any differences in VO2max, maximal ventilation, or submaximal running economy. Superior distance running performance of the black athletes was not due to a greater (+/- 50%) percentage of type I fibers but was associated with lower blood lactate concentrations during exercise. Time to fatigue during repetitive isometric muscle contractions was also longer in black runners (169 +/- 65 vs. 97 +/- 69 s; P < 0.05), but whether this observation explains the superior endurance or was due to the lower peak muscle strength (46.3 +/- 10.3 vs. 67.5 +/- 18.0 Nm/l lean thigh volume; P < 0.01) remains to be established.
Nicotine is responsible for airway irritation evoked by cigarette smoke inhalation in men
Authors: Lee L. Y. , Gerhardstein D. C. , Wang A. L. , Burki N. K.
Published: December 2017

To determine whether nicotine is involved in evoking the irritant effects of cigarette smoke in airways, we studied the responses to inhalation of a single puff (30 ml) of three types of smoke (high nicotine, low nicotine, and gas phase) in healthy male nonsmokers. After the upper airways were locally anesthetized, the subjects, breathing through a mouthpiece, were instructed to signal the detection and the intensity of airway irritation with a push-button device. Inhalation of high-nicotine smoke consistently triggered an intense airway irritation in the lower neck and upper chest region; the total number of push-button signals generated in the first 5 s was 6.61 +/- 0.87 (mean +/- SE, n = 12), with a detection latency of 0.93 +/- 0.11 s. By contrast, inhalation of low-nicotine and gas phase smoke either was not detected or caused only very mild irritation (0.89 +/- 0.4 and 0.36 +/- 0.22, respectively). In addition, the intensity of smoke-induced airway irritation was markedly reduced after premedication with aerosolized hexamethonium, a nicotinic receptor antagonist (P < 0.01, n = 8). Furthermore, inhalation of nicotine aerosol also immediately evoked intense airway irritation and coughs (n = 5). Thus we conclude that the airway irritation evoked by inhaling cigarette smoke results from an activation of sensory endings located in the central airways and nicotine is the primary agent responsible for this action.
Muscle metabolism during exercise in young and older untrained and endurance-trained men
Authors: Coggan A. R. , Abduljalil A. M. , Swanson S. C. , Earle M. S. , Farris J. W. , Mendenhall L. A. , Robitaille P. M.
Published: December 2017

To examine effects of aging and endurance training on human muscle metabolism during exercise, 31P magnetic resonance spectroscopy was used to study the metabolic response to exercise in young (21–33 yr) and older (58–68 yr) untrained and endurance-trained men (n = 6/group). Subjects performed graded plantar flexion exercise with the right leg, with metabolic responses measured using a 31P surface coil placed over the lateral head of the gastrocnemius muscle. Muscle biopsy samples were also obtained for determination of citrate synthase activity. Rate of increase in P(i)-to-phosphocreatine ratio with increasing power output was greater (P < 0.01) in older untrained [0.058 +/- 0.022 (SD) W-1] and trained men (0.042 +/- 0.010 W-1) than in young untrained (0.038 +/- 0.017 W-1) and trained men (0.024 +/- 0.010 W-1). Plantar flexor muscle cross-sectional area and volume (determined using 1H magnetic resonance imaging) were 11–12% (P < 0.05) and 16–18% (P < 0.01) smaller, respectively, in older men. When corrected for this difference in muscle mass, age-related differences in metabolic response to exercise were reduced by approximately 50% but remained significant (P < 0.05). Citrate synthase activity was approximately 20% lower (P < 0.001) in older untrained and trained men than in corresponding young groups and was inversely related to P(i)-phosphocreatine slope (r = -0.63, P < 0.001). Age-related reductions in exercise capacity were associated with an altered muscle metabolic response to exercise, which appeared to be due to smaller muscle mass and lower muscle respiratory capacity of older subjects.(ABSTRACT TRUNCATED AT 250 WORDS)