bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant transport modulates peripheral airway reactivity and inflammation during ozone exposure
Authors: Freed Arthur N. , Cueto Rafael , Pryor William A.
Published: December 2017

We examined the effects of ozone (O3) and endogenous antioxidant transport on canine peripheral airway function, central airway function, epithelial integrity, and inflammation. Dogs were either untreated or pretreated with probenecid (an anion-transport inhibitor) and exposed for 6 h to 0.2 parts/million O3. Peripheral airway resistance (Rpa) and reactivity (ΔRpa) were monitored in three sublobar locations before and after exposure to either air or O3. Pulmonary resistance and transepithelial potential difference in trachea and bronchus were also recorded. Bronchoalveolar lavage fluid (BALF) was collected before, during, and after exposure. O3increased Rpa and ΔRpa only in probenecid-treated dogs and in a location-dependent fashion. Pulmonary resistance and potential difference in bronchus increased after O3exposure regardless of treatment. O3markedly increased BALF neutrophils only in untreated dogs. With the exception of hexanal, O3did not alter any BALF constituent examined. Probenecid reduced BALF ascorbate, BALF protein, and plasma urate. We conclude that 1) a 6-h exposure to 0.2 parts/million O3represents a subthreshold stimulus in relation to its effects on peripheral airway function in dogs, 2) antioxidant transport contributes to the maintenance of normal airway tone and reactivity under conditions of oxidant stress, 3) O3-induced changes in Rpa and ΔRpa are dependent on location, and 4) peripheral airway hyperreactivity and inflammation reflect independent responses to O3exposure. Finally, although anion transport mitigates the effect of O3on peripheral airway function, it contributes to the development of airway inflammation and may represent a possible target for anti-inflammatory prevention or therapy.
Increase in epinephrine-induced responsiveness during microgravity simulated by head-down bed rest in humans
Authors: Barbe P. , Galitzky J. , Thalamas C. , Langin D. , Lafontan M. , Senard J. M. , Berlan M.
Published: December 2017

The epinephrine (Epi)-induced effects on the sympathetic nervous system (SNS) and metabolic functions were studied in men before and during a decrease in SNS activity achieved through simulated microgravity. Epi was infused at 3 graded rates (0.01, 0.02, and 0.03 μg ⋅ kg−1 ⋅ min−1for 40 min each) before and on the fifth day of head-down bed rest (HDBR). The effects of Epi on the SNS (assessed by plasma norepinephrine levels and spectral analysis of systolic blood pressure and heart rate variability), on plasma levels of glycerol, nonesterified fatty acids (NEFA), glucose and insulin, and on energy expenditure were evaluated. HDBR decreased urinary norepinephrine excretion (28.1 ± 4.2 vs. 51.5 ± 9.1 μg/24 h) and spectral variability of systolic blood pressure in the midfrequency range (16.3 ± 1.9 vs. 24.5 ± 0.9 normalized units). Epi increased norepinephrine plasma levels ( P < 0.01) and spectral variability of systolic blood pressure ( P < 0.009) during, but not before, HDBR. No modification of Epi-induced changes in heart rate and systolic and diastolic blood pressures were observed during HDBR. Epi increased plasma glucose, insulin, and NEFA levels before and during HDBR. During HDBR, the Epi-induced increase in plasma glycerol and lactate levels was more pronounced than before HDBR ( P < 0.005 and P < 0.001, respectively). Epi-induced energy expenditure was higher during HDBR ( P < 0.02). Our data suggest that the increased effects of Epi during simulated microgravity could be related to both the increased SNS response to Epi infusion and/or to the β-adrenergic receptor sensitization of end organs, particularly in adipose tissue and skeletal muscle.
Effect of locomotor respiratory coupling on respiratory evaporative heat loss in the sheep
Authors: Entin Pauline L. , Robertshaw David , Rawson Richard E.
Published: December 2017

During galloping, many animals display 1:1 coupling of breaths and strides. Locomotor respiratory coupling (LRC) may limit respiratory evaporative heat loss (REHL) by constraining respiratory frequency (f). Five sheep were exercised twice each, according to a five-step protocol: 5 min at the walk, 5 min at the trot (trot1), 10 min at the gallop, 5 min at the trot (trot2), and 5 min at the walk. Rectal temperature (Tre), stride frequency, f, REHL, and arterial CO2tension and pH were measured at each step. Tidal volume (Vt) was calculated. LRC was observed only during galloping. The coupling ratio remained at 1:1 while Vt increased continuously during galloping, causing REHL to increase from 2.9 ± 0.2 (SE) W/kg at the end of trot1 to a peak of 5.3 ± 0.3 W/kg. Trerose from 39.0 ± 0.1°C preexercise to 40.2 ± 0.2°C at the end of galloping. At the gallop-trot2 transition, Vt fell and f rose, despite a continued rise in Tre. Arterial CO2tension fell from 36.5 ± 1.1 Torr preexercise to 31.8 ± 1.4 Torr by the end of trot1 and then further to 21.5 ± 1.2 Torr by the end of galloping, resulting in alkalosis. In conclusion, LRC did not prevent increases in REHL in sheep because Vt increased. The increased Vt caused hypocapnia and presumably elevated the cost of breathing.
Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise
Authors: Dela F. , Mikines K. J. , Larsen J. J. , Galbo H.
Published: December 2017

Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle training, 30 min/day, 6 days/wk for 10 wk at ∼70% of maximal O2 uptake) and untrained (UT) legs of healthy men (H) [ n = 6, age 60 ± 2 (SE) yr] and patients with Type 2 diabetes mellitus (DM) ( n = 4, age 56 ± 3 yr) during a hyperinsulinemic (∼16,000 pmol/l), isoglycemic clamp with a final 30 min of superimposed two-legged exercise at 70% of individual maximal heart rate. With superimposed exercise, leg glucose extraction decreased ( P < 0.05), and leg blood flow and leg glucose clearance increased ( P < 0.05), compared with hyperinsulinemia alone. During exercise, leg blood flow was similar in both groups of subjects and between T and UT legs, whereas glucose extraction was always higher ( P < 0.05) in T compared with UT legs (15.8 ± 1.2 vs. 14.6 ± 1.8 and 11.9 ± 0.8 vs. 8.8 ± 1.8% for H and DM, respectively) and leg glucose clearance was higher in T (H: 73 ± 8, DM: 70 ± 10 ml ⋅ min−1 ⋅ kg leg−1) compared with UT (H: 63 ± 8, DM: 45 ± 7 ml ⋅ min−1 ⋅ kg leg−1) but not different between groups ( P > 0.05). From these results it can be concluded that, in both diabetic and healthy aged muscle, exercise adds to a maximally insulin-stimulated glucose clearance and that glucose extraction and clearance are both enhanced by training.
V˙o2kinetics of mild exercise are altered by RER
Authors: Molé Paul A. , Hoffmann James J.
Published: December 2017

We propose that variations in fat and carbohydrate (CHO) oxidation by working muscle alter O2uptake (V˙o2) kinetics. This hypothesis provides two predictions: 1) the kinetics should comprise two exponential components, one fast and the other slow, and 2) their contribution should change with variations in fat and CHO oxidation, as predicted by steady-state respiratory exchange ratio (RER). The purpose of this study was to test these predictions by evaluating theV˙o2kinetic model:V˙o2( t) = αR+ αF{1 − exp[( t − TD)/−τF]} + αC{1 − exp[( t − TD)/−τC]} for short-term, mild leg cycling in 38 women and 44 men, whereV˙o2( t) describes the time course, αRis resting V˙o2, t is time after onset of exercise, TD is time delay, αFand τFare asymptote and time constant, respectively, for the fast (fat) oxidative term, and αCand τCare the corresponding parameters for the slow (CHO) oxidative term. We found that 1) this biexponential model accurately described the V˙o2kinetics over a wide range of RERs, 2) the contribution of the fast (αF, fat) component was inversely related to RER, whereas the slow (αC, CHO) component was positively related to RER, and 3) this assignment of the fast and slow terms accurately predicted steady-state respiratory quotient and CO2output. Therefore, the kinetic model can quantify the dynamics of fat and CHO oxidation over the first 5–10 min of mild exercise in young adult men and women.
Influences of thigh cuffs on the cardiovascular system during 7-day head-down bed rest
Authors: Arbeille P. , Herault S. , Fomina G. , Roumy J. , Alferova I. , Gharib C.
Published: December 2017

Thigh cuffs, presently named “bracelets,” consist of two straps fixed to the upper part of each thigh, applying a pressure of 30 mmHg. The objective was to evaluate the cardiac, arterial, and venous changes in a group of subjects in head-down tilt (HDT) for 7 days by using thigh cuffs during the daytime, and in a control group not using cuffs. The cardiovascular parameters were measured by echography and Doppler. Seven days in HDT reduced stroke volume in both groups (−10%; P < 0.05). Lower limb vascular resistance decreased more in the cuff group than in the control group (−29 vs. −4%; P < 0.05). Cerebral resistance increased in the control group only (+6%; P < 0.05). The jugular vein increased (+45%; P < 0.05) and femoral and popliteal veins decreased in cross-sectional area in both groups (−45 and −8%, respectively; P < 0.05). Carotid diameter tended to decrease (−5%; not significant) in both groups. Heart rate, blood pressure, cardiac output, and total resistance did not change significantly. After 8 h with thigh cuffs, the cardiac and arterial parameters had recovered their pre-HDT level except for blood pressure (+6%; P < 0.05). Jugular vein size decreased from the pre-HDT level (−21%; P < 0.05), and femoral and popliteal vein size increased (+110 and +136%, respectively; P < 0.05). The thigh cuffs had no effect on the development of orthostatic intolerance during the 7 days in HDT.
Arteriolar reactivity and capillarization in chronically stimulated rat limb skeletal muscle post-MI
Authors: Thomas D. Paul , Hudlická Olga
Published: December 2017

The purpose of this study was to assess whether electrical stimulation-induced increases in muscular activity could improve capillary supply and correct previously documented abnormal vasodilator and vasoconstrictor responses of arterioles in limb skeletal muscle post-myocardial infarction (MI). Extensor digitorum longus (EDL) muscle from rats with surgically induced MI (∼30% of the left ventricle) was chronically stimulated (Stim) 8 h/day for 6 ± 1 days, at 11 wk post-MI. Third- (3A) and fourth-order (4A) arterioles in EDL from nine MI rats and four MI+Stim rats were compared with those of 11 controls (Con). Compared with Con rats, MI alone caused a reduction in the resting diameter of 3A and 4A arterioles, which was completely reversed by MI+Stim. However, Stim did not correct the attenuated vasodilator response to 10−4M adenosine seen in 4A arterioles from MI rats compared with Con. The constrictor response of both 3A and 4A vessels in MI rats to low doses of acetylcholine (10−9 M, 10−8 M) and norepinephrine (10−9 M) was accentuated in MI+Stim. The proportion of oxidative fibers in EDL was unaffected by MI or MI+Stim combination. However, Stim significantly increased ( P < 0.05) the capillary-to-fiber ratio in this muscle compared with Con. Thus, although the increase in muscle activity induced by chronic electrical stimulation normalized the reduction in resting vessel diameter seen after MI, it failed to correct the abnormalities in vasoreactivity of these same vessels.
Effect of carbohydrate or carbohydrate plus medium-chain triglyceride ingestion on cycling time trial performance
Authors: Angus Damien J. , Hargreaves Mark , Dancey Jane , Febbraio Mark A.
Published: December 2017

This study examined the effectiveness of ingesting a carbohydrate or carbohydrate + medium-chain triglycerides (MCT) on metabolism and cycling performance. Eight endurance-trained men [peak O2 uptake = 4.71 ± 0.09 (SE) l/min] completed 35 kJ/kg as quickly as possible [time trial (TT)] while consuming 250 ml/15 min of either a 6% (wt/vol) carbohydrate solution (C), a 6% carbohydrate + 4.2% MCT solution (C+M), or a sweet placebo (P). Time to complete the set amount of work was reduced in both C and C+M compared with P by 7 and 5%, respectively (C: 166 ± 7 min; C+M: 169 ± 7 min; P: 178 ± 11 min; P < 0.01). Plasma glucose concentration was maintained at or above resting values throughout both C and C+M trials but decreased ( P < 0.05) below resting values in P at the completion of the TT. The estimated rate of carbohydrate oxidation was not different during the first 90 min of exercise but thereafter was reduced ( P < 0.05) in P and was maintained in both C and C+M. These data demonstrate that carbohydrate ingestion during exercise improves 100-km TT performance compared with a sweet placebo, but the addition of MCT does not provide any further performance enhancement.
Evolution of inspiratory and expiratory muscle pressures during endurance exercise
Authors: Krishnan Bharath S. , Zintel Trevor , McParland Colm , Gallagher Charles G.
Published: December 2017

We investigated the relationship between minute ventilation (V˙e) and net respiratory muscle pressure (Pmus) throughout the breathing cycle [Total Pmus = mean Pmus, i (inspiratory) + mean Pmus, e(expiratory)] in six normal subjects performing constant-work heavy exercise (CWHE, at ∼80% maximum) to exhaustion on a cycle ergometer. Pmus was calculated as the sum of chest wall pressure (elastic + resistive) and pleural pressure, and all mean Pmus variables were averaged over the total breath duration. Pmus, i was also expressed as a fraction of volume-matched, flow-corrected dynamic capacity of the inspiratory muscles ([Formula: see text]).V˙e increased significantly from 3 min to the end of CWHE and was the result of a significantly linear increase in Total Pmus (Δ = 43 ± 9% from 3 min to end exercise, P < 0.005) in all subjects ( r = 0.81–0.99). Although mean Pmus, i during inspiratory flow increased significantly (Δ = 35 ± 10%), postinspiratory Pmus, i fell (Δ = −54 ± 10%) and postexpiratory expiratory activity was negligible or absent throughout CWHE. There was a greater increase in mean Pmus, e (Δ = 168 ± 48%), which served to increaseV˙e throughout CWHE. In five of six subjects, there were significant linear relationships betweenV˙eand mean Pmus, i( r = 0.50–0.97) and mean Pmus, e( r = 0.82–0.93) during CWHE. The subjects generated a wide range of Pmus, i/[Formula: see text]values (25–80%), and mean Pmus, i/[Formula: see text]increased significantly (Δ = 42 ± 16%) and in a linear fashion ( r = 0.69–0.99) withV˙ethroughout CWHE. The progressive increase inV˙e during CWHE is due to 1) a linear increase in Total Pmus, 2) a linear increase in inspiratory muscle load, and 3) a progressive fall in postinspiratory inspiratory activity. We conclude that the relationship between respiratory muscle pressure andV˙e during exercise is linear and not curvilinear.
CO2 homeostasis during periodic breathing in obstructive sleep apnea
Authors: Berger Kenneth I. , Ayappa Indu , Sorkin I. Barry , Norman Robert G. , Rapoport David M. , Goldring Roberta M.
Published: December 2017

The contribution of apnea to chronic hypercapnia in obstructive sleep apnea (OSA) has not been clarified. Using a model (D. M. Rapoport, R. G. Norman, and R. M. Goldring. J. Appl. Physiol. 75: 2302–2309, 1993), we previously illustrated failure of CO2 homeostasis during periodic breathing resulting from temporal dissociation between ventilation and perfusion (“temporal V˙/Q˙mismatch”). This study measures acute kinetics of CO2 during periodic breathing and addresses interapnea ventilatory compensation for maintenance of CO2 homeostasis in 11 patients with OSA during daytime sleep (37–171 min). Ventilation and expiratory CO2 and O2 fractions were measured on a breath-by-breath basis by means of a tight-fitting full facemask. Calculations included CO2excretion, metabolic CO2production, and CO2 balance (metabolic CO2 production − exhaled CO2). CO2 balance was tabulated for each apnea/hypopnea event-interevent cycle and as a cumulative value during sleep. Cumulative CO2 balance varied (−3,570 to +1,388 ml). Positive cumulative CO2 balance occurred in the absence of overall hypoventilation during sleep. For each cycle, positive CO2 balance occurred despite increased interevent ventilation to rates as high as 45 l/min. This failure of CO2 homeostasis was dependent on the event-to-interevent duration ratio. The results demonstrate that 1) periodic breathing provides a mechanism for acute hypercapnia in OSA, 2) acute hypercapnia during periodic breathing may occur without a decrease in average minute ventilation, supporting the presence of temporalV˙/Q˙ mismatch, as predicted from our model, and 3) compensation for CO2 accumulation during apnea/hypopnea may be limited by the duration of the interevent interval. The relationship of this acute hypercapnia to sustained chronic hypercapnia in OSA remains to be further explored.
Food restriction suppresses muscle growth and augments osteopenia in ovariectomized rats
Authors: Fisher Jonathan S. , Kohrt Wendy M. , Brown Marybeth
Published: December 2017

We examined effects of 4 wk of food restriction on ovariectomy-related changes in muscle, bone, and plasma insulin-like growth factor I (IGF-I). Female Sprague-Dawley rats (7 mo old) were assigned to freely eating groups: sham-operated (Sham), ovariectomized (Ovx-AL), and estrogen (estradiol)-replaced Ovx (Ovx+E2). Ovx rats were also pair fed with Sham (Ovx-PF) or weight matched with Sham by food restriction (Ovx-FR). Ovx-AL and Ovx-PF rats had similar estrogen status and body weight; therefore, the groups were combined (group: Ovx). After treatment, body weight was ∼10% greater in Ovx than in Sham rats ( P < 0.05), and muscle weight-to-body weight ratios were comparable among all groups. Bone mineral contents of whole tibiae in Ovx-FR and Ovx were ∼15% ( P < 0.05) and ∼6% lower than in Sham rats ( P < 0.05), respectively. Plasma IGF-I was ∼30% higher in Ovx than in Sham ( P < 0.05) but was similar between Sham and Ovx-FR. IGF-I was highly correlated with body weight and muscle mass. Within non-estrogen-replaced Ovx rats, IGF-I explained ∼19% of variance in bone mineral content after accounting for variance attributable to body weight. Findings suggest that estrogen acts indirectly on skeletal muscle and bone in rats through regulation of body growth by factors such as IGF-I.
A modular NIRS system for clinical measurement of impaired skeletal muscle oxygenation
Authors: Wariar Ramesh , Gaffke John N. , Haller Ronald G. , Bertocci Loren A.
Published: December 2017

Near-infrared spectrometry (NIRS) is a well-known method used to measure in vivo tissue oxygenation and hemodynamics. This method is used to derive relative measures of hemoglobin (Hb) + myoglobin (Mb) oxygenation and total Hb (tHb) accumulation from measurements of optical attenuation at discrete wavelengths. We present the design and validation of a new NIRS oxygenation analyzer for the measurement of muscle oxygenation kinetics. This design optimizes optical sensitivity and detector wavelength flexibility while minimizing component and construction costs. Using in vitro validations, we demonstrate 1) general optical linearity, 2) system stability, and 3) measurement accuracy for isolated Hb. Using in vivo validations, we demonstrate 1) expected oxygenation changes during ischemia and reactive hyperemia, 2) expected oxygenation changes during muscle exercise, 3) a close correlation between changes in oxyhemoglobin and oxymyoglobin and changes in deoxyhemoglobin and deoxymyoglobin and limb volume by venous occlusion plethysmography, and 4) a minimal contribution from movement artifact on the detected signals. We also demonstrate the ability of this system to detect abnormal patterns of tissue oxygenation in a well-characterized patient with a deficiency of skeletal muscle coenzyme Q10. We conclude that this is a valid system design for the precise, accurate, and sensitive detection of changes in bulk skeletal muscle oxygenation, can be constructed economically, and can be used diagnostically in patients with disorders of skeletal muscle energy metabolism.
Effects of high-frequency initial pulses and posttetanic potentiation on power output of skeletal muscle
Authors: Abbate F. , Sargeant A. J. , Verdijk P. W. L. , de Haan A.
Published: December 2017

The effects of high-frequency initial pulses (HFIP) and posttetanic potentiation on mechanical power output during concentric contractions were examined in the in situ medial gastrocnemius of the rat with an intact origin on the femur and blood supply. Stimulation of the muscle was performed via the severed sciatic nerve. In the experiments, HFIP or the potentiating tetanus was followed by a stimulation of 80, 120, or 200 Hz. The results showed that both HFIP and the tetanus increased power output at high contraction velocities (>75 mm/s) when followed by a train of 80 or 120 Hz (200 Hz resulted in no effects). Mechanical power output was increased maximally by HFIP to 120 and 168% by the tetanus. Furthermore, when HFIP or the tetanus were followed by a train of 80 Hz, the peak power in the power-velocity curve tended to be shifted to a higher velocity.
Effects of an androgenic steroid on exercise-induced cardiac remodeling in rats
Authors: Woodiwiss A. J. , Trifunovic B. , Philippides M. , Norton G. R.
Published: December 2017

Habitual exercise results in a rightward shift in left ventricular end diastolic (LVED) pressure-volume or internal dimension (P-D) relationships [left ventricular (LV) remodeling]. However, exercise-mediated LV hypertrophy (LVH) produces an increased LV relative wall thickness [ratio ( h/ r) of wall thickness ( h) to internal radius ( r)] and hence a decrement in diastolic wall stress despite LV remodeling. In this study, the effect of chronic administration of an androgenic steroid on exercise-induced LV remodeling and h/ r was examined in rats. Habitual exercise on voluntary running wheels resulted in LVH and a rightward shift in the LVED P-D relationships. However, LVH was sufficient to increase LVED h/r. Androgenic steroid administration to exercised rats, without influencing the development of exercise-induced LVH, produced a further rightward shift in the LVED P-D relationship associated with an increased diameter intercept. As a consequence, LVED h/r was reduced to control values. The steroid-mediated effects were not associated with alterations in either the quantity or quality of LV collagen. In conclusion, high-dose androgenic steroid administration alters exercise-induced LV remodeling and subsequently reduces the beneficial effect of physiological LVH on LV h/ r.
Effect of muscle mass and intensity of isometric contraction on heart rate
Authors: Gálvez José M. , Alonso Juan P. , Sangrador Luis A. , Navarro Gonzalo
Published: December 2017

The purpose of this study was to determine the effect of muscle mass and the level of force on the contraction-induced rise in heart rate. We conducted an experimental study in a sample of 28 healthy men between 20 and 30 yr of age (power: 95%, α: 5%). Smokers, obese subjects, and those who performed regular physical activity over a certain amount of energetic expenditure were excluded from the study. The participants exerted two types of isometric contractions: handgrip and turning a 40-cm-diameter wheel. Both were sustained to exhaustion at 20 and 50% of maximal force. Twenty-five subjects finished the experiment. Heart rate increased a mean of 15.1 beats/min [95% confidence interval (CI): 5.5–24.6] from 20 to 50% handgrip contractions, and 20.7 beats/min (95% CI: 11.9–29.5) from 20 to 50% wheel-turn contractions. Heart rate also increased a mean of 13.3 beats/min (95% CI: 10.4–16.1) from handgrip to wheel-turn contractions at 20% maximal force, and 18.9 beats/min (95% CI: 9.8–28.0) from handgrip to wheel-turn contractions at 50% maximal force. We conclude that the magnitude of the heart rate increase during isometric exercise is related to the intensity of the contraction and the mass of the contracted muscle.
Exercise exacerbates acute mountain sickness at simulated high altitude
Authors: Roach R. C. , Maes D. , Sandoval D. , Robergs R. A. , Icenogle M. , Hinghofer-Szalkay H. , Lium D. , Loeppky J. A.
Published: December 2017

.—We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure = 429 Torr, ∼4,800 m (J. B. West, J. Appl. Physiol. 81: 1850–1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (V˙e), pulmonary function, arterial oxygen saturation ([Formula: see text]), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 ± 1.0 and 1.3 ± 0.4 in Ex and Sed, respectively ( P < 0.01); but restingV˙e and[Formula: see text] were not different between trials. However, [Formula: see text] during the exercise bouts in Ex was at 76.3 ± 1.7%, lower than during either Sed or at rest in Ex (81.4 ± 1.8 and 82.2 ± 2.6%, respectively, P< 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3–6 h ( P = 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors.
Ca2+-dependent K+channels and Na+-K+-ATPase mediate H2O2- and superoxide-induced relaxations in canine trachealis
Authors: Janssen Luke J. , Netherton Stuart J. , Walters Denise K.
Published: December 2017

We examined the ionic mechanisms underlying the responses of canine trachealis to superoxide (generated in vitro by using xanthine oxidase or added exogenously) and peroxide (generated spontaneously in vitro by the dismutation of superoxide or added exogenously). Although neither had any effect on resting tone, both triggered relaxations in carbachol-precontracted tissues. These relaxations were eliminated by catalase but were much less sensitive to the hydroxyl radical scavenger dimethylthiourea, indicating they were mediated primarily by peroxide. These relaxations were decreased in magnitude and/or slowed by nifedipine (10−6M), ouabain (10−6M), or tetraethylammonium (25 mM), but not by 4-aminopyridine (5 mM), and were small or absent in tissues precontracted with 30 mM KCl. Finally, peroxide triggered membrane hyperpolarization and elevated cytosolic concentration of Ca2+(primarily via release from the internal store). Thus peroxide-mediated relaxations seem to involve Ca2+release, opening of Ca2+-dependent K+channels, hyperpolarization, closure of Ca2+channels, and relaxation. In addition, some other free radical (hydroxyl radical?) may activate the Na+-K+pump, also hyperpolarizing the membrane and causing relaxation.
Integrated response of the upper and lower respiratory tract of asthmatic subjects to frigid air
Authors: McLane Melissa L. , Nelson Jo Ann , Lenner K. A. , Hejal Rana , Kotaru Chakradhar , Skowronski Mary , Coreno Albert , Lane Elizabeth , McFadden E. R.
Published: December 2017

To evaluate the influence of cold air hyperpnea on integrated upper and lower airway behavior, 22 asthmatic volunteers hyperventilated through their mouths (OHV) and noses (NHV) while pulmonary and nasal function were determined individually and in combination. In the isolated studies, OHV at a minute ventilation of 65 ± 3 l/min lowered the 1-s forced expiratory volume (FEV1) 24 ± 2% ( P < 0.001) and NHV (40 l/min) induced a 31 ± 9% ( P < 0.001) increase in nasal resistance (NR). In the combined studies, oral hyperpnea reduced the FEV1(ΔFEV1 26 ± 2%, P < 0.001) and evoked a significant rise in NR (ΔNR 26 ± 9%, P = 0.01). In contrast, NHV only affected the upper airway. NR rose 33 ± 9% ( P = 0.01), but airway caliber did not change (ΔFEV1 2%, P = 0.27). The results of this investigation demonstrate that increasing the transfer of heat and water in the lower respiratory tract alters bronchial and nasal function in a linked fashion. Forcing the nose to augment its heat-exchanging activity, however, reduces nasal caliber but has no effect on the intrathoracic airways.
Blunted pressor and intramuscular metabolic responses to voluntary isometric exercise in multiple sclerosis
Authors: Ng A. V. , Dao H. T. , Miller R. G. , Gelinas D. F. , Kent-Braun J. A.
Published: December 2017

To test the hypothesis that a lower mean arterial pressure (MAP) response during voluntary isometric exercise in multiple sclerosis (MS) is related to a dampened muscle metabolic signal, 9 MS and 11 control subjects performed an isometric dorsiflexor contraction at 30% maximal voluntary contraction until target failure (endurance time). We made continuous and noninvasive measurements of heart rate and MAP (Finapres) and of intramuscular pH and Pi (phosphorus magnetic resonance spectroscopy) in a subset of 6 MS and 10 control subjects. Endurance times and change in heart rate were similar in MS and control subjects. The decrease in pH and increase in Pi were less throughout exercise in MS compared with control subjects, as was the change in MAP response. Differences in muscle strength accounted for some of the difference in MAP response between groups. Cardiovascular responses during Valsalva and cold pressor tests were similar in MS and control subjects, suggesting that the blunted MAP response during exercise in MS was not due to a generalized dysautonomia. The dampened metabolic response in MS subjects was not explained by inadequate central muscle activation. These data suggest that the blunted pressor response to exercise in MS subjects may be largely appropriate to a blunted muscle metabolic response and differences in contracting muscle mass.
Analysis of the mechanisms of expiratory asynchrony in pressure support ventilation: a mathematical approach
Authors: Yamada Yoshitsugu , Du Hong-Lin
Published: December 2017

A mathematical model was developed to analyze the mechanisms of expiratory asynchrony during pressure support ventilation (PSV). Solving the model revealed several results. 1) Ratio of the flow at the end of patient neural inspiration to peak inspiratory flow (V˙ti/V˙peak) during PSV is determined by the ratio of time constant of the respiratory system (τ) to patient neural inspiratory time (Ti) and the ratio of the set pressure support (Pps) level to maximal inspiratory muscle pressure (Pmus max). 2)V˙ti/V˙peakis affected more by τ/Ti than by Pps/Pmus max.V˙ti/V˙peakincreases in a sigmoidal relationship to τ/Ti. An increase in Pps/Pmus max slightly shifts theV˙ti/V˙peak-τ/Ticurve to the right, i.e.,V˙ti/V˙peakbecomes lower as Pps/Pmus max increases at the same τ/Ti. 3) Under the selected adult respiratory mechanics,V˙ti/V˙peakranges from 1 to 85% and has an excellent linear correlation with τ/Ti. 4) In mechanical ventilators, single fixed levels of the flow termination criterion will always have chances of both synchronized termination and asynchronized termination, depending on patient mechanics. An increase in τ/Ti causes more delayed and less premature termination opportunities. An increase in Pps/Pmus max narrows the synchronized zone, making inspiratory termination predisposed to be in asynchrony. Increasing the expiratory trigger sensitivity of a ventilator shifts the synchronized zone to the right, causing less delayed and more premature termination. Automation of expiratory trigger sensitivity in future mechanical ventilators may also be possible. In conclusion, our model provides a useful tool to analyze the mechanisms of expiratory asynchrony in PSV.
Phrenic motoneuron morphology during rapid diaphragm muscle growth
Authors: Prakash Y. S. , Mantilla Carlos B. , Zhan Wen-Zhi , Smithson Kenneth G. , Sieck Gary C.
Published: December 2017

In the adult rat, there is a general correspondence between the sizes of motoneurons, motor units, and muscle fibers that has particular functional importance in motor control. During early postnatal development, after the establishment of singular innervation, there is rapid growth of diaphragm muscle (Diam) fibers. In the present study, the association between Diamfiber growth and changes in phrenic motoneuron size (both somal and dendritic) was evaluated from postnatal day 21 (D21) to adulthood. Phrenic motoneurons were retrogradely labeled with fluorescent tetramethylrhodamine dextran (3,000 MW), and motoneuron somal volumes and surface areas were measured using three-dimensional confocal microscopy. In separate animals, phrenic motoneurons retrogradely labeled with choleratoxin B-fragment were visualized using immunocytochemistry, and dendritic arborization was analyzed by camera lucida. Between D21 and adulthood, Diam fiber cross-sectional area increased by ∼164% overall, with the growth of type II fibers being disproportionate to that of type I fibers. There was also substantial growth of phrenic motoneurons (∼360% increase in total surface area), during this same period, that was primarily attributable to an expansion of dendritic surface area. Comparison of the distribution of phrenic motoneuron surface areas between D21 and adults suggests the establishment of a bimodal distribution that may have functional significance for motor unit recruitment in the adult rat.
Role of endogenous nitric oxide in hyperoxia-induced airway hyperreactivity in maturing rats
Authors: Iben Sabine C. , Dreshaj Ismail A. , Farver Carol F. , Haxhiu Musa A. , Martin Richard J.
Published: December 2017

We sought to define the effects of maturation and hyperoxic stress on nitric oxide (NO)-induced modulation of bronchopulmonary responses to stimulation of vagal preganglionic nerve fibers. Experiments were performed on decerebrate, paralyzed, and ventilated rat pups at 6–7 days ( n = 21) and 13–15 days of age ( n= 23) breathing room air and on rat pups 13–15 days of age ( n = 19) after exposure to hyperoxia (≥95% inspired O2 fraction for 4–6 days). Total lung resistance (Rl) and lung elastance (El) were measured by body plethysmograph. Vagal stimulation and release of acetylcholine caused a frequency-dependent increase in Rl and El in all animals. The Rl response was significantly potentiated in normoxic animals by prior blockade of nitric oxide synthase (NOS) ( P < 0.05). Hyperoxic exposure increased responses of Rl to vagal stimulation ( P < 0.05); however, after hyperoxic exposure, the potentiation of contractile responses by NOS blockade was abolished. The response of El was potentiated by NOS blockade in the 13- to 15-day-old animals after both normoxic and hyperoxic exposure ( P < 0.01). Morphometry revealed no effect of hyperoxic exposure on airway smooth muscle thickness. We conclude that NO released by stimulation of vagal preganglionic fibers modulates bronchopulmonary contractile responses to endogenously released acetylcholine in rat pups. Loss of this modulatory effect of NO could contribute to airway hyperreactivity after prolonged hyperoxic exposure, as may occur in bronchopulmonary dysplasia.
Effects of prior heavy exercise on phase II pulmonary oxygen uptake kinetics during heavy exercise
Authors: Burnley Mark , Jones Andrew M. , Carter Helen , Doust Jonathan H.
Published: December 2017

We tested the hypothesis that heavy-exercise phase II oxygen uptake (V˙o 2) kinetics could be speeded by prior heavy exercise. Ten subjects performed four protocols involving 6-min exercise bouts on a cycle ergometer separated by 6 min of recovery: 1) moderate followed by moderate exercise; 2) moderate followed by heavy exercise; 3) heavy followed by moderate exercise; and 4) heavy followed by heavy exercise. The V˙o 2 responses were modeled using two (moderate exercise) or three (heavy exercise) independent exponential terms. Neither moderate- nor heavy-intensity exercise had an effect on the V˙o 2 kinetic response to subsequent moderate exercise. Although heavy-intensity exercise significantly reduced the mean response time in the second heavy exercise bout (from 65.2 ± 4.1 to 47.0 ± 3.1 s; P < 0.05), it had no significant effect on either the amplitude or the time constant (from 23.9 ± 1.9 to 25.3 ± 2.9 s) of theV˙o 2 response in phase II. Instead, this “speeding” was due to a significant reduction in the amplitude of the V˙o 2 slow component. These results suggest phase II V˙o 2 kinetics are not speeded by prior heavy exercise.
Wave-intensity analysis: a new approach to coronary hemodynamics
Authors: Sun Yi-Hui , Anderson Todd J. , Parker Kim H. , Tyberg John V.
Published: December 2017

In 10 anesthetized dogs, we measured high-fidelity left circumflex coronary (PLCx), aortic (PAo), and left ventricular (PLV) pressures and left circumflex velocity ( U LCx; Doppler) and used wave-intensity analysis (WIA) to identify the determinants of PLCx and U LCx. Dogs were paced from the right atrium ( control 1) or right ventricle by use of single ( control 2) and then paired pacing to evaluate the effects of left ventricular contraction on PLCx and U LCx. During left ventricular isovolumic contraction, PLCx exceeded PAo, paired pacing increasing the difference. Paired pacing increased ΔPX(the PLCx-PAo difference at the PAo-PLV crossover) and average dPLCx/d t ( P < 0.0001 for both). During this time, WIA identified a backward-going compression wave (BCW) that increased PLCx and decreased U LCx; the BCW increased during paired pacing ( P < 0.0001). After the aortic valve opened, the increase in PAo caused a forward-going compression wave that, when it exceeded the BCW, caused U LCx to increase, despite PLV and (presumably) elastance continuing to increase. Thus WIA identifies the contributions of upstream (aortic) and downstream (microcirculatory) effects on PLCx and U LCx.
Adaptation of respiratory muscle perfusion during exercise to chronically elevated ventilatory work
Authors: Hsia Connie C. W. , Takeda Shin-Ichi , Wu Eugene Y. , Glenny Robb W. , Johnson Robert L.
Published: December 2017

Pneumonectomy (PNX) leads to chronic asymmetric ventilatory loading of respiratory muscles (RM). We measured RM energy requirements during exercise from RM blood flow (Q˙) using a fluorescent microsphere technique in dogs that had undergone right PNX as adults (adult R-PNX) or as puppies (puppy R-PNX), compared with dogs subjected to right thoracotomy without PNX as puppies (Sham) and to left PNX as adults (adult L-PNX). Ventilatory work (W˙) was measured during exercise. RM weight was determined post mortem. After adult and puppy R-PNX, the right hemidiaphragm becomes grossly distorted, but W˙ and right costal muscle mass increased only after adult R-PNX. After adult L-PNX, the diaphragm was undistorted; W˙ and left hemidiaphragm RM Q˙ were elevated, but muscle mass did not increase. Mass of parasternal muscle did not increase after adult R-PNX, despite increased Q˙. Thus muscle mass increased only in response to the combination of chronic stretch and dynamic loading. There was a dorsal-to-ventral gradient of increasing Q˙ within the diaphragm, but the distribution was unaffected by anatomic distortion, hypertrophy, or workload, suggesting a fixed pattern of neural activation. The diaphragm and parasternals were the primary muscles compensating for the asymmetric loading from PNX.
Effects of cutaneous receptor stimulation on muscular atrophy developed in hindlimb unloading condition
Authors: De-Doncker Laurent , Picquet Florence , Falempin Maurice
Published: December 2017

The aim of this study was to investigate whether stimulation of the cutaneous mechanoreceptors of the rat foot sole could partially or totally prevent the soleus muscle atrophy developed after 14 days in hindlimb unloading conditions. Final experiments were achieved under deep anesthesia using pentobarbital sodium (60 mg/kg, ip injection). Atrophy was characterized by a significant decrease in muscle wet weight, fiber size, maximal twitch and tetanic tensions, contraction kinetics, and histochemical and electrophoretical changes. Our data demonstrate that the stimulation of these mechanoreceptors partially prevents the decrease in muscle weight (53%) and cross-sectional area of the soleus muscle (36%) and in all fiber types (type I: 31%; type Ic: 40%; type IIc: 49%; and type IIa: 44%) and also prevented the reductions in strength (peak twitch tension: 31%; peak tetanic tension: 25%). However, the decrease in contraction kinetics was not counteracted. Moreover, histochemical and electrophoretical changes were partially slowed. Thus our results suggest that stimulation of the sole mechanoreceptors can be used, in part, as a countermeasure to the muscular atrophy observed after a period of hindlimb unloading.
Compliance of peripheral airways deduced from morphometry
Authors: Okazawa Mitsushi , Paré Peter D. , Lambert Rodney K.
Published: December 2017

Insights into airway mechanics were sought by applying morphometric techniques to rabbit lungs fixed at several lung recoil pressures. Rabbits were treated with either nebulized carbachol followed by iv administration of carbachol or with saline solution (sham). The lungs were held at one of six values of positive end-expiratory pressure (PEEP; 10, 7, 4, 2, 0, and −4 cmH2O) while the animal was killed and formalin was circulated through the lungs. The lungs were removed and left in a bath of formalin for 24 h. Standard airway morphometric measurements were made on membranous bronchiole slices taken from representative blocks of tissue. Reductions in PEEP produced the expected reductions in lumen area in the carbachol-treated airways but not in the sham-treated airways for PEEP > 2 cmH2O. Sham-treated airways remained more open than expected until they collapsed into an oval shape at PEEPs between 4 and 2 cmH2O. The carbachol-treated airways exhibited this behavior at PEEP = −4 cmH2O. The smallest airways, which had relatively thicker walls, collapsed less than larger airways. We postulate that this behavior implies that peribronchial stress is greater than lumen pressure on collapse into the oval shape. Resistance to buckling increases with the thickness-to-radius ratio of the airway wall, which explains why the smallest airways are the most open. The development of epithelial folds appeared to follow the theoretical prediction of a previous study (Lambert RK, Codd SL, Alley MR, and Pack RJ. J Appl Physiol 77: 1206–1216, 1994).
Metabolic effects of physical training in ovariectomized and hyperestrogenic rats
Authors: Latour Martin G. , Shinoda Motoo , Lavoie Jean-Marc
Published: December 2017

This study was undertaken to evaluate the effects of regular endurance-type exercise on glucose tolerance and glucose-stimulated insulin response (GSIR) in ovariectomized (OVX) rats with and without estrogen replacement. To do that, OVX Sprague-Dawley rats were compared with an OVX estradiol-treated group (OVXE2) and a sham-operated (Sham) group. Each of these groups was subdivided into a sedentary and a treadmill-trained (8 wk) group. Intravenous glucose tolerance tests (0.5 g/kg) were conducted in all rats 48 h after the last training session. Plasma levels of 17β-estradiol and the uterus weight were significantly ( P < 0.05) lower in OVX compared with results in Sham and significantly ( P< 0.01) higher in OVXE2 (hyperestrogenic) compared with results in Sham. Body weights were significantly ( P < 0.01) different among groups, in the following decreasing order: OVX, Sham, and OVXE2. The average daily food intake was significantly ( P < 0.01) increased in OVX rats compared with Sham, whereas estradiol treatment diminished this effect ( P< 0.01). Exercise training was found to alter none of the above-mentioned variables in all three experimental conditions. Although the mean integrated area under the glucose and insulin curves was not affected by OVX, training induced a significant ( P < 0.01) reduction in the mean integrated area under the insulin curve in all three experimental conditions. It is concluded that the positive effects of physical training on improving GSIR in OVX and hyperestrogenic animals are similar to what has been found in Sham.
A new method to measure nitrate/nitrite with a NO-sensitive electrode
Authors: Berkels Reinhard , Purol-Schnabel Svenja , Roesen Renate
Published: December 2017

There are different methods to measure the unstable molecule nitric oxide (NO). We will describe a new sensitive method to measure NO by reconversion of nitrate/nitrite to NO, which will be determined with an amperometric Clark-type electrode. Nitrate and nitrite are the degradation products of NO. First, nitrate is enzymatically converted to nitrite with the use of the nitrate reductase. Second, nitrite is reduced to equimolar NO concentrations by an acidic iodide solution. The detection limit of the electrode in an aqueous solution was 2 nmol/l NO (meaning the threshold was depending on the volume added: 500 μl of a 0.2 μmol/l nitrite solution added to a 10-ml bath). This method provides the ability to assess basal and agonist-stimulated NO releases of different biological models. We measured basal and carbachol-stimulated NO release of native endothelial cells from porcine coronary arteries and porcine aortic endothelial cell cultures. Moreover, it was possible to measure the nitrate/nitrite concentration in the coronary effluent of a guinea pig heart. In conclusion, we present a valid, highly sensitive new method of measuring nitrite/NO in biological systems with a commercially available electrode.
Selected Contribution: Effect of the aldehyde acrolein on acetylcholine-induced membrane current in airway smooth muscle cells
Authors: Hyvelin Jean-Marc , Savineau Jean-Pierre , Marthan Roger
Published: December 2017

Acrolein administered to isolated airways has been shown to alter airway responsiveness as a consequence of its effect on Ca2+ signaling. To examine the mechanisms involved, we studied the effect of acrolein on ACh- and caffeine-induced membrane currents (patch-clamp) in myocytes freshly isolated from rat trachea. In cells clamped at −60 mV, ACh (0.1–10 μM) induced a concentration-dependent inward current, which, in ∼50% of the cells, was followed by current oscillations in response to high concentration of ACh (10 μM). Exposure to acrolein (0.2 μM) for 10 min significantly enhanced the amplitude of the low-ACh (0.1 μM) concentration-induced initial peak of current (318.8 ± 28.3 vs. 251.2 ± 40.3 pA; n = 25, P < 0.05). At a high-ACh concentration (10 μM), the frequency at which subsequent peaks occurred was significantly increased (13.2 ± 1.1 vs. 8.7 ± 2 min−1; n = 20, P < 0.05). ACh-induced current was identified as a Ca2+-activated Cl− current. In contrast, similar exposure to acrolein, which does not alter caffeine-induced Ca2+ release, did not alter caffeine-induced transient membrane currents (595 ± 45 and 640 ± 45 pA in control cells and in cells exposed to acrolein, respectively; n = 15). It is concluded that acrolein alters ACh-induced current as a consequence of its effect on the cytosolic Ca2+ concentration response and that the protective role of inhibitors of Cl− channels in air pollutant-induced airway hyperresponsiveness should be examined.