bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of convective O2 delivery in determiningV˙o 2 on-kinetics in canine muscle contracting at peak V˙o 2
Authors: Grassi Bruno , Hogan Michael C. , Kelley Kevin M. , Aschenbach William G. , Hamann Jason J. , Evans Ronald K. , Patillo Robin E. , Gladden L. Bruce
Published: December 2017

A previous study (Grassi B, Gladden LB, Samaja M, Stary CM, and Hogan MC, J Appl Physiol 85: 1394–1403, 1998) showed that convective O2 delivery to muscle did not limit O2 uptake (V˙o 2) on-kinetics during transitions from rest to contractions at ∼60% of peakV˙o 2. The present study aimed to determine whether this finding is also true for transitions involving contractions of higher metabolic intensities.V˙o 2 on-kinetics were determined in isolated canine gastrocnemius muscles in situ ( n = 5) during transitions from rest to 4 min of electrically stimulated isometric tetanic contractions corresponding to the muscle peakV˙o 2. Two conditions were compared: 1) spontaneous adjustment of muscle blood flow (Q˙) (Control) and 2) pump-perfused Q˙, adjusted ∼15–30 s before contractions at a constant level corresponding to the steady-state value during contractions in Control (Fast O2 Delivery). In Fast O2 Delivery, adenosine was infused intra-arterially. Q˙ was measured continuously in the popliteal vein; arterial and popliteal venous O2 contents were measured at rest and at 5- to 7-s intervals during the transition. Muscle V˙o 2 was determined as Q˙times the arteriovenous blood O2 content difference. The time to reach 63% of the V˙o 2 difference between resting baseline and steady-state values during contractions was 24.9 ± 1.6 (SE) s in Control and 18.5 ± 1.8 s in Fast O2 Delivery ( P < 0.05). FasterV˙o 2 on-kinetics in Fast O2Delivery was associated with an ∼30% reduction in the calculated O2 deficit and with less muscle fatigue. During transitions involving contractions at peak V˙o 2, convective O2 delivery to muscle, together with an inertia of oxidative metabolism, contributes in determining theV˙o 2 on-kinetics.
Hindlimb unweighting alters endothelium-dependent vasodilation and ecNOS expression in soleus arterioles
Authors: Schrage William G. , Woodman Christopher R. , Laughlin M. Harold
Published: December 2017

The purpose of this study was to test the hypothesis that endothelium-dependent dilation is impaired in soleus resistance arteries from hindlimb-unweighted (HLU) rats. Male Sprague-Dawley rats (300–350 g) were exposed to HLU ( n = 14) or weight-bearing control (Con, n = 14) conditions for 14 days. After the 14-day treatment period, soleus first-order (1A) arterioles were isolated and cannulated with micropipettes to assess vasodilator responses to an endothelium-dependent dilator, ACh (10−9–10−4 M), and an endothelium-independent dilator, sodium nitroprusside (SNP, 10−9–10−4 M). Arterioles from HLU rats were smaller than Con arterioles (maximal passive diameter = 140 ± 4 and 121 ± 4 μm in Con and HLU, respectively) but developed similar spontaneous myogenic tone (43 ± 3 and 45 ± 3% in Con and HLU, respectively). Arteries from Con and HLU rats dilated in response to increasing doses of ACh, but dilation was impaired in arterioles from HLU rats ( P = 0.03), as was maximal dilation to ACh (85 ± 4 and 65 ± 4% possible dilation in Con and HLU, respectively). Inhibition of nitric oxide (NO) synthase (NOS) with N ω-nitro-l-arginine (300 μM) reduced ACh dilation by ∼40% in arterioles from Con rats and eliminated dilation in arterioles from HLU rats. The cyclooxygenase inhibitor indomethacin (50 μM) did not significantly alter dilation to ACh in either group. Treatment with N ω-nitro-l-arginine + indomethacin eliminated all ACh dilation in Con and HLU rats. Dilation to sodium nitroprusside was not different between groups ( P = 0.98). To determine whether HLU decreased expression of endothelial cell NOS (ecNOS), mRNA and protein levels were measured in single arterioles with RT-PCR and immunoblot analysis. The ecNOS mRNA and protein expression was significantly lower in arterioles from HLU rats than in Con arterioles (20 and 65%, respectively). Collectively, these data indicate that HLU impairs ACh dilation in soleus 1A arterioles, in part because of alterations in the NO pathway.
Effects of 2-G exposure on temperature regulation, circadian rhythms, and adiposity in UCP2/3 transgenic mice
Authors: Fuller Patrick M. , Warden Craig H. , Barry Sean J. , Fuller Charles A.
Published: December 2017

Altered ambient force environments affect energy expenditure via changes in thermoregulation, metabolism, and body composition. Uncoupling proteins (UCPs) have been implicated as potential enhancers of energy expenditure and may participate in some of the adaptations to a hyperdynamic environment. To test this hypothesis, this study examined the homeostatic and circadian profiles of body temperature (Tb) and activity and adiposity in wild-type and UCP2/3 transgenic mice exposed to 1 and 2 G. There were no significant differences between the groups in the means, amplitudes, or phases of Tb and activity rhythms at either the 1- or 2-G level. Percent body fat was significantly lower in transgenic (5.2 ± 0.2%) relative to the wild-type mice (6.2 ± 0.1%) after 2-G exposure; mass-adjusted mesenteric and epididymal fat pads in transgenic mice were also significantly lower ( P < 0.05). The data suggest that 1) the actions of two UCPs (UCP2 and UCP3) do not contribute to an altered energy balance at 2 G, although 2) UCP2 and UCP3 do contribute to the utilization of lipids as a fuel substrate at 2 G.
Effect of transpulmonary pressure on airway diameter and responsiveness of immature and mature rabbits
Authors: Shen X. , Ramchandani R. , Dunn B. , Lambert R. , Gunst S. J. , Tepper R. S.
Published: December 2017

We previously demonstrated that airway responsiveness is greater in immature than in mature rabbits; however, it is not known whether there are maturational differences in the effect of transpulmonary pressure (Ptp) on airway size and airway responsiveness. The relationship between Ptp and airway diameter was assessed in excised lungs insufflated with tantalum powder. Diameters of comparable intraparenchymal airway segments were measured from radiographs obtained at Ptp between 0 and 20 cmH2O. At Ptp > 8 cmH2O, the diameters were near maximal in both groups. With diameter normalized to its maximal value, changing Ptp between 8 and 0 cmH2O resulted in a greater decline of airway caliber in immature than mature airways. The increases in lung resistance (Rl) in vivo at Ptp of 8, 5, and 2 cmH2O were measured during challenge with intravenous methacholine (MCh: 0.001–0.5 mg/kg). At Ptp of 8 cmH2O, both groups had very small responses to MCh and the maximal fold increases in Rl did not differ (1.93 ± 0.29 vs. 2.23 ± 0.19). At Ptp of 5 and 2 cmH2O, the fold increases in Rl were greater for immature than mature animals (13.19 ± 1.81 vs. 3.89 ± 0.37) and (17.74 ± 2.15 vs. 4.6 ± 0.52), respectively. We conclude that immature rabbits have greater airway distensibility and this difference may contribute to greater airway narrowing in immature compared with mature rabbits.
Inhibitors of myosin light chain kinase and phosphodiesterase reduce ventilator-induced lung injury
Authors: Parker James C. ,   (With the Technical Assistance of Sherri L. Martin)
Published: December 2017

Alveolar overdistension due to high peak inflation pressures (PIP) is associated with an increased capillary filtration coefficient ( Kfc). To determine which signal pathways contribute to this injury, we perfused isolated rat lungs with 5% bovine albumin in Krebs solution and measured Kfcafter successive 30-min periods of ventilation with peak inflation pressures (PIP) of 7, 20, 30, and 35 cmH2O. In a high-PIP control group, Kfcincreased significantly after ventilation with 30 and 35 cmH2O PIP, but significant increases were prevented by treatment with 100 μM trifluoperazine, an inhibitor of Ca2+/calmodulin, 500 nM ML-7, an inhibitor of myosin light chain kinase (MLCK), a combination of isoproterenol (20 μM) and rolipram (10 μM) to enhance intracellular cAMP levels, and a dose of KT-5720 (2 μM), which inhibits MLCK and protein kinase C. These studies suggest that the Ca2+/calmodulin-MLCK pathway augments capillary fluid leak after a modest high-PIP injury and that this is attenuated by kinase inhibition and increased intracellular cAMP.
Discharge frequencies of single motor units in human diaphragm and parasternal muscles in lying and standing
Authors: Butler J. E. , McKenzie D. K. , Gandevia S. C.
Published: December 2017

Single motor unit discharge was measured directly in diaphragm and parasternal intercostal muscles to determine whether neural drive to human inspiratory muscles changes between lying and standing. The final discharge frequency of diaphragmatic motor units increased slightly, by 1 Hz (12%; P < 0.01), when subjects were standing [182 units, median 9.1 Hz (interquartile range 7.6–11.3 Hz)] compared with lying supine [159 units, 8.1 Hz (6.6–10.3 Hz)]. However, this increase with standing occurred in only two of six subjects, in one of whom tidal volume increased significantly during standing. Parasternal intercostal motor unit final discharge frequencies did not differ between standing [116 units, 8.0 Hz (6.6–9.6 Hz)] and lying [124 units, 8.4 Hz (7.0–10.3 Hz)]. The discharge frequencies at the onset of inspiration did not differ between lying and standing for either muscle. A larger proportion of motor units in both inspiratory muscles had postinspiratory or tonic expiratory activity for lying compared with standing (15 vs. 4%; P < 0.05). We conclude that there is no major difference in the phasic inspiratory drive to the diaphragm with the change in posture.
Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload
Authors: Firstenberg Michael S. , Greenberg Neil L. , Main Michael L. , Drinko Jeanne K. , Odabashian Jill A. , Thomas James D. , Garcia Mario J.
Published: December 2017

Myocardial tissue Doppler echocardiography (TDE) has been proposed as a tool for the assessment of diastolic function. Controversy exists regarding whether TDE measurements are influenced by preload. In this study, left ventricular volume and high-fidelity pressures were obtained in eight closed-chest dogs during intermittent caval occlusion. The time constant of isovolumic ventricular relaxation (τ) was altered with varying doses of dobutamine and esmolol. Peak early diastolic myocardial ( E m) and transmitral ( E) velocities were measured before and after preload reduction. The relative effects of changes in preload and relaxation were determined for E m and compared with their effects on E. The following results were observed: caval occlusion significantly decreased E (Δ E = 16.4 ± 3.3 cm/s, 36.6 ± 13.7%, P < 0.01) and E m (Δ E m = 1.3 ± 0.4 cm/s, 32.5 ± 26.1%, P < 0.01) under baseline conditions. However, preload reduction was similar for E under all lusitropic conditions ( P = not significant), but these effects on E m decreased with worsening relaxation. At τ < 50 ms, changes in E m with preload reduction were significantly greater (Δ E m = 2.8 ± 0.6 cm/s) than at τ = 50–65 ms (Δ E m = 1.2 ± 0.2 cm/s) and at τ >65 ms (Δ E m = 0.5 ± 0.1 cm/s, P < 0.05). We concluded that TDE E m is preload dependent. However, this effect decreases with worsening relaxation.
Influence of inhaled nitric oxide on gas exchange during normoxic and hypoxic exercise in highly trained cyclists
Authors: Sheel A. William , Edwards Michael R. , Hunte Garth S. , McKenzie Donald C.
Published: December 2017

This study tested the effects of inhaled nitric oxide [NO; 20 parts per million (ppm)] during normoxic and hypoxic (fraction of inspired O2 = 14%) exercise on gas exchange in athletes with exercise-induced hypoxemia. Trained male cyclists ( n = 7) performed two cycle tests to exhaustion to determine maximal O2 consumption (V˙o 2 max) and arterial oxyhemoglobin saturation (SaO2 , Ohmeda Biox ear oximeter) under normoxic (V˙o 2 max = 4.88 ± 0.43 l/min and SaO2 = 90.2 ± 0.9, means ± SD) and hypoxic (V˙o 2 max = 4.24 ± 0.49 l/min and SaO2 = 75.5 ± 4.5) conditions. On a third occasion, subjects performed four 5-min cycle tests, each separated by 1 h at their respectiveV˙o 2 max, under randomly assigned conditions: normoxia (N), normoxia + NO (N/NO), hypoxia (H), and hypoxia + NO (H/NO). Gas exchange, heart rate, and metabolic parameters were determined during each condition. Arterial blood was drawn at rest and at each minute of the 5-min test. Arterial Po 2 (PaO2 ), arterial Pco 2, and SaO2 were determined, and the alveolar-arterial difference for Po 2 (A-aDo 2) was calculated. Measurements of PaO2 and SaO2 were significantly lower and A-aDo 2 was widened during exercise compared with rest for all conditions ( P < 0.05). No significant differences were detected between N and N/NO or between H and H/NO for PaO2 , SaO2 and A-aDo 2 ( P > 0.05). We conclude that inhalation of 20 ppm NO during normoxic and hypoxic exercise has no effect on gas exchange in highly trained cyclists.
Thermoregulation during cold exposure after several days of exhaustive exercise
Authors: Castellani John W. , Young Andrew J. , Degroot David W. , Stulz Dean A. , Cadarette Bruce S. , Rhind Shawn G. , Zamecnik Jiri , Shek Pang N. , Sawka Michael N.
Published: December 2017

This study examined the hypothesis that several days of exhaustive exercise would impair thermoregulatory effector responses to cold exposure, leading to an accentuated core temperature reduction compared with exposure of the same individual to cold in a rested condition. Thirteen men (10 experimental and 3 control) performed a cold-wet walk (CW) for up to 6 h (6 rest-work cycles, each 1 h in duration) in 5°C air on three occasions. One cycle of CW consisted of 10 min of standing in the rain (5.4 cm/h) followed by 45 min of walking (1.34 m/s, 5.4 m/s wind). Clothing was water saturated at the start of each walking period (0.75 clo vs. 1.1 clo when dry). The initial CW trial ( day 0) was performed (afternoon) with subjects rested before initiation of exercise-cold exposure. During the next 7 days, exhaustive exercise (aerobic, anaerobic, resistive) was performed for 4 h each morning. Two subsequent CW trials were performed on the afternoon of days 3 and 7, ∼2.5 h after cessation of fatiguing exercise. For controls, no exhaustive exercise was performed on any day. Thermoregulatory responses and body temperature during CW were not different on days 0, 3, and 7 in the controls. In the experimental group, mean skin temperature was higher ( P< 0.05) during CW on days 3 and 7 than on day 0. Rectal temperature was lower ( P < 0.05) and the change in rectal temperature was greater ( P < 0.05) during the 6th h of CW on day 3. Metabolic heat production during CW was similar among trials. Warmer skin temperatures during CW after days 3 and 7indicate that vasoconstrictor responses to cold, but not shivering responses, are impaired after multiple days of severe physical exertion. These findings suggest that susceptibility to hypothermia is increased by exertional fatigue.
Influence of age and gender on upper airway resistance in NREM and REM sleep
Authors: Thurnheer Robert , Wraith Peter K. , Douglas Neil J.
Published: December 2017

The prevalence of irregular breathing during sleep is age and gender dependent, but the reason for this is unknown. This study tested the hypothesis that older men have a greater sleep-related increase in respiratory resistance. In 48 healthy subjects, 12 in each of four groups of younger and older men and women, airway resistance was measured during wakefulness and sleep using a mask, pneumotachograph, and catheter-mounted pressure sensors. Total respiratory resistance and total “low-flow,” and “high-flow” oropharyngeal resistance were analyzed from 170,000 breaths, high flow being at rates above 50% maximal inspiratory flow. High-flow oropharyngeal and total respiratory resistance increased during non-rapid eye movement (NREM) sleep in all groups but not low-flow resistance. Total respiratory resistance increased from 12 ± 1.2 cmH2O · l−1 · s−1awake to 16.2 ± 2.4 in NREM sleep in young men, from 22.8 ± 3.6 to 33.6 ± 5.4 in young women, from 18 ± 3 to 34.8 ± 4.8 in older men, and from 26.6. ± 4.2 to 34.2 ± 6 in older women. The percentage of change in total respiratory resistance from awake to NREM sleep was not different between age groups or genders. We conclude that there are no major age or gender differences in the changes in airway resistance with sleep in normal subjects.
Role of ventilation strategy on perfluorochemical evaporation from the lungs
Authors: Jeng Mei-Jy , Trevisanuto Daniele , Weis Carla M. , Fox William W. , Cullen Aaron B. , Wolfson Marla R. , Shaffer Thomas H.
Published: December 2017

To study the effect of ventilation strategy on perfluorochemical (PFC) elimination profile (evaporative loss profile; EL), 6 ml/kg of perflubron were instilled into anesthetized normal rabbits. The strategy was to maintain minute ventilation (V˙e, in ml/min) in three groups:V˙e L (low-range V˙e, 208 ± 2), V˙e M (midrangeV˙e, 250 ± 9), andV˙e H (high-range V˙e, 293 ± 1) over 4 h. In three other groups, respiratory rate (RR, breaths/min) was controlled at 20, 30, or 50 with a constant V˙e and adjusted tidal volume. PFC content in the expired gas was measured, and EL was calculated. There was a significant V˙e- and time-dependent effect on EL. Initially, percent PFC saturation and loss rate decreased in the V˙e H >V˙e M >V˙e L groups, but by 3 h the lower percent PFC saturation resulted in a loss rate such thatV˙e H <V˙e M <V˙e L at 4 h. For the groups at constant V˙e, there was a significant time effect on EL but no RR effect. In conclusion, EL profile is dependent on V˙e with little effect of the RR-tidal volume combination. Thus measurement of EL andV˙e should be considered for the replacement dosing schemes during partial liquid ventilation.
Effects of strength training on muscle power and serum hormones in middle-aged and older men
Authors: Izquierdo M. , Häkkinen K. , Ibañez J. , Garrues M. , Antón A. , Zúñiga A. , Larrión J. L. , Gorostiaga E. M.
Published: December 2017

Effects of 16-wk strength training on maximal strength and power performance of the arm and leg muscles and serum concentrations [testosterone (T), free testosterone (FT), and cortisol] were examined in 11 middle-aged (M46; 46 ± 2 yr) and 11 older men (M64; 64 ± 2 yr). During the 16-wk training, the relative increases in maximal strength and muscle power output of the arm and leg muscles were significant in both groups ( P < 0.05–0.001), with no significant differences between the two groups. The absolute increases were higher ( P < 0.01–0.05) in M46 than in M64 mainly during the last 8 wk of training. No significant changes were observed for serum T and FT concentrations. Analysis of covariance showed that, during the 16-wk training period, serum FT concentrations tended to decrease in M64 and increase in M46 ( P < 0.05). However, significant correlations between the mean level of individual serum T and FT concentrations and the individual changes in maximal strength were observed in a combined group during the 16-wk training ( r = 0.49 and 0.5, respectively; P < 0.05). These data indicate that a prolonged total strength-training program would lead to large gains in maximal strength and power load characteristics of the upper and lower extremity muscles, but the pattern of maximal and power development seemed to differ between the upper and lower extremities in both groups, possibly limited in magnitude because of neuromuscular and/or age-related endocrine impairments.
Stress-induced attenuation of the hypercapnic ventilatory response in awake rats
Authors: Kinkead Richard , Dupenloup Lydie , Valois Nadine , Gulemetova Roumiana
Published: December 2017

To test the hypothesis that stress alters the performance of the respiratory control system, we compared the acute (20 min) responses to moderate hypoxia and hypercapnia of rats previously subjected to immobilization stress (90 min/day) with responses of control animals. Ventilatory measurements were performed on awake rats using whole body plethysmography. Under baseline conditions, there were no differences in minute ventilation between stressed and unstressed groups. Rats previously exposed to immobilization stress had a 45% lower ventilatory response to hypercapnia (inspiratory CO2 fraction = 0.05) than controls. In contrast, stress exposure had no statistically significant effect on the ventilatory response to hypoxia (inspiratory O2 fraction = 0.12). Stress-induced attenuation of the hypercapnic response was associated with reduced tidal volume and inspiratory flow increases; the frequency and timing components of the response were not different between groups. We conclude that previous exposure to a stressful condition that does not constitute a direct challenge to respiratory homeostasis can elicit persistent (≥24 h) functional plasticity in the ventilatory control system.
l-NAME enhances responses to atrial natriuretic peptide in the pulmonary vascular bed of the cat
Authors: Hyman Albert L. , De Witt Bracken J. , Gumusel Bulent , Hao Quingzhong , Kadowitz Philip J. , Lippton Howard L.
Published: December 2017

This study investigated the hypothesis that atrial natriuretic peptide (ANP) responses are mediated by particulate guanylate cyclase in the pulmonary vascular bed of the cat. When tone in the pulmonary vascular bed was raised to a high steady level with the thromboxane mimic U-46619, injections of ANP caused dose-related decreases in lobar arterial pressure. After administration of HS-142-1, an ANP-A- and ANP-B-receptor antagonist, vasodilator responses to ANP were reduced. The nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) enhanced ANP vasodilator responses, suggesting that inhibition of NO modulates ANP responses. l-NAME administration with constant 8-bromo-cGMP infusion attenuated the increased vasodilator response to ANP, suggesting that supersensitivity to ANP occurs upstream to activation of a cGMP-dependent protein kinase. In pulmonary arterial rings, ANP produced concentration-related vasorelaxant responses with and without endothelium. Methylene blue,l-NAME, or Nω-monomethyl-l-arginine did not alter ANP vasorelaxant responses. These data show that ANP supersensitivity observed in the intact pulmonary vascular bed is not seen in isolated pulmonary arterial segments, suggesting that it may only occur in resistance vessel elements. These results suggest that ANP responses occur through activation of ANP-A and/or -B receptors in an endothelium-independent manner and are modulated by NO in resistance vessel elements in the pulmonary vascular bed of the cat.
Is the V˙o 2 slow component dependent on progressive recruitment of fast-twitch fibers in trained runners?
Authors: Borrani F. , Candau R. , Millet G. Y. , Perrey S. , Fuchslocher J. , Rouillon J. D.
Published: December 2017

The goal of this study was to use spectral analysis of EMG data to test the hypothesis that the O2 uptake (V˙o 2) slow component is due to a recruitment of fast fibers. Thirteen runners carried out a treadmill test with a constant speed, corresponding to 95% of the velocity associated with maximal V˙o 2. TheV˙o 2 response was fit with the classical model including three exponential functions. Electrical activity of six lower limb muscles (vastus lateralis, soleus, and gastrocnemius of both sides) was measured using electromyogram surface electrodes. Mean power frequency (MPF) was used to study the kinetics of the electromyogram discharge frequency. Three main results were observed: 1) a common pattern of the MPF kinetics in the six muscles studied was noted; 2) MPF decreased in the first part of the exercise, followed by an increase for all the muscles studied, but only the vastus lateralis, and gastrocnemius muscles of both sides increased significantly ( P < 0.05); and 3) the beginning of the MPF increase of the four muscles mentioned above corresponded with the beginning of the slow component. Our results suggest a progression in the average frequency of the motor unit discharge toward the high frequencies, which coheres with the hypothesis of the progressive recruitment of fast-twitch fibers during the V˙o 2 slow component. However, this interpretation must be taken with caution because MPF is the result of a balance between several phenomena.
Establishing predictive indicators for the status of loaded soft tissues
Authors: Knight Sarah L. , Taylor Richard P. , Polliack Adrian A. , Bader Dan L.
Published: December 2017

Two complementary techniques were employed to assess the soft tissue response to applied pressure. The noninvasive methods involve the simultaneous measurement of the local tensions of oxygen and carbon dioxide (tcPo2and tcPco2) and the collection and subsequent analysis of sweat collected from the sacrum, a common site for the development of pressure sores. All tests were performed on able-bodied subjects. Results have indicated that oxygen levels (tcPo2) were lowered in soft tissues subjected to applied pressures of between 40 (5.3 kPa) and 120 mmHg (16.0 kPa). At the higher pressures, this decrease was generally associated with an increase in carbon dioxide levels (tcPco2) well above the normal basal levels of 45 mmHg (6 kPa). There were also considerable increases, in some cases up to twofold, in the concentrations of both sweat lactate and urea at the loaded site compared with the unloaded control. By comparing selected parameters, a threshold value for loaded tcPo2was identified, representing a reduction of ∼60% from unloaded values. Above this threshold, there was a significant relationship between this parameter and the loaded/unloaded concentration ratios for both sweat metabolites. These parameters may prove useful in identifying those subjects whose soft tissue may be compromised during periods of pressure ischemia.
Phase plane analysis of left ventricular hemodynamics
Authors: Eucker Stephanie A. , Lisauskas Jennifer B. , Singh Jasvindar , Kovács Sándor J.
Published: December 2017

We sought to extract additional physiological information from the time-dependent left ventricular (LV) pressure contour and thereby gain new insights into ventricular function. We used phase plane analysis to characterize high-fidelity pressure data in selected subjects undergoing elective cardiac catheterization. The standard hemodynamic indexes of LV systolic and diastolic function derived from the time-dependent LV pressure contour could be easily obtained using the phase plane method. Additional novel attributes of the phase plane pressure loop, such as phase plane pressure loop area, graphical representation of the isovolumic relaxation time constant, and quantitative measures of beat-to-beat systolic-diastolic coupling were characterized. The asymmetry between the pressures at which maximum isovolumic pressure rise and pressure fall occur, as well as their load dependence, were also easily quantitated. These results indicate that the phase plane method provides a novel window for physiological discovery and has theoretical and applied advantages in quantitative ventricular function characterization.
Role of vagal C-fiber afferents in the bronchomotor response to lactic acid in the newborn dog
Authors: Marantz Monica J. , Vincent Sandra G. , Fisher John T.
Published: December 2017

We addressed the hypothesis that vagal C-fiber afferents and cyclooxygenase products are the mechanisms responsible for lactic acid (LA)-induced bronchoconstriction in the newborn dog. Perineural capsaicin and indomethacin were used to block conduction of vagal C fibers and production of cyclooxygenase products, respectively. Perineural capsaicin eliminated (85%) the increase in lung resistance (Rl; 45 ± 5.6%) due to capsaicin (25 μg/kg), whereas the increase in Rl (54 ± 6.9%) due to LA (0.4 mmol/kg) was only inhibited by 37 ± 4.7% ( P < 0.05). Atropine reduced LA-induced bronchoconstriction (42 ± 2.1%) by an amount similar to that obtained with perineural capsaicin. However, inhibition was significantly increased when atropine was combined with indomethacin (61 ± 2.7%; P < 0.05), implicating cyclooxygenase products in the LA-induced bronchoconstrictor response. We conclude that the mechanisms responsible for LA-induced bronchoconstriction in the newborn are 1) activation of vagal C-fibers, which, through projections to medullary respiratory centers, leads to activation of vagal cholinergic efferents; 2) production of cyclooxygenase products, which cause bronchoconstriction independent of medullary involvement; and 3) an unknown bronchoconstrictor mechanism, putatively tachykinin mediated. On the basis of our data, pharmaceutical targeting of pulmonary afferents would prevent multiple downstream mechanisms that lead to airway narrowing due to inflammatory lung disease.
Nasal strips do not affect pulmonary gas exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds
Authors: Goetz Thomas E. , Manohar Murli , Hassan Aslam S. , Baker Gordon J.
Published: December 2017

The present study was carried out to examine whether nasal strip application would improve the exercise-induced arterial hypoxemia and hypercapnia, diminish anaerobic metabolism, and modify the incidence of exercise-induced pulmonary hemorrhage (EIPH) in horses. Two sets of experiments, control and nasal strip experiments, were carried out on seven healthy, sound, exercise-trained Thoroughbred horses in random order, 7 days apart. Simultaneous measurements of core temperature, arterial and mixed venous blood gases/pH, and blood lactate and ammonia concentrations were made at rest, during submaximal and near-maximal exercise, and during recovery. In both treatments, whereas submaximal exercise caused hyperventilation, near-maximal exercise induced significant arterial hypoxemia, desaturation of Hb, hypercapnia, and acidosis. However, O2content increased significantly with exercise in both treatments, while the mixed venous blood O2content decreased as O2extraction increased. In both treatments, plasma ammonia and blood lactate concentrations increased significantly with exercise. Statistically significant differences between the control and the nasal strip experiments could not be discerned, however. Also, all horses experienced EIPH in both treatments. Thus our data indicated that application of an external nasal dilator strip neither improved the exercise-induced arterial hypoxemia and hypercapnia nor diminished anaerobic metabolism or the incidence of EIPH in Thoroughbred horses performing strenuous exercise.
Invited Review: Adaptive responses of skeletal muscle to intermittent hypoxia: the known and the unknown
Authors: Clanton Thomas L. , Klawitter Paul F.
Published: December 2017

Intermittent hypoxia (IH) describes conditions of repeated, transient reductions in O2 that may trigger unique adaptations. Rest periods during IH may avoid potentially detrimental effects of long-term O2 deprivation. For skeletal muscle, IH can occur in conditions of obstructive sleep apnea, transient altitude exposures (with or without exercise), intermittent claudication, cardiopulmonary resuscitation, neonatal blood flow obstruction, and diving responses of marine animals. Although it is likely that adaptations in these conditions vary, some patterns emerge. Low levels of hypoxia shift metabolic enzyme activity toward greater aerobic poise; extreme hypoxia shifts metabolism toward greater anaerobic potential. Some conditions of IH may also inhibit lactate release during exercise. Many related cellular phenomena could be involved in the response, including activation of specific O2 sensors, reactive oxygen and nitrogen species, preconditioning, hypoxia-induced transcription factors, regulation of ion channels, and influences of paracrine/hormonal stimuli. The net effect of a variety of adaptive programs to IH may be to preserve contractile function and cell integrity in hypoxia or anoxia, a response that does not always translate into improvements in exercise performance.
Effects of fat adaptation and carbohydrate restoration on prolonged endurance exercise
Authors: Carey Andrew L. , Staudacher Heidi M. , Cummings Nicola K. , Stepto Nigel K. , Nikolopoulos Vasilis , Burke Louise M. , Hawley John A.
Published: December 2017

We determined the effect of fat adaptation on metabolism and performance during 5 h of cycling in seven competitive athletes who consumed a standard carbohydrate (CHO) diet for 1 day and then either a high-CHO diet (11 g · kg−1 · day−1 CHO, 1 g · kg−1 · day−1 fat; HCHO) or an isoenergetic high-fat diet (2.6 g · kg−1 · day−1 CHO, 4.6 g · kg−1 · day−1 fat; fat-adapt) for 6 days. On day 8, subjects consumed a high-CHO diet and rested. On day 9, subjects consumed a preexercise meal and then cycled for 4 h at 65% peak O2 uptake, followed by a 1-h time trial (TT). Compared with baseline, 6 days of fat-adapt reduced respiratory exchange ratio (RER) with cycling at 65% peak O2 uptake [0.78 ± 0.01 (SE) vs. 0.85 ± 0.02; P < 0.05]. However, RER was restored by 1 day of high-CHO diet, preexercise meal, and CHO ingestion (0.88 ± 0.01; P < 0.05). RER was higher after HCHO than fat-adapt (0.85 ± 0.01, 0.89 ± 0.01, and 0.93 ± 0.01 for days 2, 8, and 9, respectively; P < 0.05). Fat oxidation during the 4-h ride was greater (171 ± 32 vs. 119 ± 38 g; P < 0.05) and CHO oxidation lower (597 ± 41 vs. 719 ± 46 g; P < 0.05) after fat-adapt. Power output was 11% higher during the TT after fat-adapt than after HCHO (312 ± 15 vs. 279 ± 20 W; P = 0.11). In conclusion, compared with a high-CHO diet, fat oxidation during exercise increased after fat-adapt and remained elevated above baseline even after 1 day of a high-CHO diet and increased CHO availability. However, this study failed to detect a significant benefit of fat adaptation to performance of a 1-h TT undertaken after 4 h of cycling.
Molecular adaptations in human skeletal muscle to endurance training under simulated hypoxic conditions
Authors: Vogt M. , Puntschart A. , Geiser J. , Zuleger C. , Billeter R. , Hoppeler H.
Published: December 2017

This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maximal O2uptake (8.3–13.1%) and maximal power output (11.4–20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the α-subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF-1α736, a splice variant of HIF-1α newly detected in human skeletal muscle, was shown to be changed in a similar pattern as HIF-1α. Increased mRNA contents of myoglobin (+72.2%) and vascular endothelial growth factor (+52.4%) were evoked only after high-intensity training in hypoxia. Augmented mRNA levels of oxidative enzymes, phosphofructokinase, and heat shock protein 70 were found after high-intensity training under both hypoxic and normoxic conditions. Our findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training. Fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O2uptake or maximal power output.
Effects of isometric training on the elasticity of human tendon structures in vivo
Authors: Kubo Keitaro , Kanehisa Hiroaki , Ito Masamitsu , Fukunaga Tetsuo
Published: December 2017

The present study aimed to investigate the effect of isometric training on the elasticity of human tendon structures. Eight subjects completed 12 wk (4 days/wk) of isometric training that consisted of unilateral knee extension at 70% of maximal voluntary contraction (MVC) for 20 s per set (4 sets/day). Before and after training, the elongation of the tendon structures in the vastus lateralis muscle was directly measured using ultrasonography while the subjects performed ramp isometric knee extension up to MVC. The relationship between the estimated muscle force and tendon elongation ( L) was fitted to a linear regression, the slope of which was defined as stiffness of the tendon structures. The training increased significantly the volume (7.6±4.3%) and MVC torque (33.9±14.4%) of quadriceps femoris muscle. The L values at force production levels beyond 550 N were significantly shorter after training. The stiffness increased significantly from 67.5±21.3 to 106.2±33.4 N/mm. Furthermore, the training significantly increased the rate of torque development (35.8 ± 20.4%) and decreased electromechanical delay (−18.4±3.8%). Thus the present results indicate that isometric training increases the stiffness and Young's modulus of human tendon structures as well as muscle strength and size. This change in the tendon structures would be assumed to be an advantage for increasing the rate of torque development and shortening the electromechanical delay.
Dynamic effects of positive-pressure ventilation on canine left ventricular pressure-volume relations
Authors: Denault Andre Y. , Gorcsan John , Pinsky Michael R.
Published: December 2017

Positive-pressure ventilation (PPV) may affect left ventricular (LV) performance by altering both LV diastolic compliance and pericardial pressure (Ppc). We measured the effect of PPV on LV intraluminal pressure, Ppc, LV volume, and LV cross-sectional area in 17 acute anesthetized dogs. To account for changes in lung volume independent of changes in Ppc and differences in contractility, measures were made during both open- and closed-chest conditions, during closed chest with and without chest wall binding, and after propranolol-induced acute ventricular failure (AVF). Apneic end-systolic pressure-volume relations (ESPVR) were generated by inferior vena caval occlusions. With the open chest, PPV had no effects. With the chest closed, PPV inspiration decreased LV end-diastolic volume (EDV) along its diastolic compliance curve and decreased end-systolic volume (ESV) such that the end-systolic pressure-volume domain was shifted to a point left of the LV ESPVR, even when referenced to Ppc. The decrease in EDV was greater in control than in AVF conditions, whereas the shift of the ESV to the left of the ESPVR was greater with AVF than in control conditions. We conclude that the hemodynamic effects of PPV inspiration are due primarily to changes in intrathoracic pressure and that the inspiration-induced decreases of LV EDV reflect direct effects of intrathoracic pressure on LV filling. The decreases in LV ESV exceed the amount explained solely by a reduction in LV ejection pressure.
Carotid body denervation in dogs: eupnea and the ventilatory response to hyperoxic hypercapnia
Authors: Rodman J. R. , Curran A. K. , Henderson K. S. , Dempsey J. A. , Smith C. A.
Published: December 2017

We assessed the time course of changes in eupneic arterial Pco 2(PaCO2 ) and the ventilatory response to hyperoxic rebreathing after removal of the carotid bodies (CBX) in awake female dogs. Elimination of the ventilatory response to bolus intravenous injections of NaCN was used to confirm CBX status on each day of data collection. Relative to eupneic control (PaCO2 = 40 ± 3 Torr), all seven dogs hypoventilated after CBX, reaching a maximum PaCO2 of 53 ± 6 Torr by day 3post-CBX. There was no significant recovery of eupneic PaCO2 over the ensuing 18 days. Relative to control, the hyperoxic CO2 ventilatory (change in inspired minute ventilation/change in end-tidal Pco 2) and tidal volume (change in tidal volume/ change in end-tidal Pco 2) response slopes were decreased 40 ± 15 and 35 ± 20% by day 2 post-CBX. There was no recovery in the ventilatory or tidal volume response slopes to hyperoxic hypercapnia over the ensuing 19 days. We conclude that 1) the carotid bodies contribute ∼40% of the eupneic drive to breathe and the ventilatory response to hyperoxic hypercapnia and 2) there is no recovery in the eupneic drive to breathe or the ventilatory response to hyperoxic hypercapnia after removal of the carotid chemoreceptors, indicating a lack of central or aortic chemoreceptor plasticity in the adult dog after CBX.
Effect of morning exercise on counterregulatory responses to subsequent, afternoon exercise
Authors: Galassetti Pietro , Mann Stephnie , Tate Donna , Neill Ray A. , Wasserman David H. , Davis Stephen N.
Published: December 2017

The aim of this study was to determine whether a bout of morning exercise (EXE1) can alter neuroendocrine and metabolic responses to subsequent afternoon exercise (EXE2) and whether these changes follow a gender-specific pattern. Sixteen healthy volunteers (8 men and 8 women, age 27 ± 1 yr, body mass index 23 ± 1 kg/m2, maximal O2uptake 31 ± 2 ml · kg−1· min−1) were studied after an overnight fast. EXE1and EXE2each consisted of 90 min of cycling on a stationary bike at 48 ± 2% of maximal O2uptake separated by 3 h. To avoid the confounding effects of hypoglycemia and glycogen depletion, carbohydrate (1.5 g/kg body wt po) was given after EXE1, and plasma glucose was maintained at euglycemia during both episodes of exercise by a modification of the glucose-clamp technique. Basal insulin levels (7 ± 1 μU/ml) and exercise-induced insulin decreases (−3 μU/ml) were similar during EXE1and EXE2. Plasma glucose was 5.2 ± 0.1 and 5.2 ± 0.1 mmol/l during EXE1and EXE2, respectively. The glucose infusion rate needed to maintain euglycemia during the last 30 min of exercise was increased during EXE2compared with EXE1(32 ± 4 vs. 7 ± 2 μmol · kg−1· min−1). Although this increased need for exogenous glucose was similar in men and women, gender differences in counterregulatory responses were significant. Compared with EXE1, epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and cortisol responses were blunted during EXE2in men, but neuroendocrine responses were preserved or increased in women. In summary, morning exercise significantly impaired the body's ability to maintain euglycemia during later exercise of similar intensity and duration. We conclude that antecedent exercise can significantly modify, in a gender-specific fashion, metabolic and neuroendocrine responses to subsequent exercise.
Dopamine-1 receptor stimulation attenuates the vasoconstrictive response to gut ischemia
Authors: Guzman Jorge A. , Rosado Ariosto E. , Kruse James A.
Published: December 2017

The effects of fenoldopam, a dopamine-1 (DA-1) receptor agonist, were studied in two groups of anesthetized dogs before and after inducion of splanchnic ischemia by way of hemorrhage. During the first portion of the experiment, both groups received fenoldopam (1.5 μg · kg−1 · min−1) for 45 min followed by a 45-min washout. During the second portion, hemorrhage (10 ml/kg) was induced, followed by no intervention in group I (controls) and restarting of the fenoldopam infusion in group II. Prehemorrhage, fenoldopam increased composite portal blood flow by 33% ( P < 0.01). After hemorrhage-induced splanchnic ischemia, fenoldopam restored portal vein blood flow to near baseline, maintained the splanchnic fraction of cardiac output, and attenuated the rise in gut mucosal Pco 2. DA-1 receptor stimulation increased portal blood flow and redistributed blood flow away from the serosal layer in favor of the mucosa during basal conditions and after hemorrhage, suggesting a more concentrated distribution of splanchnic DA-1 receptors within the mucosal layer vasculature. Fenoldopam maintained splanchnic blood flow during hypoperfusion and attenuated the splanchnic vasoconstrictive response to hemorrhage.
Insight into skeletal muscle mechanotransduction: MAPK activation is quantitatively related to tension
Authors: Martineau Louis C. , Gardiner Phillip F.
Published: December 2017

The mechanism by which mechanical forces acting through skeletal muscle cells generate intracellular signaling, known as mechanotransduction, and the details of how gene expression and cell size are regulated by this signaling are poorly understood. Mitogen-activated protein kinases (MAPKs) are known to be involved in mechanically induced signaling in various cell types, including skeletal muscle where MAPK activation has been reported in response to contraction and passive stretch. Therefore, the investigation of MAPK activation in response to mechanical stress in skeletal muscle may yield important information about the mechanotransduction process. With the use of a rat plantaris in situ preparation, a wide range of peak tensions was generated through passive stretch and concentric, isometric, and eccentric contractile protocols, and the resulting phosphorylation of c-Jun NH2-terminal kinase (JNK), extracellular regulated kinase (ERK), and p38 MAPKs was assessed. Isoforms of JNK and ERK MAPKs were found to be phosphorylated in a tension-dependent manner, such that eccentric > isometric > concentric > passive stretch. Peak tension was found to be a better predictor of MAPK phosphorylation than time-tension integral or rate of tension development. Differences in maximal response amplitude and sensitivity between JNK and ERK MAPKs suggest different roles for these two kinase families in mechanically induced signaling. A strong linear relationship between p54 JNK phosphorylation and peak tension over a 15-fold range in tension ( r 2 = 0.89, n = 32) was observed, supporting the fact that contraction-type differences can be explained in terms of tension and demonstrating that MAPK activation is a quantitative reflection of the magnitude of mechanical stress applied to muscle. Thus the measurement of MAPK activation, as an assay of skeletal muscle mechanotransduction, may help elucidate mechanically induced hypertrophy.
Ozone absorption in the human nose during unidirectional airflow
Authors: Santiago Lizzie Y. , Hann Matthew C. , Ben-Jebria Abdellaziz , Ultman James S.
Published: December 2017

This study addresses the effect of gas flow rate and ozone (O3) concentration on the uptake of this air pollutant in the nose. A nasal exposure system was developed in which a constant flow of humidified air (V˙) containing a constant concentration of O3 (Cinlet) entered one nostril and then exited the other nostril while a subject closed the velopharyngeal aperture. Experiments were conducted on 10 healthy nonsmokers for whom O3 concentration was measured at the inlet nostril and the outlet nostril to determine the fraction of inhaled O3 that was absorbed into the nasal mucosa (Λnose). Λnose decreased from 0.80 ± 0.02 to 0.33 ± 0.02 (SE) when V˙ was increased from 3 to 15 l/min and Cinlet was fixed at 0.4 ppm. Analysis of these data with a mathematical model indicated that O3 uptake was limited by diffusion reaction through mucus, rather than by convective diffusion through the respired gas. A small decrease in Λnose from 0.36 ± 0.02 to 0.32 ± 0.01 was also observed when Cinlet was increased from 0.1 to 0.4 ppm at a fixed V˙of 15 l/min. This may have been due to nonlinear reaction kinetics between O3 and reactive substrates in mucus or an active response by a physiological process such as mucus secretion or transepithelial water influx.