bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin-converting enzyme inhibition and the norepinephrine spillover response to dynamic exercise
Authors: Leuenberger U. , Gaul L. , Noack H. , Gubin S. , Zelis R.
Published: December 2017

To determine whether prejunctional angiotensin II receptors facilitate norepinephrine (NE) release during exercise, normal volunteers exercised at approximately 25 or approximately 65% of maximal O2 consumption (VO2max) on two occasions. Steady-state NE kinetics were determined at rest and during exercise by using infusions of [3H]NE. Arterial plasma NE and [3H]NE were determined for calculation of NE spillover and clearance. Before the second bout of exercise at approximately 25% of VO2max later that day, enalaprilat (n = 8) or nitroprusside (n = 5) was administered intravenously to lower blood pressure to a comparable level and saline was infused as a time control (n = 4). Exercise at 25% of VO2max increased heart rate from 73 to 100 beats/min, plasma NE from 296 to 626 pg/ml, and NE spillover from 1.56 to 3.32 nmol.min-1.m-2. The exercise effect was significant in each subgroup. At rest and during exercise, the decrease in blood pressure and the increase in plasma NE and NE spillover were similar with enalaprilat and nitroprusside. There was no drug effect in the saline group. In a separate group (n = 7), exercise at approximately 65% of VO2max increased heart rate from 76 to 170 beats/min, plasma NE from 338 to 2,656 pg/ml, and NE spillover from 1.87 to 11.65 nmol.min-1.m-2. In this group, 3 days of oral enalapril did not affect the NE spillover response to exercise. Because the angiotensin-converting enzyme inhibitor did not attenuate the NE spillover response to exercise, we conclude that at the exercise levels tested, prejunctional angiotensin II receptors do not appear to facilitate NE release.
PCO2 affects tracheal tone during apnea in anesthetized dogs
Authors: Dickstein J. , Greenberg A. , Kruger J. , Robicsek A. , Silverman J. A. , Sommer L. Z. , Sommer D. D. , Volgyesi G. A. , Iscoe S. , Fisher J. A.
Published: December 2017

We hypothesized that CO2, like hypoxia and withdrawal of pulmonary slowly adapting receptor input, would cause tracheal constriction during neural apnea (absence of phrenic activity). In seven anesthetized paralyzed dogs ventilated to neural apnea, we increased arterial PCO2 (PaCO2) in steps by adding CO2 to the inspirate while keeping ventilation constant. Increases in PaCO2 caused tracheal constriction during neural apnea in all dogs; 69 +/- 26 (SD)% of the change in tracheal diameter occurred during neural apnea. Average sensitivity of tracheal diameter to CO2 was 0.44 mm/Torr PaCO2. Our data suggest that central chemoreceptor inputs to brain stem neurons controlling smooth muscle of the extrathoracic airway bypass central mechanisms generating inspiration.
Kinetics of pulmonary oxygen uptake and muscle phosphates during moderate-intensity calf exercise
Authors: McCreary C. R. , Chilibeck P. D. , Marsh G. D. , Paterson D. H. , Cunningham D. A. , Thompson R. T.
Published: December 2017

The purpose of this study is to directly compare the dynamic responses of phosphocreatine (PCr) and P(i) to those oxygen uptake (VO2) measured at the lung during transitions to and from moderate-intensity exercise. Changes in PCr and P(i) were measured by 31P-nuclear magnetic resonance spectroscopy, and changes in VO2 were measured breath by breath by mass spectroscopy during transitions to and from moderate-intensity square-wave ankle plantar flexion exercise in 11 subjects (7 men and 4 women; mean age 27 yr). Three repeated transitions were averaged for improvement in signal-to-noise ratio of phosphate data, and 12 transitions were averaged for VO2 measurements. Averaged transitions were fit with a monoexponential curve for determination of the time constant (tau) of the responses. Mean tau values for on transients of PCr, P(i), and phrase 2 VO2 were 47.0, 57.7, and 44.5 s, respectively, whereas means tau values for off transients were 44.8, 42.1, and 33.4 s, respectively. There were no significant differences between tau values for phosphate- and VO2-measured transients or on and off transients. The similarity of on and off kinetics supports linear first-order respiratory control models. Measurement of phase 2 pulmonary VO2 kinetics to and from moderate-intensity small-muscle-mass exercise reflect muscle phosphate kinetics (and muscle oxygen consumption).
Effects of aging and obesity on respiratory muscle phenotype in Zucker rats
Authors: Powers S. K. , Farkas G. A. , Demirel H. , Coombes J. , Fletcher L. , Hughes M. G. , Hodge K. , Dodd S. L. , Schlenker E. H.
Published: December 2017

Because obesity results in an increased work of breathing, we tested the hypothesis that the oxidative properties and myosin heavy chain (MHC) isoform profiles in respiratory muscles would differ between lean and obese animals. Furthermore, we postulated that obesity-related changes in respiratory muscles would be independent of age. To test these hypothesis, samples of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles were removed from three age groups (young, adult, and old) of obese and lean Zucker rats. Citrate synthase (CS) activity was measured as a marker of oxidative capacity, and MHC isoforms were identified with gel electrophoresis. Analysis revealed that CS activity was significantly higher in the crural and costal diaphragms and parasternal intercostal of obese animals compared with lean animals (P < 0.05); this obesity-related increased in CS activity was related independent of age. Furthermore, respiratory muscle percent type IIb MHC was lower and percent type I MHC isoforms were higher in obese animals compared with lean animals. These data support the notion that obesity results in a fast-to-slow shift in MHC phenotype and an increase in oxidative capacity in major inspiratory muscles. The shift in MHC isoforms in obese animals is also age related, whereas the obesity-mediated increase in oxidative capacity is relatively independent of age.
Glutathione metabolic responses to loaded breathing: variation among respiratory muscles
Authors: Supinski G. , Nethery D. , Murhez N. , Ciufo R. , DiMarco A.
Published: December 2017

Several studies have shown that loaded breathing elicits an oxidation of reduced glutathione (GSH) to oxidized glutathione (GSSG) within the diaphragm, but the effects of loaded breathing on GSH and GSSG levels in other respiratory muscles have not been examined. The present experiment examined this issue by using decerebrate unanesthetized rats in which a large inspiratory resistive load was applied until respiratory arrest. Subsequently, muscle samples from the triangularis sterni, diaphragm (Dia), parasternal intercostal (PI), upper rib cage lateral intercostal, lower rib cage lateral intercostal, and soleus were assayed for GSH and GSSG. Glutathione levels were also measured on samples from unloaded control animals. We found that the Dia from loaded animals had a lower GSH level than did control animals (i.e., 653 +/- 99 and 928 +/- 40 nmol/gm for loaded and control groups, respectively; P < 0.05), higher GSSG level (68 +/- 14 and 32 &/- 7 nmol/gm for loaded and control groups, respectively; P < 0.05), and higher GSSG-to-GSH ratios (GSSG/GSH; 17.0 +/- 6.0 and 3.7 +/- 0.9% for loaded and control groups, respectively; (P <0.05). Of the other muscles examined, only the PI muscles had comparable alterations in glutathione levels in response to loading. Specifically, for the PI muscles of loaded and control groups, GSH was 427 +/- 75 and 618 +/- 40 nmol/g, (P < 0.05), GSSG was 71 +/- 16 and 20 +/- 5 nmol/g (P < 0.01), and GSSG/GSH was 22 +/- 8 and 3.6 +/- 1.2%, respectively (P < 0.05). No other muscle demonstrated a significant increase in GSSG or GSSG/GSH with loading, and only the lower rib cage lateral intercostal had a significant reduction in GSH. These findings indicate variation in the degree of glutathione oxidation elicited by inspiratory loading among the different respiratory muscles. The fact that quantitatively similar glutathione alterations were observed in the Dia and PI muscles suggests that these muscle groups may share a similar propensity to generate free radicals during inspiratory loading.
Furosemide reduces accumulated oxygen deficit in horses during brief intense exertion
Authors: Hinchcliff K. W. , McKeever K. H. , Muir W. W. , Sams R. A.
Published: December 2017

Hinchcliff, K. W., K. H. McKeever, W. W. Muir, and R. A. Sams. Furosemide reduces accumulated oxygen deficit in horses during brief intense exertion. J. Appl. Physiol. 81(4): 1550–1554, 1996.—We theorized that furosemide-induced weight reduction would reduce the contribution of anaerobic metabolism to energy expenditure of horses during intense exertion. The effects of furosemide on accumulated O2deficit and plasma lactate concentration of horses during high-intensity exercise were examined in a three-way balance randomized crossover study. Nine horses completed each of three trials: 1) a control (C) trial, 2) a furosemide-unloaded (FU) trial in which the horse received furosemide 4 h before running, and 3) a furosemide weight-loaded (FL) trial during which the horse received furosemide and carried weight equal to the weight lost after furosemide administration. Horses ran for 2 min at ∼120% maximal O2consumption. Furosemide (FU) increased O2consumption (ml ⋅ 2 min−1⋅ kg−1) compared with C (268 ± 9 and 257 ± 9, P < 0.05), whereas FL was not different from C (252 ± 8). Accumulated O2deficit (ml O2equivalents/kg) was significantly ( P < 0.05) lower during FU (81.2 ± 12.5), but not during FL (96.9 ± 12.4), than during C (91.4 ± 11.5). Rate of increase in blood lactate concentration (mmol ⋅ 2 min−1⋅ kg−1) after FU (0.058 ± 0.001), but not after FL (0.061 ± 0.001), was significantly ( P < 0.05) lower than after C (0.061 ± 0.001). Furosemide decreased the accumulated O2deficit and rate of increase in blood lactate concentration of horses during brief high-intensity exertion. The reduction in accumulated O2deficit in FU-treated horses was attributable to an increase in the mass-specific rate of O2consumption during the high-intensity exercise test.
Effect of acute head-down tilt on skeletal muscle cross-sectional area and proton transverse relaxation time
Authors: Conley Michael S. , Foley Jeanne M. , Ploutz-Snyder Lori L. , Meyer Ronald A. , Dudley Gary A.
Published: December 2017

Conley, Michael S., Jeanne M. Foley, Lori L. Ploutz-Snyder, Ronald A. Meyer, and Gary A. Dudley. Effect of acute head-down tilt on skeletal muscle cross-sectional area and proton transverse relaxation time. J. Appl. Physiol.81(4): 1572–1577, 1996.—This study investigated changes in skeletal muscle cross-sectional area (CSA) evoked by fluid shifts that accompany short-term 6° head-down tilt (HDT) or horizontal bed rest, the time course of the resolution of these changes after resumption of upright posture, and the effect of altered muscle CSA, in the absence of increased contractile activity, on proton transverse relaxation time (T2). Average muscle CSA and T2were determined by standard spin-echo magnetic resonance imaging. Analyses were performed on contiguous transaxial images of the neck and calf. After a day of normal activity, 24 h of HDT increased neck muscle CSA 19 ± 4 (SE)% ( P < 0.05) while calf muscle CSA decreased 14 ± 3% ( P < 0.05). The horizontal posture (12 h) induced about one-half of these responses: an 11 ± 2% ( P < 0.05) increase in neck muscle CSA and an 8 ± 2% decrease ( P < 0.05) in the calf. Within 2 h after resumption of upright posture, neck and calf muscle CSA returned to within 0.5% ( P > 0.05) of the values assessed after a day of normal activity, with most of the change occurring within the first 30 min. No further change in muscle CSA was observed through 6 h of upright posture. Despite these large alterations in muscle CSA, T2was not altered by more than 1.1 ± 0.6% ( P > 0.05) and did not relate to muscle size. These results suggest that postural manipulations and subsequent fluid shifts modeling microgravity elicit marked changes in muscle size. Because these responses were not associated with alterations in muscle T2, it does not appear that simple movement of water into muscle can explain the contrast shift observed after exercise.
Pulmonary vascular pressures of exercising Thoroughbred horses with and without endoscopic evidence of EIPH
Authors: Manohar Murli , Goetz Thomas E.
Published: December 2017

Manohar, Murli, and Thomas E. Goetz. Pulmonary vascular pressures of exercising Thoroughbred horses with and without endoscopic evidence of EIPH. J. Appl. Physiol.81(4): 1589–1593, 1996.—Exercise-induced pulmonary hemorrhage (EIPH) is a common occurrence in racehorses. The objective of this study was to compare pulmonary vascular pressures of healthy Thoroughbred horses with and without postexertion endoscopically detectable fresh blood in the trachea. The nasopharynx, larynx, and trachea (down to the carina) of horses were examined weekly with an endoscope 55–60 min postexertion, and the diagnosis of EIPH was confirmed by the presence of fresh blood in the trachea. Measurements of heart rate and right atrial, pulmonary arterial, and pulmonary arterial wedge pressures were made during quiet rest and during treadmill exercise performed at 14.5 m/s on a 5% uphill grade. This workload elicited maximal heart rate of the horses. Mean pulmonary capillary pressure was estimated to be halfway between the mean pulmonary arterial pressure and the mean pulmonary arterial wedge pressure. These data from 7 healthy sound exercise-trained horses that were positive on 12 consecutive occasions (at 1-wk intervals) for the postexercise presence of fresh blood in the trachea were compared with those in 8 healthy horses that were consistently negative for the evidence of fresh blood in the trachea on postexercise endoscopic examination over 12–16 wk. The heart rate and the right heart and/or pulmonary vascular pressures in the two groups of horses were similar at rest. Exercise was attended by a large significant ( P < 0.05) increase in these pressures and heart rate in both groups. However, statistically significant differences between endoscopically EIPH-positive and endoscopically EIPH-negative horses for heart rate and right atrial and pulmonary vascular pressures were not found during exercise. Thus these data revealed that the magnitude of exercise-induced right atrial as well as pulmonary arterial, capillary, and venous hypertension in endoscopically EIPH-positive horses that are otherwise healthy is quite similar to that in endoscopically EIPH-negative horses during comparable exertion.
Control of the respiratory cycle in conscious humans
Authors: Rafferty G. F. , Gardner W. N.
Published: December 2017

Rafferty, G. F., and W. N. Gardner. Control of the respiratory cycle in conscious humans. J. Appl. Physiol. 81(4): 1744–1753, 1996.—We studied in conscious humans the relative strength of mechanisms controlling timing and drive components of the respiratory cycle around their resting set points. A system of auditory feedback with end-tidal[Formula: see text] held constant in mild hyperoxia via an open circuit was used to induce subjects independently to change inspiratory time (Ti) and tidal volume (Vt I) over a wide range above and below the resting values for every breath for up to 1 h. Four protocols were studied in various levels of hypercapnia (1–5% inspired CO2). We found that Ti (and expiratory time) could be changed over a wide range (1.17–2.86 s, P < 0.01 for Ti) and Vt Iincreased by ≥500 ml ( P < 0.01) without difficulty. However, in no protocol was it possible to decrease Vt I below the free-breathing resting value in response to reduction of auditory feedback thresholds by up to 600 ml. This applied at all levels of chemical drive studied, with resting Vt I values varying from 1.06 to 1.74 liters. When reduction in Vt I was forced by the more “programmed” procedure of isocapnic panting, end-expiratory volume was sacrificed to ensure that peak tidal volume reached a fixed absolute lung volume. These results suggest that the imperative for control of resting breathing is to prevent reduction of Vt I below the level dictated by the prevailing chemical drive, presumably to sustain metabolic requirements of the body, whereas respiratory timing is weakly controlled consistent with the needs for speech and other nonmetabolic functions of breathing.
Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia
Authors: Lamanna J. C. , Haxhiu M. A. , Kutina-Nelson K. L. , Pundik S. , Erokwu B. , Yeh E. R. , Lust W. D. , Cherniack N. S.
Published: December 2017

LaManna, J. C., M. A. Haxhiu, K. L. Kutina-Nelson, S. Pundik, B. Erokwu, E. R. Yeh, W. D. Lust, and N. S. Cherniack.Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia. J. Appl. Physiol. 81(4): 1772–1777, 1996.—Metabolic changes in the brain stem were measured at the time when oxygen deprivation-induced respiratory depression occurred. Eucapnic ventilation with 8% oxygen in vagotomized urethan-anesthetized rats resulted in cessation of respiratory drive, monitored by recording diaphragm electromyographic activity, on average within 11 min (range 5–27 min), presumably via central depressant mechanisms. At that time, the brain stems were frozen in situ for metabolic analyses. By using 20-μm lyophilized sections from frozen-fixed brain stem, microregional analyses of ATP, phosphocreatine, lactate, and intracellular pH were made from 1) the ventral portion of the nucleus gigantocellularis and the parapyramidal nucleus; 2) the compact and ventral portions of the nucleus ambiguus; 3) midline neurons; 4) nucleus tractus solitarii; and 5) the spinal trigeminal nucleus. At the time of respiratory depression, lactate was elevated threefold in all regions. Both ATP and phosphocreatine were decreased to 50 and 25% of control, respectively. Intracellular pH was more acidic by 0.2–0.4 unit in these regions but was relatively preserved in the chemosensitive regions near the ventral and dorsal medullary surfaces. These results show that hypoxia-induced respiratory depression was accompanied by metabolic changes within brain stem regions involved in respiratory and cardiovascular control. Thus it appears that there was significant energy deficiency in the brain stem after hypoxia-induced respiratory depression had occurred.
Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs
Authors: Brändle Marian , Patel Kaushik P. , Wang Wei , Zucker Irving H.
Published: December 2017

Brändle, Marian, Kaushik P. Patel, Wei Wang, and Irving H. Zucker. Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs. J. Appl. Physiol. 81(4): 1855–1862, 1996.—The present study was undertaken to determine the effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations that occur in the pacing-induced model of congestive heart failure. Two groups of dogs were examined: intact ( n = 9) and SAD ( n = 9). Both groups of dogs were studied in the control (prepace) state and each week after the initiation of ventricular pacing at 250 beats/min. After the pacemaker was turned off, hemodynamic and plasma norepinephrine levels returned toward control levels in the prepaced state and after 1 and 2 wk of pacing. However, by 3 wk all hemodynamic and norepinephrine levels remained relatively constant over the 10-min observation period with the pacemaker off. With the pacemaker off, left ventricular end-diastolic pressure went from 2.7 ± 1.4 (SE) mmHg during the prepace state to 23.2 ± 2.9 mmHg in the heart failure state in intact dogs ( P < 0.01). Left ventricular end-diastolic pressure increased to 27.1 ± 2.2 mmHg from a control level of 4.2 ± 1.9 mmHg in SAD dogs ( P < 0.0003). Mean arterial pressure significantly decreased in intact and SAD dogs. Resting heart rate was significantly higher in SAD dogs and increased to 135.8 ± 8.9 beats/min in intact dogs and 136.1 ± 6.5 beats/min in SAD dogs. There were no significant differences in the hemodynamic parameters between intact and SAD dogs after pacing. Plasma norepinephrine was significantly lower in intact than in SAD dogs before pacing (197.7 ± 21.6 vs. 320.6 ± 26.6 pg/ml; P < 0.005). In the heart failure state, plasma norepinephrine increased significantly in both intact (598.3 ± 44.2 pg/ml) and SAD (644.0 ± 64.6 pg/ml) groups. There were no differences in the severity or the magnitude of the developed heart failure state in SAD vs. intact dogs. We conclude from these data that the arterial baroreflex is not the sole mechanism for the increase in sympathetic drive in heart failure.
Muscle fatigue and exhaustion during dynamic leg exercise in normoxia and hypobaric hypoxia
Authors: Fulco Charles S. , Lewis Steven F. , Frykman Peter N. , Boushel Robert , Smith Sinclair , Harman Everett A. , Cymerman Allen , Pandolf Kent B.
Published: December 2017

Fulco, Charles S., Steven F. Lewis, Peter N. Frykman, Robert Boushel, Sinclair Smith, Everett A. Harman, Allen Cymerman, and Kent B. Pandolf. Muscle fatigue and exhaustion during dynamic leg exercise in normoxia and hypobaric hypoxia. J. Appl. Physiol. 81(5): 1891–1900, 1996.—Using an exercise device that integrates maximal voluntary static contraction (MVC) of knee extensor muscles with dynamic knee extension, we compared progressive muscle fatigue, i.e., rate of decline in force-generating capacity, in normoxia (758 Torr) and hypobaric hypoxia (464 Torr). Eight healthy men performed exhaustive constant work rate knee extension (21 ± 3 W, 79 ± 2 and 87 ± 2% of 1-leg knee extension O2 peak uptake for normoxia and hypobaria, respectively) from knee angles of 90–150° at a rate of 1 Hz. MVC (90° knee angle) was performed before dynamic exercise and during ≤5-s pauses every 2 min of dynamic exercise. MVC force was 578 ± 29 N in normoxia and 569 ± 29 N in hypobaria before exercise and fell, at exhaustion, to similar levels (265 ± 10 and 284 ± 20 N for normoxia and hypobaria, respectively; P > 0.05) that were higher ( P < 0.01) than peak force of constant work rate knee extension (98 ± 10 N, 18 ± 3% of MVC). Time to exhaustion was 56% shorter for hypobaria than for normoxia (19 ± 5 vs. 43 ± 7 min, respectively; P < 0.01), and rate of right leg MVC fall was nearly twofold greater for hypobaria than for normoxia (mean slope = −22.3 vs. −11.9 N/min, respectively; P < 0.05). With increasing duration of dynamic exercise for normoxia and hypobaria, integrated electromyographic activity during MVC fell progressively with MVC force, implying attenuated maximal muscle excitation. Exhaustion, per se, was postulated to relate more closely to impaired shortening velocity than to failure of force-generating capacity.
Effect of 2-chloropropionate on initial lactate uptake by rat skeletal muscle sarcolemmal vesicles
Authors: Granier P. , Dubouchaud H. , Eydoux N. , Mercier J. , Préfaut C.
Published: December 2017

Granier, P., H. Dubouchaud, N. Eydoux, J. Mercier, and C. Préfaut. Effect of 2-chloropropionate on initial lactate uptake by rat skeletal muscle sarcolemmal vesicles. J. Appl. Physiol. 81(5): 1973–1977, 1996.—2-Chloropropionate (2-CP) is a halogenated monocarboxylic acid generally used to decrease blood lactate concentration in various metabolic states. To investigate whether it has an inhibitory effect on sarcolemmal lactate transport, we compared the initial rate of lactate transport in sarcolemmal membrane vesicles purified from 20 male Wistar rats with and without 2-CP. Transport by these vesicles was measured as uptake ofl-(+)-[U-14C]lactate under pH gradient-stimulated cisinhibition. The time courses of 1 mMl-(+)-lactate uptake into vesicles both with and without 10 mM 2-CP (l- ord-) displayed saturation kinetics. Lactate uptake values were lower with 10 mMl-2-CP and 10 mMd-2-CP in comparison to the control values. Both 10 mMl-2-CP and 10 mMd-2-CP significantly inhibited 1 mM l-(+)-lactate uptake (55.8 ± 9.1 and 53.5 ± 12.1%, respectively; P < 0.001), whereas a smaller inhibition was observed with a higher lactate concentration of 50 mM (40.2 ± 11.2 and 38.7 ± 12.4%; P < 0.001 and P < 0.05, respectively). However, a higher d-2-CP concentration (50 mM) increased the inhibition of pH-stimulated 1 mMl-(+)-lactate uptake (77.0 ± 9.4%; P < 0.001).d-2-CP had a trans-stimulation effect on the initial rate of lactate efflux of 1 mMl-(+)-lactate compared with baseline efflux (9.5 ± 0.8 vs. 5.1 ± 0.4 nmol ⋅ min−1 ⋅ mg protein−1; P < 0.05). 2-CP significantly inhibited the initial rate of lactate uptake in skeletal muscle sarcolemmal membrane vesicles. This result suggests that 2-CP is a nonstereoselective substrate of the lactate muscle carrier that impairs lactate transport.
Exercise and exhaustion effects on glycogen synthesis pathways
Authors: Gunderson Hans , Wehmeyer Nadja , Burnett Diane , Nauman John , Hartzell Cynthia , Savage Scott
Published: December 2017

Gunderson, Hans, Nadja Wehmeyer, Diane Burnett, John Nauman, Cynthia Hartzell, and Scott Savage. Exercise and exhaustion effects on glycogen synthesis pathways. J. Appl. Physiol. 81(5): 2020–2026, 1996.—Female Sprague-Dawley rats were infused with [1-13C]glucose to measure the effect of endurance training and the effect of various metabolic conditions on pathways of hepatic glycogen synthesis. Four metabolic states [sedentary (S), trained (T), sedentary exhausted (SE), and trained exhausted (TE)] were studied. T and TE rats were trained on a motor-driven treadmill (30 m/min, 15% grade, 1.0 h/day, 5 days/wk) for 8–10 wk. After a 24-h fast, SE and TE rats were run to exhaustion (sedentary average = 78 min, trained average = 155 min) at a training pace and immediately infused with labeled glucose for 2 h. S and T rats were infused after a 24-h fast. After infusion, tissues were removed and glycogen was isolated and hydrolyzed to glucose. The glucose was measured for distribution of13C by using nuclear magnetic resonance. Glycogen was synthesized predominantly by the indirect pathway for all metabolic states, indicating that infused glucose was first metabolized primarily in the peripheral tissue. The direct-pathway utilization was greater in rested S than in rested T animals (30 vs. 14%); however, for exhausted animals, the trained use of the direct pathway was greater (22 vs. 9%). Both TE and rested T animals utilize the indirect pathway a comparable amount. Sedentary animals, on the other hand, dramatically decreased utilization of the direct pathway, with exhaustive exercise changing from 30 to 9%. The results indicate that endurance training modifies glucose utilization during glycogen synthesis after fasting and exhaustive exercise.
Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle
Authors: Edwards N. , Wilcox I. , Polo O. J. , Sullivan C. E.
Published: December 2017

Edwards, N., I. Wilcox, O. J. Polo, and C. E. Sullivan.Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle. J. Appl. Physiol. 81(5): 2142–2146, 1996.—We investigated the cardiovascular responses to acute hypercapnia during the menstrual cycle. Eleven female subjects with regular menstrual cycles performed hypercapnic rebreathing tests during the follicular and luteal phases of their menstrual cycles. Ventilatory and cardiovascular variables were recorded breath by breath. Serum progesterone and estradiol were measured on each occasion. Serum progesterone was higher during the luteal [50.4 ± 9.6 (SE) nmol/l] than during the follicular phase (2.1 ± 0.7 nmol/l; P < 0.001), but serum estradiol did not differ (follicular phase, 324 ± 101 pmol/l; luteal phase, 162 ± 71 pmol/l; P = 0.61). The systolic blood pressure responses during hypercapnia were 2.0 ± 0.3 and 4.0 ± 0.5 mmHg/Torr (1 Torr = 1 mmHg rise in end-tidal [Formula: see text]) during the follicular and luteal phases, respectively, of the menstrual cycle ( P < 0.01). The diastolic blood pressure responses were 1.1 ± 0.2 and 2.1 ± 0.3 mmHg/Torr during the follicular and luteal phases, respectively ( P < 0.002). Heart rate responses did not differ during the luteal (1.7 ± 0.3 beats ⋅ min−1 ⋅ Torr−1) and follicular phases (1.4 ± 0.3 beats ⋅ min−1 ⋅ Torr−1; P = 0.59). These data demonstrate a greater pressor response during the luteal phase of the menstrual cycle that may be related to higher serum progesterone concentrations.
Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle
Authors: Toussaint Jean-François , Kwong Kenneth K. , M’Kparu Fidelis , Weisskoff Robert M. , Laraia Paul J. , Kantor Howard L.
Published: December 2017

Toussaint, Jean-François, Kenneth K. Kwong, Fidelis M’Kparu, Robert M. Weisskoff, Paul J. LaRaia, and Howard L. Kantor.Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle. J. Appl. Physiol. 81(5): 2221–2228, 1996.—Using nuclear magnetic resonance (NMR), we have examined the relationship of high-energy phosphate metabolism and perfusion in human soleus and gastrocnemius muscles. With31P-NMR spectroscopy, we monitored phosphocreatine (PCr) decay and recovery in eight normal volunteers and four heart failure patients performing ischemic plantar flexion. By using echo-planar imaging, perfusion was independently measured by a local [inversion-recovery (T1-flow)] and a regional technique (NMR-plethysmography). After correction for its pH dependence, PCr recovery time constant is 27.5 ± 8.0 s in normal volunteers, with mean flow 118 ± 75 (soleus and gastrocnemius T1-flow) and 30.2 ± 9.7 ml ⋅ 100 ml−1 ⋅ min−1(NMR-plethysmography-flow). We demonstrate a positive correlation between PCr time constant and local perfusion given by y = 50 − 0.15 x( r 2 = 0.68, P = 0.01) for the 8 normal subjects, and y = 64 − 0.24 x( r 2 = 0.83, P = 0.0001) for the 12 subjects recruited in the study. Regional perfusion techniques also show a significant but weaker correlation. Using this totally noninvasive method, we conclude that aerobic ATP resynthesis is related to the magnitude of perfusion, i.e., O2availability, and demonstrate that magnetic resonance imaging and magnetic resonance spectroscopy together can accurately assess muscle functional status.
Ventilation-perfusion alterations after smoke inhalation injury in an ovine model
Authors: Shimazu Takeshi , Yukioka Tetsuo , Ikeuchi Hisashi , Mason Arthur D. , Wagner Peter D. , Pruitt Basil A.
Published: December 2017

Shimazu, Takeshi, Tetsuo Yukioka, Hisashi Ikeuchi, Arthur D. Mason, Jr., Peter D. Wagner, and Basil A. Pruitt, Jr.Ventilation-perfusion alterations after smoke inhalation injury in an ovine model. J. Appl. Physiol.81(5): 2250–2259, 1996.—To study the pathophysiological mechanism of progressive hypoxemia after smoke inhalation injury, alterations in ventilation-perfusion ratio (V˙a/Q˙) were studied in an ovine model by using the multiple inert gas elimination technique. Because ethane was detected in expired gas of some sheep, we replaced ethane with krypton, which was a unique application of the multiple inert gas elimination technique when one of the experimental gases is present in the inspirate. Severity-related changes were studied 24 h after injury in control and mild, moderate, and severe inhalation injury groups. Time-related changes were studied in controls and sheep with moderate injury at 6, 12, 24, and 72 h. Arterial [Formula: see text] decreased progressively with severity of injury as well as with time. In smoke-exposed animals, blood flow was recruited to lowV˙a/Q˙compartment (0 <V˙a/Q˙ < 0.1; 17.6 ± 10.6% of cardiac output, 24 h, moderate injury) from normalV˙a/Q˙compartment (0.1 <V˙a/Q˙< 10). However, increases in true shunt (V˙a/Q˙= 0; 5.6 ± 2.5%, 24 h, moderate injury) and dead space were not consistent findings. TheV˙a/Q˙patterns suggest the primary change in smoke inhalation injury to be a disturbance of ventilation.
Calibration of Pd-porphyrin phosphorescence for oxygen concentration measurements in vivo
Authors: Sinaasappel M. , Ince C.
Published: December 2017

Sinaasappel, M., and C. Ince. Calibration of Pd-porphyrin phosphorescence for oxygen concentration measurements in vivo. J. Appl. Physiol. 81(5): 2297–2303, 1996.—Quantitative measurement of oxygen concentrations in the microvasculature is of prime importance in issues related to oxygen transport to tissue. The introduction of the quenching of the Pd-porphyrin phosphorescence as oxygen sensor in vivo by Wilson et al. ( J. Appl. Physiol.74: 580–589, 1993) has provided in this context a major advance in this area of research. For in vivo application, the dye is coupled to albumin to restrict the dye to the circulation and to measure oxygen in the physiological range. In this study a phosphorimeter with a gated photomultiplier is presented and validated. Furthermore, a nonlinear-fit method using the Marquardt-Levenberg algorithm is used to calculate the decay time. With this new phosphorimeter, calibration measurements were performed to investigate the effects of pH, temperature, and diffusivity. The results present a preparation method for albumin coupling of the dye that eliminates the pH dependency of the quenching kinetics. Furthermore, the decreased oxygen diffusivity of serum was compared with that of water, and it was shown that calibration constants measured in water can be extrapolated to serum.
Lung tissue behavior in the mouse during constriction induced by methacholine and endothelin-1
Authors: Nagase Takahide , Matsui Hirotoshi , Aoki Tomoko , Ouchi Yasuyoshi , Fukuchi Yoshinosuke
Published: December 2017

Nagase, Takahide, Hirotoshi Matsui, Tomoko Aoki, Yasuyoshi Ouchi, and Yoshinosuke Fukuchi. Lung tissue behavior in the mouse during constriction induced by methacholine and endothelin-1. J. Appl. Physiol. 81(6): 2373–2378, 1996.—Recently, mice have been extensively used to investigate the pathogenesis of pulmonary disease because appropriate murine models, including transgenic mice, are being increasingly developed. However, little information about the lung mechanics of mice is currently available. We questioned whether lung tissue behavior and the coupling between dissipative and elastic processes, hysteresivity (η), in mice would be different from those in the other species. To address this question, we investigated whether tissue resistance (Rti) and η in mice would be affected by varying lung volume, constriction induced by methacholine (MCh) and endothelin-1 (ET-1), and high-lung-volume challenge during induced constriction. From measured tracheal flow and tracheal and alveolar pressures in open-chest ICR mice during mechanical ventilation [tidal volume = 8 ml/kg, frequency (f) = 2.5 Hz], we calculated lung resistance (Rl), Rti, airway resistance (Raw), lung elastance (El), and η (= 2πfRti/El). Under baseline conditions, increasing levels of end-expiratory transpulmonary pressure decreased Raw and increased Rti. The administration of aerosolized MCh and intravenous ET-1 increased Rl, Rti, Raw, and El in a dose-dependent manner. Rti increased from 0.207 ± 0.010 to 0.570 ± 0.058 cmH2O ⋅ ml−1 ⋅ s after 10−7 mol/kg ET-1 ( P < 0.01). After induced constriction, increasing end-expiratory transpulmonary pressure decreased Raw. However, η was not affected by changing lung volume, constriction induced by MCh and ET-1, or high-lung-volume challenge during induced constriction. These observations suggest that 1) η is stable in mice regardless of various conditions, 2) Rti is an important fraction of Rl and increases after induced constriction, and 3) mechanical interdependence may affect airway smooth muscle shortening in this species. In mammalian species, including mice, analysis of η may indicate that both Rti and El essentially respond to a similar degree.
Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men
Authors: Ross Robert , Rissanen John , Pedwell Heather , Clifford Jennifer , Shragge Peter
Published: December 2017

Ross, Robert, John Rissanen, Heather Pedwell, Jennifer Clifford, and Peter Shragge. Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men. J. Appl. Physiol. 81(6): 2445–2455, 1996.—The effects of diet only (DO) and diet combined with either aerobic (DA) or resistance (DR) exercise on subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean tissue (LT), and skeletal muscle (SM) tissue were evaluated in 33 obese men (DO, n= 11; DA, n = 11; DR, n = 11). All tissues were measured by using a whole body multislice magnetic resonance imaging (MRI) model. Within each group, significant reductions were observed for body weight, SAT, and VAT ( P < 0.05). The reductions in body weight (∼10%) and SAT (∼25%) and VAT volume (∼35%) were not different between groups ( P > 0.05). For all treatments, the relative reduction in VAT was greater than in SAT ( P < 0.05). For the DA and DR groups only, the reduction in abdominal SAT (∼27%) was greater ( P < 0.05) than that observed for the gluteal-femoral region (∼20%). Conversely, the reduction in VAT was uniform throughout the abdomen regardless of treatment ( P > 0.05). MRI-LT and MRI-SM decreased both in the upper and lower body regions for the DO group alone ( P < 0.05). Peak O2uptake (liters) was significantly improved (∼14%) in the DA group as was muscular strength (∼20%) in the DR group ( P< 0.01). These findings indicate that DA and DR result in a greater preservation of MRI-SM, mobilization of SAT from the abdominal region, by comparison with the gluteal-femoral region, and improved functional capacity when compared with DO in obese men.
Delay time adjustments to minimize errors in breath-by-breath measurement of V˙o2during exercise
Authors: Proctor David N. , Beck Kenneth C.
Published: December 2017

Proctor, David N., and Kenneth C. Beck. Delay time adjustments to minimize errors in breath-by-breath measurement ofV˙o2during exercise. J. Appl. Physiol. 81(6): 2495–2499, 1996.—If the delay time between gas concentration and flow signals is not adequately corrected during breath-by-breath analysis of expired gas, an error in calculation of oxygen consumption (V˙o2) will result. To examine the frequency and delay time dependences of errors inV˙o2measurement, six healthy men exercised at 100, 200, and 250 W on a cycle ergometer while breath-by-breath assessment ofV˙o2was made simultaneously with collection of expired air. Subjects breathed first at normal rates (15–30 breaths/min) and then at 70 breaths/min. Each subject performed each level of exercise twice by using erroneous values for the delay time between gas concentration and flow signals. At normal breathing frequencies, errors inV˙o2measurement were ±10% over the full range of delay times used, and the errors were not tightly correlated with variations in delay times from optimum. However, at 70 breaths/min, errors approached ±30% as the variations in delay times deviated ±0.1 s from the optimal, and the errors were highly correlated with the variations in delay times. We conclude that there is greater potential for errors inV˙o2measurement with incorrect delay time at higher breathing frequencies. These findings suggest that the optimal delay time for breath-by-breath systems should be adjusted by using high breathing frequencies.
Prostaglandins E2 and I2 cause greater relaxations in pulmonary veins than in arteries of newborn lambs
Authors: Gao Yuansheng , Zhou Haiyan , Ibe Basil O. , Raj J. Usha
Published: December 2017

Gao, Yuansheng, Haiyan Zhou, Basil O. Ibe, and J. Usha Raj.Prostaglandins E2 and I2 cause greater relaxations in pulmonary veins than in arteries of newborn lambs. J. Appl. Physiol. 81(6): 2534–2539, 1996.—Prostaglandins E2(PGE2) and I2(PGI2) are important vasoactive mediators in pulmonary vessels. The present study was designed to determine whether the responses of pulmonary arteries to these prostanoids are different from those of veins in newborn lambs. Fourth-generation pulmonary arterial and venous rings without endothelium were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2, 37°C), and their isometric force was measured. During contraction with endothelin-1 or U-46619 (indomethacin was present to eliminate the possible involvement of endogenous cyclooxygenase products), PGE2, PGI2, and carbacyclin (a stable analogue of PGI2) induced greater relaxations in veins than in arteries. In both vessel types, relaxations induced by PGE2 were greater than those induced by PGI2or carbacyclin. Forskolin, an activator of adenylate cyclase, also induced greater relaxation of veins than of arteries. Relaxation induced by 8-bromoadenosine 3′,5′-cyclic monophosphate, an analogue of adenosine 3′,5′-cyclic monophosphate (cAMP), was comparable in both vessel types. Radioimmunoassay revealed that the basal and calcium ionophore A-23187-induced releases of PGE2 or 6-ketoprostaglandin F1α (the stable breakdown product of PGI2) were similar between arteries and veins. Measurement of cAMP (in the presence of isobutylmethylxanthine) showed that PGE2 and forskolin induced greater increase in cAMP in veins than in arteries. Our results demonstrate that PGE2 and PGI2 are more potent vasodilators in pulmonary veins than in arteries in newborn lambs. A difference in the activity of adenylate cyclase may contribute to the differential responses to PGE2 and PGI2 between pulmonary arteries and veins. Furthermore, PGE2appears play an more important role than does PGI2 in modulating pulmonary vascular tone of newborn lambs.
Heat stroke: opioid-mediated mechanisms
Authors: Romanovsky Andrej A. , Blatteis Clark M.
Published: December 2017

Romanovsky, Andrej A., and Clark M. Blatteis. Heat stroke: opioid-mediated mechanisms. J. Appl. Physiol. 81(6): 2565–2570, 1996.—In our previous study in guinea pigs, intensive and prolonged intraperitoneal heating (IPH) caused heat stroke characterized by high mortality and accompanied by two paradoxical phenomena: ear skin vasoconstriction at a high body temperature (Tb) (hyperthermia-induced vasoconstriction) and a post-IPH Tb fall at an ambient temperature (Ta) below thermoneutrality (hyperthermia-induced hypothermia). In this study, we tested the hypothesis that the mechanisms of the two phenomena involve endogenous opioid agonists. Experiments were conducted in 24 unanesthetized, lightly restrained guinea pigs, each chronically implanted with an intraperitoneal thermode and intrahypothalamic thermocouple. The thermoregulatory effects of a wide-spectrum opioid-receptor antagonist, naltrexone (NTX; 50 or 0 μmol/kg sc), were studied in IPH-induced heat stroke and under normal conditions. IPH was accomplished by perfusing (50 ml/min; 80 min) water (45°C) through the thermode. Ta was maintained at ∼24°C. Skin vasodilation occurred at the onset of IPH but later changed to vasoconstriction despite high Tband continuing IPH. IPH-induced hyperthermia (1.8 ± 0.1°C) was followed by a post-IPH Tb fall (−5.1 ± 0.7°C; calculated for the survivors only). The 48-h mortality rate was 50%. NTX prevented the hyperthermia-induced vasoconstriction and attenuated the hyperthermia-induced hypothermia (−1.8 ± 0.4°C). None of the NTX-treated animals died. The effects of NTX on Tb regulation under normal conditions were minor. These results indicate that the phenomena of both hyperthermia-induced vasoconstriction and hyperthermia-induced hypothermia are opioid dependent. The latter is speculated to reflect opioid-mediated inhibition of metabolism; the former is thought to result from opioid-induced hemodynamic alterations. Because both phenomena did not occur in the NTX-treated survivors, the skin vasoconstriction at high Tb and the posthyperthermia Tb fall may be viewed as markers of the severity of heat stroke. It is suggested that opioid antagonists may have therapeutic potential in heat-induced disorders.
Pulmonary vasoconstrictor effects of prostacyclin in rats: potential role of thromboxane receptors
Authors: Zhao Yi-Ju , Wang Jian , Tod Mary L. , Rubin Lewis J. , Yuan Xiao-Jian
Published: December 2017

Zhao, Yi-Ju, Jian Wang, Mary L. Tod, Lewis J. Rubin, and Xiao-Jian Yuan. Pulmonary vasoconstrictor effects of prostacyclin in rats: potential role of thromboxane receptors. J. Appl. Physiol. 81(6): 2595–2603, 1996.—Endogenous prostacyclin (PGI2; epoprostenol) is a potent endothelium-derived pulmonary vasodilator. However, the effects of exogenous PGI2 on isolated arteries could be either relaxant or contractile, depending on the species and organ studied. The present study investigated the distal pathways involved in the PGI2-induced contraction in rat intrapulmonary artery (PA) and relaxation in lamb PA. When vessels were precontracted with 30 mM K+, PGI2 (1 μM) induced relaxation in lamb PA but caused contraction in rat PA. Use of 30 mM K+, phenylephrine, serotonin, angiotensin II, or hypoxia to precontract the vessels did not alter the contractile effect of PGI2 in rat PA. Nevertheless, PGI2 produced a mild relaxation in rat PA precontracted by U-46619, a thromboxane A2(TxA2)-receptor agonist, whereas the TxA2-receptor blocker SQ-29548 (0.1–0.5 μM) abolished the contractile response in rat PA. These data suggest that PGI2-induced contraction is mediated by activation of TxA2 receptors. The PGI2-induced modest relaxation in rat PA, which was only observed when TxA2 receptors were blocked by SQ-29548, suggests that the PGI2-mediated vasorelaxant pathway is diminished in these vessels. Simultaneous application of forskolin, an adenylate cyclase activator, and rolipram, a phosphodiesterase inhibitor, caused similar relaxation in both rat and lamb PA. This suggests that the adenosine 3′,5′-cyclic monophosphate-dependent relaxing pathway is intact in rat PA and is comparable to that in lamb PA. On the basis of these data, we conclude that the pathways responsible for the paradoxical effects of PGI2 on rat and lamb PA are located upstream of the adenosine 3′,5′-cyclic monophosphate-dependent relaxing pathway and that a paucity of PGI2 receptors in rat PA may be responsible.
Pseudoephedrine is without ergogenic effects during prolonged exercise
Authors: Gillies Hunter , Derman Wayne E. , Noakes Timothy D. , Smith Peter , Evans Alicia , Gabriels Gary
Published: December 2017

Gillies, Hunter, Wayne E. Derman, Timothy D. Noakes, Peter Smith, Alicia Evans, and Gary Gabriels.Pseudoephedrine is without ergogenic effects during prolonged exercise. J. Appl. Physiol. 81(6): 2611–2617, 1996.—This study was designed to measure whether a single dose of 120 mg pseudoephedrine ingested 120 min before exercise influences performance during 1 h of high-intensity exercise. The effects of exercise on urinary excretion of the drug were also studied. Ten healthy male cyclists were tested on two occasions, separated by at least 7 days, by using a randomly assigned, double-blind, placebo-controlled, crossover design. Exercise performance was tested during a 40-km trial on a laboratory cycle ergometer, and skeletal muscle function was measured during isometric contractions. On a third occasion, subjects ingested 120 mg pseudoephedrine but did not exercise [control (C)]. Pseudoephedrine did not influence either time trial performance [drug (D) vs. placebo: 58.1 ± 1.4 (SE) vs. 58.7 ± 1.5 min] or isometric muscle function. Urinary pseudoephedrine concentrations were significantly increased 1 h after exercise (D vs. C: 114.3 ± 27.2 vs. 35.4 ± 13.1 μg/ml; P < 0.05). Peak plasma pseudoephedrine concentrations ( P < 0.05) but not time taken to reach peak plasma concentrations or the area under the plasma pseudoephedrine concentration vs. time curve was significantly increased in the total group with exercise (D vs. C). In three subjects, plasma pseudoephedrine concentrations were not influenced by exercise. Only these subjects showed increased urinary pseudoephedrine excretion during exercise. We conclude that a single therapeutic dose of pseudoephedrine did not have a measurable ergogenic effect during high-intensity exercise of 1-h duration, but plasma drug concentrations and urinary excretion were altered by exercise. These findings have practical relevance to doping control regulations in international sporting competitions.