bluuebunny/crossref_metadata_2025 huggingface dataset:
Dilution acidosis: evidence for a role of intracellular pH in the control of ventilation
Authors: Kasserra C. E. , Jones D. R.
Published: December 2017

Acute hyperosmolality results in an extracellular dilution acidosis and hypercarbia that does not stimulate ventilatory compensation. The osmotic stress is also associated with shifts in water and electrolyte balance and an increase in intracellular pH. The alkaline intracellular pH was hypothesized to have a role in preventing a normal respiratory response to the extracellular acidosis and hypercarbia. Therefore, this study examined the effect of ion-exchange blockade on intra- and extracellular pH and ventilation during acute hyperosmolality in the Pekin duck (Anas platyrhynchos) by using 31P-nuclear magnetic resonance spectroscopy. Both 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and amiloride inhibited the development of the intracellular alkalosis that normally develops in muscle during acute hyperosmolality. Instead, exposure to hyperosmotic stress during ion-exchange blockade resulted in a significant acidosis both intracellularly and extracellularly. Arterial pH decreased 0.10 +/- 0.04 pH unit with a sucrose infusion after either blocker, and intracellular pH decreased 0.11 +/- 0.06 and 0.16 +/- 0.04 pH units with a sucrose infusion after DIDS and amiloride, respectively. Ventilation increased 79 +/- 28 and 122 +/- 100%, respectively, during acute hyperosmolality after ion-exchange blockade with either DIDS or amiloride. The results suggest that intracellular pH may play a role in the ventilatory response to acid-base perturbations. The data also indicate that both Cl-/HCO3- and Na+/H+ exchanges are involved in the development of the intracellular alkalosis during hyperosmotically induced extracellular acidosis.
Lymphatic tissue changes in rats flown on Spacelab Life Sciences-2
Authors: Congdon C. C. , Allebban Z. , Gibson L. A. , Kaplansky A. , Strickland K. M. , Jago T. L. , Johnson D. L. , Lange R. D. , Ichiki A. T.
Published: December 2017

Thymus, spleen, inguinal lymph node, and bone marrow specimens from rats flown on the 14-day Spacelab Life Sciences-2 mission were examined after staining of tissue sections. The primary observation was a transient retrogressive change in lymphatic tissues in the rats within a few hours after landing. There was a diffuse increase in tingible body-containing macrophages in the cortex of the thymus, thymus-dependent areas of the splenic white pulp, and inguinal lymph node. This was not observed 9 days after recovery. The in situ labeling of fragmented DNA strands catalyzed by exogenous terminal deoxynucleotidyltransferase (TdT) with ApopTag reagents (Oncor, Gaithersburg, MD) inside the tingible body-containing macrophages indicated that the process was one of apoptosis. No increase in tingible body macrophage activity was noted in thymus and spleen tissue obtained from rats in flight on flight day 13. The reaction to gravitational stress from readaptation to 1 G is the most likely explanation of the transient retrogressive change in lymphatic tissues.
Phenylbutazone increases right atrial pressure and heart rate of running horses
Authors: Mitten L. A. , Hinchcliff K. W. , Pate J. L.
Published: December 2017

The effect of inhibition of cyclooxygenase activity on the hemodynamic response to exertion was examined in 6 horses. Rates of O2 consumption and CO2 production and carotid, pulmonary arterial, and right atrial pressures were measured while the horses performed a standardized exercise test on a treadmill after treatment with phenylbutazone or a placebo. Phenylbutazone (8.8 mg/kg p.o. for 2 days and 4.4 mg/kg i.v. 60 min before exertion) abolished the exertion-induced increases in plasma 6-ketoprostaglandin F1 alpha and thromboxane B2 concentrations, confirming inhibition of cyclooxygenase activity. Phenylbutazone treatment resulted in significantly (P < 0.05) higher heart rates and right atrial pressures during exertion than did treatment with placebo, which may have been due to increased myocardial sensitivity to sympathetic stimulation and/or decreased venous compliance. There was not a detectable effect of phenylbutazone on carotid or pulmonary arterial pressures, O2 consumption, CO2 production, or blood lactate concentration. Changes in plasma volume during exertion were not influenced by phenylbutazone. These results demonstrate that cyclooxygenase products likely mediate or modulate some of the systemic hemodynamic responses to exertion in horses.
Severe dietary magnesium deficiency does not alter levels and function of myocardial Gs alpha and Gi alpha
Authors: Shi B. , Heavner J. E. , Spallholz J. E. , Boylan L. M.
Published: December 2017

Magnesium ions (Mg2+) play a crucial role in the activation and synthesis of guanine nucleotide-binding proteins (G proteins). However, there is no information about the influence of in vivo magnesium deficiency on the function and levels of G proteins. This study was done to investigate whether dietary magnesium deficiency alters function and levels of the two major myocardial G proteins, Gi alpha and Gs alpha. Severe hypomagnesemia and a significant reduction of myocardial magnesium occurred in rats fed a magnesium-deficient diet for 6 wk vs. rats fed a normal-magnesium diet (control). The magnesium-deficient rats developed focal myocardial lesions but their cardiac function was not impaired. Myocardial immunodetectable Gs alpha and Gi alpha levels of magnesium-deficient rats did not differ from control (Gs alpha: 2.39 +/- 0.52 vs. 2.76 +/- 0.72 arbitrary units/microgram protein, P > 0.05; Gi alpha: 1.60 +/- 0.52 vs. 1.89 +/- 0.30 arbitrary units/microgram protein, P > 0.05). Similarly, the function of Gs alpha and Gi alpha estimated by basal and ligand-stimulated adenylyl cyclase activity was not significantly different between the two groups of animals. The results show that dietary-derived magnesium deficiency sufficient to produce severe hypomagnesemia does not produce any significant change in levels or function of myocardial G proteins.
Excitatory amino acid concentrations in the spinal dorsal horn of cats during muscle contraction
Authors: Hand G. A. , Kramer G. L. , Petty F. , Ordway G. A. , Wilson L. B.
Published: December 2017

In anesthetized cats, static hindlimb muscle contraction reflexly increases mean arterial pressure (MAP) and heart rate (HR). Pharmacological and immunohistochemical evidence suggests that excitatory amino acids are involved in the spinal transmission of this reflex. Using microdialysis and high-performance liquid chromatography technology, we tested the hypothesis that static contraction of the triceps surae muscle increases the extracellular concentration of glutamate (Glu) and aspartate (Asp) at the L7 level of the dorsal horn of the spinal cord. With the exception of the L7 dorsal root, the L5-S2 dorsal and ventral roots were cut ipsilateral to the contracting muscle. After the insertion of microdialysis probes and a 3-h recovery period, a 2-min static contraction was electrically evoked. MAP and HR increased by 53 +/- 8 mmHg and 20 +/- 4 beats/min. The concentration of Glu increased from 324 +/- 59 to 857 +/- 80 nM, whereas Asp increased from 199 +/- 57 to 499 +/- 113 nM. These results were repeatable, in that Glu and Asp rose by similar amounts in two subsequent contractions. In both of these latter contractions, MAP and HR were also significantly increased. By contrast, in a subset of cats whose L7 dorsal roots were cut after the first contraction, neither MAP, HR, Glu, nor Asp was significantly increased over baseline levels. These data demonstrate that static contraction of the hindlimb increases the extracellular concentration of Glu and Asp in the dorsal horn. In summary, the results from this study are in agreement with previous findings suggesting that excitatory amino acids are involved in the spinal transmission of sensory information from the hindlimb muscle.
Comparison of regional cerebral blood flow with transcranial magnetic stimulation at different forces
Authors: Dettmers C. , Ridding M. C. , Stephan K. M. , Lemon R. N. , Rothwell J. C. , Frackowiak R. S.
Published: December 2017

This study's objective was to investigate regional cerebral blood flow (rCBF) within the primary motor cortex (M1) and to compare it with thresholds of transcranial magnetic stimulation (TMS) and electromyographic recordings during exertion of different force levels with the right index finger. Quantitative electromyographic recordings, TMS, and positron emission tomography scans were performed while five and six volunteers, respectively, pressed a Morse key repetitively or with constant force with the right hand at five different force levels: 5, 10, 20, 40, and 60% of the individual's maximum voluntary contraction (MVC). Although at 5% MVC muscle activity was restricted to the first dorsal interosseus muscle, superficial finger flexors, and extensors, there was progressive involvement of proximal muscles during finger flexion with increasing force. rCBF increased logarithmically in the contralateral M1 with increasing force. In ipsilateral M1, rCBF decreased at 5% MVC and then increased logarithmically at higher force levels. TMS thresholds in the contralateral hemisphere declined logarithmically to reach a plateau at high force levels. The threshold in the ipsilateral hemisphere decreased slightly at high force levels. The logarithmic increase of rCBF and decrease of TMS thresholds in the contralateral hemisphere suggest related underlying physiological phenomena; increased cortical synaptic activity and increased excitability. It suggested that the pronounced ipsilateral rCBF alterations reflect transcallosal inhibition and are more prominent during repetitive movements (as used in the positron emission tomography study) than during the generation of a constant force (as exerted during TMS).
Transcription of the rat skeletal muscle hexokinase II gene is increased by acute exercise
Authors: O'Doherty R. M. , Bracy D. P. , Granner D. K. , Wasserman D. H.
Published: December 2017

A single bout of acute exercise increases hexokinase (HK) II mRNA and enzyme activity [R. M. O'Doherty, D. P. Bracy, H. Osawa, D. H. Wasserman, and D. K. Granner. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E171-E178, 1994]. The present study addresses the mechanism of the increase in HK II mRNA. Male rats undertook a single bout of treadmill exercise and were then killed immediately or after a predetermined recovery period. The gastrocnemius/plantaris muscle complex, composed of mixed fiber types, was excised; the nuclei were isolated; and HK I, HK II, beta-actin, and alpha-tubulin gene transcription rates were measured. Genomic DNA and plasmid DNA were used as positive and negative controls, respectively. Immediately after the cessation of 30, 45, or 90 min of exercise, HK II gene transcription rates were 1.3 +/- 0.3-,2.9 +/- 0.3-, and 4.0 +/- 0.6-fold, respectively, above those of sedentary controls. The increases after 45 and 90 min of exercise were statistically significant (P < 0.01). One hour after the cessation of 30 min of exercise, HK II gene transcription was significantly increased (1.40 +/- 0.03-fold; P < 0.05). At all time points, transcription of the HK I, beta-actin, and alpha-tubulin genes was unchanged. We conclude that the exercise-induced increase in HK II gene transcription appears to play a major role in the increase of HK II mRNA and activity.
CHO feeding before prolonged exercise: effect of glycemic index on muscle glycogenolysis and exercise performance
Authors: Febbraio M. A. , Stewart K. L.
Published: December 2017

This study examined the effect of preexercise carbohydrate (CHO) ingestion on muscle CHO metabolism and performance during prolonged exercise. Six endurance-trained men performed three exercise trials on a cycle ergometer after ingesting either a high glycemic index (HGI), low glycemic index (LGI), or placebo (Con) meal 45 min before exercise. During each trial, subjects cycled at a workload corresponding to 70% peak oxygen uptake for 120 min, followed by a 15-min performance cycle where total work (kJ) was measured. Ingestion of HGI resulted in an elevated (P < 0.01) blood glucose concentration 15 min after ingestion, compared with LGI and Con, but there were no differences in the glycemic responses to the meals thereafter, despite plasma insulin concentration being higher (P < 0.01) throughout the rest period after ingestion of HGI compared with LGI and Con. Plasma free fatty acid concentrations were lower (P < 0.05) throughout exercise in HGI compared with LGI and Con. In addition, concentrations of this metabolite were lower (P < 0.05) during the first hour of exercise in LGI compared with Con. Despite these results, no differences were observed in either the rate of muscle glycogen utilization during submaximal exercise or work output during the performance cycle when the three trials were compared. These results demonstrate that preexercise CHO ingestion has no effect on muscle glycogen utilization or exercise performance, irrespective of the glycemic or insulinemic responses to the ingested meals.
Regional clearance of solute from the respiratory epithelia: 18-20 h postexposure to ozone
Authors: Foster W. M. , Stetkiewicz P. T.
Published: December 2017

Exposure of humans to ambient levels of ozone causes inflammatory changes within lung tissues. These changes have been reported for the "initial" (1- to 3-h) and "late" (18- to 20-h) postexposure periods. We hypothesized that at the late period when protein and cellular markers of inflammation in bronchoalveolar lavage remain abnormal, permeability of respiratory epithelia would be altered. To test this, we measured by gamma-camera imagery the clearance kinetics in healthy subjects (n = 9) of 99mTc-labeled solute [diethylenetriaminepentaacetic acid (DTPA)] that was deposited by aerosol onto epithelial surfaces 19 +/- 1 h after a single exposure to ozone (O3; 130 min at ambient levels between 150 and 350 parts per billion and alternate periods of rest and moderate exercise) or filtered air. At the late period, the lung clearance of 99mTc-DTPA over a 120-min period was significantly increased, i.e., 0.732%/min for O3 exposures compared with 0.661%/min for filtered-air exposures (P < 0.05). Regional analysis demonstrated that 99mTc-DTPA clearance from the periphery (excluding the lung hilum) and lung apexes were significantly increased by O3 but changes in clearance for the base of the lung were not significant. The forced expiratory volume in 1 s at the late time after O3 was slightly but significantly reduced (-2.1%) from preexposure levels. There was no relationship between the functional changes observed acutely after exposure to O3 and subsequent changes in 99mTc-DTPA clearance or forced expiratory volume in 1 s observed at the late period. These results suggest that epithelial permeability of the lung is altered 18-20 h post-O3; this injury is regional, and the lung base appears to have a different time course of response or is in an adapted state with respect to O3 exposure.
Effect of reduced training and training cessation on insulin action and muscle GLUT-4
Authors: Houmard J. A. , Tyndall G. L. , Midyette J. B. , Hickey M. S. , Dolan P. L. , Gavigan K. E. , Weidner M. L. , Dohm G. L.
Published: December 2017

This study examined the impact of a 50% reduction in training frequency or training cessation on insulin action and muscle GLUT-4 protein concentration. Middle-aged individuals were tested before and after 12 wk of exercise training (4 days/wk, 40-45 min/day). Subjects then either maintained training (n = 9), reduced training frequency by 50% (n = 11), or stopped exercising (n = 10) for the ensuing 2 wk. GLUT-4 protein concentration and insulin action (insulin sensitivity index, as determined by the minimal model) increased (P < or = 0.05) by an average of 1.6- and 1.9-fold, respectively, with the 12 wk of training. Insulin action and GLUT-4 did not increase further with the additional 2 wk of training in the maintained training group. Similarly, insulin sensitivity index and GLUT-4 concentration remained at trained levels when training frequency was reduced by 50% for 2 wk. GLUT-4 concentration and insulin action, however, were not different from sedentary values after 14 days of training cessation. These findings indicate that a 14-day 50% reduction in exercise frequency maintains the improvements in GLUT-4 protein concentration and insulin action gained with endurance training in moderately trained middle-aged adults; in contrast, these adaptations are largely lost with training cessation.
Human cerebral activity with increasing inspiratory force: a study using positron emission tomography
Authors: Fink G. R. , Corfield D. R. , Murphy K. , Kobayashi I. , Dettmers C. , Adams L. , Frackowiak R. S. , Guz A.
Published: December 2017

Human cerebral activity with increasing inspiratory force: a study using positron emission tomography. J. Appl. Physiol. 81(3): 1295-1305, 1996.--The major aim of this study was to use positron emission tomography (PET) to assess dose-dependent effects of inspiratory loads on relative regional cerebral blood flow as an indication of neuronal activation and recruitment. Six normal men underwent H2 15O-PET scanning during unloaded breathing and with external inspiratory loads (generating mouth pressures of -5, -10, and -15 cmH2O); positive-pressure ventilation against relaxed respiratory muscles acted as control. During unloaded breathing, the supplementary motor area was significantly activated. With the addition of the smallest load, activations also occurred in the right premotor area and bilaterally in the superolateral motor cortex (MI) in areas previously shown to be activated with deeper breathing. There was little further change in these areas with greater loads. Additional force-related activations occurred in the inferolateral sensorimotor cortex, parietal cortex, and midbrain/hypothalamus. The results suggest that volitionally induced increases in inspiratory muscle force are achieved via a complex integration of neuronal activations in cortical and subcortical regions associated with motor control.
Metabolic heat production during fatigue from voluntary repetitive isometric contractions in humans
Authors: Saugen E. , Vollestad N. K.
Published: December 2017

The effect of repetitive isometric knee extensions on the energy cost of contraction was examined. The rate of temperature rise (dT/dt) was determined in test contractions at 30 and 50% of maximal voluntary contraction (MVC) force before and during 30% MVC repetitive isometric exercise (RIE) to exhaustion and regularly in a 30-min postexercise recovery period (n = 9). Pulmonary O2 uptake and muscle temperature (Tmus) were determined at regular intervals. During the 30% MVC test contractions, dT/dt was 5.6 +/- 0.6 mK/s in unfatigued muscle, increasing linearly by 68% during exercise. In the 50% MVC test contractions, dT/dt rose by 84% from 9.8 +/- 1.1 mK/s. dT/dt determined during test contractions at both force levels did not decrease significantly throughout the 30-min postexercise recovery period. The rise in dT/dt was paralleled by 76% increased in O2 uptake. In contrast, Tmus rose initially and then leveled off. The present data indicate that RIE induced a gradual rise in the rate of energy turnover associated with isometric force production. Neither increased Tmus nor recruitment of less economic type II fibers can fully explain the increased energy cost. We suggest that energetic changes may occur at the cellular level and argue that this may be associated with the changes in muscle mechanics occurring during fatigue from submaximal voluntary RIE.
Wortmannin inhibits both insulin- and contraction-stimulated glucose uptake and transport in rat skeletal muscle
Authors: Wojtaszewski Jørgen F. P. , Hansen Bo F. , Ursø Birgitte , Richter Erik A.
Published: December 2017

Wojtaszewski, Jørgen F. P., Bo F. Hansen, Birgitte Ursø, and Erik A. Richter. Wortmannin inhibits both insulin- and contraction-stimulated glucose uptake and transport in rat skeletal muscle. J. Appl. Physiol. 81(4): 1501–1509, 1996.—The role of phosphatidylinositol (PI) 3-kinase for insulin- and contraction-stimulated muscle glucose transport was investigated in rat skeletal muscle perfused with a cell-free perfusate. The insulin receptor substrate-1-associated PI 3-kinase activity was increased sixfold upon insulin stimulation but was unaffected by contractions. In addition, the insulin-stimulated PI 3-kinase activity and muscle glucose uptake and transport in individual muscles were dose-dependently inhibited by wortmannin with one-half maximal inhibition values of ∼10 nM and total inhibition at 1 μM. This concentration of wortmannin also decreased the contraction-stimulated glucose transport and uptake by ∼30–70% without confounding effects on contractility or on muscle ATP and phosphocreatine concentrations. At higher concentrations (3 and 10 μM), wortmannin completely blocked the contraction-stimulated glucose uptake but also decreased the contractility. In conclusion, inhibition of PI 3-kinase with wortmannin in skeletal muscle coincides with inhibition of insulin-stimulated glucose uptake and transport. Furthermore, in contrast to recent findings in incubated muscle, wortmannin also inhibited contraction-stimulated glucose uptake and transport. The inhibitory effect of wortmannin on contraction-stimulated glucose uptake may be independent of PI 3-kinase activity or due to inhibition of a subfraction of PI 3-kinase with low sensitivity to wortmannin.
Ozone toxicity in the rat. III. Effect of changes in ambient temperature on pulmonary parameters
Authors: Wiester Mildred J. , Watkinson William P. , Costa Daniel L. , Crissman Kay M. , Richards Judy H. , Winsett Darrell W. , Highfill Jerry W.
Published: December 2017

Wiester, Mildred J., William P. Watkinson, Daniel L. Costa, Kay M. Crissman, Judy H. Richards, Darrell W. Winsett, and Jerry W. Highfill. Ozone toxicity in the rat. III. Effect of changes in ambient temperature on pulmonary parameters. J. Appl. Physiol. 81(4): 1691–1700, 1996.—Pulmonary toxicity of ozone (O3) was examined in adult male Fischer 344 rats exposed to 0.5 parts/million O3 for either 6 or 23 h/day over 5 days while maintained at an ambient temperature (Ta) of either 10, 22, or 34°C. Toxicity was evaluated by using changes in lung volumes and the concentrations of constituents of bronchoalveolar lavage fluid that signal lung injury and/or inflammation. Results indicated that toxicity increased as Tadecreased. Exposures conducted at 10°C were associated with the greatest decreases in body weight and total lung capacity and the greatest increases in lavageable protein, lysozyme, alkaline phosphatase activity, and percent neutrophils. O3 effects not modified by Ta included increases in residual volume and lavageable potassium, glucose, urea, and ascorbic acid. There was a progressive decrease in lavageable uric acid with exposure at 34°C. Most effects were attenuated during the 5 exposure days and/or returned to normal levels after 7 air recovery days, regardless of prior O3 exposure or Ta. It is possible that Ta-induced changes in metabolic rate may have altered ventilation and, therefore, the O3 doses among rats exposed at the three different Ta levels.
Platelets attenuate oxidant-induced permeability in endothelial monolayers: glutathione-dependent mechanisms
Authors: Strange Charlie , Gottehrer Andrew , Birmingham Karen , Heffner John E.
Published: December 2017

Strange, Charlie, Andrew Gottehrer, Karen Birmingham, and John E. Heffner. Platelets attenuate oxidant-induced permeability in endothelial monolayers: glutathione-dependent mechanisms. J. Appl. Physiol. 81(4): 1701–1706, 1996.—We studied the effects of adding washed human platelets or platelets with nonintact glutathione redox cycles to endothelial cell monolayers treated with glucose oxidase to initiate oxidant stress and increase permeability. Changes in125I-labeled albumin transmonolayer movement were used as the index of monolayer permeability. Washed human platelets attenuated oxidant-induced increases in albumin flux. Platelets treated with 1,3-bis(2-chloroethyl)-1-nitrosurea, 1-chloro-2,4-dinitrobenzene, or buthionine sulfoximine to inhibit selective enzymatic steps in the glutathione redox cycle decreased permeability to a lesser degree. We conclude that 1) washed human platelets attenuate monolayer permeability defects in aortic endothelial monolayers exposed to glucose oxidase and 2) the protective effects of platelets are partially dependent on an intact platelet glutathione redox cycle.
Effect of cigarette smoke extract on arteriolar dilatation in vivo
Authors: Mayhan William G. , Sharpe Glenda M.
Published: December 2017

Mayhan, William G., and Glenda M. Sharpe. Effect of cigarette smoke extract on arteriolar dilatation in vivo. J. Appl. Physiol. 81(5): 1996–2003, 1996.—The goal of this study was to determine whether cigarette smoke extract alters dilatation of arterioles in vivo in response to agonists that produce activation of ATP-sensitive potassium channels and activation of adenylate cyclase. By using intravital microscopy, we measured diameter of arterioles contained within the microcirculation of the hamster cheek pouch during suffusion with agonists in the absence and presence of cigarette smoke extract (0.1, 0.5, and 1.0%). Before treatment with cigarette smoke extract, activation of ATP-sensitive potassium channels with aprikalim and cromakalim produced dose-related dilatation of cheek pouch arterioles. Similarly, activation of adenylate cyclase with isoproterenol and forskolin produced dose-related dilatation of cheek pouch arterioles before treatment with cigarette smoke extract. Superfusion of 0.1% cigarette smoke extract did not change baseline diameter of arterioles and did not alter responses of cheek pouch arterioles to activation of ATP-sensitive potassium channels and adenylate cyclase. Superfusion of 0.5 and 1.0% cigarette smoke extract also did not alter baseline diameter of arterioles but did impair dilatation of arterioles in response to activation of ATP-sensitive potassium channels and adenylate cyclase. These findings suggest that cigarette smoke extract impairs dilatation of resistance arterioles in response to activation of important cellular dilator pathways.
Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight
Authors: Fritsch-Yelle Janice M. , Whitson Peggy A. , Bondar Roberta L. , Brown Troy E.
Published: December 2017

Fritsch-Yelle, Janice M., Peggy A. Whitson, Roberta L. Bondar, and Troy E. Brown. Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight. J. Appl. Physiol. 81(5): 2134–2141, 1996.—Postflight orthostatic intolerance is experienced by virtually all astronauts but differs greatly in degree of severity. We studied cardiovascular responses to upright posture in 40 astronauts before and after spaceflights lasting up to 16 days. We separated individuals according to their ability to remain standing without assistance for 10 min on landing day. Astronauts who could not remain standing on landing day had significantly smaller increases in plasma norepinephrine levels with standing than did those who could remain standing (105 ± 41 vs. 340 ± 62 pg/ml; P = 0.05). In addition, they had significantly lower standing peripheral vascular resistance (23 ± 3 vs. 34 ± 3 mmHg ⋅ l−1⋅ min; P = 0.02) and greater decreases in systolic (−28 ± 4 vs. −11 ± 3 mmHg; P = 0.002) and diastolic (−14 ± 7 vs. 3 ± 2 mmHg; P = 0.0003) pressures. The presyncopal group also had significantly lower supine (16 ± 1 vs. 21 ± 2 mmHg ⋅ l−1⋅ min; P = 0.04) and standing (23 ± 2 vs. 32 ± 2 mmHg ⋅ l−1⋅ min; P = 0.038) vascular resistance, supine (66 ± 2 vs. 73 ± 2 mmHg; P = 0.008) and standing (69 ± 4 vs. 77 ± 2 mmHg; P = 0.007) diastolic pressure, and supine (109 ± 3 vs. 114 ± 2 mmHg; P = 0.05) and standing (99 ± 4 vs. 108 ± 3 mmHg; P = 0.006) systolic pressures before flight. This is the first study to clearly document these differences among presyncopal and nonpresyncopal astronauts after spaceflight and also offer the possibility of preflight prediction of postflight susceptibility. These results clearly point to hypoadrenergic responsiveness, possibly centrally mediated, as a contributing factor in postflight orthostatic intolerance. They may provide insights into autonomic dysfunction in Earthbound patients.
Muscle inactivation: assessment of interpolated twitch technique
Authors: Behm D. G. , St-Pierre D. M. M. , Perez D.
Published: December 2017

Behm, D. G., D. M. M. St-Pierre, and D. Perez. Muscle inactivation: assessment of interpolated twitch technique. J. Appl. Physiol. 81(5): 2267–2273, 1996.—The validity, reliability, and protocol for the interpolated twitch technique (ITT) were investigated with isometric plantar flexor and leg extension contractions. Estimates of muscle inactivation were attempted by comparing a variety of superimposed with potentiated evoked torques with submaximal and maximal voluntary contraction (MVC) torques or forces. The use of nerve and surface stimulation to elicit ITT was reliable, except for problems in maintaining maximal stimulation with nerve stimulation at 20° plantar flexion and during leg extension. The interpolated twitch ratio-force relationship was best described by a shallow hyperbolic curve resulting in insignificant MVC prediction errors with second-order polynomials (1.1–6.9%). The prediction error under 40% MVC was approximately double that over 60% MVC, contributing to poor estimations of MVC in non-weight-bearing postimmobilized ankle fracture patients. There was no significant difference in the ITT sensitivity when twitches, doublets, or quintuplets were used. The ITT was valid and reliable when high-intensity contractions were analyzed with a second-order polynomial.
Statistical properties of breath-to-breath variations in ventilation at constant PetCO2and PetO2in humans
Authors: Liang Pei-Ji , Pandit Jaideep J. , Robbins Peter A.
Published: December 2017

Liang, Pei-Ji, Jaideep J. Pandit, and Peter A. Robbins. Statistical properties of breath-to-breath variations in ventilation at constant PetCO2and PetO2in humans. J. Appl. Physiol. 81(5): 2274–2286, 1996.—The purpose of this study was to provide a statistical description of the breath-to-breath variations in ventilation during steady breathing in both rest and during light exercise, with the end-tidal gases controlled by using an end-tidal forcing system. Sixty data sets were studied, only one of which was white (i.e., did not show autocorrelation). Three simple autoregressive moving average (ARMA) models, i.e., AR1, AR2, and AR1MA1, and one simple state-space model were fitted to the data and resulted in white residuals in 15, 31, 46, and 48 out of 60 occasions, respectively. Evolutionary spectral analysis revealed that only 13 data sets had a constant power spectrum, although 50 were uniformly modulated. An autoregressive estimate of variance could be used to “demodulate” the data in most cases, but the results were not significantly affected by fitting the model to the demodulated data. The results indicate that 1) both simple ARMA models and a simple state-space model can describe the autocorrelation present; 2) variations in spectral power were present in the data that cannot be described by these models; and 3) these variations were often due to a uniform modulation and did not significantly affect the coefficients for the models. For these kinds of data, a heteroscedastic form of state-space model provides an attractive theoretical structure for the noise processes.
Regional blood flows in the goat latissimus dorsi muscle before and after chronic stimulation
Authors: Klabunde Richard E. , Anderson William A. , Locke Marius , Ianuzzo Sigrid E. , Ianuzzo C. David
Published: December 2017

Klabunde, Richard E., William A. Anderson, Marius Locke, Sigrid E. Ianuzzo, and C. David Ianuzzo. Regional blood flows in the goat latissimus dorsi muscle before and after chronic stimulation. J. Appl. Physiol. 81(6): 2365–2372, 1996.—Latissimus dorsi muscle (LDM) regional blood flows were determined in anesthetized goats by using colored microspheres under noncontracting and contracting conditions, either before or after 8–10 wk of chronic muscle stimulation. Surgical dissection of the LDM, leaving only the thoracodorsal artery to supply the muscle, did not alter regional noncontracting blood flows but significantly reduced the normal hyperemic response to muscle contraction in muscle regions (posterior-medial) furthest from the entrance of the thoracodorsal artery. Eight to 10 wk after acute muscle dissection, posterior-medial hyperemic flows were restored. Chronic stimulation of the LDM for 8–10 wk, in either dissected or nondissected muscles, did not alter regional blood flows in noncontracting muscle; however, it significantly reduced hyperemic flows in all muscle regions, although capillary density was increased and the muscle was transformed into a predominantly type I fiber type. These results, coupled with data from previous experiments, suggest that the muscle damage observed in the posterior-medial regions of the LDM after surgical dissection and chronic stimulation may be related to reduced hyperemic flow responses caused by surgical isolation of the muscle.
Effect of expiratory flow limitation on respiratory mechanical impedance: a model study
Authors: Peslin R. , Farré R. , Rotger M. , Navajas D.
Published: December 2017

Peslin, R., R. Farré, M. Rotger, and D. Navajas.Effect of expiratory flow limitation on respiratory mechanical impedance: a model study. J. Appl. Physiol. 81(6): 2399–2406, 1996.—Large phasic variations of respiratory mechanical impedance (Zrs) have been observed during induced expiratory flow limitation (EFL) (M. Vassiliou, R. Peslin, C. Saunier, and C. Duvivier. Eur. Respir. J. 9: 779–786, 1996). To clarify the meaning of Zrs during EFL, we have measured from 5 to 30 Hz the input impedance (Zin) of mechanical analogues of the respiratory system, including flow-limiting elements (FLE) made of easily collapsible rubber tubing. The pressures upstream (Pus) and downstream (Pds) from the FLE were controlled and systematically varied. Maximal flow (V˙max) increased linearly with Pus, was close to the value predicted from wave-speed theory, and was obtained for Pus-Pds of 4–6 hPa. The real part of Zin started increasing abruptly with flow (V˙) >85%V˙max and either further increased or suddenly decreased in the vicinity of V˙max. The imaginary part of Zin decreased markedly and suddenly above 95%V˙max. Similar variations of Zin during EFL were seen with an analogue that mimicked the changes of airway transmural pressure during breathing. After pressure andV˙ measurements upstream and downstream from the FLE were combined, the latter was analyzed in terms of a serial (Zs) and a shunt (Zp) compartment. Zs was consistent with a large resistance and inertance, and Zp with a mainly elastic element having an elastance close to that of the tube walls. We conclude that Zrs data during EFL mainly reflect the properties of the FLE.
Are basal metabolic rate prediction equations appropriate for female children and adolescents?
Authors: Wong William W. , Butte Nancy F. , Hergenroeder Albert C. , Hill Rebecca B. , Stuff Janice E. , Smith E. O’Brian
Published: December 2017

Wong, William W., Nancy F. Butte, Albert C. Hergenroeder, Rebecca B. Hill, Janice E. Stuff, and E. O’Brian Smith. Are basal metabolic rate prediction equations appropriate for female children and adolescents? J. Appl. Physiol. 81(6): 2407–2414, 1996.—The basal metabolic rate (BMR), which accounts for 50–70% of total energy expenditure, is essential for estimation of patient and population energy needs. Numerous equations have been formulated for prediction of human BMR. Most equations in current use are based on measurements of Caucasians performed more than four decades ago. We evaluated 10 prediction equations commonly used for estimation of BMR in 76 Caucasian and 42 African-American girls between 8 and 17 yr of age against BMR measured by whole-body calorimetry. The majority of the prediction equations (9 of 10) overestimated BMR by 60 ± 46 kcal/day (range, 15–176 kcal/day). This overestimation was found to be significantly greater ( P < 0.05) for African-Americans (77 ± 17 kcal/day) than for Caucasians (25 ± 17 kcal/day) in six equations, controlling for age, weight, and sexual maturity. We conclude that ethnicity is an important factor in estimation of the BMR and that the current prediction equations are not appropriate for accurate estimation of the BMR of individual female children and adolescents.
Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal muscle
Authors: Thompson Marita , Becker Lisa , Bryant Debbie , Williams Gary , Levin Daniel , Margraf Linda , Giroir Brett P.
Published: December 2017

Thompson, Marita, Lisa Becker, Debbie Bryant, Gary Williams, Daniel Levin, Linda Margraf, and Brett P. Giroir. Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal muscle. J. Appl. Physiol. 81(6): 2415–2420, 1996.—Nitric oxide (NO) is a pluripotent molecule that can be secreted by skeletal muscle through the activity of the neuronal constitutive isoform of NO synthase. To determine whether skeletal muscle and diaphragm might also express the macrophage-inducible form of NO synthase (iNOS) during provocative states, we examined tissue from mice at serial times after intravenous administration of Escherichia coli endotoxin. In these studies, iNOS mRNA was strongly expressed in the diaphragm and skeletal muscle of mice 4 h after intravenous endotoxin and was significantly diminished by 8 h after challenge. Induction of iNOS mRNA was followed by expression of iNOS immunoreactive protein on Western immunoblots. Increased iNOS activity was demonstrated by conversion of arginine to citrulline. Immunochemical analysis of diaphragmatic explants exposed to endotoxin in vitro revealed specific iNOS staining in myocytes, in addition to macrophages and endothelium. These results may be important in understanding the pathogenesis of respiratory pump failure during septic shock, as well as skeletal muscle injury during inflammation or metabolic stress.
Membranous bronchioles and connective tissue network of normal and emphysematous lungs
Authors: Verbeken E. K. , Cauberghs M. , Van De Woestijne K. P.
Published: December 2017

Verbeken, E. K., M. Cauberghs, and K. P. Van de Woestijne.Membranous bronchioles and connective tissue network of normal and emphysematous lungs. J. Appl. Physiol.81(6): 2468–2480, 1996.—Three-dimensional reconstructions of the septal system of normal human lungs revealed that airways course within the interlobular septa, i.e., between the two blades formed by the peripheral boundaries of adjacent lobuli of whatever order, and enter the supplied pulmonary unit at its side. This is not in keeping with the classic view of a peripheral airway in the center of a lung unit and submitted to radial traction by attached alveolar septa. The basic design of the lung fibrous scaffold appears to be in conformity with the laws of fractal geometry. Similar reconstructions in centrilobular emphysema disclosed tortuosities of both intra-acinar and interlobular septa, with consequent distortions of the corresponding intraseptal bronchioles and collapse of lung units of different sizes. It is suggested that in centrilobular emphysema competition for space, besides intrinsic airways narrowing because of inflammation and loss of elastic recoil, is a cause of flow limitation.
Lactate and epinephrine during exercise in altitude natives
Authors: Kayser Bengt , Favier Roland , Ferretti Guido , Desplanches Dominique , Spielvogel Hilde , Koubi Harry , Sempore Brigitte , Hoppeler Hans
Published: December 2017

Kayser, Bengt, Roland Favier, Guido Ferretti, Dominique Desplanches, Hilde Spielvogel, Harry Koubi, Brigitte Sempore, and Hans Hoppeler. Lactate and epinephrine during exercise in altitude natives. J. Appl. Physiol. 81(6): 2488–2494, 1996.—We tested the hypothesis that the reported low blood lactate accumulation ([La]) during exercise in altitude-native humans is refractory to hypoxia-normoxia transitions by investigating whether acute changes in inspired O2 fraction ([Formula: see text]) affect the [La] vs. power output (W˙) relationship or, alternatively, as reported for lowlanders, whether changes in [La] vs. W˙ on changes in[Formula: see text] are related to changes in blood epinephrine concentration ([Epi]). Altitude natives [ n = 8, age 24 ± 1 (SE) yr, body mass 62 ± 3 kg, height 167 ± 2 cm] in La Paz, Bolivia (3,600 m) performed incremental exercise with two legs and one leg in chronic hypoxia and acute normoxia (AN). Submaximal one- and two-leg O2 uptake (V˙o 2) vs.W˙ relationships were not altered by[Formula: see text]. AN increased two-leg peak V˙o 2 by 10% and peakW˙ by 7%. AN paradoxically decreased one-leg peak V˙o 2 by 7%, whereas peak W˙ remained the same. The [La] vs. W˙ relationships were similar to those reported in unacclimatized lowlanders. There was a shift to the right on AN, and maximum [La] was reduced by 7 and 8% for one- and two-leg exercises, respectively. [Epi] and [La] were tightly related (mean r = 0.81) independently of[Formula: see text]. Thus normoxia attenuated the increment in both [La] and [Epi] as a function of W˙, whereas the correlation between [La] and [Epi] was unaffected. These data suggest loose linkage of glycolysis to oxidative phosphorylation under influence from [Epi]. In conclusion, high-altitude natives appear to be not fundamentally different from lowlanders with regard to the effect of acute changes in[Formula: see text] on [La] during exercise.
Appropriate thermal manipulations eliminate tremors in rats recovering from halothane anesthesia
Authors: Grahn D. A. , Heller M. C. , Larkin J. E. , Heller H. C.
Published: December 2017

Grahn, D. A., M. C. Heller, J. E. Larkin, and H. C. Heller.Appropriate thermal manipulations eliminate tremors in rats recovering from halothane anesthesia. J. Appl. Physiol. 81(6): 2547–2554, 1996.—Tremors are common in mammals emerging from anesthesia. To determine whether appropriate thermal manipulations immediately before emergence from anesthesia are sufficient to eliminate these tremors, electroencephalographic (EEG) and electromyographic (EMG) activities, hypothalamic temperature (Thy), and O2 consumption were monitored in 12 rats recovering from halothane anesthesia under three thermal regimes. EEG and EMG activities were recorded throughout anesthesia and served as feedback signals for controlling anesthetic depth. During anesthesia, Thy was either 1) allowed to fall to 32–34°C, 2) maintained at 37–39°C, or 3) allowed to fall to 32–34°C and then raised to 37–39°C. When hypothermic on emergence from anesthesia, all of the animals exhibited postanesthetic tremors that persisted until Thy values returned to normothermia. None of the animals expressed postanesthetic tremors when normothermic on emergence from anesthesia. In addition, the time between emergence from anesthesia (as determined by EEG/EMG parameters) and the initiation of coordinated motor activities was significantly decreased in the normothermic animals.
Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100 km
Authors: Madsen Klavs , Maclean Dave A. , Kiens Bente , Christensen Dirk
Published: December 2017

Madsen, Klavs, Dave A. MacLean, Bente Kiens, and Dirk Christensen. Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100 km. J. Appl. Physiol. 81(6): 2644–2650, 1996.—This study was undertaken to determine the effects of ingesting either glucose ( trial G) or glucose plus branched-chain amino acids (BCAA; trial B), compared with placebo ( trial P), during prolonged exercise. Nine well-trained cyclists with a maximal oxygen uptake of 63.1 ± 1.5 ml O2 ⋅ min−1 ⋅ kg−1performed three laboratory trials consisting of 100 km of cycling separated by 7 days between each trial. During these trials, the subjects were encouraged to complete the 100 km as fast as possible on their own bicycles connected to a magnetic brake. No differences in performance times were observed between the three trials (160.1 ± 4.1, 157.2 ± 4.5, and 159.8 ± 3.7 min, respectively). In trial B, plasma BCAA levels increased from 339 ± 28 μM at rest to 1,026 ± 62 μM after exercise ( P < 0.01). Plasma ammonia concentrations increased during the entire exercise period for all three trials and were significantly higher in trial B compared with trials G and P ( P< 0.05). The respiratory exchange ratio was similar in the three trials during the first 90 min of exercise; thereafter, it tended to drop more in trial P than in trials G and B. These data suggest that neither glucose nor glucose plus BCAA ingestion during 100 km of cycling enhance performance in well-trained cyclists.
Estimating exercise stroke volume from asymptotic oxygen pulse in humans
Authors: Whipp Brian J. , Higgenbotham Michael B. , Cobb Frederick C.
Published: December 2017

Whipp, Brian J., Michael B. Higgenbotham, and Frederick C. Cobb. Estimating exercise stroke volume from asymptotic oxygen pulse in humans. J. Appl. Physiol.81(6): 2674–2679, 1996.—Noninvasive techniques have been devised to estimate cardiac output (Q˙) during exercise to obviate vascular cannulation. However, although these techniques are noninvasive, they are commonly not nonintrusive to subjects’ spontaneous ventilation and gas-exchange responses. We hypothesized that the exercise stroke volume (SV) and, hence, Q˙might be accurately estimated simply from the response pattern of two standardly determined variables: O2 uptake (V˙o 2) and heart rate (HR). Central to the theory is the demonstration that the product ofQ˙ and mixed venous O2 content is virtually constant ( k) during steady-state exercise. Thus from the Fick equation, V˙o 2 =Q˙ ⋅ CaCO2 − k, where CaCO2 is the arterial CO2 content, the O2 pulse (O2-P) equals SV ⋅ CaCO2 − ( k/HR). Because the arterial O2 content ([Formula: see text]) is usually relatively constant in normal subjects during exercise, O2-P should change hyperbolically with HR, asymptoting at SV ⋅ [Formula: see text]. In addition, because the asymptotic O2-P equals the slope (S) of the linear O2-HR relationship, exercise SV may be predicted as S/[Formula: see text]. We tested this prediction in 23 normal subjects who underwent a 3-min incremental cycle-ergometer test with direct determination of[Formula: see text] and mixed venous O2content from indwelling catheters. The predicted SV closely reflected the measured value ( r = 0.80). We therefore conclude that, in normal subjects, exercise SV may be estimated simply as five times S of the linearV˙o 2-HR relationship (where 5 is approximately 1/[Formula: see text]).
Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia
Authors: Albert T. S. E. , Tucker V. L. , Renkin E. M.
Published: December 2017

Albert, T. S. E., V. L. Tucker, and E. M. Renkin.Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia. J. Appl. Physiol. 82(1): 102–110, 1997.—Arterial oxygen tensions ([Formula: see text]), atrial natriuretic peptide (ANP) concentrations, and circulating plasma volumes (PV) were measured in anesthetized rats ventilated with room air or 15, 10, or 8% O2( n = 5–7). After 10 min of ventilation, [Formula: see text] values were 80 ± 3, 46 ± 1, 32 ± 1, and 35 ± 1 Torr and plasma immunoreactive ANP (irANP) levels were 211 ± 29, 229 ± 28, 911 ± 205, and 4,374 ± 961 pg/ml, respectively. At[Formula: see text] ≤40 Torr, irANP responses were more closely related to inspired O2( P = 0.014) than to[Formula: see text] ( P= 0.168). PV was 36.3 ± 0.5 μl/g in controls but 8.5 and 9.9% lower ( P ≤ 0.05) for 10 and 8% O2, respectively. Proportional increases in hematocrit were observed in animals with reduced PV; however, plasma protein concentrations were not different from control. Between 10 and 50 min of hypoxia, small increases (+40%) in irANP occurred in 15% O2; however, there was no further change in PV, hematocrit, plasma protein, or irANP levels in the lower O2groups. Urine output tended to fall during hypoxia but was not significantly different among groups. These findings are compatible with a role for ANP in mediating PV contraction during acute alveolar hypoxia.