bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated intracellular Ca2+ and myofibrillar Ca2+ sensitivity cause iodoacetate-induced muscle contractures
Authors: Ruff R. L.
Published: December 2017

Ischemic stimulation of iodoacetic acid (IAA)-treated rat extensor digitorum longus (EDL) muscles produced contractures. Similar ischemic stimulation of control EDL muscles did not result in contracture. At the onset of contracture, ATP concentration was not reduced, phosphocreatine concentration was reduced > 75%, ADP concentration was increased 9-fold, Ca2+ concentration ([Ca2+]) was increased approximately 11-fold, and inorganic phosphate concentration increased less in IAA-treated muscles than in stimulated control muscles. To test whether contracture resulted from elevated [Ca2+] and/or increased Ca2+ sensitivity of the contractile proteins, this laboratory made skinned fiber-activating solutions that simulated four different conditions: unstimulated IAA-treated and control muscles, IAA-treated muscles at contracture, and ischemically simulated control muscles. Skinned EDL fibers had lower single-fiber tensions and reduced Ca2+ sensitivities in activating solutions that mimicked the conditions in stimulated control muscles compared with activating solutions that simulated the conditions in unstimulated muscles. In contrast, the maximum tension was maintained and Ca2+ sensitivity was increased in activating solutions that simulated contracture. Tension at contracture resulted from increased intracellular [Ca2+] and increased myofibrillar Ca2+ sensitivity compared with the Ca2+ sensitivity of stimulated control fibers.
Regulation of Ca(2+)-activated K+ channels in pulmonary vascular smooth muscle cells: role of nitric oxide
Authors: Peng W. , Hoidal J. R. , Farrukh I. S.
Published: December 2017

Nitric oxide (NO.) is believed to mediate nitrovasodilators and acetylcholine-induced vasodilatation via increasing intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels. The cellular mechanisms involved in No.-mediated pulmonary vasodilatation are complex and include membrane hyperpolarization. Using the patch-clamp technique in cell-attached and inside-out configurations, we examined the effect of NO. gas, 3-morpholinosydnomimine hydrochloride (SIN-1), and perfusate from ACh-stimulated human pulmonary arterial endothelial cells, or endothelium-derived relaxing factors (EDRF), on the Ca(2+)-dependent K+ (KCa) channels in isolated cultured human pulmonary arterial smooth muscle cells (HPSMC). NO., SIN-1, and EDRF caused similar increases in KCa channel activity. Inhibiting cGMP generation with methylene blue or inhibiting the effect(s) of cGMP with the cGMP antagonist 8-bromoguanosine 3',5'-cyclic monophosphorothioate Rp isomer Rp-cGMPS prevented the NO.- and SIN-1-mediated activation of KCa channels, respectively. Treating the human pulmonary arterial endothelial cells with methylene blue blocked the EDRF-mediated activation of KCa channels in HPSMC. The cGMP analogue 8-bromo-cGMP increased KCa channel activity in intact cells and in excised inside-out HPSMC membrane patches. In the presence of cGMP and ATP, the alpha-isozyme of the cGMP-dependent protein kinase (I alpha-cGMP-PK) significantly increased KCa channel activity, and the channel activation was further increased on addition of the protein phosphatase inhibitors okadaic acid and calyculin A. Furthermore, the cGMP-mediated KCa channel activation was reduced by the cyclic nucleotide-dependent protein kinase inhibitor N-[2-methylamino)ethyl]-5-isoquinlinesulfonamide (H-8). Thus, in HPSMC, the mechanism of NO.- and native EDRF-induced KCa channel activation appears to be mediated via cGMP-I alpha-cGMP-PK phosphorylation of KCa channels.
Comparison of the effects of endotoxin on limb, respiratory, and cardiac muscles
Authors: Supinski G. , Nethery D. , Stofan D. , DiMarco A.
Published: December 2017

Recent work has shown that endotoxin administration produces reductions in respiratory muscle contractility and an increase in indexes of free radical-mediated lipid peroxidation within these muscles. It is not known, however, whether endotoxin-induced lipid peroxidation occurs only in the respiratory muscles or is a widespread phenomenon affecting all striated muscles. We therefore examined the effects of administration of a range of doses of endotoxin on the isometric force-generating ability and lipid peroxidation of three muscles: the diaphragm (Dia), a leg muscle [i.e., the flexor halluces longus (FHL)], and papillary cardiac muscle (Card). Studies were performed on hamsters divided into groups injected over 2 days with either saline or low, medium, or high doses of endotoxin. The animals were killed on the third study day, force generation by the three muscles was examined in vitro, and the muscles were assayed for 8-isoprostane, an index of lipid peroxidation. We found that endotoxin produced significant reductions in both FHL and Dia force generation, but Card force generation was unaffected. Changes in 8-isoprostane largely paralleled alterations in force, with endotoxin eliciting marked increases in Dia and FHL 8-isoprostane levels but no change in Card 8-isoprostane. These findings suggest that 1) lipid peroxidation and muscle dysfunction in response to endotoxin administration are not limited to the respiratory muscles but also occur in limb skeletal muscle and 2) cardiac muscle appear to be resistant to this particular mechanism of endotoxin-induced dysfunction.
Effects of ischemia on intracellular sodium and phosphates in the in vivo rat liver
Authors: Xia Z. F. , Horton J. W. , Zhao P. Y. , Babcock E. E. , Sherry A. D. , Malloy C. R.
Published: December 2017

Metabolic factors that influence the transition form reversible to irreversible ischemic injury were studied in the rat liver in vivo with 31P-nuclear magnetic resonance (NMR) spectroscopy. Hepatic ischemia for 15, 35, or 65 min was produced by occlusion of the hepatic artery and portal vein in rats. Ischemia caused a rapid decrease in the ATP concentration ([ATP])-to-P(i) concentration ratio and pH within 5 min, but there was little change in these variables detectable by 31P-NMR with longer periods of ischemia. After reperfusion, the [ATP] and P(i) concentration returned toward normal values in livers exposed to 15 or 35 min of ischemia, but 65 min of ischemia were associated with only modest recovery in [ATP], and the [ATP] later decreased. Because the 31P-NMR spectrum was similar after brief compared with prolonged ischemia, it appears that neither ATP depletion, P(i) accumulation, nor acidosis predicts metabolic recovery. Hepatic intracellular NA+ was also measured in separate groups of animals by 23Na-NMR in the presence of a shift agent, thulium (III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene-phosphonate) (TmDOTP5-), and by atomic absorption spectroscopy. Under baseline conditions, the concentration of intracellular Na+ was 15.2 mM by atomic absorption spectroscopy and 16.5 mM by 23Na-NMR. Although the 31P-NMR spectrum responded very rapidly to the onset of ischemia, intracellular Na+ concentration measured by 23Na-NMR increased gradually but steadily at approximately 1.0 mM/min during early (up to 15 min) ischemia. These observations demonstrate that a rise in intracellular Na+ does occur early ischemia, that TmDOTP5- can be applied in vivo for analysis of intracellular Na+ in the ischemic liver, and that 31P-NMR spectroscopy is very sensitive to early ischemic injury.
Effect of sprint cycle training on activities of antioxidant enzymes in human skeletal muscle
Authors: Hellsten Ylva , Apple Fred S. , Sjödin Bertil
Published: December 2017

Hellsten, Ylva, Fred S. Apple, and Bertil Sjödin.Effect of sprint cycle training on activities of antioxidant enzymes in human skeletal muscle. J. Appl. Physiol. 81(4): 1484–1487, 1996.—The effect of intermittent sprint cycle training on the level of muscle antioxidant enzyme protection was investigated. Resting muscle biopsies, obtained before and after 6 wk of training and 3, 24, and 72 h after the final session of an additional 1 wk of more frequent training, were analyzed for activities of the antioxidant enzymes glutathione peroxidase (GPX), glutathione reductase (GR), and superoxide dismutase (SOD). Activities of several muscle metabolic enzymes were determined to assess the effectiveness of the training. After the first 6-wk training period, no change in GPX, GR, or SOD was observed, but after the 7th week of training there was an increase in GPX from 120 ± 12 (SE) to 164 ± 24 μmol ⋅ min−1 ⋅ g dry wt−1( P < 0.05) and in GR from 10.8 ± 0.8 to 16.8 ± 2.4 μmol ⋅ min−1 ⋅ g dry wt−1( P < 0.05). There was no significant change in SOD. Sprint cycle training induced a significant ( P < 0.05) elevation in the activity of phosphofructokinase and creatine kinase, implying an enhanced anaerobic capacity in the trained muscle. The present study demonstrates that intermittent sprint cycle training that induces an enhanced capacity for anaerobic energy generation also improves the level of antioxidant protection in the muscle.
Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis
Authors: Kelley George
Published: December 2017

Kelley, George. Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis. J. Appl. Physiol. 81(4): 1584–1588, 1996.—With use of the meta-analytic approach, the purpose of this study was to examine the effects of mechanical overload on skeletal muscle fiber number in animals. A total of 17 studies yielding 37 data points and 360 subjects met the initial inclusion criteria: 1) “basic” research studies published in journals, 2) animals (no humans) as subjects, 3) control group included, 4) some type of mechanical overload (stretch, exercise, or compensatory hypertrophy) used to induce changes in muscle fiber number, and 5) sufficient data to accurately calculate percent changes in muscle fiber number. Across all designs and categories, statistically significant increases were found for muscle fiber number [15.00 ± 19.60% (SD), 95% confidence interval = 8.65–21.53], muscle fiber area (31.60 ± 44.30%, 95% confidence interval = 16.83–46.37), and muscle mass (90.50 ± 86.50%, 95% confidence interval = 61.59–119.34). When partitioned according to the fiber-counting technique, larger increases in muscle fiber number were found by using the histological vs. nitric acid digestion method (histological = 20.70%, nitric acid digestion = 11.10%; P = 0.14). Increases in fiber number partitioned according to species were greatest among those groups that used an avian vs. mammalian model (avian = 20.95%, mammalian = 7.97%; P = 0.07). Stretch overload yielded larger increases in muscle fiber number than did exercise and compensatory hypertrophy (stretch = 20.95%, exercise = 11.59%, compensatory hypertrophy = 5.44%; P = 0.06). No significant differences between changes in fiber number were found when data were partitioned according to type of control (intra-animal = 15.20%, between animal = 13.90%; P = 0.82) or fiber arrangement of muscle (parallel = 15.80%, pennate = 11.60%; P = 0.61). The results of this study suggest that in several animal species certain forms of mechanical overload increase muscle fiber number.
Dependence of muscleV˙o 2on blood flow dynamics at onset of forearm exercise
Authors: Hughson R. L. , Shoemaker J. K. , Tschakovsky M. E. , Kowalchuk J. M.
Published: December 2017

Hughson, R. L., J. K. Shoemaker, M. E. Tschakovsky, and J. M. Kowalchuk. Dependence muscle ofV˙o 2on blood flow dynamics at the onset of forearm exercise. J. Appl. Physiol. 81(4): 1619–1626, 1996.—The hypothesis that the rate of increase in muscle O2 uptake (V˙o 2 mus) at the onset of exercise is influenced by muscle blood flow was tested during forearm exercise with the arm either above or below heart level to modify perfusion pressure. Ten young men exercised at a power of ∼2.2 W, and five of these subjects also worked at 1.4 W. Blood flow to the forearm was calculated from the product of blood velocity and cross-sectional area obtained with Doppler techniques. Venous blood was sampled from a deep forearm vein to determine O2 extraction. The rate of increase inV˙o 2 musand blood flow was assessed from the mean response time (MRT), which is the time to achieve ∼63% increase from baseline to steady state. In the arm below heart position during the 2.2-W exercise, blood flow andV˙o 2 musboth increased, with a MRT of ∼30 s. With the arm above the heart at this power, the MRTs for blood flow [79.8 ± 15.7 (SE) s] and V˙o 2 mus(50.2 ± 4.0 s) were both significantly slower. Consistent with these findings were the greater increases in venous plasma lactate concentration over resting values in the above heart position (2.8 ± 0.4 mmol/l) than in the below heart position (0.9 ± 0.2 mmol/l). At the lower power, both blood flow andV˙o 2 musalso increased more rapidly with the arm below compared with above the heart. These data support the hypothesis that changes in blood flow at the onset of exercise have a direct effect on oxidative metabolism through alterations in O2transport.
Exercise training and the glucose transport system in obese SHHF/Mcc-facprats
Authors: Ferrara Cynthia M. , Sherman W. Michael , Leenders Nicole , McCune Sylvia A. , Roehrig Karla
Published: December 2017

Ferrara, Cynthia M., W. Michael Sherman, Nicole Leenders, Sylvia A. McCune, and Karla Roehrig. Exercise training and the glucose transport system in obese SHHF/ Mcc-facprats. J. Appl. Physiol. 81(4): 1670–1676, 1996.—The effects of a similar exercise training stimulus on maximal insulin-stimulated (MIS) plasma membrane glucose transporter number and glucose transport were determined in lean and obese SHHF/ Mcc-facprats. Six-week-old lean and obese male rats were randomly divided into four groups: lean sedentary (LSed), obese sedentary (OSed), lean exercise (LEx), and obese exercise (OEx). An 8- to 12-wk treadmill running program equalized daily muscular work for LEx and OEx. Plasma membranes were isolated from control and MIS muscles of mixed fiber types. MIS significantly increased glucose transport (3.4- and 2.8-fold) in LSed and OSed, respectively. MIS significantly increased glucose transporter number (2.5-fold) in LSed, but there was no increase in glucose transporter number in OSed. Peak oxygen uptake and citrate synthase activity were increased a similar amount for LEx and OEx groups, demonstrating a similar training stimulus. MIS significantly and similarly increased glucose transport in LEx and OEx (4.4- and 5.1-fold, respectively). The effects of MIS on plasma membrane glucose transporter number in the exercise-trained rats were similar to the responses observed in the sedentary lean and obese groups. MIS significantly increased glucose transporter number (2.6-fold) in LEx, whereas there was no increase in glucose transporter number in OEx. The reduction in MIS glucose transport in OSed appears to be related to a defect in the processes associated with the translocation of glucose transporters to the plasma membrane. Exercise training of the obese rats apparently did not alter this defect. Similar increases in peak oxygen uptake, citrate synthase, and MIS glucose transport in LEx and OEx groups suggest that insulin resistance does not limit the ability of the glucose transport system to adapt to exercise training in the obese male SHHF/ Mcc-facprats.
Terbutaline stimulates alveolar fluid resorption in hyperoxic lung injury
Authors: Lasnier Joseph M. , Wangensteen O. Douglas , Schmitz Laura S. , Gross Cynthia R. , Ingbar David H.
Published: December 2017

Lasnier, Joseph M., O. Douglas Wangensteen, Laura S. Schmitz, Cynthia R. Gross, and David H. Ingbar. Terbutaline stimulates alveolar fluid resorption in hyperoxic lung injury. J. Appl. Physiol. 81(4): 1723–1729, 1996.—Alveolar fluid resorption occurs by active epithelial sodium transport and is accelerated by terbutaline in healthy lungs. We investigated the effect of terbutaline on the rate of alveolar fluid resorption from rat lungs injured by hyperoxia. Rats exposed to >95% O2 for 60 h, sufficient to increase wet-to-dry lung weight and cause alveolar edema, were compared with air-breathing control rats. After anesthesia, the animals breathed 100% O2 for 10 min through a tracheostomy. Ringer solution was instilled into the alveoli, and the steady-state rate of volume resorbed at 6 cmH2O pressure was measured via a pipette attached to the tracheostomy tubing. Ringer solution in some animals contained terbutaline (10−3 M), ouabain (10−3 M), or both. Normoxic animals resorbed 49 ± 6 μl ⋅ kg−1 ⋅ min−1; ouabain reduced this by 39%, whereas terbutaline increased the rate by 75%. The effect of terbutaline was blocked by ouabain. Hyperoxic animals absorbed 78 ± 9 μl ⋅ kg−1 ⋅ min−1; ouabain reduced this by 44%. Terbutaline increased the rate by a mean of 39 μl ⋅ kg−1 ⋅ min−1, similar to the absolute effect seen in the normoxic group, and this was blocked by ouabain. Terbutaline accelerates fluid resorption from both normal and injured rat lungs via its effects on active sodium transport.
Changes in airway resistance induced by nasal inhalation of cold dry, dry, or moist air in normal individuals
Authors: Fontanari Pierre , Burnet Henri , Zattara-Hartmann Marie Caroline , Jammes Yves
Published: December 2017

Fontanari, Pierre, Henri Burnet, Marie Caroline Zattara-Hartmann, and Yves Jammes. Changes in airway resistance induced by nasal inhalation of cold dry, dry, or moist air in normal individuals. J. Appl. Physiol. 81(4): 1739–1743, 1996.—Nasopulmonary bronchomotor reflexes elicited by mechanical or irritant stimulation of the nose have been described in animals and asthmatic patients. However, few studies were devoted to the consequences of nasal breathing of cold and dry air or of only dry or only moist air on the bronchomotor control in normal individuals. The present study reported changes in interruption resistance (Rint) measured during eupneic breathing of moderately cold (−4 or −10°C) and dry [0.3% relative humidity (RH)] air or of room air at 23°C that is either dry (0.3% RH) or moist (97% RH). Nasal inhalation of cold (−4°C) dry air or of only dry air significantly increased baseline Rint value (17 and 21%, respectively) throughout the 15-min test periods. The response to cold was significantly accentuated when the air temperature was lowered to −10°C (42%). After nasal anesthesia or inhalation of a cholinergic antagonist, cold air did not induce a change in Rint. Nasal inhalation of moist room air had no effect. No Rint changes were measured during oral breathing of the three test agents. It is concluded that the activation of cold receptors or osmoreceptors in the nasal mucosa induces protective bronchoconstrictor responses in normal individuals.
Regional ventilation in statically and dynamically hyperinflated dogs
Authors: Hubmayr Rolf D. , Margulies Susan S.
Published: December 2017

Hubmayr, Rolf D., and Susan S. Margulies. Regional ventilation in statically and dynamically hyperinflated dogs. J. Appl. Physiol. 81(4): 1815–1821, 1996.—Using the parenchymal marker technique in normal anesthetized dogs, we compared the dynamics of regional lung expansion between two ventilation strategies designed to increase mean thoracic volume. Dynamic hyperinflation (DH) was produced by ventilating the lungs at a rate of 50 breaths/min and with a duty cycle of 0.5. Static hyperinflation (SH) was produced through the application of extrinsic positive end-expiratory pressure while the lungs were ventilated at a rate of 15 breaths/min and with a duty cycle of 0.15. Regional tidal volume (Vt,r), regional functional residual volume, and the time delay between regional expansion and the flow signal at the common airway were computed for up to 100 regions/lobe in 5 animals. Ventilation strategy had no effect on the overall variance of Vt,r within lobes. Although the Vt,r measured during SH correlated with Vt,r measured during DH, the average correlation coefficient was only 0.69. Ventilation rate-related differences in Vt,r and regional functional residual capacity varied with the regional time delay in ways qualitatively consistent with parallel inhomogeneity of unit time constants. However, a large component of frequency-dependent behavior remains unexplained by established mechanisms. We conclude that DH and SH should not be considered equivalent lung unit recruitment strategies.
Prediction of barometric pressures at high altitudes with the use of model atmospheres
Authors: West John B.
Published: December 2017

West, John B. Prediction of barometric pressures at high altitudes with the use of model atmospheres. J. Appl. Physiol. 81(4): 1850–1854, 1996.—It would be valuable to have model atmospheres that allow barometric pressures (Pb) to be predicted at high altitudes. Attempts to do this in the past using the International Civil Aviation Organization or United States Standard Atmosphere model have brought such models into disrepute because the predicted pressures at high altitudes are usually much too low. However, other model atmospheres have been developed by geophysicists. The critical variable is the change of air temperature with altitude, and, therefore, model atmospheres have been constructed for different latitudes and seasons of the year. These different models give a large range of pressures at a given altitude. For example, the maximum difference of pressure at an altitude of 9 km is from 206 to 248 Torr, i.e., ∼20%. However, the mean of the model atmospheres for latitude of 15° (in all seasons) and 30° (in the summer) predicts Pb at many locations of interest at high altitude very well, with predictions within 1%. The equation is Pb(Torr) = exp (6.63268 − 0.1112 h − 0.00149 h2), where h is the altitude in kilometers. The predictions are good because many high mountain sites are within 30° of the equator and also many studies are made during the summer. Other models should be used for latitudes of 45° and above. Model atmospheres have considerable value in predicting Pb at high altitude if proper account is taken of latitude and season of the year.
Evidence against an increase in capillary permeability in subjects exposed to high altitude
Authors: Kleger Gian-Reto , Bärtsch Peter , Vock Peter , Heilig Bernhard , Roberts L. Jackson , Ballmer Peter E.
Published: December 2017

Kleger, Gian-Reto, Peter Bärtsch, Peter Vock, Bernhard Heilig, L. Jackson Roberts II, and Peter E. Ballmer. Evidence against an increase in capillary permeability in subjects exposed to high altitude. J. Appl. Physiol.81(5): 1917–1923, 1996.—A potential pathogenetic cofactor for the development of acute mountain sickness and high-altitude pulmonary edema is an increase in capillary permeability, which could occur as a result of an inflammatory reaction and/or free radical-mediated injury to the lung. We measured the systemic albumin escape by intravenously injecting 5 μCi of125I-labeled albumin and the plasma concentrations of cytokines, F2-isoprostanes (products of lipid peroxidation), and acute-phase proteins in 24 subjects exposed to 4,559 m. Ten subjects developed acute mountain sickness, and four subjects developed high-altitude pulmonary edema. The transcapillary escape rate of albumin was 6.9 ± 2.0%/h (SD) at low (550 m) and 6.3 ± 1.9%/h at high (4,559 m) altitude ( P= 0.23; n = 24). The subjects with high-altitude pulmonary edema had a modest but insignificant increase in the transcapillary escape rate of albumin (4.6 ± 1.9%/h at low vs. 5.7 ± 1.9%/h at high altitude; P = 0.42; n = 4). Plasma concentrations of fibrinogen, α1-acid glycoprotein, C-reactive protein, and interleukin-6 were unchanged in the early phases and significantly increased by the end of the observation period in the subjects with high-altitude pulmonary edema, whereas tumor necrosis factor-α and F2-isoprostanes did not change at all. This suggests that the inflammatory reaction was rather a consequence than a causative factor of high-altitude pulmonary edema. In summary, these data argue against a dominant role for increased systemic capillary permeability in the development of acute mountain sickness and high-altitude pulmonary edema.
Supraglottic airway pressure-flow relationships during oronasal airflow partitioning in dogs
Authors: Amis T. C. , O’Neill N. , Van Der Touw T. , Tully A. , Brancatisano A.
Published: December 2017

Amis, T. C., N. O’Neill, T. Van der Touw, A. Tully, and A. Brancatisano. Supraglottic airway pressure-flow relationships during oronasal airflow partitioning in dogs. J. Appl. Physiol. 81(5): 1958–1964, 1996.—We studied pressure-flow relationships in the supraglottic airway of eight prone mouth-open anesthetized (intravenous chloralose or pentobarbital sodium) crossbred dogs (weight 15–26 kg) during increasing respiratory drive (CO2administration; n = 4) and during graded-voltage electrical stimulation (SV; n = 4) of the soft palate muscles. During increased respiratory drive, inspiratory airflow occurred via both the nose (V˙n) and mouth (V˙m), with the ratio of V˙n toV˙m [%(V˙n/V˙m)] decreasing maximally from 16.0 ± 7.0 (SD) to 2.4 ± 1.6% ( P < 0.05). Simultaneously, oral airway resistance at peak inspiratory flow decreased from 2.1 ± 1.0 to 0.4 ± 0.4 cmH2O ( P < 0.05), whereas nasal airway resistance did not change (14.4 ± 7.2 to 13.1 ± 5.4 cmH2O; P = 0.29). Inspiratory pressure-flow plots of the oral airway were inversely curvilinear or more complex in nature. Nasal pathway plots, however, demonstrated a positive linear relationship in all animals ( r = 0.87 ± 0.11; all P < 0.001). During electrical stimulation of soft palate muscle contraction accompanied by graded constant-inspiratory airflows of 45–385 ml/s through an isolated upper airway, %(V˙n/V˙m) decreased from 69 ± 50 to 10 ± 13% at a SV of 84 ± 3% of maximal SV ( P < 0.001). At a SV of 85 ± 1% of maximum, normalized oral airway resistance (expressed as percent baseline) fell to 5 ± 3%, whereas normalized nasal resistance was 80 ± 9% (both P< 0.03). Thus control of oronasal airflow partitioning in dogs appears mediated more by alterations in oral route geometry than by closure of the nasopharyngeal airway.
Hypothyroidism alters diaphragm muscle development
Authors: Sieck Gary C. , Wilson Louise E. , Johnson Bruce D. , Zhan Wen-Zhi
Published: December 2017

Sieck, Gary C., Louise E. Wilson, Bruce D. Johnson, and Wen-Zhi Zhan. Hypothyroidism alters diaphragm muscle development. J. Appl. Physiol. 81(5): 1965–1972, 1996.—The impact of hypothyroidism (Hyp) on myosin heavy chain (MHC) isoform expression, maximum specific force (Po), fatigability, and maximum unloaded shortening velocity ( Vo) was determined in the rat diaphragm muscle (Dia) at 0, 7, 14, 21, and 28 days of age. Hyp was induced by treating pregnant rats with 6- n-propyl-2-thiouracil (0.05% in drinking water) beginning at gestational day 10 and was confirmed by reduced plasma levels of 3,5,3′-triiodothyronine and thyroxine. MHC isoforms were separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and analyzed by densitometry. Isometric Poand fatigue resistance of the Dia were measured in vitro at 26°C, and Vowas determined at 15°C with the slack test. Compared with control muscles, expression of MHC-slow was higher and expression of adult fast MHC isoforms was lower in Hyp Dia at all ages. The neonatal isoform of MHC continued to be expressed in the Hyp Dia until day 28. At each age, Poand fatigability were reduced and Vowas slower in the Hyp Dia. We conclude that Hyp-induced alterations in MHC isoform expression do not fully predict the changes in Dia contractile properties.
Ventilatory response to exercise in diabetic subjects with autonomic neuropathy
Authors: Tantucci C. , Bottini P. , Dottorini M. L. , Puxeddu E. , Casucci G. , Scionti L. , Sorbini C. A.
Published: December 2017

Tantucci, C., P. Bottini, M. L. Dottorini, E. Puxeddu, G. Casucci, L. Scionti, and C. A. Sorbini. Ventilatory response to exercise in diabetic subjects with autonomic neuropathy. J. Appl. Physiol. 81(5): 1978–1986, 1996.—We have used diabetic autonomic neuropathy as a model of chronic pulmonary denervation to study the ventilatory response to incremental exercise in 20 diabetic subjects, 10 with (Dan+) and 10 without (Dan−) autonomic dysfunction, and in 10 normal control subjects. Although both Dan+ and Dan− subjects achieved lower O2 consumption and CO2 production (V˙co 2) than control subjects at peak of exercise, they attained similar values of either minute ventilation (V˙e) or adjusted ventilation (V˙e/maximal voluntary ventilation). The increment of respiratory rate with increasing adjusted ventilation was much higher in Dan+ than in Dan− and control subjects ( P < 0.05). The slope of the linearV˙e/V˙co 2relationship was 0.032 ± 0.002, 0.027 ± 0.001 ( P < 0.05), and 0.025 ± 0.001 ( P < 0.001) ml/min in Dan+, Dan−, and control subjects, respectively. Both neuromuscular and ventilatory outputs in relation to increasingV˙co 2 were progressively higher in Dan+ than in Dan− and control subjects. At peak of exercise, end-tidal [Formula: see text] was much lower in Dan+ (35.9 ± 1.6 Torr) than in Dan− (42.1 ± 1.7 Torr; P < 0.02) and control (42.1 ± 0.9 Torr; P < 0.005) subjects. We conclude that pulmonary autonomic denervation affects ventilatory response to stressful exercise by excessively increasing respiratory rate and alveolar ventilation. Reduced neural inhibitory modulation from sympathetic pulmonary afferents and/or increased chemosensitivity may be responsible for the higher inspiratory output.
Measurement of pulmonary blood flow by fractal analysis of flow heterogeneity in isolated canine lungs
Authors: Barman Scott A. , McCloud Laryssa L. , Catravas John D. , Ehrhart Ina C.
Published: December 2017

Barman, Scott A., Laryssa L. McCloud, John D. Catravas, and Ina C. Ehrhart. Measurement of pulmonary blood flow by fractal analysis of flow heterogeneity in isolated canine lungs. J. Appl. Physiol. 81(5): 2039–2045, 1996.—Regional heterogeneity of lung blood flow can be measured by analyzing the relative dispersion (RD) of mass (weight)-flow data. Numerous studies have shown that pulmonary blood flow is fractal in nature, a phenomenon that can be characterized by the fractal dimension and the RD for the smallest realizable volume element (piece size). Although information exists for the applicability of fractal analysis to pulmonary blood flow in whole animal models, little is known in isolated organs. Therefore, the present study was done to determine the effect of blood flow rate on the distribution of pulmonary blood flow in the isolated blood-perfused canine lung lobe by using fractal analysis. Four different radiolabeled microspheres (141Ce,95Nb,85Sr, and51Cr), each 15 μm in diameter, were injected into the pulmonary lobar artery of isolated canine lung lobes ( n = 5) perfused at four different flow rates ( flow 1 = 0.42 ± 0.02 l/min; flow 2 = 1.12 ± 0.07 l/min; flow 3 = 2.25 ± 0.17 l/min; flow 4 = 2.59 ± 0.17 l/min), and the pulmonary blood flow distribution was measured. The results of the present study indicate that under isogravimetric blood flow conditions, all regions of horizontally perfused isolated lung lobes received blood flow that was preferentially distributed to the most distal caudal regions of the lobe. Regional pulmonary blood flow in the isolated perfused canine lobe was heterogeneous and fractal in nature, as measured by the RD. As flow rates increased, fractal dimension values (averaging 1.22 ± 0.08) remained constant, whereas RD decreased, reflecting more homogeneous blood flow distribution. At any given blood flow rate, high-flow areas of the lobe received a proportionally larger amount of regional flow, suggesting that the degree of pulmonary vascular recruitment may also be spatially related.
Interstitial fluid, plasma protein, colloid, and leukocyte uptake into initial lymphatics
Authors: Ikomi Fumitaka , Hunt James , Hanna Gayda , Schmid-Schönbein Geert W.
Published: December 2017

Ikomi, Fumitaka, James Hunt, Gayda Hanna, and Geert W. Schmid-Schönbein. Interstitial fluid, plasma protein, colloid, and leukocyte uptake into initial lymphatics. J. Appl. Physiol. 81(5): 2060–2067, 1996.—Lymphatics serve to remove from the interstitium a range of materials, including plasma proteins, colloid materials, and cells. Lymph flow rates can be enhanced by periodic tissue compression or venous pressure elevation, but little is known to what degree enhancement of lymph flow affects material transport. The objective was to examine the uptake of plasma proteins, a colloidal perflubron emulsion (LA-11063, mean particle diameter = 0.34 μm), and leukocytes into lymphatics. Prenodal collecting lymphatics in the lower hindlimb of rabbits were cannulated with and without foot massage and after elevation of venous pressure (40 mmHg). The average lymph flow rates were elevated ∼22-fold by the skin massage but only about threefold by venous pressure elevation. Lymph-to-plasma protein concentration ratio remained unchanged by the massage but decreased significantly after venous pressure elevation. Lymph colloid concentration and leukocyte counts were elevated on average 47 and 8.5 times, respectively, by foot massage, but both decreased after venous pressure elevation. These results suggest that skin movement by massage and elevation of the venous pressure lead to opposite lymph transport kinetics of protein, colloids, and cells. Massage is more effective to enhance material transport out of the interstitium into the initial lymphatics.
Eccentric contractions require unique activation strategies by the nervous system
Authors: Enoka Roger M.
Published: December 2017

Enoka, Roger M. Eccentric contractions require unique activation strategies by the nervous system. J. Appl. Physiol. 81(6): 2339–2346, 1996.—Eccentric contractions occur when activated muscles are forcibly lengthened. This mode of muscle function occurs frequently in the activities of daily living and in athletic competition. This review examines the experimental evidence that provides the foundation for our current understanding of the benefits, consequences, and control of eccentric contractions. Over the past several decades, numerous studies have established that eccentric contractions can maximize the force exerted and the work performed by muscle; that they are associated with a greater mechanical efficiency; that they can attenuate the mechanical effects of impact forces; and that they enhance the tissue damage associated with exercise. More recent evidence adds a new feature to this repertoire by suggesting a new hypothesis: that the neural commands controlling eccentric contractions are unique. Examination of this hypothesis is critical because the existence of such a control scheme would increase substantially the complexity of the strategies that the nervous system must use to control movement.
Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation
Authors: Matsumoto Koichiro , Aizawa Hisamichi , Inoue Hiromasa , Shigyo Mutsumi , Takata Shohei , Hara Nobuyuki
Published: December 2017

Matsumoto, Koichiro, Hisamichi Aizawa, Hiromasa Inoue, Mutsumi Shigyo, Shohei Takata, and Nobuyuki Hara. Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation. J. Appl. Physiol. 81(6): 2358–2364, 1996.—We investigated the role of neurogenic inflammation and the subsequent mechanisms in cigarette smoke-induced airway hyperresponsiveness in guinea pigs. Exposure to cigarette smoke was carried out at tidal volume for 3 min. Airway responsiveness to histamine was determined before and after smoke exposure followed by bronchoalveolar lavage (BAL). Plasma extravasation was evaluated by measuring the extravasation of Evans blue dye in the airway. Cigarette smoke produced significant airway hyperresponsiveness and plasma extravasation, with an influx of neutrophils in BAL fluid. FK-224 (10 mg/kg iv), a tachykinin antagonist at NK1and NK2receptors, significantly inhibited these changes. The thromboxane (Tx) B2concentration was increased in BAL fluid after smoke exposure and was significantly inhibited by FK-224. OKY-046 (10 mg/kg iv), a Tx synthase inhibitor, significantly inhibited airway hyperresponsiveness but had no effect on neutrophil influx or plasma extravasation. The results suggest that neurogenic inflammation and the subsequent generation of Tx in the airway are important in the development of the airway hyperresponsiveness induced by cigarette smoke.
Arginine-induced pancreatic hormone secretion during exercise in rats
Authors: Trabelsi Fethi , Lavoie Jean-Marc
Published: December 2017

Trabelsi, Fethi, and Jean-Marc Lavoie. Arginine-induced pancreatic hormone secretion during exercise in rats. J. Appl. Physiol. 81(6): 2528–2533, 1996.—The aim of the present investigation was to 1) determine whether arginine-induced pancreatic hormone secretion can be modified during an exercise bout, and 2) verify whether the sectioning of the hepatic branch of the vagus nerve can alter the arginine-induced insulin and glucagon secretion during exercise in rats. To this end, we studied the effects of an intraperitoneal injection of arginine (1 g/kg body mass) during an exercise bout (30 min, 26 m/min, 0% grade) on the pancreatic hormone responses. These effects were determined in one group of sham-operated exercising rats and compared with three control groups: one group of resting rats, one group of saline-injected exercising rats, and one group of hepatic-vagotomized exercising rats. Five minutes after the injection of arginine, significant ( P < 0.05) increases in insulin, glucagon, and C-peptide concentrations were observed in exercising as well as in resting rats. These responses were not, however, altered by the hepatic vagotomy and/or by the exercise bout. It is concluded that arginine is a potent stimulus of pancreatic hormone secretion during exercise, even though the sympathoadrenal system is activated. These results also indicate that a hepatic vagotomy does not seem to influence arginine-induced hormonal pancreatic responses and question the role of the putative hepatic arginoreceptors in the control of the pancreatic hormone secretion during exercise.
Endurance training affects myosin heavy chain phenotype in regenerating fast-twitch muscle
Authors: Bigard Xavier A. , Janmot Chantal , Merino Danièle , Lienhard Françoise , Guezennec Yannick C. , D’Albis Anne
Published: December 2017

Bigard, Xavier A., Chantal Janmot, Danièle Merino, Françoise Lienhard, Yannick C. Guezennec, and Anne D’Albis.Endurance training affects myosin heavy chain phenotype in regenerating fast-twitch muscle. J. Appl. Physiol. 81(6): 2658–2665, 1996.—The aim of this study was to analyze the effects of treadmill training (2 h/day, 5 days/wk, 30 m/min, 7% grade for 5 wk) on the expression of myosin heavy chain (MHC) isoforms during and after regeneration of a fast-twitch white muscle [extensor digitorum longus (EDL)]. Male Wistar rats were randomly assigned to a sedentary ( n = 10) or an endurance-trained (ET; n = 10) group. EDL muscle degeneration and regeneration were induced by two subcutaneous injections of a snake toxin. Five days after induction of muscle injury, animals were trained over a 5-wk period. It was verified that ∼40 days after venom treatment, central nuclei were present in the treated EDL muscles from sedentary and ET rats. The changes in the expression of MHCs in EDL muscles were detected by using a combination of biochemical and immunocytochemical approaches. Compared with contralateral nondegenerated muscles, relative concentrations of types I, IIa, and IIx MHC isoforms in ET rats were greater in regenerated EDL muscles (146%, P < 0.05; 76%, P < 0.01; 87%, P < 0.01, respectively). Their elevation corresponded to a decrease in the relative concentration of type IIb MHC (−36%, P < 0.01). Although type I accounted for only 3.2% of total myosin in regenerated muscles from the ET group, the cytochemical analysis showed that the proportion of positive staining with the slow MHC antibody was markedly greater in regenerated muscles than in contralateral ones. Collectively, these results demonstrate that the regenerated EDL muscle is sensitive to endurance training and suggest that the training-induced shift in MHC isoforms observed in these muscles resulted from an additive effect of regeneration and repeated exercise.
Air entry in infant resuscitation: oral or nasal routes?
Authors: Wilson-Davis S. L. , Tonkin S. L. , Gunn T. R.
Published: December 2017

Wilson-Davis, S. L., S. L. Tonkin, and T. R. Gunn. Air entry in infant resuscitation: oral or nasal routes?. J. Appl. Physiol.82(1): 152–155, 1997.—The current recommendation for resuscitation of infants is to blow air into both the nose and mouth. We have observed that mothers cannot cover both the nose and mouth of their infants. We compared postmortem tracheal and esophageal air entry by using the nose, combined nose and mouth, and mouth routes in eight infants. Air entry into the trachea occurred at lower pressures ( P < 0.05) via a nose mask than via a combined nose and mouth mask or via a mouth mask. Air entry into the trachea occurred at lower pressures ( P< 0.05) via the nose route in the neutral and extended neck positions compared with the flexed position. We were unable to demonstrate an effect of the route of air entry on esophageal air entry. The findings indicate that the nasal route of air entry is more effective than the combined nose and mouth or mouth routes and that neck flexion impedes air entry. We recommend that parents are taught to blow air into their infants’ noses if the infant stops breathing.
Peak force and maximal shortening velocity of soleus fibers after non-weight-bearing and resistance exercise
Authors: Widrick Jeffrey J. , Fitts Robert H.
Published: December 2017

Widrick, Jeffrey J., and Robert H. Fitts. Peak force and maximal shortening velocity of soleus fibers after non-weight-bearing and resistance exercise. J. Appl. Physiol. 82(1): 189–195, 1997.—This study examined the effectiveness of resistance exercise as a countermeasure to non-weight-bearing-induced alterations in the absolute peak force, normalized peak force (force/fiber cross-sectional area), peak stiffness, and maximal shortening velocity ( V o) of single permeabilized type I soleus muscle fibers. Adult rats were subjected to one of the following treatments: normal weight bearing (WB), non-weight bearing (NWB), or NWB with exercise treatments (NWB+Ex). The hindlimbs of the NWB and NWB+Ex rats were suspended for 14 days via tail harnesses. Four times each day, the NWB+Ex rats were removed from suspension and performed 10 climbs (∼15 cm each) up a steep grid with a 500-g mass (∼1.5 times body mass) attached to their tail harness. NWB was associated with significant reductions in type I fiber diameter, absolute force, normalized force, and stiffness. Exercise treatments during NWB attenuated the decline in fiber diameter and absolute force by almost 60% while maintaining normalized force and stiffness at WB levels. Type I fiber V oincreased by 33% with NWB and remained at this elevated level despite the exercise treatments. We conclude that in comparison to intermittent weight bearing only (J. J. Widrick, J. J. Bangart, M. Karhanek, and R. H. Fitts. J. Appl. Physiol. 80: 981–987, 1996), resistance exercise was more effective in attenuating alterations in type I soleus fiber absolute force, normalized force, and stiffness but was less effective in restoring type I fiber V oto WB levels.
Pliometric contraction-induced injury of mouse skeletal muscle: effect of initial length
Authors: Hunter Kam D. , Faulkner John A.
Published: December 2017

Hunter, Kam D., and John A. Faulkner. Pliometric contraction-induced injury of mouse skeletal muscle: effect of initial length. J. Appl. Physiol. 82(1): 278–283, 1997.—For single pliometric (lengthening) contractions initiated from optimal fiber length ( L f), the most important factor determining the subsequent force deficit is the work input during the stretch. We tested the hypothesis that regardless of the initial length, the force deficit is primarily a function of the work input. Extensor digitorum longus muscles of mice were maximally activated in situ and lengthened at 2 L f /s from one of three initial fiber lengths (90, 100, or 120% of L f) to one of three final fiber lengths (150, 160, or 170% of L f). Maximal isometric force production was assessed before and after the pliometric contraction. No single mechanical factor, including the work input ( r 2= 0.34), was sufficient to explain the differences in force deficits observed among groups. Therefore, the force deficit appears to arise from a complex interaction of mechanical events. With the data grouped by initial fiber length, the correlation between the average work and the average force deficit was high ( r 2= 0.97–0.99). Consequently, differences in force deficits among groups were best explained on the basis of the initial fiber length and the work input during the stretch.
Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction
Authors: Charan Nirmal B. , Carvalho Paula
Published: December 2017

Charan, Nirmal B., and Paula Carvalho. Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction. J. Appl. Physiol. 82(1): 284–291, 1997.—We studied the effects of left pulmonary artery (LPA) ligation on the bronchial circulatory system (BCS) by using a sheep model. LPA was ligated in the newborn lambs soon after birth ( n = 8), and when the sheep were ∼3 yr of age anatomic studies revealed marked angiogenesis in BCS. Bronchial blood flow and cardiac output were studied by placing flow probes around the bronchial and pulmonary arteries in four adult sheep. After LPA ligation, bronchial blood flow increased from 35 ± 6 to 134 ± 42 ml/min in ∼3 wk ( P < 0.05). We also studied gas-exchange functions of BCS ∼3 yr after the ligation of LPA in newborn lambs ( n = 4) and used a control group ( n = 12) in which LPA was ligated acutely. In the left lung, O2 uptake after acute ligation was 16 ± 3 ml/min and was similar to the chronic model, whereas CO2 output in the control group was 27 ± 3 ml/min compared with 79 ± 12 ml/min in the chronic preparation ( P < 0.05). We conclude that LPA ligation causes marked angiogenesis in BCS that is capable of performing some gas-exchange functions.
Age-related changes in the twitch contractile properties of human thenar motor units
Authors: Doherty Timothy J. , Brown William F.
Published: December 2017

Doherty, Timothy J., and William F. Brown. Age-related changes in the twitch contractile properties of human thenar motor units. J. Appl. Physiol. 82(1): 93–101, 1997.—The purpose of this study was to examine the effects of aging on the contractile and electrophysiological properties of human thenar motor units (MUs). Percutaneous electrical stimulation of single motor axons within the median nerve was used to isolate and examine the twitch tensions, contractile speeds, and surface-detected MU action potential (S-MUAP) sizes of 48 thenar MUs in 17 younger subjects (25–53 yr) and 44 thenar MUs in 9 older subjects (64–77 yr). A wide range of twitch tensions, contractile speeds, and S-MUAP sizes was observed in both age groups. However, older subjects had significantly larger MU twitch tensions and slower MU twitch contraction and half-relaxation times. These changes were accompanied by increased S-MUAP sizes. These findings suggest that the human thenar MU pool undergoes significant age-related increase in MU size and slowing of contractile speed. Such adaptation may help to overcome previously reported age-related losses of thenar MUs.