bluuebunny/crossref_metadata_2025 huggingface dataset:
Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness
Authors: Colice Gene L. , Hill Nicholas , Lee Yan-Jie , Du Hongkai , Klinger James , Leiter James C. , Ou Lo-Chang
Published: December 2017

Colice, Gene L., Nicholas Hill, Yan-Jie Lee, Hongkai Du, James Klinger, James C. Leiter, and Lo-Chang Ou. Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness. J. Appl. Physiol. 83(1): 25–31, 1997.—Hilltop (H) strain Sprague-Dawley rats are more susceptible to chronic mountain sickness than are the Madison (M) strain rats. It is unclear what role pulmonary vascular remodeling, polycythemia, and hypoxia-induced vasoconstriction play in mediating the more severe pulmonary hypertension that develops in the H rats during chronic hypoxia. It is also unclear whether the increased sensitivity of the H rats to chronic mountain sickness is specific for a hypoxia effect or, instead, reflects a general propensity toward the development of pulmonary hypertension. Monocrotaline (MCT) causes pulmonary vascular remodeling and pulmonary hypertension. We hypothesized that the difference in the pulmonary vascular response to chronic hypoxia between H and M rats reflects an increased sensitivity of the H rats to any pulmonary hypertensive stimuli. Consequently, we expected the two strains to also differ in their susceptibility to MCT-induced pulmonary hypertension. Pulmonary arterial pressures in conscious H and M rats were measured 3 wk after a single dose of MCT, exposure to a simulated high altitude of 18,000 ft (barometric pressure = 380 mmHg), and administration of a single dose of saline as a placebo. The H rats had significantly higher pulmonary arterial pressures and right ventricular weights after MCT and chronic hypoxia than did the M rats. The H rats also had more pulmonary vascular remodeling, i.e., greater wall thickness as a percentage of vessel diameter, after MCT and chronic hypoxia than did the M rats. The H rats had significantly lower arterial[Formula: see text] than did the M rats after MCT, but the degree of hypoxemia was mild [arterial[Formula: see text] of 72.5 ± 0.8 (SE) Torr for H rats vs. 77.4 ± 0.8 Torr for M rats after MCT]. The H rats had lower arterial [Formula: see text] and larger minute ventilation values than did the M rats after MCT. These ventilatory differences suggest that MCT caused more severe pulmonary vascular damage in the H rats than in the M rats. These data support the hypothesis that the H rats have a general propensity to develop pulmonary hypertension and suggest that differences in pulmonary vascular remodeling account for the increased susceptibility of H rats, compared with M rats, to both MCT and chronic hypoxia-induced pulmonary hypertension.
Purified ACE attenuates smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa
Authors: Gao Xiao-Pei , Suzuki Hideyuki , Olopade Christopher O. , Pakhlevaniants Sergei , Rubinstein Israel
Published: December 2017

Gao, Xiao-pei, Hideyuki Suzuki, Christopher O. Olopade, Sergei Pakhlevaniants, and Israel Rubinstein. Purified ACE attenuates smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa. J. Appl. Physiol. 83(1): 74–81, 1997.—The purpose of this study was to determine whether purified angiotensin I-converting enzyme (ACE) attenuates smokeless tobacco extract (STE)-induced increase in macromolecular efflux from the in situ oral mucosa. By using intravital microscopy, we found that suffusion of an aqueous extract of smokeless tobacco elicited significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass, 70 kDa) from the hamster cheek pouch ( P< 0.05). Suffusion of purified rabbit lung ACE significantly attenuated these responses in a concentration-dependent fashion ( P < 0.05). These effects were specific because purified ACE also significantly attenuated the increase in macromolecular efflux elicited by bradykinin, which is produced in the cheek pouch during suffusion of STE, but did not attenuate the increase elicted by adenosine. Moreover, suffusion of heat-inactivated purified ACE and purified superoxide dismutase had no significant effects on STE- and bradykinin-induced responses. Collectively, these data suggest that exogenous ACE attenuates STE-induced increase in macromolecular efflux from the in situ oral mucosa, in part, by promoting local bradykinin catabolism.
Pathogenesis of nitrofen-induced congenital diaphragmatic hernia in fetal rats
Authors: Allan Douglas W. , Greer John J.
Published: December 2017

Allan, Douglas W., and John J. Greer. Pathogenesis of nitrofen-induced congenital diaphragmatic hernia in fetal rats. J. Appl. Physiol. 83(2): 338–347, 1997.—Congenital diaphragmatic hernia (CDH) is a developmental anomaly characterized by the malformation of the diaphragm and impaired lung development. In the present study, we tested several hypotheses regarding the pathogenesis of CDH, including those suggesting that the primary defect is due to abnormal 1) lung development, 2) phrenic nerve formation, 3) developmental processes underlying diaphragmatic myotube formation, 4) pleuroperitoneal canal closure, or 5) formation of the primordial diaphragm within the pleuroperitoneal fold. The 2,4-dichloro-phenyl- p-nitrophenyl ether (nitrofen)-induced CDH rat model was used for this study. The following parameters were compared between normal and herniated fetal rats at various stages of development: 1) weight, protein, and DNA content of lungs; 2) phrenic nerve diameter, axonal number, and motoneuron distribution; 3) formation of the phrenic nerve intramuscular branching pattern and diaphragmatic myotube formation; and 4) formation of the precursor of the diaphragmatic musculature, the pleuroperitoneal fold. We demonstrated that previously proposed theories regarding the primary role of the lung, phrenic nerve, myotube formation, and the closure of pleuroperitoneal canal in the pathogenesis of CDH are incorrect. Rather, the primary defect associated with CDH, at least in the nitrofen rat model, occurs at the earliest stage of diaphragm development, the formation of the pleuroperitoneal fold.
More tetanic contractions are required for activating glucose transport maximally in trained muscle
Authors: Kawanaka Kentaro , Tabata Izumi , Higuchi Mitsuru
Published: December 2017

Kawanaka, Kentaro, Izumi Tabata, and Mitsuru Higuchi. More tetanic contractions are required for activating glucose transport maximally in trained muscle. J. Appl. Physiol. 83(2): 429–433, 1997.—Exercise training increases contraction-stimulated maximal glucose transport and muscle glycogen level in skeletal muscle. However, there is a possibility that more muscle contractions are required to maximally activate glucose transport in trained than in untrained muscle, because increased glycogen level after training may inhibit glucose transport. Therefore, the purpose of this study was to investigate the relationship between the increase in glucose transport and the number of tetanic contractions in trained and untrained muscle. Male rats swam 2 h/day for 15 days. In untrained epitrochlearis muscle, resting glycogen was 26.6 μmol glucose/g muscle. Ten, 10-s-long tetani at a rate of 1 contraction/min decreased glycogen level to 15.4 μmol glucose/g muscle and maximally increased 2-deoxy-d-glucose (2-DG) transport. Training increased contraction-stimulated maximal 2-DG transport (+71%; P < 0.01), GLUT-4 protein content (+78%; P < 0.01), and resting glycogen level (to 39.3 μmol glucose/g muscle; P < 0.01) on the next day after the training ended, although this training effect might be due, at least in part, to last bout of exercise. In trained muscle, 20 tetani were necessary to maximally activate glucose transport. Twenty tetani decreased muscle glycogen to a lower level than 10 tetani (18.9 vs. 24.0 μmol glucose/g muscle; P < 0.01). Contraction-stimulated 2-DG transport was negatively correlated with postcontraction muscle glycogen level in trained ( r = −0.60; P < 0.01) and untrained muscle ( r = −0.57; P < 0.01).
Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women
Authors: Brooks E. M. , Morgan A. L. , Pierzga J. M. , Wladkowski S. L. , O’Gorman J. T. , Derr J. A. , Kenney W. L.
Published: December 2017

Brooks, E. M., A. L. Morgan, J. M. Pierzga, S. L. Wladkowski, J. T. O’Gorman, J. A. Derr, and W. L. Kenney. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women. J. Appl. Physiol. 83(2): 477–484, 1997.—This investigation examined effects of chronic (≥2 yr) hormone replacement therapy (HRT), both estrogen replacement therapy (ERT) and estrogen plus progesterone therapy (E+P), on core temperature and skin blood flow responses of postmenopausal women. Twenty-five postmenopausal women [9 not on HRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for 1 h at an ambient temperature of 36°C. Cutaneous vascular conductance (CVC) was monitored by laser-Doppler flowmetry, and forearm vascular conductance (FVC) was measured by using venous occlusion plethysmography. Iontophoresis of bretylium tosylate was performed before exercise to block local vasoconstrictor (VC) activity at one skin site on the forearm. Rectal temperature (Tre) was ∼0.5°C lower for the ERT group ( P < 0.01) compared with E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (Tb) and CVC: Tbcurves were shifted ∼0.5°C leftward for the ERT group ( P < 0.0001). Baseline CVC was significantly higher in the ERT group ( P < 0.05), but there was no interaction between bretylium treatment and groups once exercise was initiated. These results suggest that 1) chronic ERT likely acts centrally to decrease Tre, 2) ERT lowers the Treat which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition of exogenous progestins in HRT effectively blocks these effects.
Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. I. Physiology and biochemistry
Authors: Simonson Steven G. , Welty-Wolf Karen E. , Huang Yuh-Chin T. , Taylor David E. , Kantrow Stephen P. , Carraway Martha S. , Crapo James D. , Piantadosi Claude A.
Published: December 2017

Simonson, Steven G., Karen E. Welty-Wolf, Yuh-Chin T. Huang, David E. Taylor, Stephen P. Kantrow, Martha S. Carraway, James D. Crapo, and Claude A. Piantadosi. Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. I. Physiology and biochemistry. J. Appl. Physiol. 83(2): 550–558, 1997.—Prolonged hyperoxia causes lung injury and respiratory failure secondary to oxidative tissue damage mediated, in part, by the superoxide anion. We hypothesized that aerosol treatment with recombinant human manganese superoxide dismutase (rhMnSOD) would attenuate hyperoxic lung damage in primates. Adult baboons were anesthetized and ventilated with 100% oxygen for 96 h or until death. Six animals were treated with aerosolized rhMnSOD (3 mg ⋅ kg−1⋅ day−1in divided doses), and six control animals did not receive enzyme therapy. Physiological variables were recorded every 12 h, and ventilation-perfusion ratio relationships were evaluated by using the multiple inert-gas elimination technique. After the experiments, surfactant composition and lung edema were measured. We found that rhMnSOD significantly decreased pulmonary shunt fraction ( P < 0.01) and preserved arterial oxygenation ( P < 0.01) during hyperoxia. The rhMnSOD increased lung phospholipids, phosphatidylcholine and disaturated phosphatidylcholine, and decreased lung edema in this model. Testing of higher and lower doses of MnSOD (1 and 10 mg ⋅ kg−1⋅ day−1) in two other groups of baboons produced variable physiological protection, suggesting a “window” of effective dosage. We conclude that aerosolized MnSOD (3 mg ⋅ kg−1⋅ day−1) affords significant preservation of pulmonary gas exchange during hyperoxic lung injury.
Pulmonary vasoreactivity to serotonin during hypoxia is modulated by ATP-sensitive potassium channels
Authors: Barman Scott A.
Published: December 2017

Barman, Scott A. Pulmonary vasoreactivity to serotonin during hypoxia is modulated by ATP-sensitive potassium channels. J. Appl. Physiol. 83(2): 569–574, 1997.—The role of ATP-sensitive K+-channel modulation in the canine pulmonary vascular response to serotonin during hypoxia was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured by using vascular occlusion techniques. Under normoxia, serotonin (10−5 M) significantly increased precapillary and postcapillary resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. During hypoxia, the effect of serotonin was potentiated on both precapillary and postcapillary resistance and capillary pressure, as well as on microvascular compliance and large-vessel compliance. Under normoxia, the ATP-sensitive K+-channel opener cromakalim (10−5 M) inhibited the serotonergic response on postcapillary resistance and microvascular compliance, whereas during hypoxia cromakalim inhibited the potentiated effect of serotonin on both precapillary and postcapillary resistance, capillary pressure, and both microvascular and large-vessel compliances. These results indicate that canine pulmonary vasoreactivity to serotonin is heightened under hypoxic conditions and that ATP-sensitive K+ channels modulate the pressor response to serotonin, an effect that is more pronounced during hypoxia.
Role for anions in pulmonary endothelial permeability
Authors: Griffin M. Pamela
Published: December 2017

Griffin, M. Pamela. Role for anions in pulmonary endothelial permeability. J. Appl. Physiol. 83(2): 615–622, 1997.—β-Adrenergic stimulation reduces albumin permeation across pulmonary artery endothelial monolayers and induces changes in cell morphology that are mediated by Cl−flux. We tested the hypothesis that anion-mediated changes in endothelial cells result in changes in endothelial permeability. We measured permeation of radiolabeled albumin across bovine pulmonary arterial endothelial monolayers when the extracellular anion was Cl−, Br−, I−, F−, acetate (Ac−), gluconate (G−), and propionate (Pr−). Permeability to albumin ( Palbumin) was calculated before and after addition of 0.2 mM of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), which reduces permeability. In Cl−, the Palbuminwas 3.05 ± 0.86 × 10−6cm/s and fell by 70% with the addition of IBMX. The initial Palbuminwas lowest for Pr−and Ac−. Initial Palbuminwas higher in Br−, I−, G−, and F−than in Cl−. A permeability ratio was calculated to examine the IBMX effect. The greatest IBMX effect was seen when Cl−was the extracellular anion, and the order among halide anions was Cl−> Br−> I−> F−. Although the level of extracellular Ca2+concentration ([Ca2+]o) varied over a wide range in the anion solutions, [Ca2+]odid not systematically affect endothelial permeability in this system. When Cl−was the extracellular anion, varying [Ca2+]ofrom 0.2 to 2.8 mM caused a change in initial Palbuminbut no change in the IBMX effect. The anion channel blockers 4-acetamido-4′-isothiocyanotostilbene-2,2′-disulfonic acid (0.25 mM) and anthracene-9-carboxylic acid (0.5 mM) significantly altered initial Palbuminand the IBMX effect. The anion transport blockers bumetanide (0.2 mM) and furosemide (1 mM) had no such effects. We conclude that extracellular anions influence bovine pulmonary arterial endothelial permeability and that the pharmacological profile fits better with the activity of anion channels than with other anion transport processes.
Acid-base regulation after maximal exercise testing in late gestation
Authors: Kemp Justin G. , Greer Felicia A. , Wolfe Larry A.
Published: December 2017

Kemp, Justin G., Felicia A. Greer, and Larry A. Wolfe.Acid-base regulation after maximal exercise testing in late gestation. J. Appl. Physiol. 83(2): 644–651, 1997.—This study employed Stewart’s physicochemical approach to quantify the effects of pregnancy and strenuous exercise on the independent determinants of plasma H+ concentration ([H+]). Subjects were nine physically active pregnant women [mean gestational age = 33 ± 1 (SE) wk] and 14 age-matched nonpregnant controls. Venous blood samples and respiratory data were obtained at rest and during 15 min of recovery from a maximal cycle ergometer test that involved 20 W/min increases in work rate to exhaustion. Mean values for [H+],[Formula: see text], and total protein increased, whereas those for bicarbonate concentration ([[Formula: see text]]) and the strong ion difference ([SID]) decreased in the transition from rest to maximal exercise within both groups. At rest and throughout postexercise recovery, the pregnant group exhibited significantly lower mean values for [Formula: see text], [[Formula: see text]], and total protein, whereas [SID] was significantly lower at rest and early recovery from exercise. [H+] was also lower at all sampling times in the pregnant group, but this effect was significant only at rest. Our results support the hypothesis that reduced [Formula: see text] and weak acid concentration are important mechanisms to regulate plasma [H+] and to maintain a less acidic plasma environment at rest and after exercise in late gestation compared with the nonpregnant state. These effects are established in the resting state and appear to be maintained after maximal exertion.
In vivo exposure to ozone produces an increase in a 72-kDa heat shock protein in guinea pigs
Authors: Su Wei Yi , Gordon Terry
Published: December 2017

Su, Wei Yi, and Terry Gordon. In vivo exposure to ozone produces an increase in a 72-kDa heat shock protein in guinea pigs. J. Appl. Physiol. 83(3): 707–711, 1997.—Although several lines of evidence have suggested that oxidizing agents can induce heat shock proteins (HSPs) in vitro, little is known about the induction of HSPs during in vivo exposure to oxidants. Guinea pigs were exposed to ozone for 6 h and euthanized up to 72 h later. Proteins from lavage cells and lung tissue were characterized by immunoblotting with 72- and 73/72-kDa HSP monoclonal antibodies. Although 73-kDa HSP was expressed constituitively in lung tissue, it was not affected by ozone. In contrast, 72-kDa HSP was significantly increased in lavage cells and lung tissue of animals exposed to 0.4 and 0.66 parts/million of ozone. Both heat treatment and arsenite induced 72-kDa HSP in cultured alveolar macrophages. The increase in 72-kDa HSP in the lavage cell pellet peaked at 24 h after ozone, whereas the influx of polymorphonuclear leukocytes peaked at 4 h. Examination of the induction of HSPs by ozone may provide clues to the development of ozone tolerance in humans and animals.
Estimation of thickness of airway surface liquid in ferret trachea in vitro
Authors: Duneclift S. , Wells U. , Widdicombe J.
Published: December 2017

Duneclift, S., U. Wells, and J. Widdicombe. Estimation of thickness of airway surface liquid in ferret trachea in vitro. J. Appl. Physiol. 83(3): 761–767, 1997.—The tracheae of ferrets and rabbits were mounted in vitro in organ baths. While the tracheae were liquid filled, the permeability coefficient ( P) was determined, and then while the tracheae were air filled, the percent clearance for99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) was determined. The thickness of airway surface liquid (ASL) was estimated by three methods. 1) The initial concentration of99mTc-DTPA and the total amount of99mTc-DTPA (the sum of that entering the outside medium, that draining from the trachea, and that washed out at the end of 40 min) gave the initial volume of ASL and thus its thickness. Mean values were 45.7 μm for the ferret and 41.9 μm for the rabbit. 2) Estimates of ASL thickness at the end of the 40-min period, based on the final99mTc-DTPA concentration and the amount in the washout, were 42.9 μm for ferret and 45.4 μm for rabbit. 3) The ratio of Pto percent clearance gave mean ASL thickness values of 49.2 μm for the ferret and 40.3 μm for the rabbit. Thus three separate methods for determining ASL thickness give very similar results, with means in the range 40–49 μm. Administration of methacholine or atropine to ferret tracheae did not significantly change ASL thickness.
Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs
Authors: Wu Zhong-Xin , Morton Robert F. , Lee Lu-Yuan
Published: December 2017

Wu, Zhong-Xin, Robert F. Morton, and Lu-Yuan Lee. Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs. J. Appl. Physiol. 83(3): 958–965, 1997.—Acute exposure to ozone (O3) induces airway hyperresponsiveness to various inhaled bronchoactive substances. Inhalation of cigarette smoke, a common inhaled irritant in humans, is known to evoke a transient bronchoconstrictive effect. To examine whether O3 increases airway responsiveness to cigarette smoke, effects of smoke inhalation challenge on total pulmonary resistance (Rl) and dynamic lung compliance (Cdyn) were compared before and after exposure to O3 (1.5 ppm, 1 h) in anesthetized guinea pigs. Before O3 exposure, inhalation of two breaths of cigarette smoke (7 ml) at a low concentration (33%) induced a mild and reproducible bronchoconstriction that slowly developed and reached its peak (ΔRl= 67 ± 19%, ΔCdyn = −29 ± 6%) after a delay of >1 min. After exposure to O3 the same cigarette smoke inhalation challenge evoked an intense bronchoconstriction that occurred more rapidly, reaching its peak (ΔRl = 620 ± 224%, ΔCdyn = −35 ± 7%) within 20 s, and was sustained for >2 min. By contrast, sham exposure to room air did not alter the bronchomotor response to cigarette smoke challenge. Pretreatment with CP-99994 and SR-48968, the selective antagonists of neurokinin type 1 and 2 receptors, respectively, completely blocked the enhanced responses of Rl and Cdyn to cigarette smoke challenge induced by O3. These results show that O3 exposure induces airway hyperresponsiveness to inhaled cigarette smoke and that the enhanced responses result primarily from the bronchoconstrictive effect of endogenous tachykinins.
Effects of haloperidol on ventilation during isocapnic hypoxia in humans
Authors: Pedersen Michala E. F. , Dorrington Keith L. , Robbins Peter A.
Published: December 2017

Pedersen, Michala E. F., Keith L. Dorrington, and Peter A. Robbins. Effects of haloperidol on ventilation during isocapnic hypoxia in humans. J. Appl. Physiol.83(4): 1110–1115, 1997.—Exposure to isocapnic hypoxia produces an abrupt increase in ventilation [acute hypoxic ventilatory response (AHVR)], which is followed by a subsequent decline [hypoxic ventilatory depression or decline (HVD)]. In cats, both anesthetized and awake, haloperidol has been reported to increase AHVR and almost entirely abolish HVD. To investigate whether this occurs in humans, the ventilatory responses of 15 healthy young volunteers to 20 min of isocapnic hypoxia (end-tidal [Formula: see text] = 50 Torr) were assessed at 1, 2, and 4.5 h after placebo (control) and after oral haloperidol (Seranace, 0.05 mg/kg) on different days. Three subjects were unable to complete the study because of akathisia. AHVR was significantly greater with haloperidol compared with control ( P < 0.01, analysis of variance). However, no significant change in HVD was found [control HVD = 9.3 ± 1.6 (SD) l/min, haloperidol HVD = 9.9 ± 2.1 l/min; P = not significant, analysis of variance]. We conclude that combined central and peripheral dopamine-receptor antagonism in humans with haloperidol produces a similar pattern of change to that reported previously with the peripheral antagonist domperidone. We have been unable to show in humans a decrease in HVD by the centrally acting drug as observed in cats.
A bout of resistance exercise increases urinary calcium independently of osteoclastic activation in men
Authors: Ashizawa Noriko , Fujimura Rei , Tokuyama Kumpei , Suzuki Masashige
Published: December 2017

Ashizawa, Noriko, Rei Fujimura, Kumpei Tokuyama, and Masashige Suzuki. A bout of resistance exercise increases urinary calcium independently of osteoclastic activation in men. J. Appl. Physiol. 83(4): 1159–1163, 1997.—Metabolic acidosis increases urinary calcium excretion in humans as a result of administration of ammonium chloride, an increase in dietary protein intake, and fasting-induced ketoacidosis. An intense bout of exercise, exceeding aerobic capacity, also causes significant decrease in blood pH as a result of increase in blood lactate concentration. In this study we investigated changes in renal calcium handling, plasma parathyroid hormone concentration, and osteoclastic bone resorption after a single bout of resistance exercise. Ten male subjects completed a bout of resistance exercise with an intensity of 60% of one repetition maximum for the first set and 80% of one repetition maximum for the second and third sets. After exercise, blood and urine pH shifted toward acidity and urinary calcium excretion increased. Hypercalciuria was observed in the presence of an increased fractional calcium excretion and an unchanged filtered load of calcium. Therefore, the observed increase in urinary calcium excretion was due primarily to decrease in renal tubular reabsorption of calcium. Likely causes of the increase in renal excretion of calcium are metabolic acidosis itself and decreased parathyroid hormone. When urinary calcium excretion increased, urinary deoxypyridinoline, a marker of osteoclastic bone resorption, decreased. These results suggest that 1) strenuous resistance exercise increased urinary calcium excretion by decreasing renal tubular calcium reabsorption, 2) urinary calcium excretion increased independently of osteoclast activation, and 3) the mechanism resulting in postexercise hypercalciuria might involve non-cell-mediated physicochemical bone dissolution.
Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits
Authors: Shen X. , Gunst S. J. , Tepper R. S.
Published: December 2017

Shen, X., S. J. Gunst, and R. S. Tepper. Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits. J. Appl. Physiol.83(4): 1202–1208, 1997.—We evaluated the effects of the rate and volume of tidal ventilation on airway resistance (Raw) during intravenous methacholine (MCh) challenge in mechanically ventilated rabbits. Five rabbits were challenged at tidal volumes of 5, 10, and 20 ml/kg at a frequency of 15 breaths/min and also under static conditions (0 ml/kg tidal volume). Four rabbits were subjected to MCh challenge at frequencies of 6 and 30 breaths/min with a tidal volume of 10 ml/kg and also under static conditions. In both groups, the increase in Raw with MCh challenge was significantly greater under static conditions than during tidal ventilation at any frequency or volume. Increases in the volume or frequency of tidal ventilation resulted in significant decreases in Raw in response to MCh. We conclude that tidal breathing suppresses airway responsiveness in rabbits in vivo. The suppression of narrowing in response to MCh increases as the magnitude of the volume or the frequency of the tidal oscillations is increased. Our findings suggest that the effect of lung volume changes on airway responsiveness in vivo is primarily related to the stretch of airway smooth muscle.
Effect of increased muscle temperature on oxygen uptake kinetics during exercise
Authors: Koga Shunsaku , Shiojiri Tomoyuki , Kondo Narihiko , Barstow Thomas J.
Published: December 2017

Koga, Shunsaku, Tomoyuki Shiojiri, Narihiko Kondo, and Thomas J. Barstow. Effect of increased muscle temperature on oxygen uptake kinetics during exercise. J. Appl. Physiol. 83(4): 1333–1338, 1997.—To test whether increased muscle temperature (Tm) would improve O2 uptake (V˙o 2) kinetics, seven men performed transitions from rest to a moderate work rate [below the estimated lactate threshold (LTest)] and a heavy work rate (V˙o 2 = 50% of the difference between LTest and peakV˙o 2) under conditions of normal Tm (N) and increased Tm (H), produced by wearing hot water-perfused pants before exercise. Quadriceps Tm was significantly higher in H, but rectal temperature was similar for the two conditions. There were no significant differences in the amplitudes of the fast component ofV˙o 2 or in the time constants of the on and off transients for moderate and heavy exercise between the two conditions. The increment inV˙o 2 between the 3rd and 6th min of heavy exercise was slightly but significantly smaller for H than for N. These data suggest that elevated Tm before exercise onset, which would have been expected to increase O2 delivery and off-loading to the muscle, had no appreciable effect on the fast exponential component ofV˙o 2 kinetics (invariant time constant). These data further suggest that elevated Tm does not contribute to the slow component of V˙o 2 during heavy exercise.
Interaction between ion transporters and the mucociliary transport system in dog and baboon
Authors: Winters Scot L. , Yeates Donovan B.
Published: December 2017

Winters, Scot L., and Donovan B. Yeates. Interaction between ion transporters and the mucociliary transport system in dog and baboon. J. Appl. Physiol. 83(4): 1348–1359, 1997.—To gain insight into the role of epithelial ion channels, pumps, and cotransporters in regulating airway water and mucociliary transport, we administered inhibitors of the Na+channel (amiloride), 3Na-2K-adenosinetriphosphatase (acetylstrophanthidin), and Na-K-2Cl cotransporter (furosemide) to anesthetized dogs and/or baboons. Tracheal ciliary beat frequency was measured by using heterodyne laser light scattering. Tracheal mucus velocity (TMV) and bronchial mucociliary clearance (BMC) or lung mucociliary clearance were measured by using radioaerosols and nuclear imaging. Respiratory tract fluid output was collected by using a secretion-collecting endotracheal tube. In six dogs, amiloride aerosol [lung deposition, 96 ± 11 μg (means ± SE)] had minimal effect, whereas acetylstrophanthidin aerosol (lung deposition, 71 ± 9 μg) increased BMC, and furosemide (40 mg iv) markedly increased TMV. In five baboons, TMV increased after iv furosemide administration (2 mg/kg) as well as by aerosol (lung deposition, 20 ± 3 mg), coincident with increases in ciliary-mucus coupling from 11.5 ± 0.1 to 29.5 ± 0.4 and 46.5 ± 0.7 μm/beat, respectively. Furosemide also increased lung mucociliary clearance in baboons. In dogs, respiratory tract fluid output increased after intravenous furosemide from 2.2 ± 0.5 to 6.8 ± 1.7 mg/min. When combined with dry-air inhalation, furosemide failed to stimulate TMV and reversed the inhibition of BMC by dry air. Thus pharmacological manipulation of the Na-K-2Cl cotransporter and the 3Na-2K-adenosinetriphosphatase pump may provide increases of clinical relevance in airway hydration and mucociliary transport.
Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis
Authors: Hsia C. C. W. , Chuong C. J. C. , Johnson R. L.
Published: December 2017

Hsia, C. C. W., C. J. C. Chuong, and R. L. Johnson, Jr.Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis. J. Appl. Physiol. 83(4): 1397–1404, 1997.—To understand the effects of dynamic shape distortion of red blood cells (RBCs) as it develops under high-flow conditions on the standard physiological and morphometric methods of estimating pulmonary diffusing capacity, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of equally spaced RBCs. RBCs are circular or parachute shaped, with the same perimeter length. Total CO diffusing capacity (Dl CO) and membrane diffusing capacity (Dm CO) were calculated by a finite element method. Dl COcalculated at two levels of alveolar[Formula: see text] were used to estimate Dm CO by the Roughton-Forster (RF) technique. The same capillary model was subjected to morphometric analysis by the random linear intercept method to obtain morphometric estimates of Dm CO. Results show that shape distortion of RBCs significantly reduces capillary diffusive gas uptake. Shape distortion exaggerates the conceptual errors inherent in the RF technique ( J. Appl. Physiol.79: 1039–1047, 1995); errors are exaggerated at a high capillary hematocrit. Shape distortion also introduces additional error in morphometric estimates of Dm CO caused by a biased sampling distribution of random linear intercepts; errors are exaggerated at a low capillary hematocrit.
Chest wall motion during tidal breathing
Authors: De Groote A. , Wantier M. , Cheron G. , Estenne M. , Paiva M.
Published: December 2017

De Groote, A., M. Wantier, G. Cheron, M. Estenne, and M. Paiva. Chest wall motion during tidal breathing. J. Appl. Physiol. 83(5): 1531–1537, 1997.—We have used an automatic motion analyzer, the ELITE system, to study changes in chest wall configuration during resting breathing in five normal, seated subjects. Two television cameras were used to record the x-y-z displacements of 36 markers positioned circumferentially at the level of the third (S1) and fifth (S2) costal cartilage, corresponding to the lung-apposed rib cage; midway between the xyphoid process and the costal margin (S3), corresponding to the abdomen-apposed rib cage; and at the level of the umbilicus (S4). Recordings of different subsets of markers were made by submitting the subject to five successive rotations of 45–90°. Each recording lasted 30 s, and three-dimensional displacements of markers were analyzed with the Matlab software. At spontaneous end expiration, sections S1–3 were elliptical but S4 was more circular. Tidal changes in chest wall dimensions were consistent among subjects. For S1–2, changes during inspiration occurred primarily in the cranial and ventral directions and averaged 3–5 mm; displacements in the lateral direction were smaller (1–2 mm). On the other hand, changes at the level of S4 occurred almost exclusively in the ventral direction. In addition, both compartments showed a ventral displacement of their dorsal aspect that was not accounted for by flexion of the spine. We conclude that, in normal subjects breathing at rest in the seated posture, displacements of the rib cage during inspiration are in the cranial, lateral outward, and ventral directions but that expansion of the abdomen is confined to the ventral direction.
Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep
Authors: Schneider H. , Schaub C. D. , Andreoni K. A. , Schwartz A. R. , Smith P. L. , Robotham J. L. , O’Donnell C. P.
Published: December 2017

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz, R. L. Smith, J. L. Robotham, and C. P. O’Donnell. Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5): 1671–1680, 1997.—We examined the hemodynamic responses to normal breathing and induced upper airway obstructions during sleep in a canine model of obstructive sleep apnea. During normal breathing, cardiac output decreased (12.9 ± 3.5%, P < 0.025) from wakefulness to non-rapid-eye-movement sleep (NREM) but did not change from NREM to rapid-eye-movement (REM) sleep. There was a decrease ( P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures from wakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg, P < 0.025), but not pulmonary, arterial pressures decreased from NREM to REM sleep. During repetitive airway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiac output (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased ( P < 0.05), without a change in stroke volume, compared with normal breathing during NREM sleep. During single obstructive events, left (7.8 ± 3.0%, P < 0.05) and right (7.1 ± 0.7%, P < 0.01) ventricular outputs decreased during the apneic period. However, left (20.7 ± 1.6%, P < 0.01) and right (24.0 ± 4.2%, P < 0.05) ventricular outputs increased in the postapneic period because of an increase in heart rate. Thus 1) the systemic, but not the pulmonary, circulation vasodilates during REM sleep with normal breathing; 2) heart rate, rather than stroke volume, is the dominant factor modulating ventricular output in response to apnea; and 3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.
Effects of anatomic variability on blood flow and pressure gradients in the pulmonary capillaries
Authors: Dhadwal Amit , Wiggs Barry , Doerschuk Claire M. , Kamm Roger D.
Published: December 2017

Dhadwal, Amit, Barry Wiggs, Claire M. Doerschuk, and Roger D. Kamm. Effects of anatomic variability on blood flow and pressure gradients in the pulmonary capillaries. J. Appl. Physiol. 83(5): 1711–1720, 1997.—A theoretical model is developed to simulate the flow of blood through the capillary network in a single alveolar septum. The objective is to study the influence of random variability in capillary dimension and compliance on flow patterns and pressures within the network. The capillary bed is represented as an interconnected rectangular grid of capillary segments and junctions; blood flow is produced by applying a pressure gradient across the network. Preferred flow channels are shown to be a natural consequence of random anatomic variability, the effect of which is accentuated at low transcapillary pressures. The distribution of pressure drops across single capillary segments widens with increasing network variability and decreasing capillary transmural pressure. Blockage of one capillary segment causes the pressure drop across that segment to increase by 60%, but the increase falls to <10% at a distance of three segments. The factors that cause nonuniform capillary blood flow through the capillary network are discussed.
Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis
Authors: Kleen Martin , Welte Martin , Lackermeier Peter , Habler Oliver , Kemming Gregor , Messmer Konrad
Published: December 2017

Kleen, Martin, Martin Welte, Peter Lackermeier, Oliver Habler, Gregor Kemming, and Konrad Messmer. Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis. J. Appl. Physiol.83(6): 1832–1841, 1997.—We analyzed the effects of shock and small-volume resuscitation in the presence of coronary stenosis on fractal dimension ( D) and spatial correlation (SC) of regional myocardial perfusion. Hemorrhagic shock was induced and maintained for 1 h. Pigs were resuscitated with hypertonic saline-dextran 60 [HSDex, 10% of shed blood volume (SBV)] or normal saline (NS; 80% of SBV). Therapy was continued after 30 min with dextran (10% SBV). At baseline, D was 1.39 ± 0.06 (mean ± SE; HSDex group) and 1.34 ± 0.04 (NS group). SC was 0.26 ± 0.07 (HSDex) and 0.26 ± 0.04 (NS). Left anterior descending coronary artery stenosis changed neither D nor SC. Shock significantly reduced D(i.e., homogenized perfusion): 1.26 ± 0.06 (HSDex) and 1.23 ± 0.05 (NS). SC was increased: 0.41 ± 0.1 (HSDex) and 0.48 ± 0.07 (NS). Fluid therapy with HSDex further decreased D to 1.22 ± 0.05, whereas NS did not change D. SC was increased by both HSDex (0.56 ± 0.1) and NS (0.53 ± 0.06). At 1 h after resuscitation, SC was constant in both groups, and D was reduced only in the NS group (1.18 ± 0.02). We conclude that hemorrhagic shock homogenized regional myocardial perfusion in coronary stenosis and that fluid therapy failed to restore this.
Growth hormone/IGF-I and/or resistive exercise maintains myonuclear number in hindlimb unweighted muscles
Authors: Allen David L. , Linderman Jon K. , Roy Roland R. , Grindeland Richard E. , Mukku Venkat , Edgerton V. Reggie
Published: December 2017

Allen, David L., Jon K. Linderman, Roland R. Roy, Richard E. Grindeland, Venkat Mukku, and V. Reggie Edgerton. Growth hormone/IGF-I and/or resistive exercise maintains myonuclear number in hindlimb unweighted muscles. J. Appl. Physiol. 83(5): 1857–1861, 1997.—In the present study of rats, we examined the role, during 2 wk of hindlimb suspension, of growth hormone/insulin-like growth factor I (GH/IGF-I) administration and/or brief bouts of resistance exercise in ameliorating the loss of myonuclei in fibers of the soleus muscle that express type I myosin heavy chain. Hindlimb suspension resulted in a significant decrease in mean soleus wet weight that was attenuated either by exercise alone or by exercise plus GH/IGF-I treatment but was not attenuated by hormonal treatment alone. Both mean myonuclear number and mean fiber cross-sectional area (CSA) of fibers expressing type I myosin heavy chain decreased after 2 wk of suspension compared with control (134 vs. 162 myonuclei/mm and 917 vs. 2,076 μm2, respectively). Neither GH/IGF-I treatment nor exercise alone affected myonuclear number or fiber CSA, but the combination of exercise and growth-factor treatment attenuated the decrease in both variables. A significant correlation was found between mean myonuclear number and mean CSA across all groups. Thus GH/IGF-I administration and brief bouts of muscle loading had an interactive effect in attenuating the loss of myonuclei induced by chronic unloading.
Regional intramuscular pressure development and fatigue in the canine gastrocnemius muscle in situ
Authors: Ameredes Bill T. , Provenzano Mark A.
Published: December 2017

Ameredes, Bill T., and Mark A. Provenzano. Regional intramuscular pressure development and fatigue in the canine gastrocnemius muscle in situ. J. Appl. Physiol. 83(6): 1867–1876, 1997.—Intramuscular pressure (PIM) was measured simultaneously in zones of the medial head of the gastrocnemius-plantaris muscle group (zone I, popliteal origin; zone II, central; zone III, near calcaneus tendon) to determine regional muscle mechanics during isometric tetanic contractions. Peak PIM averages were 586, 1,676, and 993 mmHg deep in zones I, II, and III and 170, 371, and 351 mmHg superficially in zones I, II, and III, respectively. During fatigue, loss of PIM across zones was greatest in zone III (−81%) and least in zone I (−60%) when whole muscle tension loss was −49%. Recovery of PIM was greatest in zone III and least in zone II, achieving 86% and 67% of initial PIM, respectively, when tension recovered to 89%. These data demonstrate that 1) regional mechanical performance can be measured as PIM within a whole muscle, 2) PIM is nonuniform within the canine gastrocnemius-plantaris muscle, being greatest in the deep central zone, and 3) fatigue and recovery of PIM are dissimilar across regions. These differences suggest distinct local effects that integrate to determine whole muscle mechanical capacity during and after intense exercise.
Neural-mechanical coupling of breathing in REM sleep
Authors: Smith C. A. , Henderson K. S. , Xi L. , Chow C.-M. , Eastwood P. R. , Dempsey J. A.
Published: December 2017

Smith, C. A., K. S. Henderson, L. Xi, C.-M. Chow, P. R. Eastwood, and J. A. Dempsey. Neural-mechanical coupling of breathing in REM sleep. J. Appl. Physiol. 83(6): 1923–1932, 1997.—During rapid-eye-movement (REM) sleep the ventilatory response to airway occlusion is reduced. Possible mechanisms are reduced chemosensitivity, mechanical impairment of the chest wall secondary to the atonia of REM sleep, or phasic REM events that interrupt or fractionate ongoing diaphragm electromyogram (EMG) activity. To differentiate between these possibilities, we studied three chronically instrumented dogs before, during, and after 15–20 s of airway occlusion during non-REM (NREM) and phasic REM sleep. We found that 1) for a given inspiratory time the integrated diaphragm EMG ([Formula: see text]Di) was similar or reduced in REM sleep relative to NREM sleep; 2) for a given[Formula: see text]Di in response to airway occlusion and the hyperpnea following occlusion, the mechanical output (flow or pressure) was similar or reduced during REM sleep relative to NREM sleep; 3) for comparable durations of airway occlusion the [Formula: see text]Di and integrated inspiratory tracheal pressure tended to be smaller and more variable in REM than in NREM sleep, and 4) significant fractionations (caused visible changes in tracheal pressure) of the diaphragm EMG during airway occlusion in REM sleep occurred in ∼40% of breathing efforts. Thus reduced and/or erratic mechanical output during and after airway occlusion in REM sleep in terms of flow rate, tidal volume, and/or pressure generation is attributable largely to reduced neural activity of the diaphragm, which in turn is likely attributable to REM effects, causing reduced chemosensitivity at the level of the peripheral chemoreceptors or, more likely, at the central integrator. Chest wall distortion secondary to the atonia of REM sleep may contribute to the reduced mechanical output following airway occlusion when ventilatory drive is highest.
Effect of microgravity and hypergravity on deposition of 0.5- to 3-μm-diameter aerosol in the human lung
Authors: Darquenne Chantal , Paiva Manuel , West John B. , Prisk G. Kim
Published: December 2017

Darquenne, Chantal, Manuel Paiva, John B. West, and G. Kim Prisk. Effect of microgravity and hypergravity on deposition of 0.5- to 3-μm-diameter aerosol in the human lung. J. Appl. Physiol. 83(6): 2029–2036, 1997.—We measured intrapulmonary deposition of 0.5-, 1-, 2-, and 3-μm-diameter particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (μG) and at ∼1.6 G. Subjects breathed aerosols at a constant flow rate (0.4 l/s) and tidal volume (0.75 liter). At 1 G and ∼1.6 G, deposition increased with increasing particle size. In μG, differences in deposition as a function of particle size were almost abolished. Deposition was a nearly linear function of the G level for 2- and 3-μm-diameter particles, whereas for 0.5- and 1.0-μm-diameter particles, deposition increased less between μG and 1 G than between 1 G and ∼1.6 G. Comparison with numerical predictions showed good agreement for 1-, 2-, and 3-μm-diameter particles at 1 and ∼1.6 G, whereas the model consistently underestimated deposition in μG. The higher deposition observed in μG compared with model predictions might be explained by a larger deposition by diffusion because of a higher alveolar concentration of aerosol in μG and to the nonreversibility of the flow, causing additional mixing of the aerosols.
Long-term creatine intake is beneficial to muscle performance during resistance training
Authors: Vandenberghe K. , Goris M. , Van Hecke P. , Van Leemputte M. , Vangerven L. , Hespel P.
Published: December 2017

Vandenberghe, K., M. Goris, P. Van Hecke, M. Van Leemputte, L. Vangerven, and P. Hespel. Long-term creatine intake is beneficial to muscle performance during resistance training. J. Appl. Physiol. 83(6): 2055–2063, 1997.—The effects of oral creatine supplementation on muscle phosphocreatine (PCr) concentration, muscle strength, and body composition were investigated in young female volunteers ( n = 19) during 10 wk of resistance training (3 h/wk). Compared with placebo, 4 days of high-dose creatine intake (20 g/day) increased ( P < 0.05) muscle PCr concentration by 6%. Thereafter, this increase was maintained during 10 wk of training associated with low-dose creatine intake (5 g/day). Compared with placebo, maximal strength of the muscle groups trained, maximal intermittent exercise capacity of the arm flexors, and fat-free mass were increased 20–25, 10–25, and 60% more ( P < 0.05), respectively, during creatine supplementation. Muscle PCr and strength, intermittent exercise capacity, and fat-free mass subsequently remained at a higher level in the creatine group than in the placebo group during 10 wk of detraining while low-dose creatine was continued. Finally, on cessation of creatine intake, muscle PCr in the creatine group returned to normal within 4 wk. It is concluded that long-term creatine supplementation enhances the progress of muscle strength during resistance training in sedentary females.