bluuebunny/crossref_metadata_2025 huggingface dataset:
Shear stress alters pleural mesothelial cell permeability in culture
Authors: Waters C. M. , Glucksberg M. R. , Depaola N. , Chang J. , Grotberg J. B.
Published: December 2017

The sliding motion of the lung against the chest wall creates a shear stress in the pleural space, which can be as high as 60 dyn/cm2, depending on the respiration rate. Such shear stresses may affect the mesothelial cells that line the pleural space on the lung (visceral pleura) and chest wall (parietal pleura). When exposed to shear stress (17 dyn/cm2) in a parallel-plate flow chamber for 22 h, rat visceral pleura mesothelial cells were not altered morphologically and did not align in the direction of flow, in contrast to the shape changes observed for bovine aortic endothelial cells. By using mesothelial cells cultured on porous microcarrier beads, we measured the permeability of the cells at different flows in a cell-column chromatography assay. The permeabilities to sodium fluorescein and cyanocobalamin increased from 8.2 +/- 1.0 and 7.8 +/- 0.7 x 10(-5) cm/s to 22.5 +/- 1.2 and 21.8 +/- 3.0 x 10(-5) cm/s, respectively, when the flow was increased from 0.9 to 3.5 ml/min (corresponding to average shear stresses of 4.7-18.4 dyn/cm2). The permeabilities returned to baseline values when the flow was reduced. Cytochalasin D stimulated an increase in permeability that was not augmented by a subsequent increase in shear stress. These results suggest that the barrier function of mesothelial cells is responsive to changes in fluid shear stress.
Effect of ATP-induced permeabilization on loading of the Na+ probe SBFI into endothelial cells
Authors: Cutaia M. , Davis R. , Parks N. , Rounds S.
Published: December 2017

The fluoroprobe sodiumbinding benzofuran isophthalate (SBFI) is used to measure intracellular cytosolic sodium concentration ([Na]i). A problem with the use of this probe is the difficulty in loading it into cells. ATP reversibly increases membrane permeability of some cells via activation of receptors of the tetrabasic form of ATP (ATP4-). We investigated the effect of ATP-induced membrane permeabilization on loading of the acetoxymethyl ester (AM) form of SBFI (SBFI-AM) into bovine pulmonary arterial endothelial cells. Monolayers were incubated in a series of solutions that reversibly opened pores, loaded the fluoroprobe, and finally sealed the proes. ATP (1-5 mM) or 3'-O-(4-benzoyl)benzoyl-ATP (0.1-1 mM), an analogue 30-100x more specific for ATP4- receptors, was utilized to permeabilize the cell membrane. The signal-to-background ratio of the intracellular SBFI fluorescent signal was used as an indicator of the effectiveness of dye loading. ATP and 3'-O-(4-benzoyl)benzoyl-ATP significantly increased the signal-to-background ratio compared with the values obtained with the standard dye-loading procedure without ATP, indicating that permeabilization increased SBFI-AM entry into the cells. The permeabilization procedure produced a small decrease in cell viability, as determined with a fluorescent viability assay (ethidium dimer uptake), compared with the standard method of loading SBFI-AM. We used the procedure to measure baseline [Na]i and changes in [Na]i after the administration of ouabain (10(-4) M) and monensin (10(-5) M). Baseline [Na]i with this procedure (19.7 +/- 2.7 mM; n = 15 monolayers) was similar to measurements made in other cell types with the standard method of loading the probe. We conclude that 1) the ATP-induced permeabilization technique is an improved dye-loading method for SBFI-AM in endothelial cell monolayers that facilitates measurement of [Na]i and 2) these data suggest the presence of an ATP4 pore-forming mechanism in this cell type.
Validation of a telemetry system for long-term measurement of blood pressure
Authors: Brooks D. , Horner R. L. , Kozar L. F. , Waddell T. K. , Render C. L. , Phillipson E. A.
Published: December 2017

We have used an implanted telemetry system to continuously monitor blood pressure (BP) in three dogs for durations ranging from 28 to 75 wk after implantation. Measurements of BP obtained by telemetry were compared every 3–12 wk, with measurements of BP recorded with a manometer-tipped catheter that was inserted into a femoral artery. Over a wide range of both physiological and pharmacologically manipulated pressures (40–200 mmHg), the values of BP obtained by the two methods were highly correlated (all r > 0.966; all P < or = 0.0001). However, the mean differences between the values obtained by the two systems were different from zero (range +29.6 to -1.5 mmHg; P < or = 0.0001), indicating an offset in the BP values recorded from the implanted system. Furthermore, this offset was dependent on the absolute level of the BP. The findings indicate that, for a period of at least 28 wk and up to 75 wk after implantation, the telemetry system accurately measures acute changes in BP and can reliably measure absolute BP provided that the system is properly validated.
Telemetry monitoring of pulmonary arterial pressure in freely moving rats
Authors: Hess P. , Clozel M. , Clozel J. P.
Published: December 2017

Several rat models of pulmonary hypertension have been developed. However, up until now it has been difficult to monitor pulmonary arterial pressure for long periods of time. The goal of the present study was to develop a telemetry system allowing chronic monitoring of pulmonary arterial pressure in freely moving rats. For this purpose, while animals were under anesthesia, a sensing catheter was implanted into the pulmonary arterial trunk through the right ventricle. This catheter was connected to an emitter implanted in the abdomen. Validation of the system was performed in three steps. First, acutely, we controlled that the pressure signal transmitted by the telemetry system was accurate and corresponded to a signal obtained with a high-fidelity Millar catheter. Second, we evaluated the chronic consequences of implantation of the system. Third, we used the system to monitor pulmonary arterial pressure in a model of monocrotaline-induced hypertension in which the effects of bosentan, an endothelin-receptor antagonist, were evaluated. The telemetry system was reliable and did not lead to damage of the right ventricle and/or to chronic pulmonary embolism. After a recovery period of 8–10 days, mean pulmonary arterial pressure was stable. With the use of this telemetry system, it was possible to follow the increase of pulmonary arterial pressure induced by monocrotaline. In this model, bosentan decreased mean pulmonary arterial pressure by 13% (P = 0.07), suggesting a role of endothelin in this model of pulmonary hypertension. We conclude that it is possible to use this telemetry system to monitor pulmonary arterial pressure in freely moving conscious rats.
Autoregressive spectral analysis of phrenic neurogram during eupnea and gasping
Authors: Akay M. , Melton J. E. , Welkowitz W. , Edelman N. H. , Neubauer J. A.
Published: December 2017

During hypoxic gasping, the phrenic neurogram (PN) has a steeper rate of rise, an augmented amplitude, and a shorter duration than is seen during eupnea. Because hypoxia reduces neuronal activity, we hypothesized that gasping would be characterized in the frequency domain by enhanced low-frequency power compared with eupnea. Autoregressive (AR) spectral analysis of the PN in chloralose-anesthetized, vagotomized, peripherally chemodenervated cats was performed during eupnea and hypoxic gasping. During eupnea, significant spectral peaks were seen at 41 +/- 2 and 93 +/- 2 (SE) Hz. In all cats, the 41-Hz spectral peak disappeared during hypoxic gasping and was replaced by a high-power, low-frequency peak at 26 +/- 1 Hz. No consistent change in the frequency or power of the high-frequency spectral peak was seen during gasping. To determine whether changes in the AR spectrum of the PN during gasping result from augmented respiratory output, we compared the AR spectra of the PN during gasping, hypercapnia (end-tidal CO2 fraction = 0.09), and carotid sinus nerve stimulation. Unlike during gasping, there was no shift in power toward lower frequencies during hypercapnia and carotid sinus nerve stimulation. We conclude that the spectral characteristics of gasping, loss of the medium-frequency peak and the appearance of low-frequency (< 30-Hz) power, are unique to this respiratory pattern.
Influence of reduced carotid body drive during sustained hypoxia on hypoxic depression of ventilation in humans
Authors: Dahan A. , Ward D. , van den Elsen M. , Temp J. , Berkenbosch A.
Published: December 2017

To evaluate whether the intact hypoxic drive from the carotid bodies during sustained hypoxia is required for the generation of hypoxic depression of ventilation (VE), 16 volunteers were exposed to two consecutive periods of isocapnic hypoxia (first period 20 min; second period 5 min; end-tidal PO2 45 Torr) separated by 6 min of normoxia. In study A, saline was given. In study B, 3 micrograms.kg-1.min-1 i.v. dopamine (DA), a carotid body inhibitor, was given during the first hypoxic exposure followed by saline during normoxia and the second hypoxic exposure. In study C, 20 min of normoxia with DA preceded 6 min of normoxia and 5 min of hypoxia without DA. The first peak hypoxic VE (PHV) in study A was approximately 100% above normoxic VE. After 20 min of hypoxia, VE declined to 60% above normoxic VE. The second PHV in study A was only 60% of the first PHV. We relate this delayed recovery from hypoxia to "ongoing" effects of hypoxic depression. During DA infusion, the changes in VE due to sustained hypoxia were insignificant (study B). The second PHV in study B was not different from the PHV after air breathing in studies A and C. This indicates that the recovery from sustained hypoxia with a suppressed carotid body drive was complete within 6 min. Our results show that despite central hypoxia the absence of ventilatory changes during 20 min of isocapnic hypoxia due to intravenous DA prevented the generation of central hypoxic depression and the depression of a subsequent hypoxic response.
Effects of S-isopropyl isothiourea, a potent inhibitor of nitric oxide synthase, in severe hemorrhagic shock
Authors: Vromen A. , Szabo C. , Southan G. J. , Salzman A. L.
Published: December 2017

We characterized the response to intravenous S-isopropyl isothiourea (IPTU), a novel potent nitric oxide synthase (NOS) inhibitor, in rodent and porcine models of hemorrhagic shock (HS). IPTU (at 300 micrograms/kg, administered as 3 subsequent bolus injections), in anesthetized rats hemorrhaged to a mean arterial blood pressure (MAP) of 35 mmHg, increased MAP and improved survival over 120 min. In anesthetized pigs hemorrhaged to a MAP of 45 mmHg, IPTU (0.3 mg/kg plus 1 mg.kg-1.h-1) increased MAP and systemic vascular resistance. IPTU did not alter the cardiac index, renal blood flow, arterial and portal oxygen content, or splanchnic oxygen consumption or extraction. In contrast, infusion of norepinephrine (100 micrograms.kg-1.h-1) did not alter MAP and increased mortality in the rat model, whereas it caused a transient increase in MAP and a tachycardia in the porcine model of HS without significantly affecting the other parameters studied. Inhibition of the endothelial NOS in early severe HS may have beneficial effects on blood pressure and survival without altering cardiac output and splanchnic and renal perfusion.
Hydrogen peroxide disrupts Ca2+ release from the sarcoplasmic reticulum of rat skeletal muscle fibers
Authors: Brotto M. A. , Nosek T. M.
Published: December 2017

Reactive oxygen species such as superoxide (O2-) and H2O2 are produced at low levels in resting muscles and at substantially higher levels in exercising muscles. Increased respiratory activity with exercise leads to O2- production by the NADPH oxidase reaction and the subsequent generation of H2O2 from O2- by spontaneous dismutation or by the superoxide dismutase reaction. The long-lasting (24-h) depression of contractile function after exercise has been linked to damage of one or more proteins important in the excitation-contraction coupling process. We studied mechanically and chemically skinned fibers from the extensor digitorum longus muscle of the rat to evaluate the effects of a 5-min exposure to 1.0 mM H2O2 on muscle function. We found that H2O2 had no effect on the isometric force-producing properties of the contractile apparatus or on Ca2+ uptake by the sarcoplasmic reticulum. It did, however, significantly affect Ca2+ release from the sarcoplasmic reticulum. Maximum depolarization-induced Ca2+ release was inhibited, and the sensitivity to depolarization was decreased. Ca(2+)-induced release was completely blocked. We conclude that elevated levels of H2O2 with exercise are capable of damaging one or more proteins of the excitation-contraction coupling process to produce a disruption in function that can account, at least in part, for the long-lasting effects of fatiguing stimulation.
Bronchial vascular reabsorption of low-protein interstitial edema liquid in perfused sheep lungs
Authors: Fukue M. , Serikov V. B. , Jerome E. H.
Published: December 2017

Previously, we quantified reabsorption of interstitial pulmonary edema liquid into the pulmonary circulation during recovery from hydrostatic edema. To determine whether the bronchial circulation also reabsorbs edema liquid, we induced very-low-protein interstitial edema in seven sheep lungs by perfusion of the pulmonary circulation with diluted blood and 1% albumin in Krebs-Henseleit buffer containing 125I-labeled albumin for 70 +/- 40 min. In eight control sheep we perfused the lungs with diluted blood and 5% albumin in Krebs-Henseleit buffer containing 125I-albumin without causing significant edema formation. Subsequently, we washed the intravascular tracer from the pulmonary circulation with buffered saline and then perfused the bronchial vessels via the bronchoesophageal artery with whole or diluted blood (normal protein osmotic pressure). We measured flow, hematocrit, and 125I-albumin concentration in the venous outflow into the left atrium and into the azygos vein for 2 h. We calculated the volume of liquid reabsorbed on the basis of the change in hematocrit and 12I-albumin concentration in the outflow. On the basis of hematocrit dilution, the net clearance of interstitial liquid (edema minus control) averaged 21 ml (15% of the induced edema). One the basis of 125I-albumin reabsorption, the net clearance of interstitial liquid was 12 ml. We conclude that the bronchial circulation may be a clearance route for interstitial liquid and protein during recovery from low-protein hydrostatic edema.
Changes in serum enzyme activities after injection of bupivacaine into rat tibialis anterior
Authors: Nosaka K.
Published: December 2017

This study investigated the time course of changes in serum creatine kinase (CK), aspartate aminotransferase (AST), and alanine amino-transferase (ALT) activities after intramuscular injection of bupivacaine into the tibialis anterior (TA) of rats. Morphological changes in muscle cells, relationships between the amount of increase in the enzyme activities and the muscle mass damaged, and responses of serum enzymes to additional injections of bupivacaine hydrochloride (BPVC) were also examined. Adult male Wistar rats (24 wk) were placed into one of four groups. Group A (n = 7) was a control, and no injection was applied. Saline solution (0.5 ml of 0.9%) was injected into the right TA for group B (n = 5). BPVC (0.5 ml of 0.5%) was injected into the right TA for group C (n = 9) and into both the right and left TA for group D (n = 9). No increases in CK, AST, and ALT were observed for groups A and B. After BPVC injection, groups C and D showed significant (P < 0.01) increases in serum enzyme activities. CK peaked 4 h after BPVC injection, and AST and ALT peaked 12 h postinjection, then returned to the baseline by the time infiltration of mononuclear cells into the damaged muscle cells progressed. The amount of enzyme increase was significantly larger (P < 0.01) for group D compared with group C. Injection of BPVC into the right then into the left TA 4 h later displayed a bipolar response, and the second injection into the TA 12 wk after the first injection resulted in smaller increase in serum enzyme activities. It appeared that increases in serum enzyme activities reflected muscle damage; however, changes in enzymes occurred in the early stage of myonecrosis.
Circulatory sequelae of administering CPAP in hyperdynamic sepsis are time dependent
Authors: Fox G. A. , Lam C. J. , Darragh W. B. , Neal A. M. , Inman K. J. , Rutledge F. S. , Sibbald W. J.
Published: December 2017

Evidence questions the circulation's ability to acutely compensate for abrupt changes in O2 delivery (Qo2). Because both sepsis and continuous positive airway pressure (CPAP) may alter the metabolic regulation of tissue oxygenation, we designed an experiment to determine the interaction, if any, between sepsis and time on circulatory homeostasis after the application of CPAP. Twenty-four sheep were randomized to cecal ligation and perforation (CLP) or sham procedure (Sham) and then rerandomized to receive either CPAP (10 mmHg) or no CPAP (No CPAP; CLP/CPAP, n = 8; CLP/No CPAP, n = 8; Sham/CPAP, n = 4; Sham/No CPAP, n = 4). Forty-eight hours later, CLP animals demonstrated an elevated cardiac index (+63%), systemic Qo2 (+49%), and systemic O2 uptake (+28%). Organ blood flow, measured with radiolabeled microspheres, was augmented to the heart and depressed in organs comprising the splanchnic circulation. Compared with the CLP/No CPAP group and both Sham groups, myocardial Qo2 in the CLP/ CPAP group was significantly elevated when measured both 2 and 8 h after CPAP. These changes were unrelated to differences in mean heart work between the study groups. Simultaneously, QO2 to all of the small gut, large gut, pancreas, and kidney in the CLP/CPAP group was elevated during the 2-h study yet reverted to levels not different from baseline by the 8-h study. These data demonstrate 1) a unique sepsis x time interaction with the use of 10 mmHg of CPAP, particularly in the "nonvital" circulations, and 2) CPAP effects on the septic coronary circulation, which were unexplained by changes in external determinants of myocardial O2 need.
Measurement of respiratory parameters by using inspired oxygen sinusoidal forcing signals
Authors: Williams E. M. , Hamilton R. , Sutton L. , Hahn C. E.
Published: December 2017

A companion paper (C. E. W. Hahn. J. Appl. Physiol 81: 985–997, 1996) described a continuous-flow gas-exchange mathematical model, which predicted that forced inspired oxygen sinusoids could be used to measure respiratory parameters rapidly, in place of the inert gas argon. We therefore made simultaneous measurements of dead space volume (VD) and alveolar volume (VA) in an animal model, using argon and oxygen inspired gas concentration sinusoid forcing signals, and then compared the results. Our data confirmed the model prediction that the attenuations of the oxygen and argon sinusoid perturbations are identical in the alveolar gas space, even though there is a net uptake of oxygen by the body. Our results show that the calculated values of VD and VA, obtained by using inspired oxygen forcing signals, were independent of both the mean fractional inspired oxygen concentration (FIO2; range 0.18–0.80% vol/vol) and the oxygen forcing signal amplitude (range +/- 2–6% vol/vol). In these studies, oxygen forcing signals, with forcing periods between 1 and 2 min, were able to measure controlled changes in instrument dead space to within 16 ml and also measure positive end-expiratory pressure-induced changes in VA. Under hyperoxic conditions, intravascular oxygen sensors confirmed that the sinusoidal PO2 signal passed into the arterial blood but not into the mixed-venous blood. However, the sinusoid perturbation PO2 signal did pass into the mixed-venous blood when the mean FIO2 was mildly hypoxic (FIO2 = 0.18% vol/vol). These data show that oxygen can be used instead of argon to measure airways dead space and VA.
Variability of triacylglycerol content in human skeletal muscle biopsy samples
Authors: Wendling P. S. , Peters S. J. , Heigenhauser G. J. , Spriet L. L.
Published: December 2017

The variability of the triacylglycerol store in human skeletal muscle (TGm) was examined using the needle biopsy technique. In 13 subjects, three biopsies were sampled from the vastus lateralis muscle of one leg at rest and after 90 min of cycling at 65% of maximal O2 uptake on one or two occasions. Visible fat and blood were removed before the samples were frozen, and remaining blood, connective tissue, and fat were removed from freeze-dried fiber bundles. TGm content was measured in two aliquots of powdered muscle from each biopsy. Within-biopsy variability was low at 6%. Despite precautions, many biopsies from inactive subjects were contaminated with adipose tissue. The TGm between-biopsy coefficient of variation (CV) was 23.5 +/- 14.6% (SD, n = 24) for rest and exercise time points where three noncontaminated biopsies existed. The between-biopsy variability at rest (19.8 +/- 7.9%, n = 10) was not significantly different from that at exercise (26.1 +/- 17.4%, n = 14). The muscle glycogen between-biopsy CV for rest and exercise time points was 10.0 +/- 10.3%. The resting TGm content was 26.3 +/- 4.3 mmol/kg dry muscle, and the net utilization during the 90 min of exercise was less than the between-biopsy variability. It is concluded that the TGm store measured in repeated biopsies of human skeletal muscle is variable, with a CV of 20-26%. Therefore, because of this high variability, only changes greater than approximately 24% of resting TGm content may be considered meaningful.
Quantitative magnetic resonance imaging of upper airways musculature in an animal model of sleep apnea
Authors: Schotland H. M. , Insko E. K. , Panckeri K. A. , Leigh J. S. , Pack A. I. , Hendricks J. C.
Published: December 2017

Electromyographic studies of patients with sleep apnea and of the English bulldog, an animal model of sleep apnea, indicate that there is increase activity of the airways dilator muscles. The muscles, when biopsied, show both adaptation and muscle injury. In this study we have utilized quantitative magnetic resonance imaging to characterize changes in the upper airway musculature of the bulldog in vivo. The imaging procedure utilized provided a quantitative measurement of the T2 relaxation times of airway muscle (geniohyoid, sternohyoid, sternothyroid, thyropharyngeus, and hyopharyngeus) and nonairway muscles spatially localized to submillimeter-resolution levels. Quantitative differences between the medians and distributions of T2 relaxation times of airway vs. nonairway muscles were demonstrated. These differences were related to the degree of sleep-disordered breathing. The changes observed are compatible with the hypothesis that there is both increased edema and fibrosis in upper airway muscle in sleep apnea.
Strain-induced growth of the immature lung
Authors: Zhang Shaoping , Garbutt Vicki , McBride John T.
Published: December 2017

Zhang, Shaoping, Vicki Garbutt, and John T. McBride.Strain-induced growth of the immature lung. J. Appl. Physiol. 81(4): 1471–1476, 1996.—To investigate the relationship between strain and postnatal lung growth, two groups of weanling ferrets were tracheotomized: the study group was exposed for 2 wk to a continuous positive airway pressure (CPAP) of 6 cmH2O and the other group was exposed to atmospheric pressure (control). Total lung capacity after 2 wk was ∼40% higher in the CPAP-exposed animals than in the control animals ( n = 19 for the control group and 18 for the study group; P < 0.01). CPAP exposure was also associated with increases in lung weight and total lung protein and DNA contents. Lung recoil, measured in a subgroup of animals, was characterized by air-filled and saline-filled static expiratory pressure-volume curves. Neither in the air-filled lungs nor in the saline-filled lungs was there a significant difference between CPAP-exposed and control animals in lung recoil at equal fractions of total lung capacity. These data indicate that mechanical strain was associated with an acceleration of lung growth in immature ferrets. The preservation of volume-corrected lung recoil and the expected contribution of surface forces and tissue forces to lung recoil in CPAP-exposed animals suggest that this response did not involve simple lung distension but included a remodeling of the lung parenchyma.
Exercise training improves lusitropy by isoproterenol in papillary muscles from aged rats
Authors: Taffet George E. , Michael Lloyd A. , Tate Charlotte A.
Published: December 2017

Taffet, George E., Lloyd A. Michael, and Charlotte A. Tate.Exercise training improves lusitropy by isoproterenol in papillary muscles from aged rats. J. Appl. Physiol. 81(4): 1488–1494, 1996.—Aging is associated with a decreased cardiac responsiveness to β-adrenergic stimulation. We examined the effect of endurance exercise training of old Fischer 344 male rats on β-adrenergic stimulation of the function of isolated left ventricular papillary muscle. Three groups were examined: sedentary mature (SM; 12-mo old), sedentary old (SO; 23–24 mo old), and exercised old (EO; 23–24 mo old) that were treadmill trained for 4–8 wk. The isometric contractile properties were studied at 0.2 Hz and 0.75 mM calcium. Without β-adrenergic stimulation, there were no group differences for peak tension, maximum rate of tension development (+dP/d t), or maximum rate of tension dissipation (−dP/d t). The time to peak tension was longer ( P < 0.05) for both EO and SO than for SM rats. Half relaxation time (RT1/2) was prolonged ( P < 0.05) for SO compared with SM and EO (which did not differ). The three groups did not differ in the β-adrenergic stimulation by isoproterenol of peak tension, −dP/d t, time to peak tension, or contraction duration. The inotropic response (+dP/d t) of SM was greater ( P < 0.05) than that in SO or EO rats (which did not differ); however, the lusitropic response (RT1/2) was lesser ( P < 0.05) in SO than in SM or EO rats (which did not differ). Thus exercise training of old rats improved the lusitropic response to isoproterenol without altering the age-associated impairment in inotropic response.
Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability
Authors: Bush Michele L. , Asplund Patrick T. , Miles Kristen A. , Ben-Jebria Abdellaziz , Ultman James S.
Published: December 2017

Bush, Michele L., Patrick T. Asplund, Kristen A. Miles, Abdellaziz Ben-Jebria, and James S. Ultman. Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability. J. Appl. Physiol. 81(4): 1651–1657, 1996.—Because the National Ambient Air Quality Standard for ozone (O3) is intended to protect the most sensitive individuals in the general population, it is necessary to identify sources of intersubject variation in the exposure-dose-response cascade. We hypothesize that differences in lung anatomy can modulate exposure-dose relationships between individuals, and this results in differences between their responsiveness to O3 at a fixed exposure condition. During quiet breathing, the conducting airways remove the majority of inhaled O3, so the volume of this region should have an important impact on O3 dose distribution. Employing the bolus inhalation method, we measured the distribution of O3 absorption with respect to penetration volume (VP), and using the Fowler single-breath N2washout method, we determined the dead space volume (Vd) in the lungs of 10 men and 10 women at a fixed respiratory flow of 250 ml/s. On average, the women absorbed O3 at smaller VP than the men, and the women had smaller Vd than the men. When expressed in terms of VP/ Vd, the absorption distribution of the men and women was indistinguishable. Moreover, an interpretation of the O3 distribution in terms of an intrinsic mass transfer parameter ( Ka) indicated that differences between the O3 dosimetry in all subjects, whether men or women, could be explained by a unique correlation with anatomic dead space: Ka (in s−1) = 610 Vd −1.05(in ml). Application of this result to measurements of O3 exposure response indicated that previously reported gender differences may be due to a failure in properly accounting for tissue surface within the conducting airways.
Effect of macroscopic deformation on lung microstructure
Authors: Butler James P. , Miki Hiroshi , Squarcia Stephanie , Rogers Rick A. , Lehr John L.
Published: December 2017

Butler, James P., Hiroshi Miki, Stephanie Squarcia, Rick A. Rogers, and John L. Lehr. Effect of macroscopic deformation on lung microstructure. J. Appl. Physiol.81(4): 1792–1799, 1996.—Using an anisotropic theory of diffuse light scattering in lungs, we measured the fractional changes in geometric mean linear intercepts in orthogonal directions when freshly excised rabbit lungs were subjected to isovolume uniaxial strains. Results from the optical technique were compared with morphometric estimates of fractional changes in mean linear intercepts from the same strained and unstrained (control) lobes, with the conclusion that diffuse light scattering is adequate to estimate changes in mean free paths in different directions. We compared optical estimates of fractional changes in mean linear intercepts with the macroscopic strain field measured by displacements of pleural markers; this relationship did not significantly differ from the line of identity. We conclude that the microscopic strain field is closely matched to the macroscopic strain field during uniaxial distortion. This suggests that surface reorientation may not play a large role in the origin of the low shear modulus of the lung, but this cannot be definitively stated without comparison of these experimental results to specific model predictions of the changes in mean linear intercepts in shear deformation.
Methods for detecting local intestinal ischemic anaerobic metabolic acidosis by P CO 2
Authors: Rozenfeld Ranna A. , Dishart Michael K. , Tønnessen Tor Inge , Schlichtig Robert
Published: December 2017

Rozenfeld, Ranna A., Michael K. Dishart, Tor Inge Tønnessen, and Robert Schlichtig. Methods for detecting local intestinal ischemic anaerobic metabolic acidosis by[Formula: see text]. J. Appl. Physiol. 81(4): 1834–1842, 1996.—Gut ischemia is often assessed by computing an imaginary tissue interstitial pH from arterial plasma [Formula: see text] and the[Formula: see text] in a saline-filled balloon tonometer after equilibration with tissue[Formula: see text](P[Formula: see text]). P[Formula: see text] may alternatively be assumed equal to venous[Formula: see text]([Formula: see text]) in that region of gut. The idea is that as blood flow decreases, gut P[Formula: see text] and[Formula: see text] will increase to the maximum aerobic value, i.e., maximum respiratory[Formula: see text]([Formula: see text]). Above a “critical” anaerobic threshold, lactate (La−) generation, by titration of tissue [Formula: see text], should raise P[Formula: see text]above[Formula: see text]. During progressive selective whole intestinal flow reduction in six pentobarbital-anesthetized pigs, we used[Formula: see text] electrodes to test the hypotheses that critical P[Formula: see text]is achieved earlier in mucosa than in serosa and that[Formula: see text], computed using an in vitro model, predicts critical P[Formula: see text]. We defined critical P[Formula: see text] as the inflection of P[Formula: see text]-[Formula: see text]vs. O2delivery (Q˙o2) plots. CriticalQ˙o2for O2uptake was 12.55 ± 2 ml ⋅ kg−1⋅ min−1. Critical P[Formula: see text] for mucosa and serosa was achieved at similar whole intestineQ˙o2(13.90 ± 5 and 13.36 ± 5 ml ⋅ kg−1⋅ min−1, P = NS). Critical P[Formula: see text] (129 ± 24 and 96 ± 21 Torr) exceeded[Formula: see text](62 ± 3 Torr). During ischemia, La−excretion into portal venous blood was matched by K+excretion, causing [Formula: see text] to increase only slightly, despite P[Formula: see text] rising to 380 ± 46 (mucosa) and 280 ± 38 (serosa) Torr. These results suggest that mucosa and serosa become dysoxic simultaneously, that ischemic dysoxic gut is essentially unperfused, and that in vitro predicted[Formula: see text]underestimates critical P[Formula: see text].
Coca chewing for exercise: hormonal and metabolic responses of nonhabitual chewers
Authors: Favier Roland , Caceres Esperanza , Guillon Laurent , Sempore Brigitte , Sauvain Michel , Koubi Harry , Spielvogel Hilde
Published: December 2017

Favier, Roland, Esperanza Caceres, Laurent Guillon, Brigitte Sempore, Michel Sauvain, Harry Koubi, and Hilde Spielvogel. Coca chewing for exercise: hormonal and metabolic responses of nonhabitual chewers. J. Appl. Physiol. 81(5): 1901–1907, 1996.—To determine the effects of acute coca use on the hormonal and metabolic responses to exercise, 12 healthy nonhabitual coca users were submitted twice to steady-state exercise (∼75% maximal O2 uptake). On one occasion, they were asked to chew 15 g of coca leaves 1 h before exercise, whereas on the other occasion, exercise was performed after 1 h of chewing a sugar-free chewing gum. Plasma epinephrine, norepinephrine, insulin, glucagon, and metabolites (glucose, lactate, glycerol, and free fatty acids) were determined at rest before and after coca chewing and during the 5th, 15th, 30th, and 60th min of exercise. Simultaneously to these determinations, cardiorespiratory variables (heart rate, mean arterial blood pressure, oxygen uptake, and respiratory gas exchange ratio) were also measured. At rest, coca chewing had no effect on plasma hormonal and metabolic levels except for a significantly reduced insulin concentration. During exercise, the oxygen uptake, heart rate, and respiratory gas exchange ratio were significantly increased in the coca-chewing trial compared with the control (gum-chewing) test. The exercise-induced drop in plasma glucose and insulin was prevented by prior coca chewing. These results contrast with previous data obtained in chronic coca users who display during prolonged submaximal exercise an exaggerated plasma sympathetic response, an enhanced availability and utilization of fat (R. Favier, E. Caceres, H. Koubi, B. Sempore, M. Sauvain, and H. Spielvogel. J. Appl. Physiol. 80: 650–655, 1996). We conclude that, whereas coca chewing might affect glucose homeostasis during exercise, none of the physiological data provided by this study would suggest that acute coca chewing in nonhabitual users could enhance tolerance to exercise.
Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia
Authors: Roach Robert C. , Loeppky Jack A. , Icenogle Milton V.
Published: December 2017

Roach, Robert C., Jack A. Loeppky, and Milton V. Icenogle.Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia. J. Appl. Physiol. 81(5): 1908–1910, 1996.—Acute mountain sickness (AMS) strikes those in the mountains who go too high too fast. Although AMS has been long assumed to be due solely to the hypoxia of high altitude, recent evidence suggests that hypobaria may also make a significant contribution to the pathophysiology of AMS. We studied nine healthy men exposed to simulated altitude, normobaric hypoxia, and normoxic hypobaria in an environmental chamber for 9 h on separate occasions. To simulate altitude, the barometric pressure was lowered to 432 ± 2 (SE) mmHg (simulated terrestrial altitude 4,564 m). Normobaric hypoxia resulted from adding nitrogen to the chamber (maintained near normobaric conditions) to match the inspired[Formula: see text] of the altitude exposure. By lowering the barometric pressure and adding oxygen, we achieved normoxic hypobaria with the same inspired[Formula: see text] as in our laboratory at normal pressure. AMS symptom scores (average scores from 6 and 9 h of exposure) were higher during simulated altitude (3.7 ± 0.8) compared with either normobaric hypoxia (2.0 ± 0.8; P < 0.01) or normoxic hypobaria (0.4 ± 0.2; P < 0.01). In conclusion, simulated altitude induces AMS to a greater extent than does either normobaric hypoxia or normoxic hypobaria, although normobaric hypoxia induced some AMS.
Reduced oxidation rates of ingested glucose during prolonged exercise with low endogenous CHO availability
Authors: Jeukendrup Asker E. , Borghouts Lars B. , Saris Wim H. M. , Wagenmakers Anton J. M.
Published: December 2017

Jeukendrup, Asker E., Lars B. Borghouts, Wim H. M. Saris, and Anton J. M. Wagenmakers. Reduced oxidation rates of ingested glucose during prolonged exercise with low endogenous CHO availability. J. Appl. Physiol. 81(5): 1952–1957, 1996.—This study investigated the effect of endogenous carbohydrate (CHO) availability on oxidation rates of ingested glucose during moderate-intensity exercise. Seven well-trained cyclists performed two trials of 120 min of cycling exercise in random order at 57% maximal O2 consumption. Preexercise glycogen concentrations were manipulated by glycogen-lowering exercise in combination with CHO restriction [low-glycogen (LG) trial] or CHO loading [moderate-to-high-glycogen (HG) trial]. In the LG and HG trials, subjects ingested 4 ml/kg body wt of an 8% corn-derived glucose solution of high natural13C abundance at the start, followed by boluses of 2 ml/kg every 15 min. The third trial, in which potato-derived glucose was ingested, served as a control test for background correction. Exogenous glucose oxidation rates were calculated from the 13C enrichment of the ingested glucose and of the breath CO2. Total CHO oxidation was lower in the LG trial than in the HG trial during 60–120 min of exercise [84 ± 7 (SE) vs. 116 ± 8 g; P < 0.05]. Exogenous CHO oxidation in this period was 28% lower in the LG trial compared with the HG trial. Maximal exogenous oxidation rates were also lower ( P < 0.05) in the LG trial (0.64 ± 0.05 g/min) than in the HG trial (0.88 ± 0.04 g/min). This decreased utilization of exogenous glucose was accompanied by increased plasma free fatty acid levels (2–3 times higher) and lower insulin concentrations. It is concluded that glycogen-lowering exercise, performed the evening before an exercise bout, in combination with CHO restriction leads to a reduction of the oxidation rate of ingested glucose during moderate-intensity exercise.
Developmental changes in endothelium-dependent relaxation of pulmonary arteries: role of EDNO and prostanoids
Authors: O’Donnell Denise C. , Tod Mary L. , Gordon John B.
Published: December 2017

O’Donnell, Denise C., Mary L. Tod, and John B. Gordon.Developmental changes in endothelium-dependent relaxation of pulmonary arteries: role of EDNO and prostanoids. J. Appl. Physiol. 81(5): 2013–2019, 1996.—We hypothesized that maturational changes in both prostaglandin and endothelium-derived nitric oxide (EDNO) activity contribute to developmental changes in endothelium-dependent relaxation of newborn pulmonary arteries. Responses to endothelium-dependent vasodilators acetylcholine, bradykinin, and calcium ionophore A-23187 were determined in phenylephrine-constricted third- and fourth-generation (1- to 2-mm-diameter) pulmonary artery rings from 2-day (2d)- and 1-mo (1m)-old lambs under control conditions (Con), after inhibition of EDNO synthesis with N ω-nitro-l-arginine (l-NNA), after inhibition of prostanoid synthesis with meclofenamate (Mec), or both modulators with both inhibitors. Endothelium-independent responses to sodium nitroprusside (SNP) were also measured in Con rings. Endothelium-dependent relaxation was greater in 2d than 1m Con rings, particularly at high concentrations when an increase in tension occurred in 1m rings. l-NNA attenuated endothelium-dependent relaxation more in 2d rings, and SNP caused greater relaxation in 2d rings. However, Mec abolished all age-related differences by attenuating relaxation in 2d rings and constriction in 1m rings. These data suggest that developmental changes in endothelium-dependent responses of ovine pulmonary artery rings reflect both a decrease in EDNO activity and maturational differences in the relative influence of dilator and constrictor prostanoids.
Coordination, the determinant of velocity specificity?
Authors: Almåsbakk Bjørn , Hoff Jan
Published: December 2017

Almåsbakk, Bjørn, and Jan Hoff. Coordination, the determinant of velocity specificity? J. Appl. Physiol.80(5): 2046–2052, 1996.—Initial strength gains were examined in the context of learning a new skill. Forty female volunteers were randomly assigned to one of four groups: a bench-press training group utilizing heavy loads in its training, a bench-press training group utilizing almost no load, an alternative training group using different exercises, or a control group that did not train. Training period was 6 wk, with three training sessions per week. Emphasis was put on keeping the coordination and muscular adaptation demands in the bench-press groups as invariant as possible. Bench-press training with a light or with a heavy weight was shown to be equally effective in improving the maximal velocity of contraction for a given absolute resistance. Mean velocity with loads of 0.37, 6.6, 16.6, and 20 kg improved by 21.1, 15.8, 16.9, and 19.5%, respectively. No significant differences in the percent improvement at the four different loads were apparent, indicating that no significant velocity-specific adaptations were present. The bench-press training group, utilizing heavy loads in its training, was the only group with improved one repetition maximum. Overall, findings point to the development of coordination as the determining factor in early velocity-specific strength gains.
Chronic hypoxia alters nitric oxide-dependent pulmonary vascular responses in lungs of newborn pigs
Authors: Fike Candice D. , Kaplowitz Mark R.
Published: December 2017

Fike, Candice D., and Mark R. Kaplowitz. Chronic hypoxia alters nitric oxide-dependent pulmonary vascular responses in lungs of newborn pigs. J. Appl. Physiol. 81(5): 2078–2087, 1996.—Almost all of the studies evaluating the effect of chronic hypoxia on lung nitric oxide production have been performed in adult animals. Because results of studies in adult lungs should not be extrapolated to represent the newborn lung, we performed studies to determine whether decreased nitric oxide production might be involved in the pathogenesis of chronic hypoxia-induced pulmonary hypertension in newborns. We kept newborn pigs in chambers filled with room air (control) or 11–12% O2 for either 3–5 (short) or 10–12 (long) days. Using isolated lungs, we measured pulmonary vascular responses to agents that either stimulate or inhibit the synthesis of nitric oxide. To define the vascular sites of altered production of nitric oxide, we applied the micropuncture technique and measured small venular pressures before and after treatment with a nitric oxide synthesis inhibitor. Pulmonary vascular responses to acetylcholine were blunted in chronically hypoxic piglets of both the short and long groups. The nitric oxide synthesis inhibitor had a different effect in the lungs of control piglets than in those of chronically hypoxic piglets of the long but not of the short group. For the long group, the nitric oxide synthesis inhibitors caused constriction of both arteries and veins in lungs of control but not of chronically hypoxic piglets. These findings support the idea that decreased pulmonary vascular nitric oxide production occurs with chronic hypoxia in newborn pigs and might therefore contribute to the pathogenesis of pulmonary hypertension in newborns.
Effect of episodic eucapnic and hypocapnic hypoxia on systemic blood pressure in hypertension-prone rats
Authors: Fletcher Eugene C. , Bao Gang
Published: December 2017

Fletcher, Eugene C., and Gang Bao. Effect of episodic eucapnic and hypocapnic hypoxia on systemic blood pressure in hypertension-prone rats. J. Appl. Physiol. 81(5): 2088–2094, 1996.—Repetitive episodic (18–24 s twice per minute) hypocapnic hypoxia (HH) administered chronically (7 h/day, 35 days) to Sprague-Dawley or Wistar-Kyoto rats results in a sustained increase in daytime blood pressure (BP). We examined acute and chronic BP response to episodic HH and eucapnic hypoxia (EH) in borderline hypertensive rats [first generation (F1) cross between spontaneously hypertensive and Wistar-Kyoto rats]. We hypothesized that episodic HH and EH would create a greater increase in acute and chronic BP in this breed of rat than in previously studied strains. We also examined neural mechanisms by which BP changes from hypoxia are induced. BP and heart rate were examined acutely in nine F1 rats during baseline, HH, EH, EH with prazosin, and EH with prazosin and atropine. Five groups of male F1 rats were studied after 35-day exposure to the following: Unhandled ( n = 8): no treatment; Sham ( n = 10): episodic compressed air; HH ( n = 14): daily episodic hypoxia (2.7%); EH1 ( n = 12): hypoxia 2.9%, CO2 8.4%; and EH2 ( n = 11): hypoxia 2.8% and CO2 10.5%. Under acute conditions, HH caused a 34.2-mmHg and EH a 77.9-mmHg increase in mean BP. Prazosin partially blocked the increase in BP. Under chronic conditions, HH caused a 10.3-mmHg increase in daytime mean BP, whereas EH caused a fall in mean BP of 16.6 and 9.3 mmHg in the two separately studied groups. In the F1 rat, acute EH causes an elevation of BP but chronic EH causes a fall in BP. The acute response to EH is not predictive of what occurs after chronic exposure in the hypertension-prone F-1 rat.
Phrenic motoneuron discharge during sustained inspiratory resistive loading
Authors: Iscoe Steve
Published: December 2017

Iscoe, Steve. Phrenic motoneuron discharge during sustained inspiratory resistive loading. J. Appl. Physiol. 81(5): 2260–2266, 1996.—I determined whether prolonged inspiratory resistive loading (IRL) affects phrenic motoneuron discharge, independent of changes in chemical drive. In seven decerebrate spontaneously breathing cats, the discharge patterns of eight phrenic motoneurons from filaments of one phrenic nerve were monitored, along with the global activity of the contralateral phrenic nerve, transdiaphragmatic pressure, and fractional end-tidal CO2 levels. Discharge patterns during hyperoxic CO2 rebreathing and breathing against an IRL (2,500–4,000 cmH2O ⋅ l−1 ⋅ s) were compared. During IRL, transdiaphragmatic pressure increased and then either plateaued or decreased. At the highest fractional end-tidal CO2 common to both runs, instantaneous discharge frequencies in six motoneurons were greater during sustained IRL than during rebreathing, when compared at the same time after the onset of inspiration. These increased discharge frequencies suggest the presence of a load-induced nonchemical drive to phrenic motoneurons from unidentified source(s).