bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between histamine and physiological changes during the early response to nasal antigen provocation
Authors: Baroody Fuad M. , Ford Stephen , Proud David , Kagey-Sobotka Anne , Lichtenstein Lawrence , Naclerio Robert M.
Published: December 2017

To investigate the temporal relationships of mediator release and physiological changes during the early response to allergen, we challenged allergic individuals intranasally with antigen and followed their responses. This was done by using small filter paper disks to challenge one nostril and collect secretions from both the challenged and the contralateral nostril, thus enabling us to evaluate the nasonasal reflex. There was a significant increase in sneezing after allergen challenge that peaked within 2 min and returned to baseline. The weights of nasal secretions as well as nasal symptoms increased immediately and remained significantly elevated for 20 min in both nostrils. Nasal airway resistance increased slowly, reaching its peak at ∼6 min after challenge on the ipsilateral side, but it did not change on the contralateral side. Histamine levels peaked 30 s after removal of the allergen disk on the side of challenge, whereas albumin levels peaked after those of histamine. Lactoferrin paralleled the increase in secretion weights and occurred in both nostrils. Increasing doses of antigen produced dose-dependent increases in all parameters, whereas control challenges produced no response. These studies describe a human model for the evaluation of the allergic response that is capable of simultaneously measuring mediator release and the physiological response, including the nasonasal reflex. This model should prove useful in studying the mechanism of allergic rhinitis in humans.
Mechanism of mosaic attenuation of the lungs on computed tomography in induced bronchospasm
Authors: Gückel Claudius , Wells Athol U. , Taylor David A. , Chabat François , Hansell David M.
Published: December 2017

The purpose of this study was to investigate whether hypoxic pulmonary vasoconstriction is the major determinant of the computed tomography (CT) pattern of mosaic attenuation in asthmatic patients with induced bronchoconstriction. Thin-section CT was performed at suspended full inspiration immediately and 30 min after methacholine bronchoprovocation in 22 asthmatic subjects, who were randomly assigned to breathe room air ( group A, n = 8), oxygen via nasal prongs at 5 l/min ( group B, n = 8), and oxygen via face mask at 12 l/min ( group C, n = 6). CT changes were quantified in terms of global lung density and density in hypodense and hyperdense areas. Lung parenchymal density increases were greatest in group C and greater in group B than in group A, globally ( P = 0.03) and in hypodense regions ( P = 0.01). On bivariate analysis, the only change in cross-sectional area was related to change in global density. In hypodense regions, density change was related both to reduction in cross-sectional area ( P < 0.0005) and to oxygen administration ( P = 0.01). After correction for changes in global lung density, only oxygen was independently related to density increase in hypodense areas ( P = 0.02). In induced bronchoconstriction, the CT appearance of mosaic attenuation can be largely ascribed to hypoxic vasoconstriction rather than to changes in lung inflation.
Peptide toxin blockers of voltage-sensitive K+channels: inotropic effects on diaphragm
Authors: van Lunteren Erik , Moyer Michelle
Published: December 2017

Agents that block many types of K+channels (e.g., the aminopyridines) have substantial inotropic effects in skeletal muscle. Specific blockers of ATP-sensitive and Ca2+-activated K+channels, on the other hand, do not, or minimally, alter the force of nonfatigued muscle, consistent with a predominant role for voltage-gated K+channels in regulating muscle force. To test this more directly, we examined the effects of peptide toxins, which in other tissues specifically block voltage-gated K+channels, on rat diaphragm in vitro. Twitch force was increased in response to α-, β-, and γ-dendrotoxin and tityustoxin Kα (17 ± 6, 22 ± 5, 42 ± 14, and 13 ± 5%; P < 0.05, < 0.01, < 0.05, < 0.05, respectively) but not in response to δ-dendrotoxin or BSA (in which toxins were dissolved). Force during 20-Hz stimulation was also increased significantly by α-, β-, and γ-dendrotoxin and tityustoxin Kα. Among agents, increases in twitch force correlated with the degree to which contraction time was prolonged ( r = 0.88, P < 0.02). To determine whether inotropic effects could be maintained during repeated contractions, muscle strips underwent intermittent 20-Hz train stimulation for a duration of 2 min in presence or absence of γ-dendrotoxin. Force was significantly greater with than without γ-dendrotoxin during repetitive stimulation for the first 60 s of repetitive contractions. Despite the ∼55% higher value for initial force in the presence vs. absence of γ-dendrotoxin, the rate at which fatigue occurred was not accelerated by the toxin, as assessed by the amount of time over which force declined by 25 and 50%. These data suggest that blocking voltage-activated K+channels may be a useful therapeutic strategy for augmenting diaphragm force, provided less toxic blockers of these channels can be found.
Command-related distribution of regional cerebral blood flow during attempted handgrip
Authors: Nowak Markus , Olsen Karsten S. , Law Ian , Holm Søren , Paulson Olaf B. , Secher Niels H.
Published: December 2017

To localize a central nervous feed-forward mechanism involved in cardiovascular regulation during exercise, brain activation patterns were measured in eight subjects by employing positron emission tomography and oxygen-15-labeled water. Scans were performed at rest and during rhythmic handgrip before and after axillary blockade with bupivacaine. After the blockade, handgrip strength was reduced to 25% (range 0–50%) of control values, whereas handgrip-induced heart rate and blood pressure increases were unaffected (13 ± 3 beats/min and 12 ± 5 mmHg, respectively; means ± SE). Before regional anesthesia, handgrip caused increased activation in the contralateral sensory motor area, the supplementary motor area, and the ipsilateral cerebellum. We found no evidence for changes in the activation pattern due to an interaction between handgrip and regional anesthesia. This was true for both the blocked and unblocked arm. It remains unclear whether the activated areas are responsible for the increase in cardiovascular variables, but neural feedback from the contracting muscles was not necessary for the activation in the mentioned areas during rhythmic handgrip.
Pulmonary perfusion is more uniform in the prone than in the supine position: scintigraphy in healthy humans
Authors: Nyrén Sven , Mure Margareta , Jacobsson Hans , Larsson Stig A. , Lindahl Sten G. E.
Published: December 2017

The main purpose of this study was to find out whether the dominant dorsal lung perfusion while supine changes to a dominant ventral lung perfusion while prone. Regional distribution of pulmonary blood flow was determined in 10 healthy volunteers. The subjects were studied in both prone and supine positions with and without lung distension caused by 10 cmH2O of continuous positive airway pressure (CPAP). Radiolabeled macroaggregates of albumin, rapidly trapped by pulmonary capillaries in proportion to blood flow, were injected intravenously. Tomographic gamma camera examinations (single-photon-emission computed tomography) were performed after injections in the different positions. All data acquisitions were made with the subject in the supine position. CPAP enhanced perfusion differences along the gravitational axis, which was more pronounced in the supine than prone position. Diaphragmatic sections of the lung had a more uniform pulmonary blood flow distribution in the prone than supine position during both normal and CPAP breathing. It was concluded that the dominant dorsal lung perfusion observed when the subjects were supine was not changed into a dominant ventral lung perfusion when the subjects were prone. Lung perfusion was more uniformly distributed in the prone compared with in the supine position, a difference that was more marked during total lung distension (CPAP) than during normal breathing.
Increased cerebral extracellular adenosine and decreased PGE2during ethanol-induced inhibition of FBM
Authors: Watson Carole S. , White Susan E. , Homan Jacobus H. , Kimura Karen A. , Brien James F. , Fraher Laurence , Challis John R. G. , Bocking Alan D.
Published: December 2017

Adenosine and PGE2are neuromodulators, both of which inhibit fetal breathing movements (FBM). Although circulating PGE2has been implicated as a mediator of ethanol-induced inhibition of FBM in the late-gestation ovine fetus, a role for adenosine has not been examined. The objective of this study was to determine the effect of maternal ethanol infusion on ovine fetal cerebral extracellular fluid adenosine and PGE2concentrations by using in utero microdialysis and to relate any changes to ethanol-induced inhibition of FBM. Dialysate samples were obtained from the fetal parietal cortex over 70 h after surgery to determine steady-state extracellular fluid adenosine and PGE2concentrations. On each of postoperative days 3 and 4, after a 2-h baseline period, ewes received a 1-h infusion of ethanol (1 g/kg maternal body wt) or an equivalent volume of saline, and the fetus was monitored for a further 11 h with 30-min dialysate samples collected throughout. Immediately after surgery, dialysate PGE2and adenosine concentrations were 3.7 ± 0.7 and 296 ± 127 nM, respectively. PGE2did not change over the 70 h, whereas adenosine decreased to 59 ± 14 nM ( P < 0.05) at 4 h and then remained unchanged. Ethanol decreased dialysate PGE2concentration for 2 h (3.3 ± 0.3 to 1.9 ± 0.4 nM; P < 0.05) and increased adenosine concentration for 6 h (87 ± 13 to a maximum of 252 ± 59 nM, P < 0.05). Ethanol decreased FBM incidence from 47 ± 7 to 16 ± 5% ( P < 0.01) for 8 h. Saline infusion did not change dialysate adenosine or PGE2concentrations or FBM incidence. These data are consistent with the hypothesis that fetal cerebral adenosine, and not PGE2, is the primary mediator of ethanol-induced inhibition of FBM at 123 days of gestation in sheep.
Influence of increased abdominal pressure on steady-state cardiac performance
Authors: Kitano Yoshihiro , Takata Masao , Sasaki Nobuyoshi , Zhang Qinming , Yamamoto Shin , Miyasaka Katsuyuki
Published: December 2017

The effect of steady-state increases in abdominal pressure (Pab) on cardiac performance was studied in seven acutely instrumented swine with pneumoperitoneum (PP). The animal was placed on volume-preset ventilation, and PP was created by air insufflation. Cardiac output (CO), right atrial (Pra), left atrial (Pla), pericardial (Ppe), and abdominal inferior vena cava pressures (Pivc) were measured while Pab was increased from baseline to 7.5, 15, and 30 mmHg (PP7.5, PP15, and PP30, respectively). Cardiac function curves of the right and left ventricle (RV and LV, respectively) were compared between baseline and PP30. CO presented biphasic changes, with an inital slight increase at PP7.5 followed by a fall at PP30. A significant discrepancy was observed between Pra and Pivc at PP15 and PP30, consistent with development of a “vascular waterfall.” Transmural Pla (Pla − Ppe) showed parallel changes with CO, whereas transmural Pra (Pra − Ppe) exhibited a sustained increase. The RV cardiac-function curve was more depressed than was that of the LV at PP30; this suggests an increased RV afterload produced by the elevated airway pressure. These results support the hypothesis that our previously proposed concept of abdominal vascular zone conditions (M. Takata, R. A. Wise, and J. L. Robotham. J. Appl. Physiol. 69: 1961–1972, 1990) is also applicable to steady-state hemodynamic analyses. The abdominal zones appear to play an important role in determining CO, with increases in Pab, by modulating systemic venous return and the LV preload. Simultaneous measurements of Pra and Pivc may provide useful information in the hemodynamic care of patients with elevated Pab.
Altered contractile sensitivity of isolated bronchial artery to phenylephrine in ovalbumin-sensitized rabbits
Authors: Zschauer A. O. A. , Sielczak M. W. , Wanner A.
Published: December 2017

We tested the hypothesis that atopy and/or allergic lung inflammation enhances α1-adrenoceptor-mediated contractions of the bronchial artery. Bronchial arterial resistance vessels were isolated from rabbits that had undergone either systemic ovalbumin (OVA) sensitization followed by saline aerosol challenge (OVA/saline rabbits), or OVA sensitization followed by OVA aerosol challenge (OVA/OVA rabbits), or no sensitization followed by saline aerosol challenge (control rabbits). In OVA/OVA rabbits, bronchoalveolar lavage and lung histology revealed lymphocytic and eosinophilic inflammation. Arterial rings were contracted with phenylephrine (PE). In endothelium-intact arteries isolated from OVA/saline and OVA/OVA rabbits, PE responsiveness was enhanced compared with that of arteries isolated from controls. The nitric oxide synthase (NOS) inhibitor N G-nitro-l-arginine methyl ester increased the contractile response to PE in all three experimental groups to a similar degree, suggesting that depressed NOS activity was not involved in the enhanced PE responsiveness in OVA/saline and OVA/OVA rabbits. After endothelium removal, arteries from OVA/saline and control rabbits showed similar PE responsiveness, indicating that the enhancement of PE responsiveness was endothelium dependent, possibly due to an endothelial constricting factor. In OVA/OVA rabbits, endothelium-denuded arteries showed decreased PE responsiveness compared with the other two groups; this difference was abolished by N G-nitro-l-arginine methyl ester. We conclude that systemic sensitization with OVA per se enhances PE-induced contractions of isolated bronchial arteries in rabbits by an endothelium-dependent mechanism and that allergic lung inflammation attenuates this effect by increased nonendothelial NOS activity.
Validity of methods of body composition assessment in young and older men and women
Authors: Clasey J. L. , Kanaley J. A. , Wideman L. , Heymsfield S. B. , Teates C. D. , Gutgesell M. E. , Thorner M. O. , Hartman M. L. , Weltman A.
Published: December 2017

We examined the validity of percent body fat (%Fat) estimation by two-compartment (2-Comp) hydrostatic weighing (Siri 2-Comp), 3-Comp dual-energy X-ray absorptiometry (DEXA 3-Comp), 3-Comp hydrostatic weighing corrected for the total body water (Siri 3-Comp), and anthropometric methods in young and older individuals ( n = 78). A 4-Comp model of body composition served as the criterion measure of %Fat (Heymsfield 4-Comp; S. B. Heymsfield, S. Lichtman, R. N. Baumgartner, J. Wang, Y. Kamen, A. Aliprantis, and R. N. Pierson Jr., Am. J. Clin. Nutr. 52: 52–58, 1990.). Comparison of the Siri 3-Comp with the Heymsfield 4-Comp model revealed mean differences of ≤0.4 %Fat, r values ≥ r = 0.997, total error values ≤ 0.85 %Fat, and 95% confidence intervals (Bland-Altman analysis) of ≤1.7 %Fat. Comparison of Siri 2-Comp, DEXA, and anthropometric models with the Heymsfield 4-Comp revealed that total error scores ranged from ±4.0 to ±10.7 %Fat, and 95% confidence intervals associated with the Bland-Altman analysis ranged from ±5.1 to ±15.0 %Fat. We conclude that the Siri 3-Comp model provides valid and accurate body composition data when compared with a 4-Comp criterion model. However, the individual variability associated with the Siri 2-Comp, DEXA 3-Comp, and anthropometric models may limit their use in research settings. The use of anthropometric estimation methods resulted in large mean differences and a considerable amount of interindividual variability. These data suggest that the use of these techniques should be viewed with caution.
Pattern of expiratory muscle activation during lower thoracic spinal cord stimulation
Authors: DiMarco A. F. , Romaniuk J. R. , Kowalski K. E. , Supinski G.
Published: December 2017

Large positive airway pressures (Paws) can be generated by lower thoracic spinal cord stimulation (SCS), which may be a useful method of restoring cough in spinal cord-injured patients. Optimal electrode placement, however, requires an assessment of the pattern of current spread during SCS. Studies were performed in anesthetized dogs to assess the pattern of expiratory muscle recruitment during SCS applied at different spinal cord levels. A multicontact stimulating electrode was positioned over the surface of the lower thoracic and upper lumbar spinal cord. Recording electromyographic electrodes were placed at several locations in the abdominal and internal intercostal muscles. SCS was applied at each lead, in separate trials, with single shocks of 0.2-ms duration. The intensity of stimulation was adjusted to determine the threshold for development of the compound action potential at each electrode lead. The values of current threshold for activation of each muscle formed parabolas with minimum values at specific spinal root levels. The slopes of the parabolas were relatively steep, indicating that the threshold for muscle activation increases rapidly at more cephalad and caudal sites. These results were compared with the effectiveness of SCS (50 Hz; train duration, 1–2 s) at different spinal cord levels to produce changes in Paw. Stimulation at the T9 and T10 spinal cord level resulted in the largest positive Paws with a single lead. At these sites, threshold values for activation of the internal intercostal (7–11th interspaces) upper portions of external oblique, rectus abdominis, and transversus abdominis were near their minimum. Threshold values for activation of the caudal portions of the abdominal muscles were high (>50 mA). Our results indicate that 1) activation of the more cephalad portions of the abdominal muscles is more important than activation of caudal regions in the generation of positive Paws and 2) it is not possible to achieve complete activation of the expiratory muscles with a single electrode lead by using modest current levels. In support of this latter conclusion, a two-electrode lead system results in more uniform expiratory muscle activation and significantly greater changes in Paw.
Ventilatory effects of 8 h of isocapnic hypoxia with and without β-blockade in humans
Authors: Clar Christine , Dorrington Keith L. , Robbins Peter A.
Published: December 2017

This study investigated whether changing sympathetic activity, acting via β-receptors, might induce the progressive ventilatory changes observed in response to prolonged hypoxia. The responses of 10 human subjects to four 8-h protocols were compared: 1) isocapnic hypoxia (end-tidal[Formula: see text] = 50 Torr) plus 80-mg doses of oral propranolol; 2) isocapnic hypoxia, as in protocol 1, with oral placebo; 3) air breathing with propranolol; and 4) air breathing with placebo. Exposures were conducted in a chamber designed to maintain end-tidal gases constant by computer control. Ventilation (V˙e) was measured at regular intervals throughout. Additionally, the subjects’ ventilatory hypoxic sensitivity and their residual V˙e during hyperoxia (5 min) were assessed at 0, 4, and 8 h by using a dynamic end-tidal forcing technique. β-Blockade did not significantly alter either the rise in V˙e seen during 8 h of isocapnic hypoxia or the changes observed in the acute hypoxic ventilatory response and residual V˙e in hyperoxia over that period. The results do not provide evidence that changes in sympathetic activity acting via β-receptors play a role in the mediation of ventilatory changes observed during 8 h of isocapnic hypoxia.
Interactions of exercise training and ACE inhibition on insulin action in obese Zucker rats
Authors: Steen Michelle S. , Foianini Kara R. , Youngblood Erik B. , Kinnick Tyson R. , Jacob Stephan , Henriksen Erik J.
Published: December 2017

Exercise training or chronic treatment with angiotensin-converting enzyme (ACE) inhibitors can ameliorate glucose intolerance, insulin resistance of muscle glucose metabolism, and dyslipidemia associated with the obese Zucker rat. The purpose of the present study was to determine the interactions of exercise training and ACE inhibition (trandolapril) on these parameters in the obese Zucker rat. Animals were assigned to a sedentary control, a trandolapril-treated (1 mg ⋅ kg−1⋅ day−1for 6 wk), an exercise-trained (treadmill running for 6 wk), or a combined trandolapril-treated and exercise-trained group. Exercise training, alone or with trandolapril, significantly ( P < 0.05) increased peak O2consumption by 31–34%. Similar decreases in fasting plasma insulin (34%) and free fatty acids (31%) occurred with exercise training alone or in combination with trandolapril. Compared with control, exercise training or trandolapril alone caused smaller areas under the curve (AUC) for glucose (12–14%) and insulin (28–33%) during an oral glucose tolerance test. The largest decreases in the glucose AUC (40%) and insulin AUC (53%) were observed in the combined group. Similarly, whereas exercise training or trandolapril alone improved maximally activated insulin-stimulated glucose transport in isolated epitrochlearis (26–34%) or soleus (39–41%) muscles, the greatest improvements in insulin action (67 and 107%, respectively) were seen in the combined group and were associated with similarly enhanced muscle GLUT-4 protein and total hexokinase levels. In conclusion, these results indicate combined exercise training and ACE inhibition improve oral glucose tolerance and insulin-stimulated muscle glucose transport to a greater extent than does either intervention alone.
A tidal breathing model for the multiple inert gas elimination technique
Authors: Whiteley J. P. , Gavaghan D. J. , Hahn C. E. W.
Published: December 2017

The tidal breathing lung model described for the sine-wave technique (D. J. Gavaghan and C. E. W. Hahn. Respir. Physiol. 106: 209–221, 1996) is generalized to continuous ventilation-perfusion and ventilation-volume distributions. This tidal breathing model is then applied to the multiple inert gas elimination technique (P. D. Wagner, H. A. Saltzman, and J. B. West. J. Appl. Physiol. 36: 588–599, 1974). The conservation of mass equations are solved, and it is shown that 1) retentions vary considerably over the course of a breath, 2) the retentions are dependent on alveolar volume, and 3) the retentions depend only weakly on the width of the ventilation-volume distribution. Simulated experimental data with a unimodal ventilation-perfusion distribution are inserted into the parameter recovery model for a lung with 1 or 2 alveolar compartments and for a lung with 50 compartments. The parameters recovered using both models are dependent on the time interval over which the blood sample is taken. For best results, the blood sample should be drawn over several breath cycles.
Resetting of the carotid arterial baroreflex during dynamic exercise in humans
Authors: Norton K. H. , Boushel R. , Strange S. , Saltin B. , Raven P. B.
Published: December 2017

Recent investigations have demonstrated that at the onset of low-to-moderate-intensity leg cycling exercise (L) the carotid baroreflex (CBR) was classically reset in direct relation to the intensity of exercise. On the basis of these data, we proposed that the CBR would also be classically reset at the onset of moderate- to maximal-intensity L exercise. Therefore, CBR stimulus-response relationships were compared in seven male volunteers by using the neck pressure-neck suction technique during dynamic exercise that ranged in intensity from 50 to 100% of maximal oxygen uptake (V˙o 2 max). L exercise alone was performed at 50 and 75%V˙o 2 max, and L exercise combined with arm (A) exercise (L + A) was performed at 75 and 100%V˙o 2 max. O2 consumption and heart rate (HR) increased in direct relation with the increases in exercise intensity. The threshold and saturation pressures of the carotid-cardiac reflex at 100% V˙o 2 max were >75% V˙o 2 max, which were in turn >50%V˙o 2 max( P < 0.05), without a change in the maximal reflex gain (Gmax). In addition, the HR response value at threshold and saturation at 75%V˙o 2 max was >50%V˙o 2 max( P < 0.05) and 100%V˙o 2 max was >75%V˙o 2 max( P < 0.07). Similar changes were observed for the carotid-vasomotor reflex. In addition, as exercise intensity increased, the operating point (the prestimulus blood pressure) of the CBR was significantly relocated further from the centering point (Gmax) of the stimulus-response curve and was at threshold during 100%V˙o 2 max. These findings identify the continuous classic rightward and upward resetting of the CBR, without a change in Gmax, during increases in dynamic exercise intensity to maximal effort.
Blood lactate accumulation and muscle deoxygenation during incremental exercise
Authors: Grassi Bruno , Quaresima Valentina , Marconi Claudio , Ferrari Marco , Cerretelli Paolo
Published: December 2017

Near-infrared spectroscopy (NIRS) could allow insights into controversial issues related to blood lactate concentration ([La]b) increases at submaximal workloads (w˙). We combined, on five well-trained subjects [mountain climbers; peak O2 consumption (V˙o 2peak), 51.0 ± 4.2 (SD) ml ⋅ kg−1 ⋅ min−1] performing incremental exercise on a cycle ergometer (30 W added every 4 min up to voluntary exhaustion), measurements of pulmonary gas exchange and earlobe [La]b with determinations of concentration changes of oxygenated Hb (Δ[O2Hb]) and deoxygenated Hb (Δ[HHb]) in the vastus lateralis muscle, by continuous-wave NIRS. A “point of inflection” of [La]b vs.w˙ was arbitrarily identified at the lowest [La]b value which was >0.5 mM lower than that obtained at the following w˙. Total Hb volume (Δ[O2Hb + HHb]) in the muscle region of interest increased as a function ofw˙ up to 60–65% ofV˙o 2 peak, after which it remained unchanged. The oxygenation index (Δ[O2Hb − HHb]) showed an accelerated decrease from 60– 65% ofV˙o 2 peak. In the presence of a constant total Hb volume, the observed Δ[O2Hb − HHb] decrease indicates muscle deoxygenation (i.e., mainly capillary-venular Hb desaturation). The onset of muscle deoxygenation was significantly correlated ( r 2 = 0.95; P < 0.01) with the point of inflection of [La]bvs. w˙, i.e., with the onset of blood lactate accumulation. Previous studies showed relatively constant femoral venous[Formula: see text] levels at w˙ higher than ∼60% of maximal O2consumption. Thus muscle deoxygenation observed in the present study from 60–65% ofV˙o 2 peak could be attributed to capillary-venular Hb desaturation in the presence of relatively constant capillary-venular[Formula: see text] levels, as a consequence of a rightward shift of the O2Hb dissociation curve determined by the onset of lactic acidosis.
Differences in acute hypoxic pulmonary vasoresponsiveness between rat strains: role of endothelium
Authors: Salameh Gabriel , Karamsetty Mallikharjuna R. , Warburton Rod R. , Klinger James R. , Ou Lo Chang , Hill Nicholas S.
Published: December 2017

Intact Madison (M) rats have greater pulmonary pressor responses to acute hypoxia than Hilltop (H) rats. We tested the hypothesis that the difference in pressor response is intrinsic to pulmonary arteries and that endothelium contributes to the difference. Pulmonary arteries precontracted with phenylephrine (10−7 M) from M rats had greater constrictor responses [hypoxic pulmonary vasoconstriction (HPV)] to acute hypoxia (0% O2) than those from H rats: 473 ± 30 vs. 394 ± 29 mg ( P < 0.05). Removal of the endothelium or inhibition of nitric oxide (NO) synthase by N ω-nitro-l-arginine (l-NA, 10−3 M) significantly blunted HPV in both strains. Inhibition of cyclooxygenase by meclofenamate (10−5 M) or blockade of endothelin type A and B receptors by BQ-610 (10−5 M) + BQ-788 (10−5 M), respectively, had no effect on HPV. Constrictor responses to phenylephrine, endothelin-1, and prostaglandin F2α were similar in pulmonary arteries from both strains. The relaxation response to ACh, an NO synthase stimulator, was significantly greater in M than in H rats (80 ± 3 vs. 62 ± 4%, P < 0.01), but there was no difference in response to sodium nitroprusside, an NO donor.l-NA potentiated phenylephrine-induced contraction to a greater extent in pulmonary arteries from M than from H rats. These findings indicate that at least part of the strain-related difference in acute HPV is attributable to differences in endothelial function, possibly related to differences in NO production.
Effect of I/E ratio on mean alveolar pressure during high-frequency oscillatory ventilation
Authors: Pillow J. J. , Neil H. , Wilkinson M. H. , Ramsden C. A.
Published: December 2017

This study investigated factors contributing to differences between mean alveolar pressure ([Formula: see text]) and mean pressure at the airway opening (Pao) during high-frequency oscillatory ventilation (HFOV). The effect of the inspiratory-to-expiratory time (I/E) ratio and amplitude of oscillation on the magnitude of [Formula: see text] −Pao (Pdiff) was examined by using the alveolar capsule technique in normal rabbit lungs ( n = 4) and an in vitro lung model. The effect of ventilator frequency and endotracheal tube (ETT) diameter onPdiff was further examined in the in vitro lung model at an I/E ratio of 1:2. In both lung models,[Formula: see text] fell belowPao during HFOV when inspiratory time was shorter than expiratory time. Under these conditions, differences between inspiratory and expiratory flows, combined with the nonlinear relationship between resistive pressure drop and flow in the ETT, are the principal determinants of Pdiff. In our experiments, the magnitude of Pdiff at each combination of I/E, frequency, lung compliance, and ETT resistance could be predicted from the difference between the mean squared inspiratory and expiratory velocities in the ETT. These observations provide an explanation for the measured differences in mean pressure between the airway opening and the alveoli during HFOV and will assist in the development of optimal strategies for the clinical application of this technique.
Surfactant effects in model airway closure experiments
Authors: Cassidy K. J. , Halpern D. , Ressler B. G. , Grotberg J. B.
Published: December 2017

The capillary instability that occurs on an annular film lining a tube is studied as a model of airway closure. Small waves in the film can amplify and form a plug across the tube. This dynamical behavior is studied using theoretical models and bench-top experiments. Our model predicts the initial growth rate of the instability and its dependence on surfactant effects. In experiments, an annular film is formed by infusion of water into an initially oil-filled glass capillary tube. The thickness of the oil film varies with the infusion flow rate. The instability growth rate and closure time are measured for a range of film thicknesses. Our theory predicts that a thinner film and higher surfactant activity enhance stability; surfactant can decrease the growth rate to 25% of its surfactant-free value. In experiments, we find that surfactant can decrease the growth rate to 20% and increase the closure time by a factor of 3.8. Functional values of a critical film thickness for closure support the theory that it increases in the presence of surfactant.
The free-convective anomaly
Authors: Steadman Robert G.
Published: December 2017

Persons exposed to high temperature, or to equivalent environmental factors, have quantifiable reactions, such as reducing the resistance to both heat and moisture flow in skin tissues and clothing needed to maintain thermal equilibrium. The one-to-one relationship between this resistance in the walking person and temperature, with the other factors neutral, is the basis for the apparent temperature scale and the derived heat index. When this approach is taken to assess the thermal environment for a still person exposed to heat in still air, there is a zone of ambient conditions in which there are three solutions to the heat-balance equation. Extraordinary thermal stress occurs, depending slightly on other conditions, at ambient temperatures near 41°C, especially at high humidity, because of the difficulty in carrying sweat vapor from the person when free convection is minimal. This anomaly is examined for a range of ambient vapor pressures and extra radiation. The rapid rise in heat stress when ambient temperature just exceeds body temperature in still conditions may explain the severity of some observed distress.
mRNA levels for α-subunit of prolyl 4-hydroxylase and fibrillar collagens in immobilized rat skeletal muscle
Authors: Han Xiao-Yan , Wang Wei , Myllylä Raili , Virtanen Paula , Karpakka Jarmo , Takala Timo E. S.
Published: December 2017

There is evidence that immobilization causes a decrease in total collagen synthesis in skeletal muscle within a few days. In this study, early immobilization effects on the expression of prolyl 4-hydroxylase (PH) and the main fibrillar collagens at mRNA and protein levels were investigated in rat skeletal muscle. The right hindlimb was immobilized in full plantar flexion for 1, 3, and 7 days. Steady-state mRNAs for α- and β-subunits of PH and type I and III procollagen, PH activity, and collagen content were measured in gastrocnemius and plantaris muscles. Type I and III procollagen mRNAs were also measured in soleus and tibialis anterior muscles. The mRNA level for the PH α-subunit decreased by 49 and 55% ( P < 0.01) in gastrocnemius muscle and by 41 and 39% ( P < 0.05) in plantaris muscle after immobilization for 1 and 3 days, respectively. PH activity was decreased ( P < 0.05–0.01) in both muscles at days 3 and 7. The mRNA levels for type I and III procollagen were decreased by 26–56% ( P < 0.05–0.001) in soleus, tibialis anterior, and plantaris muscles at day 3. The present results thus suggest that pretranslational downregulation plays a key role in fibrillar collagen synthesis in the early phase of immobilization-induced muscle atrophy.
Sarcoplasmic reticulum Ca2+release and muscle fatigue
Authors: Favero Terence G.
Published: December 2017

Efforts to examine the relevant mechanisms involved in skeletal muscle fatigue are focusing on Ca2+handling within the active muscle cell. It has been demonstrated time and again that reductions in sarcoplasmic reticulum (SR) Ca2+release resulting from increased or intense muscle contraction will compromise tension development. This review seeks to accomplish two related goals: 1) to provide an up-to-date molecular understanding of the Ca2+-release process, with considerable attention devoted to the SR Ca2+channel, including its associated proteins and their regulation by endogenous compounds; and 2) to examine several putative mechanisms by which cellular alterations resulting from intense and/or prolonged contractile activity will modify SR Ca2+release. The mechanisms that are likely candidates to explain the reductions in SR Ca2+channel function following contractile activity include elevated Ca2+concentrations, alterations in metabolic homeostasis within the “microcompartmentalized” triadic space, and modification by reactive oxygen species.
Muscle kinematics for minimal work of breathing
Authors: Wilson Theodore A. , Angelillo Maurizio , Legrand Alexandre , de Troyer André
Published: December 2017

A mathematical model was analyzed to obtain a quantitative and testable representation of the long-standing hypothesis that the respiratory muscles drive the chest wall along the trajectory for which the work of breathing is minimal. The respiratory system was modeled as a linear elastic system that can be expanded either by pressure applied at the airway opening (passive inflation) or by active forces in respiratory muscles (active inflation). The work of active expansion was calculated, and the distribution of muscle forces that produces a given lung expansion with minimal work was computed. The calculated expression for muscle force is complicated, but the corresponding kinematics of muscle shortening is simple: active inspiratory muscles shorten more during active inflation than during passive inflation, and the ratio of active to passive shortening is the same for all active muscles. In addition, the ratio of the minimal work done by respiratory muscles during active inflation to work required for passive inflation is the same as the ratio of active to passive muscle shortening. The minimal-work hypothesis was tested by measurement of the passive and active shortening of the internal intercostal muscles in the parasternal region of two interspaces in five supine anesthetized dogs. Fractional changes in muscle length were measured by sonomicrometry during passive inflation, during quiet breathing, and during forceful inspiratory efforts against a closed airway. Active muscle shortening during quiet breathing was, on average, 70% greater than passive shortening, but it was only weakly correlated with passive shortening. Active shortening inferred from the data for more forceful inspiratory efforts was ∼40% greater than passive shortening and was highly correlated with passive shortening. These data support the hypothesis that, during forceful inspiratory efforts, muscle activation is coordinated so as to expand the chest wall with minimal work.
Interactions between angiotensin II and nitric oxide during exercise in normal and heart failure rats
Authors: Symons J. David , Stebbins Charles L. , Musch Timothy I.
Published: December 2017

We hypothesized that nitric oxide (NO) opposes ANG II-induced increases in arterial pressure and reductions in renal, splanchnic, and skeletal muscle vascular conductance during dynamic exercise in normal and heart failure rats. Regional blood flow and vascular conductance were measured during treadmill running before (unblocked exercise) and after 1) ANG II AT1-receptor blockade (losartan, 20 mg/kg ia), 2) NO synthase (NOS) inhibition [ NG-nitro-l-arginine methyl ester (l-NAME); 10 mg/kg ia], or 3) ANG II AT1-receptor blockade + NOS inhibition (combined blockade). Renal conductance during unblocked exercise (4.79 ± 0.31 ml ⋅ 100 g−1⋅ min−1⋅ mmHg−1) was increased after ANG II AT1-receptor blockade (6.53 ± 0.51 ml ⋅ 100 g−1⋅ min−1⋅ mmHg−1) and decreased by NOS inhibition (2.12 ± 0.20 ml ⋅ 100 g−1⋅ min−1⋅ mmHg−1) and combined inhibition (3.96 ± 0.57 ml ⋅ 100 g−1⋅ min−1⋅ mmHg−1;all P < 0.05 vs. unblocked). In heart failure rats, renal conductance during unblocked exercise (5.50 ± 0.66 ml ⋅ 100 g−1⋅ min−1⋅ mmHg−1) was increased by ANG II AT1-receptor blockade (8.48 ± 0.83 ml ⋅ 100 g−1⋅ min−1⋅ mmHg−1) and decreased by NOS inhibition (2.68 ± 0.22 ml ⋅ 100 g−1⋅ min−1⋅ mmHg−1; both P < 0.05 vs. unblocked), but it was unaltered during combined inhibition (4.65 ± 0.51 ml ⋅ 100 g−1⋅ min−1⋅ mmHg−1). Because our findings during combined blockade could be predicted from the independent actions of NO and ANG II, no interaction was apparent between these two substances in control or heart failure animals. In skeletal muscle, l-NAME-induced reductions in conductance, compared with unblocked exercise ( P < 0.05), were abolished during combined inhibition in heart failure but not in control rats. These observations suggest that ANG II causes vasoconstriction in skeletal muscle that is masked by NO-evoked dilation in animals with heart failure. Because reductions in vascular conductance between unblocked exercise and combined inhibition were less than would be predicted from the independent actions of NO and ANG II, an interaction exists between these two substances in heart failure rats.l-NAME-induced increases in arterial pressure during treadmill running were attenuated ( P < 0.05) similarly in both groups by combined inhibition. These findings indicate that NO opposes ANG II-induced increases in arterial pressure and in renal and skeletal muscle resistance during dynamic exercise.
Muscle O2 consumption by NIRS: a theoretical model
Authors: Binzoni T. , Colier W. , Hiltbrand E. , Hoofd L. , Cerretelli P.
Published: December 2017

In the past, the measurement of O2 consumption (O˙2) by the muscle could be carried out noninvasively by near-infrared spectroscopy from oxyhemoglobin and/or deoxyhemoglobin measurements only at rest or during steady isometric contractions. In the present study, a mathematical model is developed allowing calculation, together with steady-state levels ofO˙2, of the kinetics of O˙2readjustment in the muscle from the onset of ischemic but aerobic constant-load isotonic exercises. The model, which is based on the known sequence of exoergonic metabolic pathways involved in muscle energetics, allows simultaneous fitting of batched data obtained during exercises performed at different workloads. A Monte Carlo simulation has been carried out to test the quality of the model and to define the most appropriate experimental approach to obtain the best results. The use of a series of experimental protocols obtained at different levels of mechanical power, rather than repetitions of the same load, appears to be the most suitable procedure.
Effects of oral contraceptives on body fluid regulation
Authors: Stachenfeld Nina S. , Silva Celso , Keefe David L. , Kokoszka Cheryl A. , Nadel Ethan R.
Published: December 2017

To test the hypothesis that estrogen reduces the operating point for osmoregulation of arginine vasopressin (AVP), thirst, and body water balance, we studied nine women (25 ± 1 yr) during 150 min of dehydrating exercise followed by 180 min of ad libitum rehydration. Subjects were tested six different times, during the early-follicular (twice) and midluteal (twice) menstrual phases and after 4 wk of combined [estradiol-norethindrone (progestin), OC E + P] and 4 wk of norethindrone (progestin only, OC P) oral contraceptive administration, in a randomized crossover design. Basal plasma osmolality (Posm) was lower in the luteal phase (281 ± 1 mosmol/kgH2O, combined means, P < 0.05), OC E + P (281 ± 1 mosmol/kgH2O, P < 0.05), and OC P (282 ± 1 mosmol/kgH2O, P < 0.05) than in the follicular phase (286 ± 1 mosmol/kgH2O, combined means). High plasma estradiol concentration lowered the Posm threshold for AVP release during the luteal phase and during OC E + P [ x-intercepts, 282 ± 2, 278 ± 2, 276 ± 2, and 280 ± 2 mosmol/kgH2O, for follicular, luteal (combined means), OC E + P, and OC P, respectively; P < 0.05, luteal phase and OC E + P vs. follicular phase] during exercise dehydration, and 17β-estradiol administration lowered the Posm threshold for thirst stimulation [ x-intercepts, 280 ± 2, 279 ± 2, 276 ± 2, and 280 ± 2 mosmol/kgH2O for follicular, luteal, OC E + P, and OC P, respectively; P < 0.05, OC E + P vs. follicular phase], without affecting body fluid balance. When plasma 17β-estradiol concentration was high, Posm was low throughout rest, exercise, and rehydration, but plasma arginine vasopressin concentration, thirst, and body fluid retention were unchanged, indicating a lowering of the osmotic operating point for body fluid regulation.
Age-associated differential expression of Na+-K+-ATPase subunit isoforms in skeletal muscles of F-344/BN rats
Authors: Sun Xiwu , Nagarajan Murali , Beesley Philip W. , Ng Yuk-Chow
Published: December 2017

Skeletal muscle expresses multiple isoforms of the Na+-K+-ATPase. Their expression has been shown to be differentially regulated under pathophysiological conditions. In addition, previous studies suggest possible age-dependent alterations in Na+-K+pump function. The present study tests the hypothesis that advancing age is associated with altered Na+-K+-ATPase enzyme activity and isoform-specific changes in expression of the enzyme subunits. Red and white gastrocnemius (Gast) as well as soleus muscles of male Fischer 344/Brown Norway (F-344/BN) rats at 6, 18, and 30 mo of age were examined. Na+-K+-ATPase activity, measured by K+-stimulated 3- O-methylfluorescein phosphatase activity, increased by ∼50% in a mixed Gast homogenate from 30-mo-old compared with 6- and 18-mo-old rats. Advancing age was associated with markedly increased α1- and β1-subunit, and decreased α2- and β2-subunit in red and white Gast. In soleus, there were similar changes in expression of α1- and α2-subunits, but levels of β1-subunit were unchanged. Functional Na+-K+-ATPase units, measured by [3H]ouabain binding, undergo muscle-type specific changes. In red Gast, high-affinity ouabain-binding sites, which are a measure of α2-isozyme, increased in 30-mo-old rats despite decreased levels of α2-subunit. In white Gast, by contrast, decreased levels of α2-subunit were accompanied by decreased high-affinity ouabain-binding sites. Finally, patterns of expression of the four myosin heavy chain (MHC) isoforms (type I, IIA, IIX, and IIB) in these muscles were similar in the three age groups examined. We conclude that, in the skeletal muscles of F-344/BN rats, advancing age is associated with muscle type-specific alterations in Na+-K+-ATPase activity and patterns of expression of α- and β-subunit isoforms. These changes apparently occurred without obvious shift in muscle fiber types, since expression of MHC isoforms remained unchanged. Some of the alterations occurred between middle-age (18 mo) and senescence (30 mo), and, therefore, may be attributed to aging of skeletal muscle.
Spaceflight suppresses exercise-induced release of bioassayable growth hormone
Authors: McCall G. E. , Goulet C. , Roy R. R. , Grindeland R. E. , Boorman G. I. , Bigbee A. J. , Hodgson J. A. , Greenisen M. C. , Edgerton V. R.
Published: December 2017

We have reported that bed rest suppressed the release of bioassayable growth hormone (BGH) that normally occurs after an acute bout of unilateral plantar flexor exercise (G. E. McCall, C. Goulet, R. E. Grindeland, J. A. Hodgson, A. J. Bigbee, and V. R. Edgerton. J. Appl. Physiol. 83: 2086–2090, 1997). In the present study, the effects of spaceflight on the hormonal responses to this exercise protocol were examined. Four male astronauts on the National Aeronautics and Space Administration Shuttle Transport System (STS-78) mission completed the exercise protocol before, during, and after a 17-day spaceflight. The maximal voluntary contraction torque output at the onset of exercise was similar on all test days. Before spaceflight, plasma BGH increased 114–168% from pre- to postexercise. During spaceflight and after 2 days recovery at normal gravity (1 G), the BGH response to exercise was absent. After 4 days of recovery, this response was restored. Plasma concentrations of immunoassayable growth hormone were similar at all time points. The preexercise plasma immunoassayable insulin-like growth factor I (IGF-I) levels were elevated after 12 or 13 days of microgravity, and a ≈7% postexercise IGF-I increase was independent of this spaceflight effect. The suppression of the BGH response to exercise during spaceflight indicates that some minimum level of chronic neuromuscular activity and/or loading is necessary to maintain a normal exercise-induced BGH release. Moreover, these results suggest that there is a muscle afferent-pituitary axis that can modulate BGH release.