bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma volume with alternative tilting: effect of fluid ingestion
Authors: Hinghofer-Szalkay H. G. , Sauseng-Fellegger G. , Greenleaf J. E.
Published: December 2017

The present study determines the effect of repeated 70 degrees head-up tilt (HUT) on plasma volume (PV) shifts by measuring blood density (BD), plasma density (PD), and hematocrit (Hct). Eight men (18–26 yr) underwent a predrink period with two supine (P1 and P3) and two HUT (P2 and P4) phases of 45 min each. At the end of P4 they drank 10 ml/kg body wt of isotonic (290 mosmol/kg) sodium chloride (Iso) or hypotonic (< 10 mosmol/kg) unsweetened tea (Hypo) or nothing [control (Con)]. The following periods continued the supine (P5, P7)/upright (P6) sequence. BD and PD were measured from ear lobe blood; they were different (P < 0.05) between Con, Hypo, and Iso P6 and P7. The density of fluid that moved between intra- and extravascular compartments was 1,008.2 +/- 0.4 g/l and did not differ with test situations. In Con (P3, P5, P7), supine PV steadily decreased compared with P1 (P < 0.05). PV in P1, P2, and P3 of all treatments averaged 120 +/- 1, 101 +/- 1, and 115 +/- 1%, respectively, of PV in P4. Tilt-induced PV shifts ranged from -9.7 to -16.7% compared with PV during the respective previous phases. After drinking, PV increased (P < 0.05) above Con values at the end of P7 by 12.9% with Iso and by 6.6% with Hypo. Progressive hemoconcentration occurred in the nondrink supine periods; isotonic saline ingestion increased supine PV to Con level but did not stop or reverse the decrease of upright hemoconcentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of eccentric exercise on natural killer cell activity
Authors: Palmo J. , Asp S. , Daugaard J. R. , Richter E. A. , Klokker M. , Pedersen B. K.
Published: December 2017

The effect of eccentric one-legged exercise on natural killer (NK) cell activity was studied in eight healthy males. To distinguish between local and systemic effects, blood samples were collected from veins in the exercising leg and resting arm. However, the results did not significantly differ between the leg and arm. To eliminate diurnal variations, the results were compared with a control group that did not exercise but had blood samples collected at the same time points. In the exercising group, plasma creatine kinase increased progressively during and up to 4 days after exercise. The percentage of CD16+ NK cells increased during exercise, which was paralleled by an increase in the NK cell activity per fixed number of blood mononuclear cells. The NK cell activity on a per NK cell basis did not change. The percentage of CD3+, CD4+, CD8+, CD19+, and CD14+ cells did not change significantly during exercise. The present study thus showed that eccentric exercise with a relatively small muscle mass (1 quadriceps femoris muscle) causes systemic effects on NK cells. It is suggested that the increase in plasma epinephrine during eccentric exercise is responsible for the observed increase in the percentage of CD16+ cells.
Comparison of aerobic capacity between racing standardbred horses
Authors: Gauvreau G. M. , Staempfli H. , McCutcheon L. J. , Young S. S. , McDonell W. N.
Published: December 2017

A standardized treadmill test was used to compare metabolic and ventilatory measurements between 10 standardbred racehorses. The horses were divided into two groups: group A (n = 5) had mean racing speeds of 4.4 s faster than group B (n = 5) over a 1-mi. distance. Each horse was fitted with a venous catheter and connected to a valved gas-collection system. The exercise test consisted of 1-min incremental workloads ranging from 4.0 to 12.0 m/s at a treadmill incline of 3 degrees. Group A had significantly higher (P < 0.05) measurements of maximal O2 consumption (VO2max), O2 pulse, and tidal volume. Venous lactate concentration and respiratory exchange ratio measured at VO2max were also significantly higher (P < 0.05) in group A. Similar treadmill velocities were required to achieve a respiratory exchange ratio of > 1 and venous blood lactate concentration of > 4 mmol/l; however, group A was able to complete a significantly higher (P < 0.01) number of workloads before fatigue. The high aerobic and anaerobic capacity of group A horses may be a major contributor to a faster racing performance.
Effect of recurrent episodic hypocapnic, eucapnic, and hypercapnic hypoxia on systemic blood pressure
Authors: Fletcher E. C. , Bao G. , Miller C. C.
Published: December 2017

We have described a rat model that responds to chronic (8 h/day, 35 days) repetitive nonapneic episodic (cycled every 30 s) hypocapnic hypoxia with sustained increase in systemic blood pressure. Because the usual blood gas change of apnea is mildly increased CO2, we hypothesized that episodic hypoxia ranging from eucapnea to hypercapnia might cause a greater chronic increase in blood pressure than hypocapnic hypoxia in this model. Five groups of male Sprague-Dawley rats were studied: unhandled group received no treatment, sham group received compressed air in their chambers, hypocapnic hypoxic group received episodic hypoxia for 35 days, eucapnic hypoxic group received the same level of hypoxia but with 7–10% inspired fraction of CO2, and hybercarbic hypoxic group received hypoxia with 11–14% inspired fraction of CO2. Mean arterial blood pressure was measured in unrestrained conscious animals at baseline and after 35 days under their respective study conditions. Neither episodic eucapnic nor hypercarbic hypoxia had any additional effect on the changes in chronic diurnal blood pressure compared with hypocapnic hypoxia. These results suggest that the sympathetic nervous system or other neurohumoral systems contributing to chronic diurnal blood pressure elevation may be maximally stimulated by hypoxia or there may be some protective mechanism limiting the blood pressure response to asphyxia in this rat model.
Cardiac output during exercise measured by acetylene rebreathing, thermodilution, and Fick techniques
Authors: Hsia C. C. , Herazo L. F. , Ramanathan M. , Johnson R. L.
Published: December 2017

In dogs during exercise, respiratory rate can reach 200 breaths/min, blood temperature can exceed 42 degrees C, and hematocrit can approach 60%. To determine whether these changes significantly affect the measurement of cardiac output by the acetylene rebreathing method (QcRB), we compared estimates of QcRB with those measured by thermodilution and Fick (QcFI) techniques in nine dogs at rest and during steady-state exercise on a treadmill up to near-maximal workloads. Solubility of acetylene in blood was corrected to the simultaneously measured blood temperature and hematocrit. Results were also adjusted for mixing efficiency. Up to a QcFI of 20 l/min, QcRB was not significantly different from QcFI (P > 0.05). However, cardiac output measured by thermodilution was consistently higher than those measured by the other techniques (P < 0.0001). We conclude that the overall agreement between QcRB and QcFI estimates supports the validity of the rebreathing technique under exercise conditions where body temperature and hematocrit are changing rapidly and the breathing pattern is unrestrained. Systematic error by the thermodilution technique may be related to a variety of methodological issues as well as possible dissipation of cooling into the myocardial tissue and subsequent incomplete washout.
Leukocyte adhesion induced by inhibition of nitric oxide production in skeletal muscle
Authors: Akimitsu T. , Gute D. C. , Korthuis R. J.
Published: December 2017

Superfusion of rat cremaster muscles with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) elicited significant leukocyte adhesion to postcapillary venules (20- to 30-microns diameter), an effect that was attenuated by pretreatment with L-arginine (an NO precursor) or sodium nitroprusside (SNP) (an exogenous source of NO). In contrast to the effects of pretreatment, addition of SNP or L-arginine to the superfusate 30 min after the initiation of NO synthase inhibition failed to reverse the L-NAME-induced leukocyte adherence. However, this effect was reversed by administration of an anti-CD18 monoclonal antibody or 8-bromoguanosine 3′,5′-cyclic monophosphate 30 min after L-NAME superfusion was initiated. These findings indicate that L-NAME promotes leukocyte adhesion to venular endothelium by a CD18-dependent mechanism in skeletal muscle and suggest that the failure of L-arginine or SNP to reverse L-NAME-induced leukocyte adherence is not due to a defect in signaling events that occur subsequent to activation of guanylate cyclase by NO derived from these agents. Because the simultaneous administration of superoxide dismutase (scavenges superoxide radicals) and SNP or L-arginine, but not superoxide dismutase alone, decreased L-NAME-induced leukocyte adherence, our results suggest that leukocyte adhesion caused by NO synthase inhibition may result in the generation of superoxide.
Pulmonary function alterations after 3 wk of exposure to hypobaria and/or hypoxia in growing rats
Authors: Sekhon H. S. , Wright J. L. , Thurlbeck W. M.
Published: December 2017

We studied lung growth in rats between 4 and 7 wk of age under different conditions. There were five groups, seven animals in each: 1) general controls (ambient pressure and room air, food ad libitum); 2) hypobaric normoxic [barometric pressure (PB) 410 mmHg, PO2 153 Torr]; 3) normobaric hypoxic (ambient pressure, PO2 80 Torr); 4) hypobaric hypoxic (PB 410 mmHg, PO2 80 Torr); and 5) weight-matched controls to hypobaric hypoxic. Residual volume, functional residual capacity, vital capacity, and total lung capacity grew 10–20% more in both hypoxic groups than in weight-matched and general controls. Expiratory flow rates corrected for forced vital capacity decreased, and specific airway resistance increased significantly. In addition, the ratio of forced expiratory volume in 0.1 s to %forced vital capacity, peak expiratory flow rate, and forced maximal midexpiratory flow were also lower in normobaric hypoxic animals compared with weight-matched controls. Above a transpulmonary pressure of 6 cmH2O, flows were reduced in both hypoxic groups. No differences were observed between hypobaric normoxic and general control groups for lung volume and lung function. In weight-matched animals, total lung capacity decreased but lung function remained unchanged. We conclude that accelerated lung growth in hypobaric hypoxia and normobaric hypoxia is dysanaptic. Lung growth in hypobaric hypoxia is primarily induced by low oxygen, but differences between hypobaric hypoxia and normobaric hypoxia suggest a beneficial effect of low pressure.
Immunohistochemical demonstration of four subunits of neutrophil NAD(P)H oxidase in type I cells of carotid body
Authors: Kummer W. , Acker H.
Published: December 2017

We demonstrate, by means of immunohistochemistry, that type I cells of human, guinea pig, and rat carotid bodies react with antisera raised against the subunits p22phox, gp91phox, p47phox, and p67phox of the NAD(P)H oxidase isolated from human neutrophil granulocytes. The findings support previous photometric studies that indicate that carotid body type I cells possess a putative oxygen sensor protein that is similar to the neutrophil NAD(P)H oxidase and consists of a hydrogen peroxide generating low-potential cytochrome b558 with cofactors regulating the electron transfer to oxygen.
Plasticity of myonuclear number in hypertrophied and atrophied mammalian skeletal muscle fibers
Authors: Allen D. L. , Monke S. R. , Talmadge R. J. , Roy R. R. , Edgerton V. R.
Published: December 2017

Although a mammalian skeletal muscle fiber may contain thousands of myonuclei, the importance of this number or the potential to modulate it in adult muscle has not been clearly demonstrated. Using immunohistochemistry and confocal microscopy, we examined the plasticity of myonuclear number and fiber size in isolated fast and slow fiber segments from adult cat hindlimb muscles in response to chronic alterations in neuromuscular activity and loading. Compared with slow fibers in the soleus of control cats, myonuclear number in presumably transformed fast fibers was 32% lower and fiber size was decreased 73% after elimination of neuromuscular activation for 6 mo by spinal isolation. Slow fibers in the soleus of spinal-isolated cats had smaller cross-sectional areas, whereas myonuclear number was not significantly different than that in the control cats. Myonuclear number in fast plantaris fibers was more than threefold higher and fiber size was 2.8-fold higher after 3 mo of functional overload compared with the plantaris of control cats. Compared with control slow plantaris fibers, myonuclear number and fiber size also increased in overloaded slow plantaris fibers. These results demonstrate that changes in myonuclear number are associated with changes in myosin type and suggest that modulations in the amount of available DNA may be a factor in regulating cytoplasmic volume of muscle fibers in response to chronic changes in neuromuscular activity.
Cerebral blood flow and systemic hemodynamics during exposure to 2 kPa CO2-300 kPa O2 in rats
Authors: Bergo G. W. , Tyssebotn I.
Published: December 2017

Cerebral blood flow (CBF), systemic hemodynamics, and arterial blood gases were measured during control conditions and during and after exposure to either 300 kPa O2 (group 1) or 300 kPa O2 with 2 kPa CO2 (group 2) in awake rats. The respiratory frequency fell with no change of arterial PCO2 (PaCO2) in group 1, but in group 2, respiratory frequency and PaCO2 increased linearly. The cardiac output (CO) and heart rate (HR) fell and systolic arterial pressure (SAP) rose independent of PACO2. O2 breathing caused CBF to fall by 30% in group 1, whereas CBF rose linearly with the PaCO2 increase and pH decline in group 2. Regional CBF (rCBF) fell in group 1, whereas rCBF rose gradually in all regions in group 2, but the responses varied similarly in both groups. Regional brain O2 supply was unaltered in most areas. However, the O2 supply was possibly reduced in the brain stem in group 1 but markedly increased in group 2. After decompression, HR and SAP were high, whereas CO returned to its control value. CBF and all rCBF levels remained markedly elevated in group 2. In group 1, CBF returned to control levels. By contrast, rCBF and O2 delivery to brain stem regions remained subnormal. In conclusion, the O2-induced changes in HR, CO, and SAP were not influenced by hypercapnia. CBF and rCBF fell despite unaltered PaCO2, whereas hypercapnia prevented these declines. An uneven effect of O2 was observed on rCBF, most pronounced in brain stem regions, independent of the PaCO2. There was a prolonged suppression of O2 supply to brain stem regions both during and after the exposure to O2 in the absence of CO2.
Enhanced cardiac metabolism of plasma glucose in high-altitude natives: adaptation against chronic hypoxia
Authors: Holden J. E. , Stone C. K. , Clark C. M. , Brown W. D. , Nickles R. J. , Stanley C. , Hochachka P. W.
Published: December 2017

The metabolism of glucose in mammalian heart is 25–50% more O2 efficient than the metabolism of free fatty acids. To assess the role of substrate preference in adaptations to chronic hypoxia, positron emission tomographic measurements of heart regional glucose uptake rates after an overnight fast were made in volunteer Quechua subjects and in Sherpa subjects, both indigenous to altitudes of over 3,000 m, and in a group of lowlander volunteers. Highest uptake rates were found in the Quechuas on arrival and in the Sherpas after a 3-wk period at low altitude, intermediate rates in Quechuas after a 3-wk period at low altitude and in the lowlanders, and lowest rates in Sherpas on arrival. These low values were probably related to the stress of travel to the site of the experiments. Measured plasma catecholamines, hormones, and substrates indicated that glucose concentrations correlated best with observed variations in glucose uptake, with a negative correlation for the control subjects and a positive correlation for the Quechuas and Sherpas. Uptake values in Quechuas declined significantly after a 3-wk period at low altitude, but the positive correlation with glucose levels persisted. We conclude that an elevated glucose preference in heart is a true metabolic adaptation in humans adapted over generations to chronic hypoxia.
N-acetylcysteine administration and loaded breathing
Authors: Supinski G. S. , Stofan D. , Ciufo R. , DiMarco A.
Published: December 2017

Recent work has shown that loaded breathing produces alterations in diaphragmatic glutathione metabolism. Moreover, it has been suggested that alterations in glutathione levels may be related to the development of respiratory muscle fatigue and respiratory failure during loading. The purpose of this study was to determine whether it was possible to augment diaphragmatic stores of reduced glutathione (GSH) and thereby delay the development of respiratory failure during loaded breathing by administering N-acetylcysteine (NAC), a glutathione precursor. We compared the effects of massive inspiratory loading on saline- and NAC-treated groups of decerebrate unanesthetized rats with loading continuing until respiratory arrest occurred. As controls, we also studied unloaded saline- and NAC-treated animals. After arrest, diaphragms were excised, measurement was made of diaphragmatic GSH and oxidized glutathione (GSSG) concentrations, and assessment was made of in vitro diaphragmatic contractility (i.e., the force-frequency relationship and in vitro fatigability). We found that loading of saline-treated animals produced reductions in the diaphragmatic force-frequency curve, reductions in GSH, and increases in GSSG levels. NAC administration blunted loading-induced decreases in diaphragmatic GSH levels and reduced the in vitro fatigability of excised diaphragm muscle strips. NAC did not significantly alter the time to respiratory arrest, however, and also failed to alter the effect of loaded breathing on the diaphragmatic force-frequency relationship. These findings suggest that free radical-mediated GSH depletion is not the limiting factor determining the development of respiratory failure in this model of loaded breathing.
Mucociliary function in the mouse measured in explanted lung tissue
Authors: Kurosawa H. , Wang C. G. , Dandurand R. J. , King M. , Eidelman D. H.
Published: December 2017

To develop a method for the study of mucociliary clearance in small-caliber airways, we investigated ciliary function in an in vitro lung tissue culture technique in mice. Lungs were excised from 45 anesthetized mice [weight 30.9 +/- 6.2 (SD) g] and inflated with 2% liquid agarose at 37 degrees C via the trachea. After cooling to 4 degrees C, the lungs were cut into 0.5- to 1.0-mm thick slices and cultured overnight. Ciliary beat frequency (CBF) was measured in airways cut in cross section using a computerized image processing system. In some experiments, charcoal particle transport (PT) in tangentially cut airways was also measured. Airway diameter ranged from 0.3 to 0.8 mm. In this preparation CBF was stable over a 3-h period and unaffected by minor pH changes. Both CBF and PT exhibited a linear dependency on temperature. CBF and PT were significantly correlated with each other. CBF at 37 degrees C (18.7 +/- 2.93 Hz) was almost twofold higher than values at 22 degrees C (9.74 +/- 3.11 Hz). Isoproterenol increased CBF in a dose-dependent fashion (50% effective concentration of 10(-6.75) M); the effect of isoproterenol could be blocked by propranolol. Administration of forskolin (10 microM) also increased both CBF and PT significantly. These findings demonstrate the feasibility of measuring the major aspects of mucociliary clearance in this system. This approach holds promise as a technique suitable to the investigation of both the small airways of humans and other large animals as well as of airways in murine genetic models of respiratory disease.
Distribution of pulmonary capillary red blood cell transit times
Authors: Presson R. G. , Graham J. A. , Hanger C. C. , Godbey P. S. , Gebb S. A. , Sidner R. A. , Glenny R. W. , Wagner W. W.
Published: December 2017

In theory, red blood cells can pass through the pulmonary capillaries too rapidly to be completely saturated with oxygen during exercise. This idea has not been directly tested because the transit times of the fastest red blood cells are unknown. We report the first measurements of the entire transit time distribution for red blood cells crossing single subpleural capillary networks of canine lung using in vivo fluorescence videomicroscopy and compare those times with the distribution of plasma transit times in the same capillary networks. On average, plasma took 1.4 times longer than red blood cells to pass through the capillary bed. Decreased transit times with increased cardiac output were mitigated by both capillary recruitment and a narrowing of the transit time distribution. This design feature of the pulmonary capillary bed kept the shortest times from falling below the theoretical minimum time for complete oxygenation.
Viral infection potentiates the increase in airway blood flow produced by substance P
Authors: Yamawaki I. , Geppetti P. , Bertrand C. , Chan B. , Massion P. , Piedimonte G. , Nadel J. A.
Published: December 2017

We examined the effect of respiratory tract infection with Sendai virus on the responsiveness of airway blood flow to substance P (SP) in rats. Pathogen-free rats were inoculated with either Sendai virus suspension or sterile viral growth medium into each nostril. Five days later, we measured airway and esophageal blood flows before and immediately after injection of SP or histamine into the left ventricle of rats in both groups using a modification of the reference-sample microsphere technique. Viral infection potentiated the increase in airway blood flow evoked by SP but not by histamine. We also examined the effect of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the SP-induced increase in airway blood flow. Both phosphoramidon (NEP inhibitor) and captopril (ACE inhibitor) potentiated the increase in airway blood flow produced by SP in pathogen-free rats. In the presence of both peptidase inhibitors, a submaximal dose of SP increased blood flow to a similar level in infected and pathogen-free rats. Thus decreased activity of both ACE and NEP may be involved in the exaggerated increase in airway blood flow evoked by SP in virus-infected rats.
Fatty acid kinetic responses to running above or below lactate threshold
Authors: Kanaley J. A. , Mottram C. D. , Scanlon P. D. , Jensen M. D.
Published: December 2017

During running exercise above the lactate threshold (LT), it is unknown whether free fatty acid (FFA) mobilization can meet the energy demands for fatty acid oxidation. This study was performed to determine whether FFA availability is reduced during running exercise above compared with below the LT and to assess whether the level of endurance training influences FFA mobilization. Twelve marathon runners and 12 moderately trained runners ran at a workload that was either above or below their individual LT. Fatty acid oxidation (indirect calorimetry) and FFA release ([1–14C]palmitate) were measured at baseline, throughout exercise, and at recovery. The plasma FFA rate of appearance increased during exercise in both groups; running above or below the LT, but the total FFA availability for 30 min of exercise was greater (P < 0.01) in the below LT group (marathon, 23 +/- 2 mmol; moderate, 21 +/- 2 mmol) than in the above LT group (18 +/- 3 and 13 +/- 3 mmol, respectively). Total fatty acid oxidation (indirect calorimetry) greatly exceeded circulating FFA availability, regardless of training or exercise group (P < 0.01). No statistically significant exercise intensity or training differences in fatty acid oxidation were found (above LT: marathon, 71 +/- 12, moderate, 64 +/- 17 mmol/30 min; below LT: marathon 91 +/- 12, moderate, 60 +/- 5 mmol/30 min). In conclusion, during exercise above or below LT, circulating FFA cannot meet the oxidative needs and intramuscular triglyceride stores must be utilized. Further marathon training does not enhance effective adipose tissue lipolysis during exercise compared with moderate endurance training.
Low chemoresponsiveness and inadequate hyperventilation contribute to exercise-induced hypoxemia
Authors: Harms C. A. , Stager J. M.
Published: December 2017

Is inadequate hyperventilation a cause of the exercise-induced hypoxemia observed in some athletes during intense exercise? If so, is this related to low chemoresponsiveness? To test the hypothesis that exercise-induced hypoxemia, inadequate hyperventilation, and chemoresponsiveness are related, 36 nonsmoking healthy men were divided into hypoxemic (Hyp; n = 13) or normoxemic (Nor; n = 15) groups based on arterial oxygen saturation (SaO2; Hyp < or = 90%, Nor > 92%) observed during maximum O2 uptake (VO2max). Men with intermediate SaO2 values (n = 8) were only included in correlation analysis. Ventilatory parameters were collected at rest, during a treadmill maximal oxygen consumption (VO2max) test, and during a 5-min run at 90% VO2max. Chemoresponsiveness at rest was assessed via hypoxic ventilatory response (HVR) and hypercapnic ventilatory response (HCVR). VO2max was not significantly different between Nor and Hyp. SaO2 was 93.8 +/- 0.9% (Nor) and 87.7 +/- 2.0% (Hyp) at VO2max. End-tidal PO2 and the ratio of minute ventilation to oxygen consumption (VE/VO2) were lower while PETCO2 was higher for Hyp (P < or = 0.01). End-tidal PO2, end-tidal PCO2, and VE/VO2 correlated (P < or = 0.05) to SaO2 (r = 0.84, r = -0.70, r = 0.72, respectively), suggesting that differences in oxygenation were due to differences in ventilation. HVR and HCVR were significantly lower for Hyp. HVR was related to VE/VO2 (r = 0.43), and HCVR was related to the ratio of VE to CO2 production at VO2max (r = 0.61)
Ventilatory effects of specific carotid body hypocapnia in dogs during wakefulness and sleep
Authors: Smith C. A. , Saupe K. W. , Henderson K. S. , Dempsey J. A.
Published: December 2017

We used extracorporeal perfusion of the vascularly isolated carotid sinus region to determine the effects of specific carotid body chemoreceptor hypocapnia-alkalosis on ventilatory control in the unanesthetized dog. Eight female dogs were studied during wakefulness, non-rapid-eye-movement (NREM) sleep, and rapid eye movement (REM) sleep. Carotid body perfusions lasted from 1 to 2 min, and each trial was preceded by a 1-min control period. Two levels of carotid body hypocapnia were employed, approximately 7 and 14 Torr below eupneic levels in a given dog. We found that 1) During wakefulness and NREM sleep, carotid body hypocapnia caused reduced tidal volume (VT) but not apnea or expiratory time prolongation. 2) The inhibition of ventilation in response to carotid body hypocapnia was graded below normocapnia, showing the highest sensitivity at carotid body PCO2 near 7 Torr below eupneic values. Inhibition reached a maximum near 14 Torr below the eupneic level; VT, inspiratory minute ventilation (VI), and VT-to-inspiratory time ratio fell 31, 23, and 27% in wakefulness and 30, 23, and 30% in NREM sleep. 3) Reductions in ventilation in response to carotid body hypocapnia are lessened but still persist throughout perfusion (up to at least 130 s) despite significant systemic hypercapnia. 4) During REM sleep, carotid body hypocapnia had no consistent inhibitory effect on ventilation until carotid body PCO2 was reduced to values near 14 Torr below the eupneic level, at which point ventilation was similar to wakefulness and NREM. 5) Moderate carotid body hypocapnia was as effective as carotid body hyperoxia in reducing VT and VI. We conclude that carotid body hypocapnia-alkalosis can significantly inhibit eupneic VT and ventilation during wakefulness and NREM sleep and, if the hypocapnia is severe enough, during REM sleep.
Effect of K+ channel blockade on fatigue in rat diaphragm muscle
Authors: Van Lunteren E. , Moyer M. , Torres A.
Published: December 2017

K+ channel blockers increase skeletal muscle force during twitch contractions; the present study determined whether K+ channel blockade also modulates force during longer term and higher frequency stimulation. 4-Aminopyridine (4-AP; 0.3 mM) increased rat diaphragm force during twitch, 5-Hz and 20-Hz but not 100-Hz stimulation, and prolonged isometric contraction but not half-relaxation time. In response to continuous 5-Hz stimulation, the rate of force decline was accelerated by 4-AP so that over time force dropped below that of control muscle strips. In response to intermittent 20-Hz stimulation, 4-AP produced an early force potentiation; the 4-AP-induced force increase was maintained throughout repetitive stimulation despite an accelerated rate of force decline. In response to continuous 100-Hz stimulation, 4-AP did not affect rate of force decline. During 5- and 20-Hz stimulation, there was an interaction between 4-AP and duration of stimulation in prolonging contraction and especially half-relaxation time. Tetraethylammonium (10 mM) augmented diaphragm force less than did 4-AP, did not affect rate of force decline during 5-Hz stimulation, and did not interact with fatigue to prolong isometric twitch kinetics. These data indicate that K+ channel blockade with 4-AP increases diaphragm force at low to intermediate stimulation frequencies, may increase early force potentiation during repetitive contraction, and depending on stimulation pattern either accelerates or has no effect on rate of fatigue.
Modeling steady-state inert gas exchange in the canine trachea
Authors: George S. C. , Souders J. E. , Babb A. L. , Hlastala M. P.
Published: December 2017

The functional dependence between tracheal gas exchange and tracheal blood flow has been previously reported using six inert gases (sulfur hexafluoride, ethane, cyclopropane, halothane, ether, and acetone) in a unidirectionally ventilated (1 ml/s) canine trachea (J. E. Souders, S. C. George, N. L. Polissar, E. R. Swenson, and M. P. Hlastala. J. Appl. Physiol. 79: 918–928, 1995). To understand the relative contribution of perfusion-, diffusion- and ventilation-related resistances to airway gas exchange, a dynamic model of the bronchial circulation has been developed and added to the existing structure of a previously described model (S. C. George, A. L. Babb, and M. P. Hlastala. J. Appl. Physiol. 75: 2439–2449, 1993). The diffusing capacity of the trachea (in ml gas.s-1.atm-1) was used to optimize the fit of the model to the experimental data. The experimental diffusing capacities as predicted by the model in a 10-cm length of trachea are as follows: sulfur hexafluoride, 0.000055; ethane, 0.00070; cyclopropane, 0.0046; halothane, 0.029; ether, 0.10; and acetone, 1.0. The diffusing capacities are reduced relative to an estimated diffusing capacity. The ratio of experimental to estimated diffusing capacity ranges from 4 to 23%. The model predicts that over the ventilation-to-tracheal blood flow range (10–700) attained experimentally, tracheal gas exchange is limited primarily by perfusion- and diffusion-related resistances. However, the contribution of the ventilation-related resistance increases with increasing gas solubility and cannot be neglected in the case of acetone. The increased role of diffusion in tracheal gas exchange contrasts with perfusion-limited alveolar exchange and is due primarily to the increased thickness of the bronchial mucosa.
Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs
Authors: Lalloo U. G. , Fox A. J. , Belvisi M. G. , Chung K. F. , Barnes P. J.
Published: December 2017

Acidic solutions mimick many of the effects of capsaicin (Cap), including pain, bronchoconstriction, cough, and sensory neuropeptide release. Evidence from the use of the Cap antagonist capsazepine suggests that in some cases protons act at the Cap receptor. In the present study, we have investigated whether cough evoked by Cap and citric acid (CA) is mediated specifically via the Cap receptor on airway sensory nerves. We have examined the effects of capsazepine on Cap-, CA-, and hypertonic saline-induced cough and also on CA-induced nasal irritation in awake guinea pigs. Capsazepine was nebulized for 5 min before cough challenges with Cap for 5 min and CA for 10 min. Control animals were pretreated with vehicle alone. Capsazepine (100 microM) inhibited the cough response to 30 microM Cap from 0.77 +/- 0.14 coughs/min in control animals to 0.23 +/- 0.08 coughs/min (P < 0.05) and to 80 microM Cap from 1.4 +/- 0.23 to 0.3 +/- 0.11 coughs/min (P < 0.01). There was no effect, however, of lower concentrations of capsazepine (5 and 10 microM) against Cap-evoked cough. At a concentration of 100 microM, capsazepine also inhibited the coughing induced by 0.25 M CA from 1.8 +/- 0.26 to 0.93 +/- 0.31 coughs/min (P < 0.05) but not that induced by 0.5 M CA. Nasal irritation induced by 0.25 M CA, but not by 0.5 M CA, was also inhibited by capsazepine from 2.47 +/- 0.37 to 0.75 +/- 0.31 nose wipes/min (P < 0.05). This inhibitory effect of capsazepine did not appear to reflect a nonspecific suppression of the cough reflex, since cough evoked by exposure to hypertonic (7%) saline for 10 min was unaffected by pretreatment with capsazepine (100 microM). These data show that capsazepine is a specific inhibitor of Cap- and CA-induced cough in guinea pigs. Moreover, they suggest that low pH stimuli evoke cough and nasal irritation by an action at the Cap receptor, either directly or through the release of an intermediate agent.
Gas exchange, blood lactate, and plasma catecholamines during incremental exercise in hypoxia and normoxia
Authors: Hughson R. L. , Green H. J. , Sharratt M. T.
Published: December 2017

The interrelationships among blood lactate (La-) and plasma norepinephrine (NE) and epinephrine (Epi) were studied simultaneously with measures of ventilation (VE) and gas exchange during incremental exercise to exhaustion in nine healthy young men. We wanted to observe whether the tight coupling that exists during normoxic exercise between the concentrations of La- ([La-]) and of both NE and Epi would also be found in hypoxia (inspired O2 fraction = 0.14). In addition, we used recently advocated methods of V slope [CO2 output vs. O2 uptake (VO2)] to select the ventilatory threshold (VT) and log-log transformation of [La-] and VO2 to select the lactate threshold (LT). Peak VO2 was reduced from 4,164 +/- 184 ml/min in normoxia to 3,635 +/- 144 ml/min in hypoxia (P < 0.05). The increase in [La-] was linearly related to the increases in both NE and Epi concentrations in the normoxic and hypoxic tests (r = 0.92–0.96). Estimates of VO2 at VT were significantly greater than those at LT in both normoxia and hypoxia, but these estimates were poorly correlated (r = -0.11–0.46). VT and LT were reduced by hypoxia. Visual interpretation of the VT by examination of VE vs. VO2 and VE/VO2 vs. VO2 did not differ from the LT, but they were less than the VTs by the V-slope method (P < 0.05); yet, all were poorly correlated. The tight coupling between the increase in [La-] and the increase in plasma catecholamines might indicate a common mechanism for the increase or a causative link. VT and LT provided estimates of the general trend in the data, but the poor correlation between them questions the utility of attempting to predict one from the other.
Myoglobin saturation in free-diving Weddell seals
Authors: Guyton G. P. , Stanek K. S. , Schneider R. C. , Hochachka P. W. , Hurford W. E. , Zapol D. G. , Liggins G. C. , Zapol W. M.
Published: December 2017

Although the consumption of myoglobin-bound O2 (MbO2) stores in seal muscles has been demonstrated in seal muscles during laboratory simulations of diving, this may not be a feature of normal field diving in which measurements of heart rate and lactate production show marked differences from the profound diving response induced by forced immersion. To evaluate the consumption of muscle MbO2 stores during unrestrained diving, we developed a submersible dual-wavelength laser near-infrared spectrophotometer capable of measuring MbO2 saturation in swimming muscle. The probe was implanted on the surface of the latissimus dorsi of five subadult male Weddell seals (Leptonychotes weddelli) released into a captive breathing hole near Ross Island, Antarctica. Four seals had a monotonic decline of muscle O2 saturation during free diving to depths up to 300 m with median slopes of -5.12 +/- 4.37 and -2.54 +/- 1.95%/min for dives lasting < 17 and > 17 min, respectively. There was no correlation between the power consumed by swimming and the desaturation rate. Two seals had occasional partial muscle resaturations late in dives, indicating transfer of O2 from circulating blood to muscle myoglobin. Weddell seals partially consume their MbO2 stores during unrestrained free diving.
Maximal airway response in mature and immature rabbits during tidal ventilation
Authors: Tepper R. S. , Shen X. , Bakan E. , Gunst S. J.
Published: December 2017

Airway closure during maximal methacholine (MCh) challenge was evaluated using alveolar capsules in eight immature and eight mature anesthetized rabbits in vivo during imposed tidal ventilation. Changes in airway opening and alveolar pressures (delta PA) and pulmonary resistance (RL) were measured during MCh challenge at a positive end-expiratory pressure of 5 cmH2O. In immature rabbits, delta PA remained > 3 cmH2O in all animals, indicating no detectable airway closure. This contrasts to our previous study of isolated immature rabbit lungs under static conditions in which delta PA was < 0.1 cmH2O during maximal MCh challenge, findings consistent with airway closure. Airway closure also did not occur in mature animals during tidal ventilation in vivo; however, the frequency of closure in isolated lungs under static conditions was very low. With increasing MCh, end-expiratory PA increased in immature but not in mature rabbits. RL did not reach a plateau in immature rabbits during MCh, whereas a plateau was reached in mature rabbits. Immature rabbits also had greater increases in RL. These results suggest that tidal ventilation can limit bronchoconstriction in immature rabbits and prevent airway closure during maximal MCh challenge. Tidal ventilation may limit bronchoconstriction by inhibitory effects of stretch on airway smooth muscle contraction and also by causing hyperinflation and thereby increasing transpulmonary pressure.
Vagal neuroeffector mechanisms affecting transpulmonary pressure in the intact rat
Authors: Haselton J. R. , Reynolds A. Y. , Schultz H. D.
Published: December 2017

Experiments were conducted with chloralose-urethan anesthetized rats to assess the effects of 1) bilateral stimulation of the cervical vagus nerves and 2) parasympathomimetic and sympathomimetic agents. Transpulmonary pressure (Ptp) was used as an index of airway smooth muscle tone, and peak inspiratory Ptp (Ptppeak) values were used for a comparison of responses. In untreated animals, vagal stimulation elicited an increase in Ptppeak of 155%. Cooling of the vagus nerves to 15 degrees C abolished the response of Ptppeak to vagal stimulation. Although isoproterenol (1–10 micrograms/kg i.v.) did not alter resting Ptppeak, it did prevent vagal stimulation from evoking an increase in Ptppeak. Nadolol (1.5 mg/kg i.v.) augmented the increase in Ptppeak elicited by vagal stimulation. Vagal stimulation did not evoke any change in Ptppeak after the administration of both nadolol and atropine or after combined administration of nadolol, atropine, and either serotonin aerosol or prostaglandin F2 alpha. In rats pretreated with capsaicin 1 wk before the experiment, vagal stimulation evoked an increase in Ptppeak that was not statistically different from that of untreated control animals. Therefore, nonadrenergic noncholinergic systems did not appear to play an independent role in the response of the airways to the activation of the vagus nerves.
Pulmonary gas exchange and its determinants during sustained microgravity on Spacelabs SLS-1 and SLS-2
Authors: Prisk G. K. , Elliott A. R. , Guy H. J. , Kosonen J. M. , West J. B.
Published: December 2017

We measured resting pulmonary gas exchange in eight subjects exposed to 9 or 14 days of microgravity (microG) during two Spacelab flights. Compared with preflight standing measurements, microG resulted in a significant reduction in tidal volume (15%) but an increase in respiratory frequency (9%). The increased frequency was caused chiefly by a reduction in expiratory time (10%), with a smaller decrease in inspiratory time (4%). Anatomic dead space (VDa) in microG was between preflight standing and supine values, consistent with the known changes in functional residual capacity. Physiological dead space (VDB) decreased in microG, and alveolar dead space (VDB-VDa) was significantly less in microG than in preflight standing (-30%) or supine (-15%), consistent with a more uniform topographic distribution of blood flow. The net result was that, although total ventilation fell, alveolar ventilation was unchanged in microG compared with standing in normal gravity (1 G). Expired vital capacity was increased (6%) compared with standing but only after the first few days of exposure to microG. There were no significant changes in O2 uptake, CO2 output, or end-tidal PO2 in microG compared with standing in 1 G. End-tidal PCO2 was unchanged on the 9-day flight but increased by 4.5 Torr on the 14-day flight where the PCO2 of the spacecraft atmosphere increased by 1–3 Torr. Cardiogenic oscillations in expired O2 and CO2 demonstrated the presence of residual ventilation-perfusion ratio (VA/Q) inequality. In addition, the change in intrabreath VA/Q during phase III of a long expiration was the same in microG as in preflight standing, indicating persisting VA/Q inequality and suggesting that during this portion of a prolonged exhalation the inequality in 1 G was not predominantly on a gravitationally induced topographic basis. However, the changes in PCO2 and VA/Q at the end of expiration after airway closure were consistent with a more uniform topographic distribution of gas exchange.
Responses of IGF-I to endogenous increases in growth hormone after heavy-resistance exercise
Authors: Kraemer W. J. , Aguilera B. A. , Terada M. , Newton R. U. , Lynch J. M. , Rosendaal G. , McBride J. M. , Gordon S. E. , Hakkinen K.
Published: December 2017

The purpose of this study was to examine the effects of a heavy-resistance exercise protocol known to dramatically elevate immunoreactive growth hormone (GH) on circulating insulin-like growth factor I (IGF-I) after the exercise stimulus. Seven men (23.1 +/- 2.4 yr) volunteered to participate in this study. Each subject was asked to perform an eight-station heavy-resistance exercise protocol consisting of 3 sets of 10 repetition maximum resistances with 1-min rest between sets and exercises followed by a recovery day. In addition, a control day followed a nonexercise day to provide baseline data. Pre- and postexercise (0, 15, and 30 min) blood samples were obtained and analyzed for lactate, creatinine kinase, GH, and IGF-I. Postexercise values for lactate and GH were significantly (P < 0.05) elevated above preexercise and resting baseline values. The highest mean GH concentration after the heavy-resistance exercise protocol was 23.8 +/- 11.8 micrograms/l, observed at the immediate postexercise time point. Significant increases in creatine kinase were observed after the exercise protocol and during the recovery day. No significant relationships were observed between creatine kinase and IGF-I concentrations. No significant changes in serum IGF-I concentrations were observed with acute exercise or between the recovery and control days. Thus, these data demonstrate that a high-intensity bout of heavy-resistance exercise that increases circulating GH did not appear to affect IGF-I concentrations over a 24-h recovery period in recreationally strength-trained and healthy young men.
Effect of surface forces on oscillatory behavior of lungs
Authors: Stamenovic D. , Barnas G. M.
Published: December 2017

The effect of alveolar surface tension on lung dynamic behavior was investigated by measuring total lung and tissue impedances in excised rabbit lungs at breathing frequencies of 0.2–0.8 Hz and tidal volumes of 10, 20, and 30 ml before and after lavage with 3-dimethyl siloxane, which provided a constant surface tension of 16 dyn/cm. The lungs were oscillated around the mean deflation pressures of 5 (control) and 8 cmH2O (lavaged), i.e., lung volume of 60% of total lung capacity. The total lung impedance was calculated from measurements of pressure and airflow at the trachea, and tissue impedance was measured by the alveolar capsule technique. The airway contribution was obtained as the difference between total lung and tissue impedances. In the lavaged lungs, dynamic elastance (Edyn) decreased and tissue resistance (Rti) increased relative to the control values over the entire frequency range. Airway resistance increased at the higher flow rates only. The decrease in Edyn could be attributed to the absence of surface film elastance in the lavaged lungs. The increase in airway resistance could be attributed to accentuated flow dependence due to changes in airway geometry and residual lavage liquid. However, the most intriguing result was the increase in Rti in the lavaged lungs. It could be attributed to altered mechanics at the alveolar duct level after lavage. It is concluded that dissipative properties of lung tissue are major determinants of Rti, whereas elastic properties of both tissue and surface film are important determinants of Edyn.
Effect on breathing of neuronal dysfunction in the caudal ventral medulla of goats
Authors: Ohtake P. J. , Forster H. V. , Pan L. G. , Lowry T. F. , Korducki M. J. , Smith K. , Forster A. L.
Published: December 2017

It has been reported that the caudal ventrolateral medulla (VLM) is important in central chemoreception and the control of breathing. The objective of this study was to determine in adult goats the effects on breathing of neuronal dysfunction of this caudal VLM region (area L; caudal to rostral hypoglossal nerve rootlet). Thermodes were chronically implanted on the VLM to cool neurons and thereby cause neuronal dysfunction. During awake and (halothane) anesthetized states, cooling the caudal VLM for 20 s to 20 degrees C did not alter breathing (P > 0.10). However, between 20 and 30 s of cooling and during recovery from cooling 0–4 mm caudal to the rostral hypoglossal rootlet, there was a 12 (awake) to 25% (anesthetized) increase (P < 0.05) in breathing. This tachypneic hyperpnea was uniform over conditions of eucapnia, hypercapnia, and hypoxia and resulted from reduced inspiratory time that increased frequency. We conclude that in goats inhibitory neurons are located in area L and the lateral caudal ventral medulla.
Changes in end-expiratory lung volume and diaphragmatic activity during hypoxia and hypercapnia in cats
Authors: Bonora M. , Vizek M.
Published: December 2017

To assess the role of diaphragmatic activity at the end of expiration (DE) in the control of end-expiratory lung volume (EELV), 1) these two parameters were correlated in anesthetized cats breathing different gas mixtures; and 2) expiratory flow volume curves in normoxia and hypoxia together with changes in esophageal pressure were measured. The influence of volume feedback on DE control was tested by applying positive end-expiratory pressure (PEEP). The effect of anesthesia was determined by measuring DE in unanesthetized cats. In hyperoxia, DE (but not EELV) decreased. In hypocapnic hypoxia (12, 10, and 8% O2), both DE and EELV gradually increased, and these changes were significantly correlated. When normocapnia was restored in 8% O2, DE and EELV decreased but remained higher than in air. Hypercapnia affected neither DE nor EELV. PEEP blocked the hypoxia-induced increase in DE. Hypoxia decreased expiratory flow and esophageal pressure. Finally, the increases in DE at 12 and 10% O2 were more pronounced when the cats were unanesthetized. These results suggest that the increase in diaphragmatic activity induced by hypocapnic hypoxia during expiration affects expiratory flow and thoracic volume and, therefore, plays a major role in increasing EELV. This phenomenon may also be controlled by volume feedback.