bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukotriene B4 induces lung injury in the rabbit: role of neutrophils and effect of indomethacin
Authors: Yoshimura K. , Nakagawa S. , Koyama S. , Kobayashi T. , Homma T.
Published: December 2017

The effects of exogenous leukotriene B4 (LTB4) on the pulmonary microvascular permeability and the roles of polymorphonuclear (PMN) leukocytes and the cyclooxygenase products of arachidonic acid in the microvascular response to LTB4 in the isolated non-blood-perfused rabbit lungs were studied. Microvascular permeability and lung edema were evaluated by use of the fluid filtration coefficient (Kf) and the wet-to-dry lung weight ratio (W/D ratio), respectively. Pulmonary capillary pressure was estimated by the double occlusion technique. We studied five groups of lungs: lungs were given 1) both PMN leukocytes and a bolus injection of LTB4 (5 micrograms, n = 6), 2) LTB4 alone (n = 5), 3) PMN leukocytes alone (n = 5), 4) control vehicles (n = 5), or 5) indomethacin (40 micrograms/ml) before PMN leukocytes and LTB4 (n = 6). We observed that LTB4 increased Kf and W/D ratio in the presence of PMN leukocytes in the perfusate without affecting the pulmonary arterial and capillary pressures. Neither LTB4 alone nor PMN leukocytes alone produced changes in Kf and W/D ratio. Indomethacin failed to inhibit the LTB4-induced increases in Kf and W/D ratio. These results suggest that LTB4 produces lung injury that is dependent on PMN leukocytes but not on the cyclooxygenase pathway of arachidonic acid metabolism.
Pulmonary vascular impedance vs. resistance in hypoxic and hyperoxic dogs: effects of propofol and isoflurane
Authors: Ewalenko P. , Stefanidis C. , Holoye A. , Brimioulle S. , Naeije R.
Published: December 2017

The pulmonary vascular effects of inhaled anesthetics have been reported variably. We compared the effects of intravenous anesthesia (propofol) and inhalational anesthesia (isoflurane) on multipoint mean [pulmonary arterial pressure (Ppa)-pulmonary arterial occluded pressure (PpaO)]/cardiac output (Q) plots and on pulmonary vascular impedance (PVZ) spectra in eight dogs alternatively ventilated in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). Q was altered by a manipulation of venous return. During propofol, hypoxia increased (Ppa-PpaO) by an average of 2–3 mmHg over the entire range of Q studied, from 1 to 2.5 l.min-1 x m-2. This hypoxic pulmonary vasoconstriction (HPV) was associated with insignificant changes in PVZ. Decreasing Q in hypoxia and hyperoxia did not affect PVZ. Compared with propofol, isoflurane decreased (Ppa-PpaO) by an average of 2–5 mmHg at all levels of Q studied in both hypoxia and hyperoxia but did not affect HPV. During isoflurane anesthesia, 0 Hz PVZ was lower (P < 0.01) in hypoxia, but otherwise the PVZ spectrum was not different from that recorded during propofol anesthesia. We conclude that, in dogs, 1 degree general anesthesia with isoflurane alone decreases pulmonary vascular tone without inhibition of HPV and that 2 degrees pressure/Q plots in the time domain are more sensitive than those in the frequency domain to subtle hemodynamic changes induced by hypoxia or isoflurane at the periphery of the pulmonary vasculature.
Slow force recovery after long-duration exercise: metabolic and activation factors in muscle fatigue
Authors: Baker A. J. , Kostov K. G. , Miller R. G. , Weiner M. W.
Published: December 2017

To investigate the roles of metabolic and nonmetabolic factors in human muscle fatigue, two relatively brief nonexhausting exercise protocols that produced similar levels of moderate fatigue were used: short-duration exercise (SDE; 2-min sustained maximal voluntary contraction) and long-duration exercise (LDE; 15- to 20-min intermittent exercise). After exercise and during recovery, multiple potential mechanisms of fatigue were studied from measurements of voluntary, twitch, and tetanic forces; intracellular metabolites (using 31P-nuclear magnetic resonance spectroscopy); and electromyographic signals. The major findings were as follows. 1) After SDE, fatigue closely correlated with increased [Pi]. Both force and [Pi] recovered within approximately 5 min after exercise. 2) After LDE, force recovered slowly, with significant fatigue beyond 15 min after exercise; however, recovery of [Pi] was not slowed. 3) Electromyographic signals were little affected by either protocol. These findings suggest that multiple mechanisms contribute to moderate fatigue. Fatigue from SDE may arise primarily from metabolic mechanisms, whereas fatigue from LDE involves an additional slowly recovering nonmetabolic mechanism that may arise from impaired activation, beyond the cell membrane, at the level of excitation contraction-coupling.
Development of conditioning programs for dressage horses based on time-motion analysis of competitions
Authors: Clayton H. M.
Published: December 2017

The time-motion characteristics of Canadian basic- and medium-level dressage competitions are described, and the results are applied in formulating sport-specific conditioning programs. One competition was analyzed at the six levels from basic 1 to medium 3. Each test was divided into a series of sequences based on the type and speed of activity. The durations of the sequences were measured from videotapes. The basic-level tests had fewer sequences, and they were shorter in distance and duration than the medium tests (P < 0.10), but the average speed did not differ between the two levels. It is recommended that horses competing at the basic levels be conditioned using 5-min exercise periods, with short (10-s) bursts of lengthened trot and canter included at basic 2 and above. In preparation for medium-level competitions, the duration of the work periods increases to 7 min, 10- to 12-s bursts of medium or extended trot and canter are included, and transitions are performed frequently to simulate the energy expenditure in overcoming inertia.
Hypoxic potentiation of the ventilatory response to dynamic forearm exercise
Authors: Fregosi R. F. , Seals D. R.
Published: December 2017

The slope of the relationship between ventilation (VI) and O2 consumption, as derived in progressive-intensity exercise tests, is increased markedly by systemic hypoxia. The mechanisms underlying the hypoxic potentiation of the ventilatory response to exercise have not been established, partly because several factors that can increase respiratory drive (e.g., metabolic rate, cardiac output, circulating catecholamine levels) change significantly and simultaneously under these conditions. In an effort to avoid these confounding changes, we sought to determine whether hypoxia potentiates the ventilatory response to dynamic forearm exercise in humans. Forearm exercise increased the O2 consumption by only 80–90 ml/min; nevertheless, hypoxia resulted in a significant potentiation of VI that was mediated by a marked increase in breathing frequency. These observations led us to hypothesize that the hypoxic potentiation of VI is due to an exaggerated stimulation of chemosensitive afferent nerve endings within the exercising muscles ("muscle chemoreceptors"). We tested this hypothesis in separate experiments under conditions of forearm ischemia so that the stimulus to the muscle chemoreceptors in normoxic and hypoxic exercise would be the same. The magnitude of the change in VI evoked by hypoxic ischemic exercise was significantly greater than the sum of the separate changes evoked by normoxic ischemic exercise and hypoxic ischemic rest. We conclude that the combination of dynamic forearm exercise and hypoxia potentiates VI and that this effect is mediated by neural structures that govern respiratory frequency. Moreover the potentiated ventilatory response cannot be attributed to an exaggerated stimulation of intramuscular chemoreceptors.
Respiratory and cardiovascular effects of inhaled and intravenous bradykinin, PGE2, and PGF2 alpha in dogs
Authors: Karlsson J. A. , Sant'Ambrogio F. B. , Forsberg K. , Palecek F. , Mathew O. P. , Sant'Ambrogio G.
Published: December 2017

Prostaglandins (PGs) and bradykinin act as potent respiratory irritants in both normal and asthmatic subjects, but their sites of action are unknown. We compared the cardiorespiratory effects of bradykinin, PGE2, and PGF2 alpha nebulized into the isolated "in situ" larynx, inhaled into the tracheobronchial tree, and injected intravenously in anesthetized spontaneously breathing dogs. Laryngeal administration only resulted in a brief burst of rapid shallow breaths produced by bradykinin (1,000 micrograms/ml) in one of five dogs. Tracheobronchial administration of bradykinin (1,000 micrograms/ml) increased breathing rate and tidal volume (VT) in four of seven dogs without changing cardiovascular parameters, whereas PGE2 (500 micrograms/ml) caused similar effects in two of six dogs. Lower concentrations of both agents were essentially without effect. PGF2 alpha (50–500 micrograms/ml) inhaled into the lower airway increased breathing rate, reduced VT, and caused a concentration-dependent bronchoconstriction that was significantly reduced by atropine. Inhaled PGF2 alpha only slightly increased arterial blood pressure (5.8 +/- 2.8%) and heart rate (12.0 +/- 6.4%). Intravenous PGF2 alpha (5 micrograms/kg) increased upper and lower airway resistances, which were accompanied by a decrease in breathing rate and VT, hypertension, and bradycardia. Bradykinin (1 micrograms/kg) and PGE2 (1 and 3 micrograms/kg) produced apnea followed by rapid shallow breathing, bradycardia, and hypotension. These results indicate that the tracheobronchial tree is considerably more responsive to aerosolized bradykinin, PGE2, and PGF2 alpha than the laryngeal region. Moreover, the stronger effects produced by intravascular administration suggest a greater accessibility of rapidly adapting stretch receptors and C-fiber endings from the vascular bed than from the airway lumen.
Facilitation and inhibition of phrenic motoneuronal activities by lung inflation
Authors: Hwang J. C. , St John W. M.
Published: December 2017

The purpose was to evaluate the facilitatory influence of pulmonary inflations on phrenic activity. In decerebrate cats, activities of phrenic motoneurons and nerve were recorded during ventilatory cycles in which the lungs were inflated to different levels and inflations were withheld. Motoneuronal activities were divided into "early" and "late" populations depending on their onset of activity. In normocapnia, facilitation was manifested by an increase in the rate of rise of phrenic activity. Facilitation increased with an increased level of inflations and fell when inflations were withheld. This facilitation was largely due to an increased rate of change and earlier onset of late motoneuronal activities. These variables for early motoneuronal activities were little altered by changes in inflations. Peak discharge frequencies of both early and late motoneurons increased during noninflation cycles. Facilitation was still evident during hypercapnia and in anesthetized animals; however, under these conditions, the earlier onset of late motoneuronal activities was no longer observed. We conclude that facilitation by pulmonary stretch receptor discharge is a constant determinant of phrenic neuronal and neural activities.
Importance of left atrial baroreceptors in the cardiopulmonary baroreflex of normal humans
Authors: Oren R. M. , Schobel H. P. , Weiss R. M. , Stanford W. , Ferguson D. W.
Published: December 2017

In animals, sympathetic responses to orthostasis are regulated in part by cardiopulmonary afferents arising from atrial and ventricular baroreceptors. To determine the relative importance of these baroreceptor regions in the cardiopulmonary baroreflex of normal humans, simultaneous measurements of left atrial and right and left ventricular volumes (cine computed tomography), invasive hemodynamics, forearm vascular resistance (plethysmography), and efferent sympathetic nerve activity to muscle (microneurography) were obtained under control conditions and with nonhypotensive lower body negative pressure (-10 mmHg, LBNP-10) in nine normal human subjects. LBNP-10 did not alter heart rate or mean systemic arterial pressure, but it did produce significant decreases in pulmonary artery diastolic and right atrial pressures. This reduction in cardiac filling pressures resulted in efferent sympathoexcitation evidenced by increases in forearm vascular resistance and efferent sympathetic nerve activity to the muscle. LBNP-10 did not alter end-diastolic volume of the left or the right ventricle. Similarly, ventricular stroke volume was unchanged during LBNP-10, as assessed by cine computed tomography or thermodilution techniques. In contrast, LBNP-10 resulted in a significant decrease in left atrial volume. Thus, LBNP produced a significant decrease in cardiac filling pressures and left atrial volumes with resultant reflex sympathoexcitation, whereas ventricular volumes were unchanged. These observations suggest an important role for left atrial (nonventricular) baroreceptor afferents in the cardiopulmonary baroreflex of normal humans.
Control of segmental upper airway resistance in patients with obstructive sleep apnea
Authors: Wasicko M. J. , Erlichman J. S. , Leiter J. C.
Published: December 2017

We sought to determine if the upper airway response to an added inspiratory resistive load (IRL) during wakefulness could be used to predict the site of upper airway collapse in patients with obstructive sleep apnea (OSA). In 10 awake patients with OSA, we investigated the relationship between resistance in three segments of the upper airway (nasal, nasopharyngeal, and oropharyngeal) and three muscles known to influence these segments (alae nasi, tensor veli palatini, and genioglossus) while the patient breathed with or without a small IRL (2 cmH2O.l–1.s). During IRL, patients with OSA exhibited increased nasopharyngeal resistance and no significant increase in either the genioglossus or tensor veli palatini activities. Neither nasal resistance nor alae nasi EMG activity was affected by IRL. We contrasted this to the response of five normal subjects, in whom we found no change in the resistance of either segment of the airway and no change in the genioglossus EMG but a significant activation of the tensor palatini. In six patients with OSA, we used the waking data to predict the site of upper airway collapse during sleep and we had limited success. The most successful index (correct in 4 of 6 patients) incorporated the greatest relative change in segmental resistance during IRL at the lowest electromyographic activity. We conclude, in patients with OSA, IRL narrows the more collapsible segment of the upper airway, in part due to inadequate activation of upper airway muscles. However, it is difficult to predict the site of upper airway collapse based on the waking measurements where upper airway muscle activity masks the passive airway characteristics.
Isolated single lung perfusion in the rat: an experimental model
Authors: Weksler B. , Schneider A. , Ng B. , Burt M.
Published: December 2017

To evaluate isolated single lung perfusion with chemotherapy in a rat lung metastasis model, we developed a model of in vivo isolated single lung perfusion. Twenty male rats were anesthetized with pentobarbital sodium (50 mg/kg) and intubated endotracheally. A left thoracotomy was performed with an operating microscope (x16 magnification), the left pulmonary artery was cannulated, and a left pulmonary venotomy was performed. Isolated left lung perfusion was performed for 10 min at 0.5 ml/min with heparinized whole blood (n = 10) or 0.9% normal saline (n = 10). Pulmonary vein effluent was collected by suction. Nineteen of the 20 (95%) animals survived isolated left single lung perfusion. Twenty-one days after isolated left lung perfusion right pneumonectomy was performed. Fifteen of the 19 animals (78%) survived right pneumonectomy. Postoperatively, animals that survived surgery recovered preoperative body weight. In vivo isolated single lung perfusion in rats is feasible with low mortality and morbidity and may be useful in the study of isolated perfusion with chemotherapy and in diverse physiological and pharmacological experiments.
Central and peripheral diaphragmatic fatigue in loaded normal and vagotomized dogs
Authors: De Vito E. L. , Roncoroni A. J.
Published: December 2017

Severe inspiratory elastic load terminated by respiratory arrest (RA) was studied in 24 anesthetized dogs (group 1, normal: n = 14; group 2, vagotomized: n = 10). The peripheral and central components of the decrease in diaphragmatic force generation and the events preceding RA were studied. We measured stimulated tetanic transdiaphragmatic pressure (Pdi), single twitch compound action potentials, integrated diaphragmatic electromyographic activity (iEMGdi), respiratory frequency (f), inspiratory time, inspiratory drive, overall diaphragmatic activation, and Pdi single twitch superimposed over peak Pdi. Imposed target pressure was -68.8 +/- 4.37 cmH2O for group 1 and -70.9 +/- 4.19 cmH2O for group 2, and the tension-time index of the diaphragm was the same for both groups (0.22 +/- 0.010). During load, 1) f increased in group 1 from 25.4 +/- 1.33 to 41.3 +/- 4.66 cycles/min, and tachypnea was prevented by vagotomy; 2) twitch occlusion persisted until RA and compound action potentials did not change; 3) iEMGdi and inspiratory drive increased and remained high until RA; 4) overall diaphragmatic activation increased 514 (group 1) and 260% (group 2) and then decreased to 228% of the basal value 10 s before RA in group 1 because of a fall in f; and 5) after RA, Pdi stimulated at 60 Hz fell to 39 (group 1; P < 0.0025) and 51% (group 2; NS with group 1) of the basal value. In summary, 1) peripheral fatigue developed without transmission failure; 2) diaphragmatic activation remained maximal until RA; 3) the fall in f appeared as a preterminal event only in group 1; and 4) vagus nerves are necessary for load-induced tachypnea.
Effects of N omega-nitro-L-arginine on total and segmental vascular resistances in developing lamb lungs
Authors: Gordon J. B. , Tod M. L.
Published: December 2017

To determine whether endothelium-derived nitic oxide (EDNO), like dilator prostaglandins, attenuates pulmonary vasomotor tone more in younger than in older newborns, we examined the effects of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NA), on total and segmental pulmonary vascular resistance (PVR) in isolated blood-perfused cyclooxygenase-inhibited lungs of < 2-day-old (2D) and 1-mo-old (1M) lambs. Total PVR was determined both from steady-state pressure-flow curves and total pressure gradients (delta PT) measured at constant flow (100 ml.kg-1 x min-1). Pressure gradients across arterial (delta Pa), middle (delta Pm), and venous (delta Pv) segments were determined by inflow-outflow occlusion. In 1M lungs (n = 6), L-NA increased delta PT, delta Pa, and delta Pv during normoxia and hypoxia. However, delta Pm increased only during hypoxia, suggesting that EDNO attenuates resistance of small vessels more when tone is high. The response to L-NA in 2D lungs was variable. In four "responders" (2D"R"), normoxic and hypoxic delta PT and all segmental resistances increased markedly after L-NA, but in five "nonresponders" (2D"NR"), L-NA had an insignificant effect on delta PT. Moreover, control delta PT values were higher in 2D"NR" than in 2D"R" lungs, suggesting that basal EDNO activity was minimal in some young newborns. Nonetheless, EDNO appears to attenuate venous resistance in newborns, because L-NA increased delta Pv in all groups. The significance of and mechanism(s) responsible for lesser modulation of PVR by EDNO in some young newborns remain to be determined.
In vivo quantification of pulmonary beta-adrenoceptor density in humans with (S)-[11C]CGP-12177 and PET
Authors: Ueki J. , Rhodes C. G. , Hughes J. M. , De Silva R. , Lefroy D. C. , Ind P. W. , Qing F. , Brady F. , Luthra S. K. , Steel C. J. , et al.
Published: December 2017

The in vivo regional distribution of pulmonary beta-adrenoceptors was imaged and quantified in humans with the hydrophilic beta-adrenoceptor antagonist (S)-CGP-12177 labeled with carbon-11 [(S)-[11C]CGP-12177] and positron emission tomography (PET). Six normal male volunteers and eight patients with hypertrophic cardiomyopathy were studied. PET scanning consisted of transmission (tissue density), C15O (blood volume), and (S)-[11C]CGP-12177 (beta-adrenoceptor) emission scans. High-specific-activity (S)-[11C]-CGP-12177 (7.1 +/- 2.0 micrograms, 6.5 +/- 2.1 GBq/mumol) was given intravenously followed by a low-specific-activity (S)-[11C]CGP-12177 injection (34.0 +/- 4.8 micrograms, 2.3 +/- 0.8 GBq/mumol). Binding capacity (Bmax) was calculated in each region of interest as picomoles per gram by normalizing it to the local extravascular tissue density. In normal subjects, average Bmax for all regions of interest was 14.8 +/- 1.6 (SD) pmol/g, which is similar to previously reported in vitro values. In both groups there were no differences in beta-adrenoceptor density between peripheral and central regions nor between right and left lungs. In patients with hypertrophic cardiomyopathy, extravascular tissue density was 24% higher than in normal subjects; Bmax per milliliter thoracic volume was correspondingly higher but was not different from that in normal subjects when expressed per gram tissue (15.8 +/- 2.6 pmol/g). These data suggest that in vivo beta-adrenoceptor density may be quantifiable in humans with the use of PET. This should offer a means to study physiological regulation through repeat measurements.
Exercise training alters cardiovascular and hormonal responses to intracranial self-stimulation
Authors: Burgess M. L. , Davis J. M. , Borg T. K. , Wilson S. P. , Burgess W. A. , Buggy J.
Published: December 2017

Both reinforcing intracranial self-stimulation (ICSS) and physical exercise result in heightened cardiovascular and endocrine responses. This study compared the cardiovascular and endocrine responses to ICSS in rats after either chronic ICSS or treadmill running. Male rats (n = 35) were implanted with bipolar electrodes aimed at the ventral tegmental area of the brain, and those that performed vigorous lever pressing for ICSS (> 50 presses/min; n = 30) were counter balanced into three groups: chronic ICSS (PRESS), chronic run training (RUN), or sedentary controls (CONT). PRESS, RUN, and CONT rats performed ICSS, ran on a motorized treadmill, or sat quietly in cages for 30 min/day, 5 day/wk, for 12 wk, respectively. All animals then performed 30 min of lever pressing for ICSS and were immediately killed. Oxygen consumption, heart rate, blood pressure, rectal temperature, and plasma norepinephrine, epinephrine, and corticosterone increased (P < 0.05) for all groups during lever pressing. PRESS rats did not differ from CONT rats for any variable studied. However, heart rate was lower and oxygen consumption, norepinephrine, and corticosterone were higher in RUN than in CONT rats. Heart and ventricle weights were higher in PRESS and RUN than in CONT rats; body weights were not different. These data suggest that chronic treadmill running results in adaptations that influence cardiovascular and hormonal responses to ICSS.
Sea-level PCO2 relates to ventilatory acclimatization at 4,300 m
Authors: Reeves J. T. , McCullough R. E. , Moore L. G. , Cymerman A. , Weil J. V.
Published: December 2017

There is considerable variation among individuals in the extent of, and the time required for, ventilatory acclimatization to altitude. Factors related to this variation are unclear. The present study tested whether interindividual variation in preascent ventilation or magnitude of hypoxic ventilatory response related to ventilatory acclimatization to altitude. Measurements in 37 healthy resting male subjects at sea level indicated a wide range (34–48 Torr) of end-tidal PCO2 values. When these subjects were taken to Pikes Peak, CO (4,300 m, barometric pressure 462 mmHg), the end-tidal PCO2 values measured on arrival and repeatedly over 19 days were correlated with the sea-level end-tidal PCO2. At 4,300 m, subjects with high end-tidal PCO2 had low values of arterial oxygen saturation (SaO2). Also, sea-level end-tidal PCO2 related to SaO2 after 19 days at 4,300 m. Twenty-six of the subjects had measurements of isocapnic hypoxic ventilatory response (HVR) at sea level. The end-tidal PCO2 values on arrival and after 19 days residence at 4,300 m were inversely related to the sea-level HVR values. Thus both the PCO2 and the HVR as measured at sea level related to the extent of subsequent ventilatory acclimatization (decrease in end-tidal PCO2) and the level of oxygenation at altitude. The finding in our cohort of subjects that sea-level end-tidal PCO2 was inversely related to HVR raised the possibility that among individuals the magnitude of the hypoxic drive to breathe influenced the amount of ventilation at all altitudes, including sea level.
The development of aerobic power in young athletes
Authors: Baxter-Jones A. , Goldstein H. , Helms P.
Published: December 2017

Previous studies investigating the effects of training in children have been hampered in their interpretation by the confounding effects of growth and development. We followed the development of maximal aerobic power (VO2max) in 453 athletes drawn from soccer, swimming, gymnastics, and tennis. Study design was of a mixed longitudinal type with five age cohorts (8, 10, 12, 14 and 16 yr) followed for 3 consecutive years. A multilevel regression modeling procedure was used to identify the independent effects of predictor variables while accounting for the effects of growth, such as changes in body size. When age, height, and weight were controlled for, VO2max in males significantly increased with pubertal status, indicated by the coefficient value of 0.15 l/min being greater than its associated SE of 0.07 l/min. Females showed a similar pattern, with a coefficient value of 0.13 +/- 0.07 l/min, although the significant increase in VO2max (P < 0.05) found in males in the latter stages of puberty was not shown in females. Swimmers had the highest VO2max values (P < 0.001) at all ages.
Method for computing the oxidation of two 13C-substrates ingested simultaneously during exercise
Authors: Peronnet F. , Adopo E. , Massicotte D. , Brisson G. R. , Hillaire-Marcel C.
Published: December 2017

This study presents a method for computing the respective amounts of two simultaneously ingested exogenous substrates (A and B) that are oxidized during a period of prolonged exercise by use of 13C labeling. This method is based on the observation that the total volume of 13CO2 produced (V13CO2tot) is the sum of 1) V13CO2 arising from the oxidation of endogenous substrates (V13CO2endo), 2) V13CO2 arising from the oxidation of substrate A (V13CO2A), and 3) V13CO2 arising from the oxidation of substrate B (V13CO2B). The equation, V13CO2tot = V13CO2endo+V13CO2A+V13CO2B, with three unknowns, can be solved from the results of three experiments conducted under the same conditions but with at least two values for the isotopic composition of A and B. This method has been used on five healthy male subjects to compute the amounts of glucose and fructose oxidized when a mixture of 15 g of glucose and 15 g of fructose is ingested (in 300 ml of water) over 60 min of cycle ergometer exercise at 65% of maximal O2 uptake. Results from three experiments indicated that 9.8 +/- 3.1 and 5.7 +/- 2.1 g of glucose and fructose, respectively, were oxidized. The total amount of exogenous carbohydrates oxidized (15.5 +/- 4.3 g) is in agreement with the oxidation rates of exogenous glucose computed in similar conditions when 30 g of glucose were ingested (13 g; Peronnet et al. Med. Sci. Sports Exercise 25: 297–302, 1993). The difference between the oxidation rates of exogenous glucose and fructose is also in line with data from the literature.
Hemodynamic changes associated with obstructive sleep apnea followed by arousal in a porcine model
Authors: Pinto J. M. , Garpestad E. , Weiss J. W. , Bergau D. M. , Kirby D. A.
Published: December 2017

To study the effects of airway obstruction (AWO) and arousal on coronary blood flow, mean arterial pressure (MAP), and heart rate, pigs were chronically instrumented with arterial catheters, Doppler flow probes on the left circumflex coronary artery, and electrodes for determination of sleep stages. A modified tracheostomy tube was placed in the trachea to obstruct the upper airway during sleep sessions. In control studies, during non-rapid-eye-movement (NREM) sleep, MAP was 84 +/- 2 mmHg before AWO and increased by 5 +/- 2 mmHg on arousal. MAP was lower during rapid-eye-movement (REM) sleep (62 +/- 2 mmHg), and the increase on arousal was fourfold greater (22 +/- 2 mmHg). Heart rate was similar in both sleep stages (NREM: 120 +/- 4 beats/min; REM: 124 +/- 5 beats/min) and increased significantly on arousal (NREM: 12 +/- 2 beats/min; REM: 18 +/- 1 beats/min). Coronary blood flow was similar during both stages (NREM: 43 +/- 4 ml/min; REM: 46 +/- 8 ml/min) and increased by 12–15% on arousal. Coronary vascular resistance index increased significantly by 24% on arousal from AWO during REM sleep. All increases and decreases were significant at P < 0.05. Receptor blockade studies were performed to assess alpha-adrenergic receptor involvement.
Airway and tissue impedances of canine lungs after step volume changes
Authors: Bates J. H. , Donoso F. A. , Peslin R.
Published: December 2017

We investigated the changes in pulmonary mechanics in five anesthetized paralyzed tracheostomized open-chest dogs after step changes in lung volume. We applied small-amplitude (10-ml) volume oscillations at 6 Hz at the tracheal opening for 50-s periods, during which we applied a step volume change of 250, 500, or 750 ml to the lungs. Alveolar capsule measurements of alveolar pressure allowed us to calculate cycle-by-cycle values for airway resistance (Raw) and reactance (Xaw) and lung tissue resistance (Rti) and reactance (Xti). Before the step changes in lung volume, when transpulmonary pressure (Ptp) had a mean value of 0.65 kPa, Raw was markedly greater than Rti. The situation was reversed after the step changes, however, when Raw decreased and Rti increased. Both Raw and Xaw showed negative dependences on Ptp and hence on airway caliber, as expected, and also decreased transiently after the step volume changes, almost certainly due to a vagally mediated bronchodilation reflex. Both Rti and Xti showed clear linear dependences on Ptp and were themselves tightly coupled. Furthermore, our estimate of bulk modulus for lung tissue at 6 Hz is comparable to its previously reported values at much lower oscillation frequencies.
Effect of estradiol on the temporal pattern of exercise-induced tissue glycogen depletion in male rats
Authors: Rooney T. P. , Kendrick Z. V. , Carlson J. , Ellis G. S. , Matakevich B. , Lorusso S. M. , McCall J. A.
Published: December 2017

The effect of 17 beta-estradiol 3-benzoate (10 micrograms.01 ml of sunflower oil-1 x 100 g body wt-1) on the temporal pattern of exercise-induced tissue glycogen depletion and tissue lipid availability during submaximal treadmill running was determined in male rats. Animal were administered estradiol or oil for 5 days and were then time matched for motorized treadmill running for 30, 60, 90, or 120 min. Significant depletion of liver, soleus muscle, and red and white vastus lateralis muscle tissue glycogen occurred in oil-administered animals run between 30 and 120 min. The greatest extent of tissue glycogen depletion occurred during the first 30 min of exercise with the rate of glycogen depletion slowing between 30 and 120 min of exercise. Administration of estradiol attenuated the temporal pattern of glycogen depletion in both liver and muscle tissues. Significant depletion of red and white vastus glycogen of estradiol-administered animals did not occur until 90 and 120 min of exercise, respectively. Administration of estradiol significantly increased resting plasma free fatty acids and red and white vastus triacylglycerol content. These data indicate that estradiol administration for 5 days resulted in significant glycogen sparing of liver and muscle tissues during submaximal treadmill running for up to 120 min by altering the temporal pattern of glycogen depletion of male rats secondary to an estradiol-mediated increase in availability of lipid substrate during exercise.
Muscle fiber type composition and fiber size in successfully and unsuccessfully endurance-raced horses
Authors: Rivero J. L. , Serrano A. L. , Henckel P. , Aguera E.
Published: December 2017

Triplicate biopsies from three different depths of the gluteus medius muscle were obtained in 36 endurance-raced horses, aged 8.42 +/- 2.85 yr. Twenty of the horses were considered excellent endurance performers according to the mean speed of their three fastest records in endurance events for the past 2 or 3 years, whereas 16 were moderate performers, with a mean racing speed < 12.5 km/h (in 120- to 180-km endurance rides), < 14 km/h (in 80- to 120-km endurance rides), or < 13.5 km/h (in 40- to 60-km endurance rides). Significant differences in muscle fiber type composition and fiber size were recorded; excellent performers had a higher percentage and a larger size of type I and type IIa fibers (high and low myosin adenosinetriphosphatase activity at pH 4.5, respectively) and a lower percentage of type IIb fibers (moderate myosin adenosinetriphosphatase activity at pH 4.5), including both type IIb oxidative (moderate to high NADH-tetrazolium reductase activity) and IIb nonoxidative (low NADH-tetrazolium reductase activity). The differences in distribution of myofiber types and in fiber sizes were more marked in the deeper parts compared with the superficial regions of muscle. Our results also imply a greater homogeneity among the fiber type sizes across the muscle in horses with a superior endurance performance than in horses that had been poorly or moderately endurance raced. Thus the results show that fiber type proportions and fiber size in equine skeletal muscle are directly related to the athletic ability of the horse for endurance events.
Measurement of hemoglobin flow and blood flow by near-infrared spectroscopy
Authors: Edwards A. D. , Richardson C. , van der Zee P. , Elwell C. , Wyatt J. S. , Cope M. , Delpy D. T. , Reynolds E. O.
Published: December 2017

A noninvasive method of measuring hemoglobin flow through an organ by near-infrared spectroscopy (NIRS) is described that allows blood flow to be calculated. The method is derived from the Fick principle and uses a small change in arterial oxyhemoglobin concentration (brought about by a change in the fractional inspired O2 concentration) as an intravascular tracer. Changes in deoxyhemoglobin and oxyhemoglobin concentrations are quantified by monitoring variations in the absorption of near-infrared light in the organ, thus providing a measure of tracer accumulation. The tracer input function is calculated from the change in arterial O2 saturation, measured by pulse oximetry. The method was used to determine hemoglobin flow in the forearms of six healthy young adults on 10 occasions. Forearm hemoglobin flow ranged from 22.5 to 82.6 mumol.l-1.min-1. Calculated forearm blood flow ranged from 1.01 to 4.01 ml.100 g-1.min-1. For comparison, forearm blood flow was measured by venous occlusion plethysmography, and the relation between flow calculated by NIRS (y) and plethysmography (x) was y = 0.93x + 0.30 (r2 = 0.95). The mean difference between the methods was 0.14 ml.100 g-1.min-1. The technique may be widely applicable.
Autonomic regulation of heart rate response to exercise in Tibetan and Han residents of Lhasa (3,658 m)
Authors: Zhuang J. , Droma T. , Sutton J. R. , McCullough R. E. , McCullough R. G. , Groves B. M. , Rapmund G. , Janes C. , Sun S. , Moore L. G.
Published: December 2017

To test the hypothesis that native high-altitude residents have less beta-sympathetic and more parasympathetic tone than newcomers, we compared the effects of beta-sympathetic and parasympathetic blockade in 10 Tibetan and 9 Han acclimatized male residents of Lhasa, Tibet Autonomous Region, China (elevation 3,658 m). Each subject was studied during cycle ergometer exercise at 70, 132, and 191 W after placebo (normal saline), beta-sympathetic (propranolol, 0.2 mg/kg iv), or parasympathetic (atropine, 0.04 mg/kg iv) blockade in random order on different days. At rest, the fall in resting heart rate with propranolol and the rise with atropine were equal in Tibetan and Han subjects. During exercise, the fall in heart rate with propranolol relative to placebo values was greater in the Han than in the Tibetan group, whereas the rise in heart rate with atropine was greater in the Tibetans. Propranolol or atropine administration did not change minute ventilation per unit O2 consumption in either group. At the highest level of exercise on the placebo day, the Tibetans achieved a higher work load and level of O2 consumption than the Han subjects. Propranolol or atropine reduced O2 consumption and work load similarly in the two groups at the highest exercise level. The results supported our hypothesis that native Tibetan residents of high altitude exhibit more para-sympathetic and less beta-sympathetic tone during exercise. Neither relatively greater parasympathetic nor less sympathetic activation appeared implicated in the greater exercise capacity of Tibetans compared with that of acclimatized newcomer residents of high altitude.
Intravasal use of pliable K(+)-selective electrodes in the femoral vein of humans during exercise
Authors: Hallen J. , Sejersted O. M.
Published: December 2017

Continuous recording of plasma K+ concentration ([K+]) during exercise would be valuable in determining K+ fluxes associated with muscle activation. Pliable polyvinyl chloride electrodes were constructed by incorporation of valinomycin into a polyvinyl chloride membrane attached to the end of a catheter with a 1 mm outer diameter. Through an outer catheter the electrode was inserted into the femoral vein of human subjects. The setup allowed easy in vivo calibration, and rapid changes of femoral venous [K+] of < 0.1 mmol/l could easily be detected. Drift over 1 h amounted to < 3 mV and was corrected for by analysis of blood samples. Rapid changes in femoral venous [K+] occurred during and after dynamic exercise, short and prolonged isometric contractions, and repetitive isometric contractions of the quadriceps muscle. Combined with arterial blood sampling and flow measurements, the electrodes will allow good approximation of 1) cellular K+ efflux rate associated with increased electrical activity, 2) rate of intramuscular reuptake of K+ mediated by the Na(+)-K+ pump, and 3) rate of K+ loss to or uptake from the circulation by the muscle.
Pathways and mechanisms involved in neural control of laryngeal submucosal gland secretion
Authors: Hejal R. , Strohl K. P. , Erokwu B. , Cherniack N. S. , Haxhiu M. A.
Published: December 2017

The purpose of this study was to define the pathways and mechanisms involved in the neural regulation of laryngeal mucosal gland functions. In anesthetized, paralyzed, and artificially ventilated dogs, the responses of laryngeal submucosal glands to stimulation of laryngeal mechanoreceptors and peripheral chemoreceptors were examined by measuring the number of hillocks and volume of secreted fluid before and after activation of sensory nerve endings. Compared with a control period, the number of hillocks and volume of secreted fluid significantly increased (P < 0.05) with mechanical stimulation of the vocal folds (n = 13) and with chemical activation of peripheral chemoreceptors by systemic administration of sodium cyanide (100 micrograms/kg; n = 11). The reflex responses induced by vocal fold stimulation and activation of peripheral chemoreceptors were slightly decreased by interrupting transmission in the recurrent laryngeal nerves (P > 0.05) and were abolished by subsequent sectioning of superior laryngeal nerves or prior intravenous administration of atropine methylnitrate (P < 0.05). In denervated animals, topical application of nicotine on laryngeal epithelium caused significant activation of submucosal glands (P < 0.05). We conclude that laryngeal secretion can be significantly altered reflexly by stimulation of laryngeal sensory nerve endings and peripheral chemoreceptors, that both superior and recurrent laryngeal nerves convey cholinergic outflow to laryngeal submucosal glands, and that nicotine acting locally activates laryngeal submucosal glands.
Histamine and exercise-induced hypoxemia in highly trained athletes
Authors: Anselme F. , Caillaud C. , Couret I. , Rossi M. , Prefaut C.
Published: December 2017

To determine whether exercise-induced hypoxemia in extreme athletes results from an increase in histamine level during maximal incremental exercise, seven young athletes [YA; age 22.2 +/- 1.23 (SE) yr] and seven master athletes (MA; age 66.2 +/- 2.94 yr), all of whom were known to develop exercise-induced hypoxemia, were compared with age-matched control groups (young controls and older controls, respectively). During maximal incremental exercise, blood samples for arterial blood gas analysis and for plasma and total histamine were drawn at rest and at 50, 75, and 100% of maximal O2 uptake. The percentage of histamine released (%H) was calculated from plasma and total histamine samples. In all athletes (MA and YA groups), exercise induced an increase in %H with a concomitant decrease in arterial PO2 (PaO2); in control groups there was no change in either histamine levels or PaO2. When the data for the YA and MA groups were combined, a correlation was observed between the increase in %H and the drop in PaO2. Nevertheless, further studies are required to establish whether histamine plays a causative role in hypoxemia or is a response to injury.
Strength training increases resting metabolic rate and norepinephrine levels in healthy 50- to 65-yr-old men
Authors: Pratley R. , Nicklas B. , Rubin M. , Miller J. , Smith A. , Smith M. , Hurley B. , Goldberg A.
Published: December 2017

Resting metabolic rate (RMR) decreases with age, largely because of an age-related decline in fat-free mass (FFM). We hypothesized that a strength-training program capable of eliciting increases in FFM would also increase RMR in older individuals. To test this hypothesis, RMR, body composition, and plasma concentrations of certain hormones known to affect RMR were measured before and after a 16-wk heavy-resistance strength-training program in 13 healthy men 50–65 yr of age. Average strength levels, assessed by the three-repetition maximum test, increased 40% with training (P < 0.001). Body weight did not change, but body fat decreased (25.6 +/- 1.5 vs. 23.7 +/- 1.7%; P < 0.001) and FFM increased (60.6 +/- 2.2 vs. 62.2 +/- 2.1 kg; P < 0.01). RMR, measured by indirect calorimetry, increased 7.7% with strength training (6,449 +/- 217 vs. 6,998 +/- 226 kJ/24 h; P < 0.01). This increase remained significant even when RMR was expressed per kilogram of FFM. Strength training increased arterialized plasma norepinephrine levels 36% (1.1 +/- 0.1 vs. 1.5 +/- 0.1 nmol/l; P < 0.01) but did not change fasting glucose, insulin, or thyroid hormone levels. These results indicate that a heavy-resistance strength-training program increases RMR in healthy older men, perhaps by increasing FFM and sympathetic nervous system activity.
Temporal capillary perfusion patterns in single alveolar walls of intact dogs
Authors: Okada O. , Presson R. G. , Godbey P. S. , Capen R. L. , Wagner W. W.
Published: December 2017

Pulmonary gas exchange reserve in the form of recruitable capillaries was first described in the 1930s, when in vivo microscopy was used to demonstrate that not all capillaries were perfused during basal conditions and that perfusion of individual capillaries varied over time. These important observations have never been directly confirmed, nor have the hemodynamic causes of the variation been investigated. We used videomicroscopy to record nine consecutive pulmonary capillary perfusion patterns during a 40-min period. Confirming the original work, we found considerable perfusion variation in about one-half of the capillaries. These variations did not correlate with changes in pulmonary arterial pressures or cardiac outputs, suggesting that factors more subtle than large-vessel hemodynamics affected capillary perfusion consistency. In contrast to this variable group, one-half of the capillary segments were consistently perfused during at least eight of the nine observations and were interconnected to form preferential pathways across the alveolar wall.
Effect of cold pressor test on single-breath DLCO in normal subjects
Authors: Frans A. , Lampert E. , Kallay O. , Nejadnik B. , Veriter C. , Arbogast R. , Lonsdorfer J.
Published: December 2017

We hypothesized that the decrease in single-breath diffusing capacity of CO (DLCO) as observed in patients with Raynaud's phenomenon (P.J. Fahey et al. Am. J. Med. 76:263–269, 1984) may be present in normal subjects. Therefore, we examined 31 healthy subjects in two different laboratories. Two series of experiments were performed. In the first series DLCO was measured in 22 volunteers before (twice) and 5, 10, and 30 min after a cold pressor test (CPT), which consisted of immersing both hands in a 12 degrees C water bath for 2 min. In the second series right heart catheterization was performed in nine healthy seated subjects. Cardiac output, mean pulmonary arterial pressure, heart rate, and pulmonary wedge pressure were measured before, during, and 10, 20, and 30 min after the CPT. In every volunteer the CPT induced a decrease in DLCO that was still present 30 min after the test. In the nine catheterized subjects DLCO increased above control values during the CPT and then decreased below control values for 30 min. The CPT had no effect on cardiac output, heart rate, or pulmonary wedge pressure. In contrast, pulmonary arterial pressure and pulmonary vascular resistance increased during the CPT and then became lower than the control values for at least 30 min. In summary, the CPT induced a biphasic evolution of DLCO in normal subjects, being increased during the CPT and decreased after it. Our data are best explained by the West model of the lung. Our data suggest that the pulmonary Raynaud's phenomenon is not specific to patients with primary Raynaud's phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation of 5-HT2Receptors in Prefrontal Pyramidal Neurons Inhibits Cav1.2 L-Type Ca2+Currents Via a PLCβ/IP3/Calcineurin Signaling Cascade
Authors: Day Michelle , Olson Patricia A. , Platzer Josef , Striessnig Joerg , Surmeier D. James
Published: December 2017

There is growing evidence linking alterations in serotonergic signaling in the prefrontal cortex to the etiology of schizophrenia. Prefrontal pyramidal neurons are richly innervated by serotonergic fibers and express high levels of serotonergic 5-HT2-class receptors. It is unclear, however, how activation of these receptors modulates cellular activity. To help fill this gap, whole cell voltage-clamp and single-cell RT-PCR studies of acutely isolated layer V–VI prefrontal pyramidal neurons were undertaken. The vast majority (>80%) of these neurons had detectable levels of 5-HT2Aor 5-HT2Creceptor mRNA. Bath application of 5-HT2agonists inhibited voltage-dependent Ca2+channel currents. L-type Ca2+channels were a particularly prominent target of this signaling pathway. The L-type channel modulation was blocked by disruption of Gαqsignaling or by inhibition of phospholipase Cβ. Antagonism of intracellular inositol trisphosphate signaling, chelation of intracellular Ca2+, or depletion of intracellular Ca2+stores also blocked this modulation. Inhibition of the Ca2+-dependent phosphatase calcineurin prevented receptor-mediated modulation of L-type currents. Last, the 5-HT2receptor modulation was robustly expressed in neurons from Cav1.3 knockout mice. These findings argue that 5-HT2receptors couple through Gαqproteins to trigger a phospholipase Cβ/inositol trisphosphate signaling cascade resulting in the mobilization of intracellular Ca2+, activation of calcineurin, and inhibition of Cav1.2 L-type Ca2+currents. This modulation and its blockade by atypical neuroleptics could have wide-ranging effects on synaptic integration and long-term gene expression in deep-layer prefrontal pyramidal neurons.