bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of feeding regimen on diurnal variation of breathing movements in late-gestation fetal sheep
Authors: Callea J. , McMillen I. C. , Walker D. W.
Published: December 2017

There is a diurnal variation in the mean incidence and amplitude of fetal breathing movements (FBMs) in sheep after approximately 120 days gestation. To determine whether this variation is caused by diurnal fluctuations in plasma glucose or prostaglandin (PG) concentrations, we studied two groups of pregnant sheep fed either once daily at 1100 h or every 2 h for 24 h. Maternal and fetal blood samples were taken every 2 h from 0900 to 0900 h the next day for assay of plasma glucose and PGE2 and PGF2 alpha concentrations. FBMs were recorded throughout the 24 h. The mean fetal plasma glucose concentrations of the once-daily and multifed groups were not different, but there was a significant difference between the two groups in the 24-h pattern of fetal glucose concentrations. In the once-daily fed group, plasma glucose concentrations reached a peak 8 h after maternal feeding and then declined, whereas in the multifed group, fetal plasma glucose concentrations reached a plateau and were constant from 1300 to 0900 h the next day. Fetal plasma PGE2 and PGF2 alpha concentrations did not show a significant change with time of day in either group. There was a significant diurnal variation in the incidence and amplitude of FBMs in each of the two feeding groups, and the 24-h pattern of FBMs did not differ significantly between groups. Therefore it would appear that the diurnal variation of FBMs is not a consequence of the maternal feeding regimen or diurnal changes in plasma glucose or PG concentrations.
Cobalt stimulates carotid body chemoreceptors
Authors: Di Giulio C. , Huang W. X. , Lahiri S. , Mokashi A. , Buerk D. G.
Published: December 2017

Because cobalt administration is known to elicit erythropoietin response, it is a reasonable hypothesis that cobalt would also stimulate the O2-sensing process in the peripheral chemoreceptors. We tested this hypothesis by measuring the effects of cobalt chloride on carotid chemosensory fibers in pentobarbital-anesthetized cats that were paralyzed and artificially ventilated. Responses of carotid chemoreceptor afferents to graded doses of cobalt given by intra-arterial injections (0.08-2.10 mumols) were measured at constant blood gases. Responses of the same chemoreceptor afferents to hypoxia, before and after a saturation dose of cobalt, were measured. In two experiments carotid body tissue PO2 was also simultaneously measured. The chemosensory fibers showed prolonged excitation after a brief period of inhibition subsequent to cobalt administration. The stimulatory effect showed a dose-dependent saturation response. Cobalt augmented rather than blocked carotid chemoreceptor response to hypoxia. The effect of cobalt was not mediated by tissue PO2. These results are consistent with the hypothesis that cobalt stimulates the O2-sensing mechanism, although a direct effect of cobalt on the excitability of the chemosensory terminal remains a possibility.
Significance of airway resistance for the pattern of breathing and lung volumes in exercising humans
Authors: Hesser C. M. , Lind F. , Linnarsson D.
Published: December 2017

The effects of increased airway resistance on lung volumes and pattern of breathing were studied in eight subjects performing leg exercise on a cycle ergometer. Airway resistance was changed 1) by increasing the density (D) of the respired gas by a factor of 4.2 and changing the inspired gas from O2 at 1.3 bar to air at 6 bar and 2) by increasing airway flow rates by exposing the subjects to incremental work loads of 0-200 W. Increased gas D caused a slower and deeper respiration at rest and during exercise and, at work loads greater than 120 W, depressed the responses of ventilation and mean inspiratory flow. Raised airway resistance induced by increases in D and/or airway flow rates altered respiratory timing by increasing the ratio of inspiratory time (TI) to total breath duration. Furthermore, analyses of the relationships between tidal volume and TI and between end-inspiratory volume and TI revealed elevation of Hering-Breuer inspiratory volume thresholds. We propose that this elevation, and hence exercise-induced increases of tidal volume, can largely be explained by previous observations that the threshold of the inspiratory off-switch mechanisms depends on central inspiratory activity (cf. C. von Euler, J. Appl. Physiol. 55: 1647-1659, 1983), which in turn increases with airway resistance (Acta Physiol. Scand. 120: 557-565, 1984).
Histochemical and enzymatic characteristics of skeletal muscle in master athletes
Authors: Coggan A. R. , Spina R. J. , Rogers M. A. , King D. S. , Brown M. , Nemeth P. M. , Holloszy J. O.
Published: December 2017

Many older athletes are capable of endurance performances equal to those of young runners who have higher maximal O2 uptakes (VO2max). To determine whether this is a result of differences in skeletal muscle characteristics, gastrocnemius muscle biopsy samples were obtained from eight master athletes [aged 63 +/- 6 (SD) yr] and eight young (aged 26 +/- 3 yr) runners. The young runners were matched with the master athletes for 10-km running performance and for their volume, pace, and type of training. Despite similar 10-km run times, VO2max was 11% lower (P less than 0.05) in the master athletes. Fiber type distribution did not differ between groups, with both groups having 60% type I and very few type IIb fibers. Succinate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase activities, however, were 31 and 24% higher in the master athletes compared with the matched young runners, whereas lactate dehydrogenase activity was 46% lower (all P less than 0.05). The capillary-to-fiber ratio was also greater in the master athletes; however, capillary density was similar in the two groups, because of the master athletes' 34% larger (P less than 0.05) type I fibers. These differences in skeletal muscle characteristics may explain the master athletes' ability to perform as well as some young runners despite having a lower VO2max.
Mechanisms of pulsus paradoxus in airway obstruction
Authors: Viola A. R. , Puy R. J. , Goldman E.
Published: December 2017

To assess the mechanisms of pulsus paradoxus (i.e., inspiratory decline of greater than or equal to 10 Torr in systolic pressure) in airway obstruction, we studied 12 patients with chronic airflow obstruction before and during breathing through an external resistance that provided loads during both inspiration and expiration. Esophageal pressure (Ppl) and brachial artery pressure, relative to either atmospheric (Pa) or esophageal pressure (Patm), were measured simultaneously during normal and loaded breathing. It was assumed that changes in intrathoracic systemic arterial transmural pressure were adequately represented by Patm. During control, no significant difference between systolic fluctuation (delta Pa) and pleural swings (delta Ppl) was found. Concurrently, inspiratory and expiratory Patm were nearly identical. By contrast, under maximally loaded conditions, higher magnitudes of delta Ppl than delta Pa were found and consequently Patm rose with inspiration. In this connection, the plot of delta Pa against delta Ppl showed that the slopes for delta Ppl less than or equal to 15 Torr (1.2 Torr delta Pa/delta Ppl) and delta Ppl greater than 15 Torr (0.4 Torr delta Pa/delta Ppl) were significantly different. Under all experimental conditions we found during inspiration a rise in diastolic Patm that is consistent with an increase in left ventricular afterload.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of thromboxane on respiration and pulmonary circulation in the cat: role of vagus nerve
Authors: Shams H. , Scheid P.
Published: December 2017

Infusion of stoichiometrically equal quantities of acid and base (neutral acid-base infusion) in the cat elicits pulmonary hypertension and rapid shallow breathing (J. Appl. Physiol. 62: 2362-2370, 1987), and thromboxane A2 (TxA2), released from platelets, is responsible for these effects (Respir. Physiol. 71: 169-183, 1988). To investigate the involvement of vagal afferent fibers in these responses, we reversibly blocked signal conduction in the vagus of the cat by bilaterally cooling the vagus nerves to 1 degree C and measured the cardiorespiratory parameters in response to neutral acid-base infusion and infusion of the TxA2 mimetic U-46619. Vagal cooling before infusion caused tidal volume (VT) to increase and respiratory frequency (fresp) to decrease, whereby total ventilation (VE) was slightly enhanced, but did not affect right ventricular blood pressure (Prv). Infusion of neutral acid-base after vagal cooling prompted Prv to rise, on average from 35 Torr to a peak of 60 Torr, and a similar rise was elicited by infusion of U-46619. However, vagal cooling abolished any effect on VT or fresp of both acid-base and U-46619 infusion. After rewarming the vagus nerves, infusion of U-46619 caused fresp to increase and VT to decrease (rapid shallow breathing) with a concomitant rise in Prv, similar to what had been observed in the earlier studies. Our data suggest that the effects of TxA2 and of its mimetic U-46619 on respiration are mediated by the stimulation of vagal afferent fibers, whereas pulmonary hypertension is unrelated to vagal activity.
Glucoregulation and hormonal responses to maximal exercise in non-insulin-dependent diabetes
Authors: Kjaer M. , Hollenbeck C. B. , Frey-Hewitt B. , Galbo H. , Haskell W. , Reaven G. M.
Published: December 2017

Maximal dynamic exercise results in a postexercise hyperglycemia in healthy young subjects. We investigated the influence of maximal exercise on glucoregulation in non-insulin-dependent diabetic subjects (NIDDM). Seven NIDDM and seven healthy control males bicycled 7 min at 60% of their maximal O2 consumption (VO2max), 3 min at 100% VO2max, and 2 min at 110% VO2max. In both groups, glucose production (Ra) increased more with exercise than did glucose uptake (Rd) and, accordingly, plasma glucose increased. However, in NIDDM subjects the increase in Ra was hastened and Rd inhibited compared with controls, so the increase in glucose occurred earlier and was greater [147 +/- 21 to 169 +/- 19 (30 min postexercise) vs. 90 +/- 4 to 100 +/- 5 (SE) mg/dl (10 min postexercise), P less than 0.05]. Glucose levels remained elevated for greater than 60 min postexercise in both groups. Glucose clearance increased during exercise but decreased postexercise to or below (NIDDM, P less than 0.05) basal levels, despite increased insulin levels (P less than 0.05). Plasma epinephrine and glucagon responses to exercise were higher in NIDDM than in control subjects (P less than 0.05). By use of the insulin clamp technique at 40 microU.m-2.min-1 of insulin with plasma glucose maintained at basal levels, glucose disposal in NIDDM subjects, but not in controls, was enhanced 24 h after exercise. It is concluded that, because of exaggerated counter-regulatory hormonal responses, maximal dynamic exercise results in a 60-min period of postexercise hyperglycemia and hyperinsulinemia in NIDDM. However, this event is followed by a period of increased insulin effect on Rd that is present 24 h after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory impedance and multibreath N2 washout in healthy, asthmatic, and cystic fibrosis subjects
Authors: Lutchen K. R. , Habib R. H. , Dorkin H. L. , Wall M. A.
Published: December 2017

We measured forced expiratory volume in 1 s (FEV1), respiratory impedance (Zrs) from 4 to 60 Hz, and a multibreath N2 washout (MBNW) in 6 normal, 10 asthmatic, and 5 cystic fibrosis (CF) subjects. The MBNW were characterized by the mean dilution number (MDN) derived by a moment analysis. The Zrs spectra were characterized by the minimum resistance (Rmin), the drop in resistance (Rdrop) from 4 Hz to Rmin, and the first resonance frequency (Fr1). Measurements were repeated after bronchodilation in three normal and all asthmatic subjects. Before bronchodilation, six of the asthmatic subjects showed close to normal FEV1. The Zrs in the normal subjects showed low Rmin (1.9 +/- 0.7 cmH2O.l-1.s), Rdrop (0.4 +/- 0.4), and Fr1 (10 +/- 2 Hz). Four of the mildly obstructed asthmatic subjects had normal Zrs but elevated MDNs (i.e., abnormal ventilation distribution). The other six asthmatic subjects had significantly elevated Rmin (4.1 +/- 0.8), Rdrop (6.3 +/- 5.8), and Fr1 (34 +/- 0.4 Hz) and elevated MDNs. The CF patients had elevated Zrs features and MDNs. After bronchodilation, no changes in FEV1, MDN, or Zrs occurred in the normal subjects. All asthmatic subjects showed increased FEV1 and decreased MDN, but the Zrs was unaltered in the four asthmatic subjects whose base-line Zrs was normal. For the other six asthmatic subjects, there were large decreases in the Rmin, Rdrop, and Fr1. Finally, there was a poor correlation between the MDN and the Zrs features but high correlation between the Zrs features alone. These results imply that significant nonuniform peripheral airway obstruction can exist such that ventilation distribution is abnormal but Zrs from 4 to 60 Hz is not. Abnormalities in Zrs from 4 to 60 Hz occur only after significant overall obstruction in the peripheral and more central airways. Combining Zrs and the MBNW may permit us to infer whether the disease is predominantly in the lung periphery or in the more central airways.
Pulmonary afferent control of breathing as end-expiratory lung volume decreases
Authors: Green J. F. , Kaufman M. P.
Published: December 2017

We studied reflex changes in breathing elicited by graded reductions in end-expiratory lung volume (EEVL) and the vagal nerves responsible. The chests of nine dogs anesthetized with alpha-chloralose were opened, and the lungs were ventilated by a phrenic nerve-driven servo-respirator. The immediate effects of a 50% reduction in end-expiratory transpulmonary pressure (EEPtp) from control (EEVL equivalent to functional residual capacity) were to significantly increase both tidal volume (VT) and breathing frequency (f) from 0.402 +/- 0.101 to 0.453 +/- 0.091 liter (mean +/- SD) and 11.8 +/- 5.4 to 15.7 +/- 6.4 breaths/min, respectively (P less than 0.05). Further reductions in EEPtp to 0 cmH2O did not change VT but augmented f to 19.6 +/- 6.6 breaths/min (P less than 0.05). The increase in f as EEVL decreased was due entirely to a reduction in expiratory time. Vagotomy abolished these reflexes. By 90 s after reduction in EEVL, arterial PCO2 fell significantly and VT returned to or below control values. We therefore repeated these experiments in five dogs whose blood gases were controlled by cardiopulmonary bypass. There were no secondary changes in VT and by 90 s breathing pattern could be characterized as rapid and deep. In another eight dogs submitted to the same collapse protocol, we recorded action potentials from all known categories of pulmonary vagal afferents. These studies demonstrated that the changes in breathing pattern induced by a 50% reduction in EEPtp were due to a withdrawal of slowly adapting stretch receptor activity; however, continued increases in f as EEVL was reduced further were due to increases in rapidly adapting stretch receptor activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Intrapericardial denervation: radial artery blood flow and heart rate responses to LBNP
Authors: McKeever K. H. , Skidmore M. G. , Keil L. C. , Sandler H.
Published: December 2017

Eight rhesus monkeys were used to study responses of radial artery blood flow velocity (RABFV) and heart rate (HR) to low (0 to -20 mmHg) and high (0 to -60 mmHg) ramp exposures during supine lower body negative pressure (LBNP). These levels were chosen to separate peripheral vascular responses associated with stimulation of low- and high-pressure baroreceptors. Four monkeys had efferent and afferent cardiac denervation by use of the Randall procedure with pharmacological (phenylephrine and atropine) verification. Animals were studied 3 wk after surgery to avoid reinnervation. Findings were compared with those of four identically treated intact animals. Denervated animals showed no change in RABFV or HR during low-level LBNP; however, HR increased significantly (P less than 0.05) when LBNP reached -50 mmHg and blood flow velocity also fell (P less than 0.05) starting at -30 mmHg pressure. In contrast, intact animals showed steady decreases in RABFV during both high- and low-pressure protocols, with HR showing a 6-beat/min increase (P less than 0.05) starting at -20 mmHg pressure. As with denervated animals, intact animals showed a more pronounced increase in HR after reaching a level of -60 mmHg suction. Cardiac output (electromagnetic flowmeter, ascending aorta) fell significantly in both groups starting at -30 mmHg pressure. Left ventricular pressure (Konigsberg pressure cell) in three intact animals showed a progressive fall in systolic pressure starting at -10 mmHg suction, which became significant at -55 mmHg pressure. These results demonstrate that cardiac denervation by use of the Randall technique significantly affects RABFV and HR responses to LBNP in rhesus monkeys. The lack of RABFV change during LBNP in denervated animals suggests that these changes coupled with HR response can be used as an effective method to verify the completeness of denervation of low-pressure baroreceptors in animals that have undergone intrapericardial denervation.
Airway and alveolar pressures during perfluorocarbon breathing in infant lambs
Authors: Curtis S. E. , Fuhrman B. P. , Howland D. F.
Published: December 2017

Previous studies exploring the utility of liquid breathing using perfluorocarbon have reported proximal airway pressures (Paw) as high as 70 Torr during inspiration, generating concern about the safety of this form of mechanical ventilation. Effects on the pulmonary capillary bed are, however, more likely related to alveolar pressure (PA) than to Paw, and data on PA during liquid breathing are limited. In this study in infant lambs, we reconstructed the pressure waveforms of PA during liquid breathing by using an occlusion technique and compared these with Paw waveforms. Peak PA (18.6 +/- 10.4 Torr) was significantly less than peak Paw (31.5 +/- 10.5 Torr, P less than 0.001), indicating a large resistive pressure drop (14.4 +/- 4.5 Torr) across the bronchial tree. Mean PA (mPA) was very similar to mean Paw (mPaw) [bias = -2.0 Torr, standard error of the average difference = 0.27 Torr, predictive value of mPaw for mPA (r2) = 0.978], suggesting that mPaw, which is easily measured, may be used to estimate mPA during perfluorocarbon liquid breathing. These data show that alveoli do not experience the same large swings in pressure as the proximal airway does during liquid breathing and that simple measurements of mPaw can be used to approximate mPA during liquid breathing.
Microvascular injury after ischemia and reperfusion in skeletal muscle of exercise-trained rats
Authors: Sexton W. L. , Korthuis R. J. , Laughlin M. H.
Published: December 2017

Ischemia and reperfusion in skeletal muscle is associated with increases in total vascular resistance (Rt) and the microvascular permeability to plasma proteins. To determine whether exercise training can attenuate ischemia and reperfusion-induced microvascular injury in skeletal muscle, intact (with skin) and skinned, maximally vasodilated (papaverine), isolated hindquarters of control (C) and exercise-trained (ET) rats were subjected to ischemia (intact 120 min; skinned 60 min) followed by 60 min of reperfusion. ET rats ran on a motorized treadmill at 32 m/min (8% grade), 2 h/day for 12 wk, whereas the C rats were cage confined. Before ischemia, ET hindquarters had higher isogravimetric flow, lower Rt, and similar solvent drag reflection coefficients (sigma f) compared with C. During reperfusion in intact hindquarters, flow was higher (P less than 0.05) and Rt tended to be lower (15 +/- 2 vs. 25 +/- 5 mmHg.ml-1.min.100 g; P less than 0.1) in ET compared with C; however, in skinned hindquarters flow and Rt (14 +/- 2 vs. 13 +/- 2 mmHg.ml-1.min.100 g) were not different between C and ET. During reperfusion, sigma f was reduced (P less than 0.05) in both intact (C 0.68 +/- 0.03; ET 0.68 +/- 0.02) and skinned (C 0.66 +/- 0.03; ET 0.68 +/- 0.03) hindquarters, indicative of an increased microvascular permeability to plasma proteins. These results indicate that exercise training did not attenuate the microvascular injury (increased Rt and decreased sigma f) associated with ischemia and reperfusion in rat skeletal muscle.
Waking and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs
Authors: Plowman L. , Lauff D. C. , Berthon-Jones M. , Sullivan C. E.
Published: December 2017

We studied waking and genioglossus electromyographic (EMGgg) responses to oscillating pressure waves applied to the upper airways of three sleeping dogs. The dogs were previously prepared with a permanent side-hole tracheal stoma and were trained to sleep with a tight-fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria, and EMGgg activity was measured using fine bipolar electrodes inserted directly into the muscle. Oscillatory pressure waves of 30 Hz and +/- 3 cmH2O (tested at atmospheric and subatmospheric upper airway pressures) were applied at the dog's nostrils or larynx, either constantly for a period of 1 min or in 0.5-s bursts. We found that the pressure stimulus had two major effects. First, it was a potentially powerful arousal-promoting stimulus. Arousal occurred in 78% of tests in slow-wave sleep (SWS) and 55% of tests in rapid-eye-movement (REM) sleep, with swallowing and sighing accompanying many of the arousals. Second, it produced an immediate and sustained augmentation of EMGgg, in wakefulness, SWS, and REM sleep. We conclude that oscillatory pressure waves in the upper airway, as found in snoring, produce reflex responses that help maintain upper airway patency during sleep. Loss of this type of reflex might contribute to the onset of obstructive sleep apnea in chronic snorers.
Measurement of peptidoleukotrienes in biological fluids
Authors: Westcott J. Y. , Johnston K. , Batt R. A. , Wenzel S. E. , Voelkel N. F.
Published: December 2017

Samples of human bronchoalveolar lavage fluid (BALF) and urine were utilized to demonstrate methods for quantitation and validation of leukotrienes (LTs). These methods utilize an enzyme immunoassay (EIA) that uses commercially available reagents, the antibody recognizing LTC4, LTD4, LTE4, and N-acetyl LTE4. BALF containing epithelial lining fluid was collected from atopic asthmatics both before and 5 min after the subjects had been challenged with a local instillation of allergen into the airways. BALF samples collected without allergen challenge had low levels of immunoreactive LTs, whereas samples collected after allergen were markedly elevated. After high-performance liquid chromatography (HPLC) separation of LTs, EIA revealed the presence of LTC4. The identity was validated by incubating LTC4 with a bovine gamma-glutamyl transpeptidase with dipeptidase activity that converted added [3H]-LTC4 as well as LTC4 immunoreactivity to LTE4. Urine samples collected from six healthy volunteers, one patient with adult respiratory distress syndrome (ARDS), and three patients in status asthmaticus were also analyzed for LTs. After HPLC separation of LTs and quantitation by EIA, urine samples from healthy subjects were found to have low but measurable LTE4. In contrast, the urine samples from the patients in status asthmaticus and from the ARDS patient had large elevations of LTE4 levels compared with healthy subjects. When the HPLC fractions containing [3H]LTE4 and LT immunoreactivity in the ARDS sample were treated with acetic anhydride, HPLC analysis indicated that both radiolabel and immunoreactivity now eluted at the retention time of N-acetyl LTE4, the derivatized product of LTE4. The methods described are relatively easy and can be used to measure and validate the existence of peptidoleukotrienes in biological samples.
Diminished arginine-stimulated insulin secretion in trained men
Authors: Dela F. , Mikines K. J. , Tronier B. , Galbo H.
Published: December 2017

Glucose-stimulated insulin secretion is depressed by training. To further elucidate the beta-cell adaptation to training, a nonglucose secretagogue was applied. Arginine was infused for 90 min to seven trained and seven untrained young men. Arginine and glucose concentrations increased identically in the groups. The insulin response was biphasic and waned despite increasing arginine concentrations. Both these phases as well as C-peptide responses were reduced in trained subjects, whereas proinsulin responses were similar in the groups. Identical increases were found in glucagon, growth hormone, catecholamines, and production and disappearance of glucose; identical decreases were found in free fatty acids, glycerol, and beta-hydroxybutyrate. In conclusion, in men training diminishes both arginine- and glucose-stimulated insulin secretion, indicating a profound beta-cell adaptation. Being enhanced, the effects of insulin on both production and disposal of glucose are changed in the opposite direction to beta-cell secretion by training. The responses of glucagon- and growth hormone-secreting cells to arginine do not change with training.
Effect of an acute bout of exercise on glucose disposal in human obesity
Authors: Burstein R. , Epstein Y. , Shapiro Y. , Charuzi I. , Karnieli E.
Published: December 2017

The effect of acute exercise on insulin action has been studied in six obese (150-250% ideal body weight) non-insulin-dependent diabetics (OD), seven obese normoglycemics (ON), and six lean healthy controls (LC). Using a three-stage euglycemic clamp, the metabolic clearance rate (MCR) of glucose under increasing insulin concentrations was measured. The insulin dose-response curve was assessed on two separate occasions: 1) a base-line test and 2) 1 h after aerobic treadmill exercise at a steady-state heart rate of 150-160 beats/min. In the base-line test, under all insulin levels, glucose MCR was significantly lower in obese compared with lean individuals (P less than 0.01). Exercise increased glucose MCR at the highest hormonal concentrations applied to 124 and 134% of base line in OD and in ON, respectively (P less than 0.05); the insulin concentration required for one-half of the maximal clearance rate of glucose achieved in this study decreased from 200 to 130 and from 160 to 95 microU/ml in OD and ON, respectively (P less than 0.05). The changes in these parameters were insignificant in LC. It is suggested that acute exercise affected the insulin dose-response curve in OD and in ON but not in LC; although enhanced by exercise, glucose MCR remained significantly lower in both obese groups compared with control subjects. We concluded that insulin resistance, which accompanies extreme obesity, could be markedly decreased but not completely reversed by one bout of exercise.
O3-induced mucosa-linked airway muscle hyperresponsiveness in the guinea pig
Authors: Murlas C. G. , Murphy T. P. , Chodimella V.
Published: December 2017

We investigated the effects of ozone exposure (3.0 ppm, 2 h) on the responsiveness of guinea pig airway muscle in vitro from animals developing bronchial hyperreactivity. Muscarinic reactivity in vivo was determined by measuring specific airway resistance (sRaw) in response to increasing concentrations of aerosolized acetylcholine (ACh) administered before and 30 min after exposure. Immediately after reactivity testing, multiple tracheal rings from ozone- and air-exposed animals were prepared and the contractile responses to increasing concentrations of substance P, ACh, or KCl were assessed in the presence of 10 microM indomethacin with or without 1 microM phosphoramidon, an inhibitor of neutral endopeptidase. Isometric force generation in vitro was measured on stimulation by cumulative concentrations of the agonists, and force generation (in g/cm2) was calculated after determination of muscle cross-sectional area. The smooth muscle of mucosa-intact airways from guinea pigs with ozone-induced bronchial hyper-reactivity proved to be hyperresponsive in vitro to substance P and ACh but not to KCl. Pretreatment with phosphoramidon abolished the increase in substance P responsiveness but had no effect on muscarinic hyperresponsiveness after ozone exposure. Furthermore, substance P responsiveness was not augmented in ozone-exposed airways in which the mucosa had been removed before testing in vitro. Likewise, muscarinic hyperresponsiveness was not present in ozone-exposed airways without mucosa. Our data indicate that airway smooth muscle responsiveness is increased in guinea pigs with ozone-induced bronchial hyperreactivity and suggest that this hyperresponsiveness may be linked to non-cyclooxygenase mucosa-derived factors.
Hydraulic conductivity of canine parietal pleura in vivo
Authors: Negrini D. , Townsley M. I. , Taylor A. E.
Published: December 2017

The hydraulic conductivity (Lp) of the parietal pleura was measured in vivo in spontaneously breathing anesthetized dogs in either the supine (n = 8) or the prone (n = 7) position and in an excised portion of the chest wall in which the pleura and its adjacent tissue were intact (n = 3). A capsule was glued to the exposed parietal pleura after the intercostal muscles were removed. The capsule was filled with either autologous plasma or isotonic saline. Transpleural fluid flow (V) was measured at several transpleural hydrostatic pressures (delta P) from the rate of meniscus movement within a graduated pipette connected to the capsule. Delta P was defined as the measured difference between capsule and pleural liquid pressures. The Lp of the parietal pleura was calculated from the slope of the line relating V to delta P by use of linear regression analysis. Lp in vivo averaged 1.36 X 10(-3) +/- 0.45 X 10(-3) (SD) ml.h-1.cmH2O-1.cm-2, regardless of whether the capsule was filled with plasma or saline and irrespective of body position. This value was not significantly different from that measured in the excised chest wall preparation (1.43 X 10(-3) +/- 1.1 X 10(-3) ml.h-1.cmH2O-1.cm-2). The parietal pleura offers little resistance to transpleural protein movement, because there was no observed difference between plasma and saline. We conclude that because the Lp for intact parietal pleura and extrapleural interstitium is approximately 100 times smaller than that previously measured in isolated stripped pleural preparations, removal of parietal pleural results in a damaged preparation.
Prior running reduces hypertrophic growth of skeletal muscle grafts
Authors: Esser K. A. , White T. P.
Published: December 2017

Run training can increase the mass of soleus muscle grafts, yet values remain lower than nongrafted muscle even with continued training. Thus we tested the hypothesis that nerve-implant soleus grafts of rats previously run trained would be refractory to the hypertrophic stimulus of ablation of synergistic muscle. We also compared the magnitude of growth of the nerve-implant soleus graft after ablation with that reported by others for the nerve-intact soleus graft. We studied eight groups that differed relative to the combination and order of treatments (running and ablation of synergistic muscle) and the graft age at the time of the ablation operation and study. Graft mass, protein concentration, and histochemical fiber composition were measured. Compared with grafts from cage-sedentary rats, the mass and protein content of the nerve-implant soleus grafts were higher (16-63%) at all times after ablation. When the ablation operation was performed at 56 days postgrafting, there was a 33% increase in protein content of the soleus graft by 84 days for cage-sedentary animals. This increase was twofold greater (P less than or equal to 0.02) than the 15% increase that followed ablation for the grafts from the animals that had been run trained before the ablation operation. Four weeks of run training before the ablation operation impaired the adaptive response of muscle grafts to the ablation of synergistic muscles, which may reflect alterations in motor unit recruitment and/or satellite cell activity. Ablation of synergistic muscles resulted in an absolute growth of the nerve-implant soleus grafts that was comparable with that reported for nerve-intact soleus grafts.
Distribution of pulmonary capillary transit times in recruited networks
Authors: Capen R. L. , Hanson W. L. , Latham L. P. , Dawson C. A. , Wagner W. W.
Published: December 2017

When pulmonary blood flow is elevated, hypoxemia can occur in the fastest-moving erythrocytes if their transit times through the capillaries fall below the minimum time for complete oxygenation. This desaturation is more likely to occur if the distribution of capillary transit times about the mean is large. Increasing cardiac output is known to decrease mean pulmonary capillary transit time, but the effect on the distribution of transit times has not been reported. We measured the mean and variance of transit times in single pulmonary capillary networks in the dependent lung of anesthetized dogs by in vivo videofluorescence microscopy of a fluorescein dye bolus passing from an arteriole to a venule. When cardiac output increased from 2.9 to 9.9 l/min, mean capillary transit time decreased from 2.0 to 0.8 s. Because transit time variance decreased proportionately (relative dispersion remained constant), increasing cardiac output did not alter the heterogeneity of local capillary transit times in the lower lung where the capillary bed was nearly fully recruited.
Rat soleus muscle ultrastructure after hindlimb suspension
Authors: Desplanches D. , Kayar S. R. , Sempore B. , Flandrois R. , Hoppeler H.
Published: December 2017

The aim of the present investigation was to determine, by quantitative electron microscopy, the effects of a 5-wk tail-suspension period on rat soleus muscle ultrastructure. A marked decline (-60%) in muscle mass occurred. The mean fiber cross-sectional area decreased to a greater extent (-75%) than the capillary-to-fiber ratio (-37%), leading to a higher capillary density (+148%) after hypokinesia. The total mitochondrial volume density remained unchanged, whereas the volume density of myofibrils was slightly but significantly reduced (-6%). A shift from subsarcolemmal to interfibrillar mitochondria occurred. Interfibrillar mitochondrial volume density was highest near the fiber border and decreased toward the fiber center. An increase in volume density of satellite cells suggested muscle regenerative events. Soleus atrophy with tail suspension greatly decreases the muscular volume but leaves the ultrastructural composition of muscle fibers relatively unaffected.
Left ventricular asynchrony in patients with pulmonary hypertension
Authors: Bhargava V. , Sunnerhagen K. S.
Published: December 2017

Left ventricular regional wall motion was evaluated in 11 patients with pulmonary hypertension and 18 control subjects. All 11 patients had secondary pulmonary hypertension and less than 20% measured diameter stenosis in any vessel. This study utilizes a video-intensity-based frame-by-frame computerized technique. All pulmonary hypertensive patients showed early diastolic asynchrony in the anterior or apical regions that lasted 100-200 ms. The size of the abnormal area varied from 2 to 20% of the ventricular silhouette. Four patients also showed systolic abnormalities. No abnormalities were detected in the control group. The cause of the asynchrony detected in pulmonary hypertension is probably due to interventricular interaction caused by pressure gradients across the septum.
Periodic flow at airway bifurcations. III. Energy dissipation
Authors: Tsuda A. , Savilonis B. J. , Kamm R. D. , Fredberg J. J.
Published: December 2017

We measured the energy dissipation associated with large-amplitude periodic flow through airway bifurcation models. Each model consisted of a single asymmetric bifurcation with a different branching angle and area ratio, with each branch terminated into an identical elastic load. Sinusoidal volumetric oscillations were applied at the parent duct so that the upstream Reynolds number (Re) varied from 30 to 77,000 and the Womersley parameter (alpha) from 4 to 30. Pressures were measured continuously at the parent duct and at both terminals, and instantaneous branch flow rates were calculated. Time-averaged energy dissipation in the bifurcation was computed from an energy budget over a control volume integrated over a cycle and was expressed as a friction factor, F. We found that when tidal volume was small [ratio of tidal volume to resident (dead space) volume, VT/VD less than 1], F was independent of branching angle and fell with increasing alpha and VT/VD. When tidal volume was large (VT/VD greater than 1), F increased with increasing branching angle and varied less strongly with alpha and VT/VD. No simple benchmark flow represented the data well over the entire experimental range. This study demonstrates that only two nondimensional parameters, alpha and VT/VD, are necessary and are sufficient to describe time-averaged energy dissipation in a given bifurcation geometry during sinusoidal flow.
Effect of ischemia reperfusion or hypoxia reoxygenation on lung vascular permeability and resistance
Authors: Allison R. C. , Kyle J. , Adkins W. K. , Prasad V. R. , McCord J. M. , Taylor A. E.
Published: December 2017

The effect of ischemia reperfusion or hypoxia reoxygenation on pulmonary vascular permeability and resistance was studied in 25 isolated blood-perfused dog lungs. Vascular permeability, assessed by determining filtration coefficient (Kf), and vascular resistances were measured at the beginning and end of the experiment. Ischemia reperfusion was produced by occluding blood flow to the lung for 3 h and reperfusing for 1 h, whereas hypoxia reoxygenation was obtained by ventilating the lung with 95% N2-5% CO2 for 3 h and then ventilating with 95% O2-5% CO2 for 1 h with no interruption of perfusion. There was a significant increase in Kf in both ischemia reperfusion and hypoxia reoxygenation groups (51 and 85%, respectively), and total vascular resistance increased greatly in both groups (386 and 532%, respectively). Two additional groups were also studied in which the ischemia reperfusion or hypoxia reoxygenation lungs were pretreated with allopurinol (20 micrograms/ml). The Kf did not significantly increase in either the allopurinol ischemia reperfusion or the allopurinol hypoxia reoxygenation groups (22 and 6%, respectively). However, total vascular resistance significantly increased in both groups (239 and 224%, respectively). Although vascular permeability is modestly increased by both ischemia reperfusion and hypoxia reoxygenation, the predominant change in these conditions is the increased vascular resistance, which predominantly affects the postcapillary resistance and would result in a greater tendency for edema to develop in these slightly damaged lungs. Allopurinol, which inhibits xanthine oxidase, attenuated the permeability changes in both groups and may be useful in preventing ischemia reperfusion injury in certain conditions.
Regional metabolic differences in the rat diaphragm
Authors: Powers S. K. , Lawler J. , Criswell D. , Silverman H. , Forster H. V. , Grinton S. , Harkins D.
Published: December 2017

This study characterized the biochemical properties of the rat diaphragm by measuring the activities of selected citric acid cycle and glycolytic enzymes. The diaphragm was removed from 10 female Sprague-Dawley rats (180 days old) and dissected into five discrete anatomic regions: crural (region 1), left posterior costal (region 2), left anterior costal (region 3), right anterior costal (region 4), and right posterior costal (region 5). Sections were assayed for total protein concentration and the activities of succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH). The SDH activity in the crural region was approximately 18% lower (P less than 0.05) than that in any costal region. Furthermore, protein concentration was significantly lower (P less than 0.05) in the crural region compared with all costal regions. In contrast, costal regions 2-5 did not significantly differ from each other in protein concentration or SDH activity. LDH activity did not differ significantly (P greater than 0.05) between regions. Finally, the LDH-to-SDH activity ratio was significantly higher (P less than 0.05) in the crural diaphragm compared with all costal regions. We conclude that the crural region of the rat diaphragm is significantly lower in oxidative capacity than all the costal regions. Investigators who use a rodent model to study diaphragmatic function and plasticity should consider the oxidative heterogeneity of the diaphragm when designing experiments.
Effect of increased central blood volume with water immersion on plasma catecholamines during exercise
Authors: Connelly T. P. , Sheldahl L. M. , Tristani F. E. , Levandoski S. G. , Kalkhoff R. K. , Hoffman M. D. , Kalbfleisch J. H.
Published: December 2017

To examine the influence of an increase in central blood volume with head-out water immersion (WI) on the sympathoadrenal response to graded dynamic exercise, nine healthy men underwent upright leg cycle exercise on land and with WI. Plasma norepinephrine and epinephrine concentrations were used as indexes of overall sympathoadrenal activity. Oxygen consumption (VO2), heart rate, systolic blood pressure, and plasma concentrations of norepinephrine, epinephrine, and lactate were determined at work loads corresponding to approximately 40, 60, 80, and 100% peak VO2. Peak VO2 did not differ on land and with WI. Plasma norepinephrine concentration was reduced (P less than 0.05) at 80 and 100% peak VO2 with WI and on land, respectively. Plasma epinephrine and lactate concentrations were similar on land and with WI at the three submaximal work stages, but both were reduced (P less than 0.05) at peak exertion with WI. Heart rate was lower (P less than 0.05) at the three highest work intensities with WI. These results suggest that the central shift in blood volume with WI reduces the sympathoadrenal response to high-intensity dynamic exercise.
Pharmacological differentiation of epithelium-derived relaxing factor from nitric oxide
Authors: Munakata M. , Masaki Y. , Sakuma I. , Ukita H. , Otsuka Y. , Homma Y. , Kawakami Y.
Published: December 2017

We examined the possibility that nitric oxide is one of the epithelium-derived relaxing factors in guinea pig airways. First we studied whether nitric oxide could relax isolated tracheal strips, and then we examined the effects of known inhibitors of endothelium-dependent relaxation (EDR) in the vascular system [hemoglobin, methylene blue, and NG-monomethyl-L-arginine (L-NMMA)] on epithelium-dependent relaxation (EpDR) induced by hyperosmotic stimuli in perfused whole tracheal preparations. Mannitol (160 mM in Krebs-Henseleit solution) applied to the epithelial surface was used as an osmotic stimulus to induce EpDR after carbachol-induced contraction (2 microM, serosal side). Nitric oxide produced concentration-dependent and complete relaxation of epithelium-denuded tracheal strips. Preincubation of the whole trachea with hemoglobin significantly inhibited osmotic-induced EpDR (P less than 0.05), but preincubation with methylene blue and L-NMMA did not. Hemoglobin introduced into the epithelial side after EpDR induced by hyperosmotic stimuli reversed relaxation, but methylene blue and L-NMMA did not. These results suggest that, although EpDR and vascular EDR have some pharmacological similarities and nitric oxide can relax airway smooth muscle, nitric oxide is not responsible for osmotic-induced EpDR.
Epithelium, contractile tone, and responses to relaxing agonists in canine bronchi
Authors: Stuart-Smith K. , Vanhoutte P. M.
Published: December 2017

Experiments were conducted in canine bronchi to determine whether the effect of epithelium removal on relaxations was affected by the contractile agent used to induce active force and the degree of contraction. Pairs of fourth-order bronchi with and without epithelium were suspended in organ chambers in physiological salt solution (95% O2-5% CO2, 37 degrees C). The bronchi were contracted to the concentration of acetylcholine or 5-hydroxytryptamine that resulted in a contraction that was 40 or 80% of the response to 10(-4) M of the agonist (ED40 or ED80). Epithelium removal reduced relaxations to isoproterenol and sodium nitroprusside during contraction to the ED80 but not the ED40 of acetylcholine. Responses to forskolin were not affected. Bronchi were significantly more sensitive to relaxing agonists in the presence of 5-hydroxytryptamine; there was no effect on epithelium removal or level of contraction. Thus 1) the influence of epithelium on bronchial relaxation is greatest during high degrees of cholinergic tone and 2) experimental conditions influence the effect of epithelium removal on relaxation.
Acute effects of atrial natriuretic peptide on lung mechanics and hemodynamics in awake sheep
Authors: Banerjee M. R. , Newman J. H.
Published: December 2017

The purpose of this study was to measure airway and hemodynamic effects of atrial natriuretic peptide (ANP) and its efficacy in counteracting the changes in lung mechanics that occur with aerosol histamine and carbachol. Synthetic human alpha-ANP was injected into the pulmonary arteries of awake sheep chronically instrumented for measurement of lung mechanics and hemodynamics (n = 7). Base-line dynamic lung compliance (Cdyn) and pulmonary resistance (RL) did not change after ANP injection. On separate days, the dose required to reduce Cdyn to 65% of base line (ED65Cdyn) to progressive doses of aerosol histamine and the dose required to increase RL by 100% of the base-line values (ED200RL) to progressive doses of aerosol carbachol were determined. ANP was given as bolus injections of 1, 5, and 10 micrograms/kg 3 min after either the ED65Cdyn or ED200RL doses of histamine and carbachol, respectively, and the airway response was monitored for 10 min. ANP significantly reversed the rise in RL after carbachol administration (n = 10). This action of ANP was not altered by cyclooxygenase inhibition with ibuprofen. ANP did not reverse the reduction in Cdyn caused by either histamine (n = 7) or carbachol. The bronchodilating effect of ANP appears to be more prominent in the larger central airways than in the peripheral airways. The hemodynamic effects of ANP were similar to those reported by others. Heart rate and cardiac output had a biphasic response, with an initial rise followed by a drop below the base line. Systemic arterial and left atrial pressures decreased significantly. Pulmonary arterial pressure did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of elastic loading on porcine trachealis muscle mechanics
Authors: Ishida K. , Pare P. D. , Blogg T. , Schellenberg R. R.
Published: December 2017

To shorten in vivo, airway smooth muscle must overcome an elastic load provided by cartilage and lung parenchyma. We examined the effects of linear elastic loads (0.2-80 g/cm) on the active changes in porcine trachealis muscle length and tension in response to electrical field stimulation in vitro. Increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening while causing an increase in tension generation of muscle strips stimulated by electrical field stimulation. Shortening was decreased by 50% at a load of 8 g/cm. At small elastic loads (less than or equal to 1 g/cm) contractile responses approximated isotonic responses (shortening approximately 60% of starting length), whereas at large loads (20 g/cm) responses approximated isometric responses with minimal shortening (20%). We conclude that elastic loading significantly alters the mechanical properties of airway smooth muscle in vitro, effects that are likely relevant to the loads against which the smooth muscle must contract in vivo.