bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered pulsatile insulin secretion associated with endurance training
Authors: Engdahl J. H. , Veldhuis J. D. , Farrell P. A.
Published: December 2017

Endurance exercise training reduces glucose-stimulated insulin secretion while elevating insulin action on target tissues. Under some conditions, hormone action is enhanced by pulsatile delivery to tissues. We tested the hypothesis that different insulin secretory pulse profiles would be observed in endurance-trained vs. sedentary men. Seven endurance-trained [T; maximal O2 consumption 62.5 +/- 4.3 (SD) ml.kg-1.min-1)] and seven untrained (UT; maximal O2 consumption 40.3 +/- 3.3 ml.kg-1.min-1) age- and weight-matched men were studied. All subjects had normal oral glucose-tolerance tests; however, the insulin responses for the T subjects were significantly lower than for the UT subjects (P < 0.05). After 2 days of no exercise and an overnight fast, arterialized venous blood was sampled at 1-min intervals for 120 min and assayed for insulin. Characteristics of the insulin pulse profile were quantified with deconvolution analysis. The mass of insulin secreted per burst was significantly lower for the T than for the UT subjects (50.1 +/- 14 vs. 107.4 +/- 35 pM; P < 0.05), as was the peak height per burst (14.3 +/- 5 vs. 37.5 +/- 3.2 pM), rate of insulin production (429.6 +/- 161 vs. 1,002.4 +/- 393 pmol/90 min), and mean plasma insulin concentration (32.2 +/- 17 vs. 53.7 +/- 35 pM). The interpulse interval between bursts and the half-duration of insulin secretory bursts were not significantly different between the groups. Nonpulsatile basal insulin secretion was similar for the T and UT subjects (3.58 +/- 1.6 vs. 5.55 +/- 2.3 pM/min). These data show that regular endurance exercise in young men is associated with an insulin pulse profile in the resting fasted state characterized by less insulin secreted per burst but a similar number of bursts over a 90-min period. As a working hypothesis, we suggest that training-induced elevations in target-tissue sensitivity to insulin reduce the requirement for pulsatile insulin secretion.
Central and peripheral sympathetic activities in rats during recovery from simulated weightlessness
Authors: Fagette S. , Somody L. , Bouzeghrane F. , Cottet-Emard J. M. , Gharib C. , Gauquelin G.
Published: December 2017

Rats were tail suspended, keeping their forelimbs weight bearing for 14 days, and then allowed to recover for a short (6-h) or a long (24-h) period to assess the behavior of the sympathetic nervous system after weightless simulation. Sympathetic activity was determined by measuring norepinephrine (NE) turnover in the brain stem cell groups involved in central blood pressure control and in organs playing a key role in the cardiovascular regulation (heart and kidneys). The NE turnover was greatly reduced in the rostral (-56%; P < 0.001) and caudal (-73%; P < 0.001) A2 nucleus of suspended rats but was unchanged in the A1, A5, and A6 cell groups compared with attached rats. The NE turnover in the cardiac atria (-34%; P < 0.001) and ventricles (-35%; P < 0.001) and kidneys (-31%; P < 0.001) was decreased after suspension. The central and peripheral sympathetic activities returned to normal within 24 h of release from suspension, but there was hyperactivity after 6 h of recovery. This raises the problem of interpreting the results obtained in animals killed a few hours after return from spaceflight.
Mechanism of action of endothelin-1 in the canine pulmonary circulation
Authors: Barman S. A. , Pauly J. R.
Published: December 2017

Possible mechanisms of action by which endothelin (ET)-1 has an effect on pulmonary vascular resistance and compliance in the canine pulmonary circulation were investigated in the isolated blood-perfused dog lung by use of vascular occlusion techniques. In the present study, ET-1 (10(-8) M) increased pulmonary vascular resistance and pulmonary capillary pressure by postcapillary vasoconstriction. In addition, ET-1 decreased total vascular compliance and middle-compartment compliance. Pretreatment with the ETA receptor antagonist BQ-610 (10(-7) M) or the protein kinase C inhibitors staurosporine (10(-6) M) and calphostin C (10(-6) M) completely blocked the pressor effect of ET-1. Elimination of extracellular calcium mobilization through voltage-dependent calcium channels by verapamil (10(-5) M) or modulation of G protein signal transduction by pertussis toxin challenge (15 micrograms/kg) had no significant effect on the ET-1-induced pulmonary vascular response. The results of the present study indicate that ET-1 causes pulmonary vasoconstriction in the canine pulmonary circulation through ETA receptor mediation and protein kinase C activation, possibly leading to intracellular calcium release. In contrast, the ET-1-induced pulmonary vascular response does not appear to involve extracellular calcium entry through voltage-dependent calcium-channel activation or pertussis toxin-sensitive G protein-signaling mechanisms.
Cocaine and exercise: alteration in carbohydrate metabolism in adrenodemedullated rats
Authors: Ojuka E. O. , Bell J. D. , Fellingham G. W. , Conlee R. K.
Published: December 2017

The combined treatment of cocaine-exercise (CE) causes an exaggerated catecholamine response, a rapid depletion of muscle glycogen, and accumulation of lactic acid. To assess the contribution of the adrenal medulla in the catecholamine response and to determine the role of epinephrine (Epi) on carbohydrate metabolism, cocaine (20 mg/kg ip) or saline was injected into sham-operated (Sham) or adrenodemedullated (AdM) rats, which then ran for 5 min at 56 m/min, 0% grade. In Sham rats, CE caused plasma Epi values (means +/- SE) to rise to 27.7 +/- 6.9 nM compared with 13.3 +/- 1.5 nM in saline-exercise (SE) and 0.8 +/- 0.2 nM in both AdM-CE and AdM-SE animals (P < 0.05). With minimal Epi in AdM, CE still caused glycogen to fall to lower levels (25.4 +/- 3.0 mumol/g vs. 40.5 +/- 2.4 mumol/g) and lactate to rise to higher levels (17 +/- 3 vs. 9 +/- 1 mumol/kg) in white vastus muscle than in SE group (P < 0.05). CE had no significant effect on soleus and red vastus glycogenolysis but it did cause lactate accumulation in red vastus. As a result, plasma lactate levels were also higher after CE compared with SE in AdM (17.9 +/- 2.0 vs. 8.5 +/- 0.5 mM, P < 0.05). We conclude that during CE 1) Epi is not essential to the alteration in carbohydrate metabolism; 2) the latter may be related to the other catecholamines; 3) the adrenal medulla is the only source of Epi; and 4) the adrenal medulla is not the source of the increased levels of norepinephrine or dopamine.
Erythropoietin pharmacokinetics in premature infants: developmental, nonlinearity, and treatment effects
Authors: Widness J. A. , Veng-Pedersen P. , Peters C. , Pereira L. M. , Schmidt R. L. , Lowe L. S.
Published: December 2017

Erythropoietin (EPO) pharmacokinetic studies were performed in premature infants (birth weight < 1.25 kg) and normal adults. Infants were divided into two subgroups on the basis of whether they received chronic treatment with recombinant human EPO (rhEPO; 500 IU.kg-1.wk-1 for 6 wk) beginning at 2-4 wk of life. Ten adults and seven rhEPO-treated infants underwent intravenous pharmacokinetic studies at escalating rhEPO doses: 10, 100, and 500 IU/kg. To test for pharmacokinetic developmental and treatment effects, an equal number of non-EPO- and EPO-treated infants were studied with 100 IU/kg on the last day of treatment. Compared with adults, very low birth weight infants demonstrated significantly greater plasma clearance and distribution volume and significantly shorter fractional elimination times (FET) and mean residence time (MRT) at all three rhEPO doses. Both infants and adults demonstrated nonlinear EPO elimination, i.e., increasing rhEPO dosing was associated with decreasing plasma clearance and increasing FET and MRT. In the absence of rhEPO treatment there were no pharmacokinetic differences between the two subgroups of infants studied 6 wk apart. In contrast, the rhEPO-treated infant subgroup demonstrated a significant increase in clearance and a decrease in FET and MRT following 6 wk of treatment. Enhancement of rhEPO efficacy in the prevention and treatment of anemia in premature infants may require higher doses administered in a progressively increasing fashion.
Effects of hypoxia on carotid body dopamine content and release in developing rabbits
Authors: Bairam A. , Basson H. , Marchal F. , Cottet-Emard J. M. , Pequignot J. M. , Hascoet J. M. , Lahiri S.
Published: December 2017

Hypoxia induces dopamine (DA) release from the carotid body (CB), but the role of DA during hypoxia in the postnatal maturation of carotid chemosensory discharge remains controversial. The aim of this study was to evaluate changes in CB content and release of DA evoked by hypoxia at different stages of development in the rabbit. Five groups of rabbits aged < or = 24 h (n = 9), 5 days (n = 27), 15 days (n = 18), 25 days (n = 16), and = or = 1 yr (n = 11) were studied. CBs were surgically removed and immediately incubated at 37 degrees C for 1 h in a surviving medium equilibrated with 100% O2 or 8% O2 in N2. The content of DA in the CB ([DA]CB) and the DA released in the surviving medium ([DA]r) were measured by high-performance liquid chromatography. [DA]CB was significantly larger in adults than in all pup groups in both 100% O2 [385.5 +/- 74.1 (SE) pmol/CB in adults and 43.6 +/- 6.0 pmol/CB in pups; P < 0.01] and hypoxia (518.1 +/- 99.9 pmol/CB in adults and 24.7 +/- 3.2 pmol/CB in pups; P < 0.01), presumably because of the larger CB mass. [DA]r was significantly larger in hypoxia than in 100% O2 only in 25-day-old rabbits (19.8 +/- 4.2 and 3.6 +/- 1.1 pmol/h, respectively; P < 0.01) and in adults (183.9 +/- 57.7 and 7.9 +/- 1.7 pmol/h, respectively; P < 0.01). The average ratio of [DA]r in hypoxia to [DA]r in 100% O2 ranged from 1.3 to 2.2 in the three younger age groups and was 5.5 and 23.3 in 25-day-old and adult rabbits, respectively. We conclude that the release of DA evoked by hypoxia is weak at birth and develops during the first weeks of life in rabbits.
Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners
Authors: Vukovich M. D. , Arciero P. J. , Kohrt W. M. , Racette S. B. , Hansen P. A. , Holloszy J. O.
Published: December 2017

The purpose of this investigation was to determine whether decreased insulin action after 6 days of inactivity in endurance-trained runners was associated with a decrease in skeletal muscle glucose transporter protein levels (GLUT-4) in the gastrocnemius muscle. Seven endurance runners (5 men and 2 women) volunteered to participate in this investigation. All subjects had normal glucose tolerance as determined by the National Diabetes Data Group guidelines. Each individual completed two hyperinsulinemic euglycemic clamps at insulin infusion rates of 15 (LO) and 40 (HI) mU.m-2.min-1, one approximately 18 h after a training bout and the second after 6 days of inactivity (IA). Muscle biopsies for the measurement of GLUT-4 were obtained from the gastrocnemius before each clamp. Glucose disposal rates during the last 30 min of each insulin infusion were significantly reduced after 6 days of IA, averaging 6.45 +/- 1.04 mg.kg fat-free mass (FFM)-1.min-1 before and 4.55 +/- 0.56 mg.kg FFM-1.min-1 after detraining for the LO insulin infusion rate and 13.77 +/- 0.88 mg.kg FFM-1.min-1 before and 11.81 +/- 0.60 mg.kg FFM-1.min-1 after detraining for the HI insulin infusion rate (both P < 0.05), despite the fact that plasma insulin was higher in the inactive state (LO, 19.2 +/- 0.9 microU/ml before and 23.4 +/- 1.5 microU/ml after detraining; HI, 56.0 +/- 2.0 microU/ml before and 61.6 +/- 1.6 microU/ml after detraining; P < 0.05)). Calculated insulin clearance was greater in the trained than in the inactive state (P < 0.03). Muscle GLUT-4 transporter protein after 6 days of IA was reduced by 17.5 +/- 5.4% (P < 0.02). These results demonstrate that 6 days of IA reduces insulin action in endurance-trained runners and suggest that a reduction in muscle GLUT-4 transporter level plays a role in the decrease in glucose disposal rates.
Muscle cytoskeletal disruption occurs within the first 15 min of cyclic eccentric contraction
Authors: Lieber R. L. , Thornell L. E. , Friden J.
Published: December 2017

The time course of loss of the 55,000-Da intermediate filament protein desmin was measured in rabbit muscles subjected to cyclic eccentric conrtraction. Rabbit extensor digitorum longus (EDL) and tibialis anterior (TA) muscles were examined 5 or 15 min after eccentric exercise and 1 h or 1 day after 30 min of an eccentric exercise protocol (n = 16 rabbits). The earliest change noted was a significant loss of desmin labeling in 2.5 +/- 0.63% of the rabbit EDL muscle fibers (P < 0.005) 5 min after initiation of eccentric exercise. Some loss of TA fiber desmin was also apparent at this time period (0.24 +/- 0.19%), but the magnitude was not significantly different from zero (P = 0.2). Fifteen minutes after initiation of exercise, desmin loss was more pronounced, increasing to 7.4 +/- 1.4 and 4.6 +/- 1.0% in the EDL and TA, respectively (P < 0.005). Finally, 1 day after 30 min of eccentric exercise, the percentage of fibers without desmin staining rose to 23.4 +/- 3.7 and 7.7 +/- 2.4% in the EDL and TA, respectively (P < 0.001). Loss of desmin staining occurred in the absence of contractile or metabolic protein disruption. Increased staining intensity of the intrasarcomeric cytoskeletal protein titin and an inability to exclude plasma fibronectin were also observed in most but not all fibers that had lost desmin staining. Desmin disruption thus represents a very early structural manifestation of muscle injury during eccentric contraction. Cytoskeletal disruption may predispose the contractile apparatus to previously reported structural damage.
Kinetics of pulmonary uptake of serotonin during exercise in dogs
Authors: Dupuis J. , Goresky C. A. , Rouleau J. L. , Bach G. G. , Simard A. , Schwab A. J.
Published: December 2017

The multiple indicator-dilution technique was employed in the exercising dog to evaluate the effect of increasing activity on the pulmonary extraction and kinetics of removal of tracer 3H-labeled serotonin (5-HT) and on the measured central blood volume and tracer-accessible extravascular lung water. 51Cr-labeled red blood cells, 125I-labeled albumin, and 14C-labeled 1,8-octanediol were injected with labeled 5-HT at rest and at two increasing levels of exercise (lower and higher in 9 dogs). Blood flow approximately tripled at the highest level of exercise, and the central blood volume increased linearly with increasing blood flow. The tracer-accessible extravascular lung water increased in the transition from rest to low-level exercise and stabilized at an average proportion of 0.85 of the gravimetric extravascular lung water at the higher values of blood flow. The average labeled 5-HT extraction at rest was 42 +/- 11%, and this slowly decreased with increase in flow. The calculated permeability-surface area product for 5-HT increased approximately directly with increasing blood flow. We conclude that exercise results in an increase in the central blood volume that is accompanied by an increase in the tracer-accessible extravascular lung water (lung tissue recruitment) over low exercise levels, with no change at higher levels of exercise, and that the pulmonary capillary surface area subserving 5-HT uptake increases almost linearly with flow over the range of flows attained.
Physiological regulation of G4 AChe in fast-twitch muscle: effects of exercise and CGRP
Authors: Fernandez H. L. , Hodges-Savola C. A.
Published: December 2017

This work addresses the physiological regulation of the tetrameric (G4) form of acetylcholinesterase (AChe) in end-plate regions of anterior gracilis muscles from adult male Sprague-Dawley rats subjected to short-term low-intensity treadmill exercise. Experiments involved analyses of muscle AChe molecular form activities, endogenous calcitonin gene-related peptide (CGRP) levels, and the effect of exogenous CGRP on AChe forms after exercise. Animals were exercised twice per day for 1 or 2 days. Daily training sessions of 135 min (10 min of walking alternating with 5 min of resting) were separated by a 105-min resting period. Results show that exercise causes a slight decline in endogenous CGRP and a selective increase in G4 AChe that is partially reversed by treatment with exogenous CGRP. These findings indicate that CGRP influences the mechanism(s) by which G4 AChe in intact fast-twitch anterior gracilis muscles adapts to enhanced motor activity. They are also consistent with the hypothesis that, in addition to acetylcholine, neurogenic CGRP participates in the regulation of G4 AChe at the neuromuscular junction.
Adaptation to eccentric exercise: effect on CD64 and CD11b/CD18 expression
Authors: Pizza F. X. , Davis B. H. , Henrickson S. D. , Mitchell J. B. , Pace J. F. , Bigelow N. , DiLauro P. , Naglieri T.
Published: December 2017

The primary purpose of the study was to examine circulating neutrophils and monocytes and their plasma membrane expression of CD64, CD11b, and CD18 after two bouts (B1 and B2) of eccentric exercise. Subjects (n = 10) performed 25 forced-lengthened contractions of the forearm flexors on two occasions separated by 3 wk. Blood samples were obtained before exercise and at 1.5, 6, 12, 24, 48, 72, and 96 h of recovery. CD64, CD11b, and CD18 expression was determined via direct immunofluorescence and used as an indicator of neutrophil and monocyte activation. Creatine kinase activity (B1 = 1,390, B2 = 108 U/l), myoglobin (B1 = 163, B2 = 41, ng/dl), and muscle soreness and tenderness were higher (P < 0.01) after B1 compared with B2. Neutrophils at 6, 12, and 96 h were higher (P < 0.05) for B1 vs. B2. CD11b expression on neutrophils was 2.7-fold higher at 72 h for B1 vs. B2. CD64 expression on neutrophils at 72 and 96 h was 1.4- and 1.9-fold higher, respectively, for B1 vs. B2. At 72 and 96 h, CD18 and CD64 expression on monocytes was 1.3-fold higher for B1 vs. B2. The observed changes were not significantly correlated with changes in creatine kinase activity or myoglobin. In conclusion, the adaptation to eccentric arm exercise was associated with a reduction in circulating neutrophils and a lower state of neutrophil and monocyte activation.
Airflow effects on amplitude and spectral content of normal breath sounds
Authors: Gavriely N. , Cugell D. W.
Published: December 2017

Even though it is well known that breath-sound amplitude (BSA) increases with airflow, the exact quantitative relationships and their distribution within the relevant frequency range have not yet been determined. To evaluate these relationships, the spectral content of tracheal and chest wall breath sounds was measured during breath hold, inspiration, and expiration in six normal men. Average spectra were measured at six flow rates from 0.5 to 3.0 l/s. The areas under the spectral curves of the breath sounds minus the corresponding areas under the breath-hold spectra (BSA) were found to have power relationships with flow (F), best modeled as BSA = k.F alpha, where k and alpha are constants. The overall mean +/- SD value of the power (alpha) was 1.66 +/- 0.35, significantly less than the previously reported second power. Isoflow inspiratory chest wall sound amplitudes were 1.99 +/- 0.70- to 2.43 +/- 0.65-fold larger than the amplitudes of the corresponding expiratory sounds, whereas tracheal sound amplitudes were not dependent on respiratory phase. Isoflow breath sounds from the left posterior base were 32% louder than those from the right lung base (P < 0.01). BSA-F relationships were not frequency dependent during expiration but were significantly stronger in higher than in lower frequencies during inspiration over both posterior bases. These data are compatible with sound generation by turbulent flow in a bifurcating network with 1) flow separation, 2) downstream movement of eddies, and 3) collision of fast-moving cores of the inflowing air with carinas, all occurring during inspiration but not during expiration.
Pulmonary responses to heparin-protamine complexes: the effects of age and species
Authors: Horiguchi T. , Enzan K. , Kawamura K. , Suzuki M.
Published: December 2017

To test the hypothesis that heparin-protamine complexes (H-P complexes) react with pulmonary intravascular macrophages, we studied the difference in the pulmonary reaction to H-P complexes between goats and rabbits and among different-aged goats. The increases in pulmonary arterial pressure (Ppa) and plasma thromboxane levels (Tx) after injection of H-P complexes (1.2 ml/kg) in goats (delta Ppa = 17 +/- 7.0 mmHg, delta Tx = 17.3 +/- 10.1 ng/ml) were significantly greater than in rabbits (delta Ppa = 0.50 +/- 1.0 mmHg, delta Tx = -0.01 +/- 0.17 ng/ml), the increase in Ppa in adult goats (= 150 days old; delta Ppa = 17 +/- 7.0 mmHg) was about sixfold higher than in newborn goats (1-3 days old; delta Ppa = 2.8 +/- 4.0 mmHg), and the increase in Tx in adult goats (delta Tx = 17.3 +/- 10.1 ng/ml) was significantly greater than those in newborn and young (19 days old) goats (delta Tx = 0.69 +/- 0.48 and 3.60 +/- 0.36 ng/ml, respectively). The pulmonary hemodynamic reaction to H-P complexes is consistent with the concept that the H-P complexes react with pulmonary intravascular macrophages.
Response of ventilator-dependent patients to different levels of proportional assist
Authors: Marantz S. , Patrick W. , Webster K. , Roberts D. , Oppenheimer L. , Younes M.
Published: December 2017

Proportional-assist ventilation (PAV) is a form of ventilatory support in which airway pressure increases in proportion to patient effort. Because it effectively reduces the mechanical load to an adjustable extent, PAV permits the study of the pattern of breathing in patients with respiratory disease when unconstrained by abnormal respiratory mechanics. We studied 11 patients with assorted medical problems requiring ventilatory support. The patients were switched to PAV, and the level of support was varied from near-maximal levels to the lowest tolerable level. Each level was maintained for several minutes while ventilation (VE), tidal volume (VT), and respiratory rate (f) were monitored. The breathing pattern observed with the highest assist varied substantially among patients. The ranges (and means) of VE, VT, and f were 5.6-18.7 (12.8) l/min, 203-844 (517) ml, and 18-33 (25) breaths/min, respectively. The correlation between VT and VE at the highest assist was very high (r = 0.91), suggesting that ventilatory demand is the most important determinant of VT variability. There were no systematic changes in breathing pattern as the level of assist was altered; at the highest and lowest levels of support, VE, VT, and f were, respectively, 12.8 +/- 5.4 (SD) vs. 11.6 +/- 4.3 l/min, 517 +/- 217 vs. 459 +/- 175 ml, and 25.0 +/- 4.2 vs. 25.7 +/- 3.9 breaths/min. These results indicate that within each patient, in a given state, there exist unique values for a desired VE, VT, and f that are largely independent of the mechanical load; if assist is increased, patient effort is decreased to maintain the desired ventilatory targets.
Airway and tissue behavior during early response in sensitized rats: role of 5-HT and LTD4
Authors: Nagase T. , Dallaire M. J. , Ludwig M. S.
Published: December 2017

We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate the role of the potential ER mediators 5-hydroxytryptamine (5-HT) and leukotriene D4 (LTD4) in the airway and tissue response. We sensitized the rats with ovalbumin (OA) and performed experiments on anesthetized, open-chested, mechanically ventilated [breathing frequency = 1 Hz, tidal volume = 12 ml/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O] animals. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw). To assess the effects of LTD4 and 5-HT, we administered the antagonists methysergide (5-HT antagonist) and MK-571 (LTD4 antagonist) before challenge. To assess lung morphometry during the ER, the lungs of four animals from each group were frozen with liquid nitrogen (PEEP = 3 cmH2O). Airway constriction was assessed by measuring the ratio of the airway lumen to the ideally relaxed airway (Abm/A*bm). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), an atelectasis index (ATI) derived by calculating the ratio of tissue to air space, and SD of the two (SD-Lm and SD-ATI). In all animals receiving OA but no antagonists, an ER was seen (RL, Rti, and Raw = 180.7 +/- 6.1, 155.4 +/- 8.2, and 223.1 +/- 14.0% of baseline, respectively). Methysergide significantly inhibited the ER (RL, Rti, and Raw = 117.0 +/- 5.9, 101.2 +/- 1.6, 133.7 +/- 10.2%, respectively), whereas MK-571 partially reduced the ER (RL, Rti, and Raw = 144.2 +/- 5.6, 132.9 +/- 5.7, and 155.5 +/- 9.2%, respectively). Abm/A*bm was significantly decreased, and SD-Lm and SD-ATI were significantly increased in animals receiving OA alone and in those receiving MK-571 before OA challenge. These data suggest that alterations in both airways and tissues contribute to the ER and that 5-HT and, to a lesser degree, LTD4 are important mediators of the ER in this rat model of extrinsic asthma.
Effect of interval from fetal corticosteriod treatment to delivery on postnatal lung function of preterm lambs
Authors: Ikegami M. , Polk D. H. , Jobe A. H. , Newnham J. , Sly P. , Kohan R. , Kelly R.
Published: December 2017

The effect of altering the interval from treatment to delivery on postnatal lung function of the preterm lamb is unknown. We treated groups of 8-10 singleton fetal sheep with 0.5 mg/kg betamethasone by fetal injection and evaluated postnatal lung function 40 min after preterm delivery at 123 days gestation 2 days after treatment or at 128 days gestation 2, 4, and 7 days after treatment relative to groups of 4-8 saline-injected control animals. At 123 days, betamethasone significantly improved arterial PCO2, dynamic thoracic compliance, and ventilatory efficiency index and doubled lung gas volume relative to a control group. Fetal treatment with betamethasone 2, 4, or 7 days before delivery at 128 days also improved these same indicators of lung function relative to controls, and the magnitude of the improvements was the same for all indicators and independent of treatment-to-delivery interval. Betamethasone suppressed the normal postnatal increase in plasma cortisol after 2 and 4 days of exposure but not after 7 days of exposure. Betamethasone also increased fetal and postnatal triiodothyronine concentrations after 2 days of exposure but not at 4 or 7 days of exposure. Although the hormone effects were transient, postnatal lung functional responses to betamethasone persisted over the 2- to 7-day interval from treatment to delivery.
Airway obstruction during sleep increases blood pressure without arousal
Authors: O'Donnell C. P. , Ayuse T. , King E. D. , Schwartz A. R. , Smith P. L. , Robotham J. L.
Published: December 2017

Recent studies suggest that arousal is the dominant factor acutely increasing blood pressure in obstructive sleep apnea and that neither stimulation of chemoreceptors nor mechanical factors associated with large negative swings in intrapleural pressure substantially contribute to the rise in blood pressure associated with each obstructive apneic event. A canine model of obstructive sleep apnea was used to examine the relative contributions of these mechanisms in the blood pressure response to induced airway obstruction during non-rapid-eye-movement sleep. In part A of the study, the arousal response was eliminated from an obstructive event by restoring airway patency just before the expected arousal, allowing blood pressure responses to be compared between obstructive events with and without arousal. In part B of the study, the protocol of Part A was repeated after pharmacological blockade of the autonomic nervous system with hexamethonium (20 mg/kg iv), eliminating neurally mediated responses due to arousal, stimulation of chemoreceptors, or other reflexes, while maintaining any mechanical effects on blood pressure related to swings in intrapleural pressure. The results of part A (n = 4 dogs) show that obstructive apneic events of 28.5 +/- 3.1 s duration, with arterial hemoglobin desaturation to 92.9 +/- 0.8% and airway pressure swings of -37.6 +/- 6 mmHg, significantly increased mean arterial pressure (MAP) by 13.8 +/- 1.5 mmHg in the absence of arousal (P < 0.005). In comparison, when arousal was allowed to occur, MAP increased by a further 11.8 +/- 1.2 mmHg (P < 0.01). In part B (n = 3 dogs), there was no change in MAP during the obstructive apneic event, and MAP fell by = 10 mmHg in the postobstruction period whether or not arousal occurred (P < 0.05). We conclude that neural reflexes, but not mechanical factors, substantially contribute to the acute blood pressure response to an obstructive apneic event and that arousal produces a separate, additional acute hypertensive response.
Delayed and diminished pressor response to muscle sympathetic nerve activity in the elderly
Authors: Sugiyama Y. , Matsukawa T. , Shamsuzzaman A. S. , Okada H. , Watanabe T. , Mano T.
Published: December 2017

We studied the effects of aging on alpha-receptor-mediated vasoconstrictive responses to sympathetic nerve activity in 16 healthy aged [75.8 +/- 2.7 (SE) yr] and young men (33.8 +/- 2.0 yr). Muscle sympathetic nerve activity (MSNA), heart rate, and blood pressure were analyzed during slow respiration (0.1 Hz). Peak amplitude and phase were calculated from a cosine function fitted with 0.1 Hz by using the least squares method. The latency of the pressor response to MSNA, defined as lag time from the peak of MSNA to diastolic blood pressure, was significantly longer in the aged than the young group (7.1 +/- 0.3 vs. 5.4 +/- 0.4 s; P < 0.01). The extent of pressor response to MSNA, defined as diastolic blood pressure rise in response to increase in total MSNA, was significantly lower in the aged than the young group (0.038 +/- 0.006 vs. 0.099 +/- 0.024 mmHg/unit, P < 0.001). These results suggest that alpha-receptor-mediated vasoconstrictive responses to MSNA may be attenuated in the elderly.
Respiratory motor nerve activities during experimental seizures in cats
Authors: Terndrup T. E. , Knuth S. L. , Gdovin M. J. , Darnall R. , Bartlett D.
Published: December 2017

We evaluated respiratory motor nerve activities during experimental seizures induced with subcortical penicillin. The activities of the phrenic (PH), nasolabial (NL), and hypoglossal (HG) nerves and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 13 anesthetized, vagotomized, paralyzed, and ventilated cats. During ictal and interictal phases of seizures, nerve activities became irregular and peak integrated nerve activities increased, particularly in the case of the PH nerve. The ictal phase of seizures was associated with increased tonic activity and decreased phasic respiratory discharges, particularly in the cases of the HG, NL, and PCA nerves. During some prolonged ictal discharges, entrainment of nerve activities by cortical spiking was associated with irregular uncoordinated activation, particularly in the TA nerve. These studies help explain respiratory impairment during seizures by providing evidence of impaired coordination between activation of muscles that regulate upper airway patency and activation of the diaphragm.
Experimental modification of rat pituitary growth hormone cell function during and after spaceflight
Authors: Hymer W. C. , Grindeland R. E. , Salada T. , Nye P. , Grossman E. J. , Lane P. K.
Published: December 2017

Space-flown rats show a number of flight-induced changes in the structure and function of pituitary growth hormone (GH) cells after in vitro postflight testing (W. C. Hymen, R. E. Grindeland, I. Krasnov, I, Victorov, K. Motter, P. Mukherjee, K. Shellenberger, and M. Vasques. J. Appl. Physiol. 73, Suppl.: 151S-157S, 1992). To evaluate the possible effects of microgravity on growth hormone (GH) cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- microM hydrocortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density < 1.071 g/cm3 (band 1), cells of density > 1.071 g/cm3 (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band 1 and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.
Regional lung volume trajectories during expiratory flow in dogs
Authors: Wilson T. A. , Hill M. J. , Hubmayr R. D.
Published: December 2017

Parenchymal markers were placed in the left caudal lobes of anesthetized dogs, and the three-dimensional positions of the markers were tracked by biplane videofluoroscopy during expiration from total lung capacity (TLC) to approximately 30% TLC at steady expiratory flows of 0.3-7% TLC/s. Regional volumes of samples of parenchyma with volumes at TLC of 1-5 cm3 were obtained by computing the volumes of tetrahedral defined by taking the markers, four at a time, as apices of the tetrahedra, Regional volume (Vr), as a fraction of volume at TLC, was plotted against average volume (VL), as a fraction of volume at TLC, and Vr was fit by a quadratic function of VL. The initial slopes of the plots, dVr/dVL at VL = 1, varied by +/- 26% from the mean slope of 1. The curvatures were highly correlated with the slopes, and the Vr vs. VL plots formed a nest of “onion skins”. The initial slopes were weakly correlated with the vertical position of the centroid of the tetrahedron, with the slope increasing by approximately 20%/cm, on average, in the dorsal direction in the supine dog. The vertical gradient in Vr accounted for approximately 30% of the total variability; small-scale heterogeneity contributed the remaining 70%. These results confirm earlier quasistatic measurements of nonuniform Vr and provide the first data on curvature of Vr trajectories. The mechanisms that cause the nongravitational component of Vr variability and the curvatures of the trajectories are unknown.
Reexamination of tympanic membrane temperature as a core temperature
Authors: Sato K. T. , Kane N. L. , Soos G. , Gisolfi C. V. , Kondo N. , Sato K.
Published: December 2017

Controversies surrounding tympanic temperature (Tty) itself and techniques for measuring it have dampened the potential usefulness of Tty in determining core temperature (operationally defined here as the body temperature taken at a deep body site). The present study was designed to address the following questions. 1) Can a tympanic membrane probe be made that is safer and more reliable than its predecessors? 2) Why is the effect of facial cooling and heating on Tty so inconsistent in reports from different laboratories? 3) Is Tty still useful as a measure of core temperature? Data from this study, obtained with a modified thermocouple probe, suggest that the widely reported facial skin cooling effect on Tty is most probably due to thermal contamination from the surrounding ear canal wall and/or suboptimal contact of the probe sensor with the tympanic membrane because 1) Tty that fell during facial cooling was increased to the precooling level by the repositioning of the probe sensor; 2) Tty determined by using a probe with a larger sensor area (the sensor soldered to a steel wire ring)tended to fall in response to facial cooling, whereas Tty determined with a thermally insulated probe ring did not; and 3) Tty obtained under careful positioning of the insulated probe was relatively insensitive to facial cooling or heating. Because Tty was practically identical to esophageal temperature (Tes) in the steady state, i.e., 36.83 +/- 0.20 (SD) degrees C for Tty and 36.87 +/- 0.16 degrees C for Tes at room temperature (n = 11), and because facial cooling had little effect on both Tty and Tes (36.86 +/- 0.17 degrees C for Tty and 36.86 +/- 0.26 degrees C for Tes during facial or scalp skin cooling), we support the postulate that Tty is a good measure of core temperature. The temperature transient in response to foot warming was detected 5 min (n = 2) faster with Tty than with Tes. Thus, with further improvements in the design of the probe. Tty can become a standard for determination of core body temperature.
Timing of exogenous surfactant administration in a rabbit model of acute lung injury
Authors: Ito Y. , Goffin J. , Veldhuizen R. , Joseph M. , Bjarneson D. , McCaig L. , Yao L. J. , Marcou J. , Lewis J.
Published: December 2017

The purpose of this study was to evaluate early vs. late administration of exogenous surfactant in an adult rabbit model of acute lung injury. Lung injury was induced by repetitive whole lung saline lavage and subsequent mechanical ventilation. Bovine lipid extract surfactant was instilled either 1 (Early) or 4 h (Late) after the last lavage. Animals were monitored for 7 h after the last lavage. Although arterial PO2 values increased significantly immediately after treatment in both the Early and Late groups, this improvement was not sustained in the Late group. There was also a higher incidence of pneumothoraxes in the Late group vs. both the Early group and a nontreated control group. The ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates was higher in the Late group compared with the Early group. Morphological analysis revealed that early surfactant treatment prevented the progression of lung injury over time. We conclude that administration of exogenous surfactant at an early time point in lung injury resulted in superior responses compared with later treatments.
Specific ventilation distribution in microgravity
Authors: Verbanck S. , Linnarsson D. , Prisk G. K. , Paiva M.
Published: December 2017

We studied the contribution of inter- and intraregional inhomogeneities of specific ventilation (delta V/Vo) from the rebreathing inert gas trace in microgravity and on Earth. The rebreathing tests were carried out by four astronauts before, during, and after the 10-day Spacelab D-2 mission. Starting from functional residual capacity, the rebreathing maneuver consisted of eight reinspirations from a bag filled with 1.8-2.2 liters of test gas mixtures containing approximately 5% argon. The rate of argon equilibration in the rebreathing bag, termed RBeq, was quantified by determining the logarithm of the actual minus the equilibrated argon concentrations normalized to the inspired minus the equilibrated argon concentrations. A compartmental model of the lung (S. Verbanck and M. Paiva. J. Appl. Physiol. 76: 445-454, 1994) was used to validate the method for determining RBeq and to simulate the influence of intra- and interregional delta V/Vo inhomogeneities on the RBeq curve. The comparison between the experimental Earth-based and microgravity RBeq curves and model simulations shows that gravity-independent delta V/Vo inhomogeneity is at least as large as gravity-dependent delta V/Vo inhomogeneity.
On the mechanism of the mediolateral gradient of parasternal activation
Authors: De Troyer A. , Legrand A. , Gayan-Ramirez G. , Cappello M. , Decramer M.
Published: December 2017

Recent studies have shown that in spontaneously breathing dogs the parasternal intercostals are activated according to a mediolateral gradient. To assess the mechanism of this regionalization of activity, we assessed the pattern of activation of these muscles after section of the dorsal roots and examined the topographic distribution of the muscle fiber types from the sternum to the chondrocostal junctions. The pattern of parasternal activity after dorsal rhizotomy was similar in all respects to that previously observed in intact animals. Thus activity in the medial parasternal bundles at the onset of inspiration frequently preceded activity in the middle bundles, and no activity was recorded from the lateral bundles. The amount of medial activity, when expressed as a percentage of the activity recorded during supramaximal tetanic stimulation of the internal intercostal nerve (maximal activity), was also consistently greater than the amount of middle activity (52.6 +/- 4.6 vs. 23.1 +/- 2.6% maximal activity; P < 0.001). Furthermore, the medial, middle, and lateral parasternal bundles had a higher proportion of slow-twitch oxidative fibers than of fast-twitch oxidative-glycolytic fibers; no topographic difference in fiber type distribution was observed. We conclude, therefore, that the mediolateral gradient of parasternal activity is probably due to the unequal distribution of central inputs throughout the pool of alpha-motoneurons.
Negative pressure-induced deformation of the upper airway causes central apnea in awake and sleeping dogs
Authors: Harms C. A. , Zeng Y. J. , Smith C. A. , Vidruk E. H. , Dempsey J. A.
Published: December 2017

We investigated the effects of negative pressure (NP) in the isolated upper airway (UA) in three unanesthetized dogs. The UA was isolated, and the dogs breathed through an endotracheal tube while wearing a fitted fiberglass snout mask. NP (-2 to -32 cmH2O) was applied in a square wave below the larynx or at the snout at end expiration and was held until inspiratory effort during wakefulness, non-rapid-eye-movement (NREM) sleep, and rapid-eye-movement (REM) sleep. During all states of consciousness, NP applied to the UA prolonged expiratory time (TE) 1) below a threshold of -8 to -10 cmH2O, which coincided with closure of the oro- and/or velopharynx; and 2) in a progressive fashion at more negative pressures than threshold, up to a mean apneic length of 324% of the control value (or 13.9 s) at -30 cmH2O. TE prolongation was less during REM sleep at a given NP (P < 0.05). Augmented tonic genioglossal electromyographic activity also occurred with the applied NP during wakefulness and NREM sleep but not with REM sleep. NP (-20 to -32 cmH2O) applied as a brief pulse (300-500 ms) during NREM sleep caused transient airway occlusion, terminated the breath during inspiration, and prolonged TE when applied at end expiration. Central apneas always persisted beyond the termination of the UA closure. TE prolongation in response to NP persisted in the presence of a topical anesthetic nebulized through the UA sufficient to abolish the laryngeal gag reflexes. We conclude that UA closure and deformation will cause significant TE prolongation during all states of consciousness and activation of the genioglossus muscle during wakefulness and NREM sleep but not during REM sleep.
Importance of muscle phosphocreatine during intermittent maximal cycling
Authors: Trump M. E. , Heigenhauser G. J. , Putman C. T. , Spriet L. L.
Published: December 2017

To examine the importance of phosphocreatine (PCr) degradation in maintaining power output during maximal intermittent cycling, seven healthy men completed three bouts of isokinetic cycling (30 s, 100 revolutions/min) with 4 min of rest between bouts. After bout 2, blood flow to one leg was occluded by cuffing the thigh (Cuff) during the rest period to prevent PCr resynthesis while the circulation to the other leg was intact (Cont). The cuff was then removed and bout 3 completed. Muscle biopsies were sampled from the vastus lateralis of both legs just before and immediately after bout 3. Total work produced by the Cuff and Cont legs was similar during bouts 1 (9.3 +/- 0.5 and 9.6 +/- 0.5 kJ, respectively) and 2 (8.1 +/- 0.4 and 8.3 +/- kJ, respectively). Cuffing prevented the resynthesis of PCr because pre-bout 3 contents were 20.7 +/- 8.4 and 63.0 +/- 3.3 mmol/kg dry muscle in the Cuff and Cont legs, respectively. Cuffing also resulted in significantly higher muscle levels of lactate, H+ concentration (287 +/- 26 vs. 217 +/- 15 nM), ADP, AMP, and acetyl-CoA before bout 3 but had no effect on other glycolytic intermediates, ATP, or acetylcarnitine. Total work in bout 3 was significantly reduced by 15% in the Cuff leg (5.8 +/- 0.4 vs. 6.8 +/- 0.6 kJ). PCr degradation during bout 3 was 3.1 and 47.5 mmol/kg dry muscle in the Cuff and Cont legs, respectively, and lactate accumulation was minimal in both legs. Changes in all other metabolites during bout 3 were not different between legs. The results suggest that PCr contributed approximately 15% of the total ATP provision during the third 30-s bout of maximal isokinetic cycling and that most of the ATP was provided during the initial 15 s. Muscle glycogenolysis contributed minimally to ATP provision (approximately 10-15%) during the third 30-s bout, suggesting that aerobic metabolism becomes the dominant source of ATP during this model of repeated sprinting.
Aqueous smokeless tobacco extract impairs endothelium-dependent vasodilation in the oral mucosa
Authors: Suzuki H. , Gao X. P. , Olopade C. O. , Jaffe H. A. , Pakhlevaniants S. , Rubinstein I.
Published: December 2017

The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) modulates vasomotor tone in the oral mucosa in situ and, if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that the extract had no significant effects on diameter of resistance (second-order) arterioles [44 +/- 5 (SD) microns] in the hamster cheek pouch. However, it significantly attenuated vasodilation elicited by two endothelium-dependent agonists, acetylcholine and bradykinin (P < 0.05). These effects were specific because smokeless tobacco extract had no significant effects on vasodilation elicited by nitroglycerin, an endothelium-independent agonist. Indomethacin, a cyclooxygenase inhibitor, and SQ-29548, a thromboxane A2/prostaglandin H2-receptor antagonist, abrogated the attenuating effects of smokeless tobacco extract on acetylcholine- and bradykinin-induced vasodilation. These data indicate that an aqueous extract of smokeless tobacco impairs endothelium-dependent vasodilation in the oral mucosa in situ in a specific fashion and that these effects are mediated, in part, by cyclooxygenase products of arachidonic acid metabolism that stimulate thromboxane A2/prostaglandin H2 receptors.
Antagonism of cholinergic nerve-mediated contractions by the sensory nerve inhibitory system in rat bronchi
Authors: Szarek J. L. , Spurlock B.
Published: December 2017

The purpose of this study was to examine the potential functional significance of the sensory nerve inhibitory system in modulating contraction. Tension development in response to electrical field stimulation (EFS) and exogenous acetylcholine was monitored in segments of intrapulmonary bronchi isolated from male Sprague-Dawley rats. Contractile responses to EFS were enhanced by desensitization of sensory nerves with capsaicin, by antagonizing neurokinin NK1 receptors with RP-67580, and by inhibition of cyclooxygenase with meclofenamate. Except for RP-67580, which had a slight inhibitory effect on acetylcholine-induced contractions, these interventions were without effect on contraction to acetylcholine. Incubation of capsaicin-desensitized airway segments with substance P attenuated contractions evoked by a half-maximal frequency of EFS by approximately 92%, whereas contractions elicited by a half-maximal concentration of acetylcholine were not affected. Contractile responses elicited by a lower concentration of acetylcholine were inhibited by approximately 50% by substance P. The inhibitory effect of substance P was blocked by RP-67580, meclofenamate, and epithelial denudation. We conclude that the sensory nerve inhibitory system modulates cholinergic contractions and thus plays a role in the regulation of airway smooth muscle tone.