bluuebunny/crossref_metadata_2025 huggingface dataset:
Alveolar endotoxin increases alveolar liquid clearance in rats
Authors: Garat C. , Rezaiguia S. , Meignan M. , D'Ortho M. P. , Harf A. , Matthay M. A. , Jayr C.
Published: December 2017

Under some pathological conditions, ion transport across alveolar epithelial cells is downregulated, whereas under other pathological conditions, it may be upregulated. Because endotoxin is a biologically relevant pathological stimulus, we investigated the effect of endotoxin on alveolar epithelial liquid clearance in vivo. Escherichia coli endotoxin (220 micrograms/kg) was instilled into the lungs via the trachea of rats. Then, 24 or 40 h after endotoxin instillation, alveolar and lung liquid clearances were studied over 1 h by instillation of a 5% albumin solution with 1.5 microCi of 125I-labeled albumin (6 ml/kg into both lungs). Alveolar liquid clearance was significantly greater at 24 h (36 +/- 5%) and 40 h (38 +/- 7%) after endotoxin exposure than in saline-instilled controls (27 +/- 6%). Although there was an influx of neutrophils into the air space, there was no increase in lung epithelial permeability to protein at 24 or 40 h. Amiloride (2 x 10(-3) M), a sodium channel inhibitor, significantly reduced alveolar liquid clearance in the rats exposed to endotoxin. However, the increase in alveolar liquid clearance was not inhibited when propranolol (2 x 10(-5) M) was added to the 5% albumin solution. Thus exposure to alveolar endotoxin upregulates net alveolar fluid clearance in vivo for up to 40 h, a potentially important mechanism for accelerating alveolar fluid clearance under some pathological conditions. The increase in alveolar liquid clearance 24 and 40 h after instillation of endotoxin into the air spaces is mediated by an increased uptake of sodium through amiloride-sensitive sodium channels.
ATP-sensitive K+ channel blockade impairs O2 extraction during progressive ischemia in pig hindlimb
Authors: Vallet B. , Curtis S. E. , Guery B. , Mangalaboyi J. , Menager P. , Cain S. M. , Chopin C. , Dupuis B. A.
Published: December 2017

Tissues maintain O2 consumption (VO2) when blood flow and O2 delivery (DO2) are decreased by better matching of blood flow to meet local cellular O2 demand, a process that increases extraction of available O2. This study tested the hypothesis that ATP-sensitive K+ channels play a significant role in the response of pig hindlimb to ischemia. We pump perfused the vascularly isolated but innervated right hindlimb of 14 anesthetized pigs with normoxic blood while measuring hindlimb DO2, VO2, perfusion pressure, and cytochrome aa3 redox state. In one-half of the pigs, the pump-perfused hindlimb was also infused with 10 micrograms.min-1.kg-1 of glibenclamide, a potent blocker of ATP-sensitive K+ channels. Control animals were infused with 5% glucose solution alone. Blood flow was then progressively reduced in both groups in 10 steps at 10-min intervals. Glibenclamide had no effect on any preischemic hindlimb or systemic measurements. Hindlimb VO2 and cytochrome aa3 redox state began to decrease at a significantly higher DO2 in glibenclamide-treated compared with control pigs. At this critical DO2, the O2 extraction ratio (VO2/DO2) was 53 +/- 4% in the glibenclamide group and 73 +/- 5% in the control group (P < 0.05). Hindlimb vascular resistance increased significantly with ischemia in the glibenclamide group but did not change in the control group. We conclude that ATP-sensitive K+ channels may be importantly involved in the vascular recruitment response that tried to meet tissue O2 needs as blood flow was progressively reduced in the pig hindlimb.
Effect of vertical loading on energy cost and kinematics of running in trained male subjects
Authors: Bourdin M. , Belli A. , Arsac L. M. , Bosco C. , Lacour J. R.
Published: December 2017

This investigation examined, in a group of 10 trained male runners, the effect of vertical loading during level treadmill running at a velocity of 5 m/s. The net energy cost of running (Cr), the external work of the center of mass of the body (Wext; both expressed in J.kg-1.m-1), and the eccentric-to-concentric ratio (Ecc/Con) of integrated electromyographic activity for the vastus lateralis (VL) and gastrocnemius lateralis muscles were measured. It was observed that Wext and Ecc/Con for the VL could explain a large part of the interindividual variations in Cr. This result reinforces the hypothesis that Ecc/Con could be a good index of effectiveness in the stretch-shortening cycle. When the subjects ran with a vertical load of 9.3% of their body mass, Cr and Wext were significantly reduced (P < 0.01 and P < 0.05, respectively), whereas Ecc/Con for the VL and gastrocnemius lateralis remained unchanged. The variations in Cr and Wext due to vertical loading were significantly correlated (r = 0.75; P < 0.01). It was then concluded that the significant improvement of Cr observed with the added load was mainly due to the fact that Wext was significantly decreased.
A simple and reliable method to calibrate respiratory magnetometers and Respitrace
Authors: Banzett R. B. , Mahan S. T. , Garner D. M. , Brughera A. , Loring S. H.
Published: December 2017

We present a simple and reliable method to calibrate respiratory magnetometers and Respitrace to infer respiratory volume changes. As in earlier methods, we assume two degrees of freedom in the chest wall and that volume displacement depends linearly on surface motion at the rib cage and abdomen. Because the area of the rib cage is larger, a given motion of its surface produces a greater lung volume change; therefore, the rib cage motion signal is given a larger gain before the two signals are added to estimate volume. In contrast to earlier methods, we use a “standard ratio” to weight relative gains of the rib cage and abdominal signals for all subjects rather than determining a gain ratio for each individual subject. Our procedure does not require subjects to perform the sometimes difficult isovolume maneuvers used in the calibration method of Konno and Mead (J. Appl. Physiol. 22: 407–422, 1967), does not require statistical computation used in the multiple-breath linear regression method, and does not produce the occasional substantial errors in gain ratio that may occur with the other methods. When magnetometers are used, the standard ratio is 4:1 (rib cage-to-abdomen); when Respitrace is used, the standard ratio is 2:1. In 11 subjects, calibration with standard ratios was as accurate as the isovolume and linear regression techniques. Accuracy during normal breathing was nearly always within 10% (median 2%), but occasional large errors occurred with both instruments.
Systemic and pulmonary hypertension after abrupt cessation of prostacyclin: role of thromboxane A2
Authors: Cuiper L. L. , Price P. V. , Christman B. W.
Published: December 2017

Chronic administration of prostacyclin (PGI2) improves hemodynamics in patients with primary pulmonary hypertension, but abrupt cessation of infusion can cause severe dyspnea of unknown etiology. We hypothesized that the discontinuation of PGI2 results in platelet activation, thromboxane A2 production, and increased pulmonary vascular tone. To test this, six sheep with indwelling catheters were monitored during infusion of PGI2 and after its cessation. Infusion of PGI2 caused a reduction in mean systemic arterial pressure (MAP) and systemic (SVR) and pulmonary vascular resistances (PVR), a rise in cardiac output (CO), and no change in pulmonary arterial or pulmonary capillary wedge pressure (PCWP). After discontinuation of PGI2, MAP and SVR rebounded to 30 and 67% above baseline, respectively, and PVR rose 26%. CO was depressed 23% within 10 min, and PCWP nearly doubled after stoppage of the drug. Concurrent treatment with a cyclooxygenase inhibitor did not attenuate these responses. 11-Dehydro-thromboxane B2 levels were not elevated during infusion or after cessation of PGI2. We conclude that the abrupt cessation of PGI2 infusion leads to systemic and pulmonary hypertension and transient cardiac dysfunction not mediated by cyclooxygenase metabolites of arachidonic acid.
On-line laser-photometric monitoring of aerosol deposition in ventilated rabbit lungs
Authors: Schmehl T. , Gebhart J. , Schutte H. , Scharmann A. , Seeger W.
Published: December 2017

A photometric technique was developed for on-line measurement of aerosol deposition in isolated, ventilated, and perfused rabbit lungs. A jet nebulizer was used for aerosolization of saline (hygroscopic particles) and di(2-ethylhexyl) sebacate (nonhygroscopic particles). Aerosol concentration (laser photometer, constructed for measurements in rabbit lungs) and flow rate (commercial pneumotachograph) were continuously monitored at the inlet of the tracheal cannula. Computer-assisted data processing allowed the breath-by-breath calculation of inhaled and exhaled aerosol mass, thus providing the deposition fraction. With the use of hygroscopic particles, however, this approach was hampered by the humidity-induced particle growth in the airways, leading to an overestimation of the aerosol concentration in exhaled air. This effect was corrected by an algorithm using a “particle growth factor” derived breath by breath from the photometer signal. To test the reliability of this approach, saline particles carrying technetium-99m label were aerosolized into rabbit lungs with the use of various ventilator settings, and the aerosol deposition was assessed in parallel by photometry and by radioactivity detection over the lung and over a trap in the exhaled-air circuit. Superimposable curves of cumulative aerosol deposition, with changes in kinetics dependent on the ventilator mode, were obtained. For a given ventilator setting, absolute values of the deposition fraction were 0.32 +/- 0.04 (radiotracer quantification) and 0.36 +/- 0.04 (photometry; means +/- SD; n = 4). We conclude that the presented laser-photometric technique allows reliable on-line monitoring of the deposition of both nonhygroscopic and hygroscopic aerosol particles in ventilated lungs.
Mechanisms of postischemic injury in skeletal muscle: intervention strategies
Authors: Rubin B. B. , Romaschin A. , Walker P. M. , Gute D. C. , Korthuis R. J.
Published: December 2017

Reperfusion of ischemic skeletal muscle leads to adverse local and systemic effects. These detrimental effects may be attenuated by interfering with or modulating the pathophysiological processes that are set in motion during ischemia and/or reperfusion. The purpose of this paper is to review the different intervention strategies that have been employed in an attempt to elucidate the mechanisms involved in the pathogenesis of skeletal muscle ischemia-reperfusion injury. The results of these studies indicate that the postischemic injury processes that lead to cell dysfunction and death are multifactorial in nature and include oxidant generation, elaboration of proinflammatory mediators, infiltration of leukocytes, Ca2+ overload, phospholipid peroxidation and depletion, impaired nitric oxide metabolism, and reduced ATP production. Although the etiopathogenesis of skeletal muscle ischemia-reperfusion is complex, careful delineation of the mechanisms that contribute to postischemic microvascular dysfunction and muscle necrosis has progressed to the point where rational intervention strategies may be proposed and implemented as potential treatments for skeletal muscle dysfunction associated with ischemia-reperfusion.
Endogenous nitric oxide contributes to strain-related differences in airway responsiveness in rats
Authors: Jia Y. , Xu L. , Turner D. J. , Martin J. G.
Published: December 2017

The effects of N(omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, on airway responsiveness were studied in the spontaneously hyperresponsive Fischer and the control normoresponsive Lewis rat strains to investigate the role of the endogenous nitric oxide (NO) pathway in strain-related differences in airway responsiveness. Responsiveness to inhaled methacholine was significantly increased in L-NNA-treated Lewis rats but not in Fischer rats. L-NNA increased carbachol-induced tracheal contractions in vitro to a larger extent in Lewis rats compared with Fischer rats. The effect of L-NNA was abolished by removal of the epithelium. Carbachol induced a NO-dependent increase in guanosine 3′,5′-cyclic monophosphate levels in tracheal tissues but to a lesser extent in Fischer (2.1-fold increase) than in Lewis (3.7-fold increase) rats. In conclusion, endogenous NO is involved in the regulation of airway responsiveness to cholinergic agonists in rats. A relatively ineffective NO-guanosine 3′,5′-cyclic monophosphate regulatory mechanism in Fischer rats contributes, in part, to strain-related differences in airway responsiveness between Fischer and Lewis rats.
Relationship between velopharyngeal dimensions and palatal EMG during progressive hypercapnia
Authors: Launois S. H. , Remsburg S. , Yang W. J. , Weiss J. W.
Published: December 2017

To examine the contribution of specific palatal muscles to velopharyngeal dimensions, we recorded electromyographic (EMG) activity in the levator veli palatini, the tensor veli palatini, and the palatoglossus while examining the velopharynx (VP) with videoendoscopy in eight awake normal adults. Simultaneous display of VP images and airflow provided precise timing of events. Video images and EMG signals were recorded during progressive hypercapnia. Every tenth breath was analyzed. For each selected breath, VP area, anteroposterior and lateral diameters, and EMG activity were determined at five points: beginning, middle, and end of inspiration and middle and end of expiration. VP measurements changed significantly during the respiratory cycle. Although maximum area was measured at end inspiration or middle expiration and minimum area at the beginning or end of the breath, respiratory-related changes in VP measurements and EMG activity were characterized by substantial inter- and intrasubject variability. This variability is similar to velopharyngeal behavior during nonrespiratory tasks and suggests that upper airway patency is determined by multiple factors.
Alterations in autonomic adjustments to acute hypoxia in conscious rats with aging
Authors: Kregel K. C.
Published: December 2017

The experimental objective was to determine whether sympathetic nervous system activity and cardiovascular adjustments to hypoxia are altered with advancing age. Norepinephrine (NE) synthesis was blocked with alpha-methyl-DL-p-tyrosine, and NE turnover rates were determined in the left ventricle of the heart, kidney, liver, and adrenal gland in groups of conscious unrestrained mature (12-mo-old) and senescent (24-mo-old) Fischer 344 rats in conditions of normoxia and acute hypocapnic hypoxia (10% O2-90% N2). Calculated NE turnover rates were similar in all four tissues sampled for both age groups in the normoxic condition. Thirty minutes of hypoxia produced elevations in NE turnover rates in the kidney, liver, and adrenal gland, but not in the heart, for both the mature and senescent groups. However, NE turnover rates were attenuated in the kidney (92 vs. 195%) and liver (119 vs. 190%) of senescent compared with mature rats. Hypoxia produced no change in mean arterial pressure from normoxic levels in the mature rats, whereas older rats had a progressive decline in mean arterial pressure (-24 +/- 3 mmHg from baseline) over the course of the hypoxic exposure. In contrast, heart rate responses were similar in the normoxic and hypoxic conditions for both age groups. These findings indicate that sympathetic nerve activity, as estimated from NE turnover rates, increases in a tissue-specific manner with moderate hypoxia, but this increase is markedly attenuated in the kidney and liver with advancing age. In addition, the ability to maintain MAP during a hypoxic challenge is impaired with aging, perhaps due, in part, to a reduced sympathetic vasoconstriction to selected internal organs.
Autoregulation during pressor response elevates wall shear rate in arterioles
Authors: Kurjiaka D. T. , Segal S. S.
Published: December 2017

Autoregulation of blood flow implies reciprocal changes in vessel diameter and red blood cell velocity (VRBC) when perfusion pressure is altered. We tested two hypotheses: 1) blood flow will be autoregulated throughout arteriolar networks during a pressor response, and 2) wall shear rate (WSR; proportional to VRBC/diameter) will increase during autoregulation. Male hamsters (109 +/- 3 g; n = 22) were anesthetized (pentobarbital sodium 60 mg/kg), and the cremaster muscle was prepared for intravital videomicroscopy. Internal diameter and VRBC were monitored in first (1A)- through fourth (4A)-order arterioles; WSR and blood flow were calculated. Data were acquired at rest and at the peak of diameter responses to bilateral carotid artery occlusion (CAO). At rest, 1) mean arterial and 1A transmural pressures were 100 +/- 5 and 59 +/- 4 mmHg, respectively; 2) as branch order increased, arteriolar diameter, VRBC, and blood flow decreased (P < 0.05); and 3) WSR and resting tone increased with branch order (P < 0.05). During pressor responses to CAO, 1) arterial and 1A pressures increased to 145 +/- 7 and 89 +/- 5 mmHg, respectively (P < 0.05); 2) 1A branches dilated while 2A, 3A, and 4A branches constricted (P < 0.05); 3) VRBC and WSR increased in all branches (P<0.05); and 4) blood flow increased in 1A and 2A branches (P < 0.05), yet was unchanged (i.e., was autoregulated) in 3A and 4A branches. Arteriolar constrictions during CAO were not affected by alpha-adrenoceptor blockade with phentolamine (10(-6) M). We conclude that autoregulation of muscle blood flow during a pressor response involves myogenic constriction of arterioles with concomitant elevation of WSR.
Altitude and beta-blockade augment glucose utilization during submaximal exercise
Authors: Roberts A. C. , Reeves J. T. , Butterfield G. E. , Mazzeo R. S. , Sutton J. R. , Wolfel E. E. , Brooks G. A.
Published: December 2017

To test the hypothesis that altitude exposure increases glucose utilization and that this increment is mediated by a beta-adrenergic mechanism, the effects of hypobaric hypoxia and beta-blockade on glucose rates of appearance (Ra), disappearance (Rd), oxidation (Rox), and leg uptake [G = 2(arteriovenous glucose difference)(1 - leg blood flow)] were measured during rest and a given submaximal exercise task. We studied six healthy beta-blocked (beta) men [26.7 +/- 1.2 (SE) yr, 74.0 +/- 6.6 kg] and five matched controls (C; 26 +/- 1.2 yr, 69.3 +/- 2.6 kg) in energy and nitrogen balance during rest and leg cycle-ergometer exercise at sea level, on acute altitude exposure to 4,300 m (barometric pressure = 463 Torr), and after 3 wk of habituation. Subjects received a primed continuous infusion of [6,6-2H]- and [1-13C]glucose, rested for = or = 90 min, and then immediately exercised for 45 min at 89 W, which elicited 49% of sea-level peak O2 consumption (VO2peak; 65% of altitude VO2peak). At sea level, resting Ra was 1.47 +/- 0.19 and 1.66 +/- 0.16 mg x kg-1 x min-1 for C and beta, respectively, and increased to 3.04 +/- 0.25 and 3.56 +/- 0.27 mg x kg-1 x min-1, respectively, during exercise. Thus glucose Ra was significantly increased by beta-blockade during rest and exercise at sea level. At sea level, beta-blockade increased leg G, which accounted for 49 and 69% of glucose disposal during exercise in C and beta, respectively. On acute altitude exposure, glucose Ra rose significantly during rest and exercise relative to sea level, whereas blockade continued to augment this increment. During exercise on acute exposure, G increased more than at sea level and accounted for a greater percentage (80 and 97%, respectively) of Rd in C and beta during exercise. Similarly, Rox values, particularly during exercise, were increased significantly at altitude relative to sea level, and beta-blockade potentiated this effect. During a given submaximal exercise task after acclimatization, glucose Ra, Rox, and G were increased relative to sea level, but these increments were less than those in response to exercise measured on acute exposure. We conclude that altitude exposure increases glucose use during rest and a given submaximal exercise bout and beta-blockade exaggerates the response.
Prolonged exercise alters beta-adrenergic responsiveness in healthy sedentary humans
Authors: Eysmann S. B. , Gervino E. , Vatner D. E. , Katz S. E. , Decker L. , Douglas P. S.
Published: December 2017

To examine whether beta-adrenergic desensitization occurs after prolonged exercise, echocardiograms, heart rate responses to isoproterenol, plasma catecholamines, and circulating lymphocyte beta-adrenergic receptors were examined in 10 sedentary normal subjects at rest and after brief (10 min) and exhaustive (mean duration 95 min) cycle exercise. Resting end-diastolic volume and ejection fraction were significantly reduced after exercise (from 120 +/- 34 to 100 +/- 26 ml and from 60 +/- 0.4 to 54 +/- 0.6%, respectively; both P < 0.05). The amount of isoproterenol needed to increase heart rate 15 and 25 beats/min increased in a dose- (exercise duration) related fashion, and the increase in amount of isoproterenol needed after prolonged exercise was closely related to the decrease in ejection fraction (r2 = 0.67, P = 0.004). Circulating lymphocyte beta-receptor density and affinity, agonist binding, and adenylylcyclase levels were unchanged with prolonged exercise. In conclusion, prolonged exercise in sedentary normal subjects resulted in reduced cardiac chronotropic responsiveness to isoproterenol that was not reflected in peripheral lymphocyte beta-adrenergic-receptor downregulation.
Hormonal and metabolic adjustments during exercise in hypoxia or normoxia in highland natives
Authors: Favier R. , Desplanches D. , Hoppeler H. , Caceres E. , Grunenfelder A. , Koubi H. , Leuenberger M. , Sempore B. , Tuscher L. , Spielvogel H.
Published: December 2017

In sea-level natives, exposure to hypoxia for a few weeks is characterized by an increased dependence on blood glucose and a decreased reliance on lactate for energy metabolism during exercise. These metabolic adjustments have been attributed to behavioral changes in the sympathoadrenergic and pancreatic systems. The aim of this study was to test the hypothesis of a reduced sympathoadrenergic activation and subsequent metabolic changes when high-altitude natives are acutely exposed to normoxia. Young Andean natives performed incremental exercise to exhaustion during hypoxia (arterial PO2 55.1 +/- 1.1 Torr) or during acute normoxia (arterial PO2 78.7 +/- 1.7 Torr). As a whole, oxygen uptake was increased in normoxia compared with hypoxia during graded exercise. This finding is not related to a decrease in anaerobic metabolism but rather is interpreted as a consequence of a shift in substrate utilization during exercise (increased contribution of fat as assessed by a reduction in the respiratory exchange ratio). These metabolic changes are not accompanied by modifications of glucoregulatory hormones (catecholamines, insulin, and glucagon). In particular, the exercise-induced catecholamine secretion was similar in chronic hypoxia and acute normoxia. As a consequence, blood lactate accumulation during incremental exercise was similar in both conditions. It is concluded that high-altitude natives do not display any sign of a greater sympathoadrenergic activation during chronic hypoxia and that the exercise-induced hormonal changes remained unaffected by acute inhalation of a normoxic gas mixture.
A simple method to monitor performance of forced vital capacity
Authors: Volta C. A. , Ploysongsang Y. , Eltayara L. , Sulc J. , Milic-Emili J.
Published: December 2017

The forced vital capacity (FVC) maneuver is the most common lung function test. One of its major prerequisites is that it be performed with sufficient effort to achieve the maximal flows that are due to expiratory flow limitation. To verify this, in nine normal subjects, short (0.25-s) pulses of negative pressure (-5 to -20 cmH2O) were applied at the mouth at different times (0.25-1 s) after the onset of 1) FVC maneuvers and 2) vital capacity expirations with submaximal expiratory efforts (SVC). All subjects were experienced in FVC maneuvers. With FVC, the expiratory flow did not change with application and removal of negative-pressure pulses, apart from brief flow transients, mainly reflecting displacement of air from the compliant oral and neck structures. With SVC, flow increased throughout the application of the negative-pressure pulses. Thus application of pulses of negative pressure provides a simple method for on-line recognition of whether an FVC maneuver is performed with sufficient effort to achieve flow limitation.
Breath isoprene: temporal changes in respiratory output after exposure to ozone
Authors: Foster W. M. , Jiang L. , Stetkiewicz P. T. , Risby T. H.
Published: December 2017

Isoprene is a major hydrocarbon found in human breath. This study was conducted to evaluate whether respiratory isoprene output could serve as a monitor for ozone exposure. Healthy young adult subjects (n = 10) underwent chamber exposure on separate days to filtered air and to a variable concentration of ozone. Exposures had durations of 130 min that included alternate periods of rest and light treadmill exercise; breath was sampled pre- and postexposure. For six subjects, breath was resampled 19 +/- 1 h postexposure. Breath samples were concentrated cryogenically and analyzed by capillary gas chromatography. Isoprene output immediately postexposure was significantly reduced by ozone or filtered air (17 and 19%, respectively). These results suggest that exercise alone reduces isoprene levels in breath without an additive ozone effect. However, in the six subjects restudied 19 +/- 1 h postexposure to ozone, breath isoprene concentrations were now increased above the preexposure output by 99% (P < 0.01) and exceeded the 51% increase in output of isoprene at this time point after filtered-air exposure (P < 0.01). Therefore, breath isoprene is proposed as a noninvasive marker of a physiological response to oxidant-induced injury to epithelial membranes and fluid linings of the lower respiratory tract by ozone.
Effects of fenoterol on inspiratory effort sensation and fatigue during inspiratory threshold loading
Authors: Suzuki J. , Suzuki S. , Okubo T.
Published: December 2017

We studied the effects of a single dose of fenoterol on the relationship between inspiratory effort sensation (IES) and inspiratory muscle fatigue induced by inspiratory threshold loading in healthy subjects. The magnitude of the threshold was 60% of maximal static inspiratory mouth pressure (PI,mmax) at functional residual capacity, and the duty cycle was 0.5. Subjects continued the threshold loaded breathing until the target mouth pressure could no longer be maintained (endurance time). The intensity of the IES was scored with a modified Borg scale. Either fenoterol (5 mg) or a placebo was given orally 2 h before loading in a randomized double-blind crossover protocol. The endurance time with fenoterol (34.4 +/- 8.6 min) was longer than that with the placebo (22.2 +/- 7.1 min; P < 0.05). The ratio of high- to low-frequency power of the diaphragmatic electromyogram (EMGdi) decreased during loading; the decrease was less with fenoterol (P < 0.05). The EMGdi also decreased with loading; the decrease was greater on fenoterol treatment (P < 0.01). The PI,mmax and maximal transdiaphragmatic pressure (Pdi) were similarly decreased after loading on either treatment. The intensity of the IES rose with time during loading in both groups but was lower with fenoterol than with the placebo (P < 0.05). The ratio of Pdi to integrated activity of the EMGdi increased with fenoterol (P < 0.05). Fenoterol treatment increased both superimposed Pdi twitch and Pdi twitch of relaxed diaphragm and decreased the value of (1-superimposed Pdi twitch/Pdi twitch of relaxed diaphragm). Thus we conclude that in normal subjects fenoterol reduces diaphragmatic fatigue and decreases the motor command to the diaphragm, resulting in a decrease in IES during inspiratory threshold loading and a prolongation of endurance.
N-tert-butyl-alpha-phenylnitrone: a free radical trap with unanticipated effects on diaphragm function
Authors: Andersen K. A. , Diaz P. T. , Wright V. P. , Clanton T. L.
Published: December 2017

The spin trap N-tert-butyl-alpha-phenylnitrone (PBN) has a high avidity for free radical species and hence functions as an antioxidant in many biological systems. As such, we hypothesized that PBN would have powerful antioxidant effects on muscle function. We examined the effects of PBN on directly stimulated in vitro (37 degrees C) rat diaphragm. First, a dose-response curve for the effects of PBN on force frequency (n = 8) was established by comparing PBN-treated muscle strips (0.01-10 mM) with time- and stimulus-matched control strips. Second, the effect of 1.0 mM PBN on muscle endurance (n = 8) was established. Our findings were as follows. 1) Compared with baseline, peak twitch and low-frequency muscle tensions increased in a dose-dependent fashion, with peak effects at 1.0 mM PBN. 2) Muscle function at all stimulation frequencies was depressed at doses above 1.0 mM PBN. 3) Complete inhibition at 10 mM PBN was reversed with caffeine administration or washout. 4) During early fatigue, 1.0 mM PBN facilitated force. However, endurance time decreased in the PBN-treated group. We conclude that PBN has direct reversible dose-dependent effects on diaphragm function. However, facilitation of low-frequency forces and the lack of fatigue-attenuating properties suggest that PBN has atypical antioxidant effects on muscle function.
Effect of eicosanoid inhibition on the development of pulmonary edema after acute lung injury
Authors: Schuster D. P. , Stephenson A. H. , Holmberg S. , Sandiford P.
Published: December 2017

In experimental models of acute lung injury, cyclooxygenase inhibition improves oxygenation, presumably by causing a redistribution of blood flow away from edematous lung regions. This effect on perfusion pattern could also reduce alveolar edema formation. On the other hand, pulmonary pressures usually increase after cyclooxygenase inhibition, an effect that could exacerbate edema accumulation. Therefore we tested the following hypothesis: the total accumulation of pulmonary edema in dogs during a 24- to 28-h period of observation after acute lung injury caused by oleic acid will be less in a group of animals treated with meclofenamate (n = 6) or with the thromboxane-receptor blocker ONO-3708 (n = 5) than in a group of animals treated with oleic acid alone (placebo, n = 6). Lung water concentrations (LWC), the regional pattern of pulmonary perfusion, and protein permeability were measured with the nuclear medicine imaging technique of positron emission tomography. After 24-28 h, LWC was significantly less (P < 0.05) in the ONO-3708 group than in the meclofenamate group (a similar trend was seen compared with the placebo group, P = 0.12). After 24-28 h, pulmonary arterial pressures were highest in the meclofenamate group. Regardless of group, the only significant correlation with the change in LWC was with the integral of pulmonary pressures over the 24- to 28-h period. The data suggest that thromboxane inhibition will reduce edema accumulation in acute lung injury but that this effect depends on reducing as much as possible the simultaneous development of pulmonary hypertension from other causes.
Experimental modification of rat pituitary prolactin cell function during and after spaceflight
Authors: Hymer W. C. , Salada T. , Avery L. , Grindeland R. E.
Published: December 2017

This study was done to evaluate the effects of microgravity on prolactin (PRL) cells of the male rat pituitary gland. We used the identical passive closed-vial cell culture system that was described for the culture of growth hormone cells (W. C. Hymen, R. E. Grindeland, T. Salada, P. Nye, E. Grossman, and P. Lane. J. Appl. Physiol. 80:955-970, 1996). After an 8-day spaceflight, all flight media (containing released PRL), as well as extracts (containing intracellular PRL), contained significantly lower amounts of immunoreactive PRL than their corresponding ground control samples. On the other hand, these same samples, when assessed for their biological activities by two different in vitro lymphocyte assays, yielded disparate results that may reflect posttranslational modifications to the hormone molecule. Other data showed that 1) the apparent molecular weights of released PRL molecules were not altered by microgravity, but 2) the region from which the PRL cells came (dorsal or ventral) made a significant difference in the amount and activity of PRL released from the flight cells. Because there is much current interest in the role that PRL may play in the regulation of the immune system and because changes in both cellular and humoral immunity accompany spaceflight, this study could help define future microgravity research in this area.
Temporal variations in the pattern of breathing
Authors: Bruce E. N.
Published: December 2017

Breath-to-breath variations in the pattern of breathing can occur as uncorrelated random variations (“white noise”), correlated random changes, or as one of two types of nonrandom variations: periodic oscillations or nonrandom nonperiodic fluctuations. White noise is probably present in all physiological processes. In many cases, periodic variations are due to oscillations originating in chemoreflex feedback loops. It has long been hypothesized that correlated random variations in breathing pattern are due to central neutral “memory mechanisms, but part of this behavior might be due to chemoreflex mechanisms. Recently it has been concluded that nonlinear interactions between pulmonary and airway afferent activities and integrative central respiratory mechanisms can produce nonrandom nonperiodic (and also periodic) variability of the respiratory pattern. These latter studies have provided new insights about the behavioral relevance of the integrative character of central respiratory mechanisms and the time-varying nature of pulmonary afferent activities and have emphasized the importance of identifying the physiological bases for these phenomena. These and other findings are interpreted assuming that respiratory rhythm generation/pattern formation occurs via a nonlinear oscillator, and novel inferences concerning temporal variations of the breathing pattern are proposed.
Hypogravity increases cyclopiazonic acid sensitivity of rat soleus muscle
Authors: Huchet-Cadiou C. , Bonnet V. , Meme W. , Leoty C.
Published: December 2017

The functional capacity of skeletal muscle sarcoplasmic reticulum was explored in slow rat soleus muscle after 21 days of hindlimb suspension. The sarcoplasmic reticulum function was assessed in intact and saponin-skinned fibers by using cyclopiazonic acid, a specific Ca(2+)-adenosinetriphosphatase inhibitor. After hindlimb unweighting, the sensitivity to cyclopiazonic acid of intact and skinned soleus fibers becomes similar to that found in fast-twitch muscles. This change could be related to the expression of fast Ca2(+)-adenosinetriphosphatase-pump protein in unloaded soleus muscles and agrees with a transformation of soleus muscle from slow- to fast-twitch type. These results also indicate that specific pharmacological tools, like cyclopiazonic acid, could be used to analyze subcellular functional changes due to hindlimb unweighting.
Anomalous behavior of helium and sulfur hexafluoride during single-breath tests in sustained microgravity
Authors: Prisk G. K. , Lauzon A. M. , Verbanck S. , Elliot A. R. , Guy H. J. , Paiva M. , West J. B.
Published: December 2017

We performed single-breath wash-in tests for He and SF6 in four subjects exposed to 14 days of microgravity (microG) during the Spacelab flight Spacelab Life Sciences-2. Subjects inspired a vital capacity breath of 5% He-1.25% SF6-balance O2 and then exhaled to residual volume at 0.5l/s. The tests were also performed with a 10-s breath hold at the end of inspiration. Measurements were also made with the subjects standing and supine in 1 G. Phase III slope was measured after the dead-space washout and before the onset of airway closure. In all subjects in 1 G, whether standing or supine, phase III slope for SF6 was significantly steeper than that for He. However, in microG, the slopes became the same. Furthermore, after breath holding in microG, the SF6 slopes were significantly flatter than those for He. On return to 1 G, the changes were reversed, and there was no difference between preflight and postflight values. Because most of the phase III slope reflects events occurring in the acinar regions of the lung, the results suggest that microG causes conformational changes in the acini or changes in cardiogenic mixing in the lung periphery, but in either case the mechanism is unclear.
Changes in stroke volume and maximal aerobic capacity with increased blood volume in men women
Authors: Mier C. M. , Domenick M. A. , Turner N. S. , Wilmore J. H.
Published: December 2017

This study determined whether the effects of acute plasma volume expansion (PVX) or 10 days of training on stroke volume during submaximal cycling and on treadmill maximal oxygen uptake (VO2max) were similar between men and women. Subjects performed a submaximal cycle test and a treadmill test to exhaustion under three conditions: control, PVX, and after training. Cycle peak VO2 (VO2peak) and blood volume were measured before and after training. Training consisted of daily 1-h bouts [30 min at 80% peak heart rate (HRpeak) and ten 2-min intervals at 95% HRpeak alternating with 1-min low-intensity pedaling] on a cycle ergometer for 10 consecutive days. Training increased cycle VO2peak in men [P < 0.05; 3.14 +/- 0.13 vs. 3.42 +/- 0.13 (SE) l/min] and women (2.11 +/- 0.10 vs. 2.37 +/- 0.12 l/min) and increased blood volume in men (67.6 +/- 3.0 vs. 72.3 +/- 3.1 ml/kg) and women (62.7 +/- 2.2 vs. 65.6 +/- 2.4 ml/kg). As a result of the greater blood volume with PVX and with training, stroke volume (ml) during submaximal cycling increased in men (control 110 +/- 4; PVX 123 +/- 4; trained 121 +/- 4) and women (control 87 +/- 5; PVX 95 +/- 6, trained 96 +/- 7). Treadmill VO2max (ml.kg-1.min-1) did not change with PVX despite a 6-7% reduction in hemoglobin concentration, whereas training resulted in an increase in VO2max in men (control 47.9 +/- 2.8; PVX 46.7 +/- 2.8; trained 49.9 +/- 2.6) and women (control 38.0 +/- 1.2; PVX 36.9 +/- 1.2; trained 39.2 +/- 1.2). The effects of PVX or training on stroke volume or VO2max did not differ between men and women. An additional finding was an increase in diastolic and mean blood pressures at 65% of cycle VO2peak with PVX and with training in women. Thus men and women hold similar cardiac reserve capacities for increasing stroke volume and, as a result, VO2max is maintained despite a reduction in hemoglobin concentration. However, gender differences in blood pressure regulation with increased blood volume might exist.
Potassium currents in cultured human pulmonary arterial smooth muscle cells
Authors: Peng W. , Karwande S. V. , Hoidal J. R. , Farrukh I. S.
Published: December 2017

In this study, using whole cell and single-channel configurations of the patch-clamp technique, we characterized K+ currents (IK) in cultured human pulmonary arterial smooth muscle cells. The net whole cell outward membrane current (IKo) was activated at potentials positive to -60 mV. One component of IKo, IK(dr), was inhibited by 4-aminopyridine (4-AP) and high concentrations of tetraethylammonium (TEA) but was Ca2+ and charybdotoxin (CTX) insensitive. The other component of IKo, IK(Ca), was voltage and Ca2+ dependent and was inhibited by CTX and low concentrations of TEA. Activation of IKo in single-channel recordings was voltage dependent and demonstrated a high-conductance channel (245 +/- 2 pS) that was Ca2+ and CTX sensitive [IK(Ca)] and a low-conductance channel (109 +/- 2 pS) that was inhibited by 4-AP [IK(dr)] but was insensitive to low concentrations of TEA or to an increase in intracellular [Ca2+]. In isolated pulmonary arterial rings, TEA and 4-AP caused an additive increase in arterial tension. To our knowledge these data provide the first characterization of the IK in human pulmonary arterial smooth muscle cells and indicate that IK(Ca) and IK(dr) play an important role in maintaining pulmonary vascular tone. The data confirm previous observations in pulmonary smooth muscle cells of animal models.
Dietary fat modifies exercise-dependent glucose transport in skeletal muscle
Authors: Liu S. , Baracos V. E. , Quinney H. A. , Clandinin M. T.
Published: December 2017

Exercise stimulates muscle glucose uptake both directly and by increasing the sensitivity of this process to insulin. This study was designed to investigate whether the level of dietary fat would interact with the action of acute exercise in the presence or absence of insulin. Weanling female Sprague-Dawley rats were fed two levels of dietary fat (5 vs. 20%; wt/wt) for 6 wk. Rats then remained sedentary or were exercised by a single bout of swimming for a total of 2 h with 5-min rest intervals each 0.5 h. Basal (insulin-independent) and insulin-stimulated glucose uptake rates were determined in isolated epitrochlearis muscles by using 3-O-[methyl-3H]methyl-D-glucose. Muscles of sedentary rats fed a high-fat diet showed decreased glucose uptake overall because of a marked decrease in insulin-stimulated uptake. Muscles of rats fed a high-fat diet also showed considerable impairment of insulin-dependent glucose uptake measured both immediately and 3.5 h after exercise. Glucose uptake was suppressed by 64% at half-maximal concentrations of insulin (0.8 nM) and by 34% at maximally stimulating (20 nM) insulin levels. This lowered sensitivity and response to insulin were not altered by acute exercise. Glucose uptake in response to acute exercise (insulin independent) was quantitatively similar in rats fed high- and low-fat diets; rats on high-fat diet, however, showed higher insulin-independent glucose uptake at 3.5 h after exercise.
Heart, liver, and skeletal muscle myeloperoxidase activity during exercise
Authors: Belcastro A. N. , Arthur G. D. , Albisser T. A. , Raj D. A.
Published: December 2017

The purpose of this study was to determine whether contractile activity associated with running exercise was a prerequisite for neutrophil infiltration into rat tissues. H2O2-dependent myeloperoxidase (MPO) activity for rat (n = 8) liver, heart, and gastrocnemius muscles was assayed after 58 +/- 11 min of running to voluntary exhaustion (25 m/min; 0% grade). MPO activity values measured with 0.6 mM H2O2 were 0.988 +/- 0.331 (SD) U/g (skeletal muscle), 1.563 +/- 0.303 U/g (heart), and 1.652 +/- 0.510 U/g (liver) for control samples, compared with 1.690 +/- 0.321, 3.128 +/- 1.221, and 2.752 +/- 0.437 U/g, respectively, for the exercise group (P < or = 0.05). Kinetic analysis revealed that maximum velocity for all tissues increased as a result of the exercise (P < 0.05). The Michaelis constant (Km) values at rest for all tissues were similar (range 0.53-0.57 mM H2O2; P = or = 0.05). Exercise did not alter the Km values for cardiac and liver samples; however, for skeletal muscle, the Km was 28% lower than control (P < or = 0.05). The results of this study show that, with prolonged running, MPO activity is elevated in most rat tissues and not exclusively in skeletal muscle. Moreover, the metabolic status of the tissues may be an important factor for neutrophil infiltration with exercise and not exclusively the type of muscle contraction, as previously hypothesized.
Muscle activation in unilateral and bilateral efforts assessed by motor nerve and cortical stimulation
Authors: Herbert R. D. , Gandevia S. C.
Published: December 2017

Voluntary muscle activation was measured with twitch interpolation in 11 subjects during attempted maximal voluntary contractions of the right thumb adductor muscles either in isolation (“thumb alone”) or as the subjects simultaneously performed maximal voluntary contractions of the left thumb adductors or left elbow flexors (“both thumbs” or “thumb and elbow”, respectively). During thumb alone contractions, median voluntary activation of the right thumb adductors was 90.3%, and subjects fully activated the thumb adductors on 22% of all contractions. Transcranial magnetic stimulation of the cortex during maximal voluntary efforts produced small twitchlike force increases, suggesting that at least part of the voluntary activation failure was attributable to suboptimal corticospinal drive. Maximal voluntary force produced by the right thumb adductors in the three conditions differed by < 2% (P = 0.21), and the ability to activate the thumb adductors in the both thumbs condition was only marginally less than during thumb alone contractions (median 88.6%; P = 0.004).Thus subjects are usually unable to fully activate their thumb adductors with maximal voluntary efforts, and simultaneous maximal contractions of contralateral muscle groups have little effect on this ability.
Central hypervolemia in the conscious rat: a model of cardiovascular deconditioning
Authors: Martel E. , Champeroux P. , Lacolley P. , Richard S. , Safar M. , Cuche J. L.
Published: December 2017

The aim of the present study as to investigate whether increased central hypervolemia induced by tail suspension (TS) in the rat is an appropriate model of cardiovascular deconditioning (CVD). First, the physiological relationship between central venous pressure (CVP) and extracellular fluid volume (ECFV) was studied. TS (20 degrees) increased CVP (5.8 +/- 0.7 vs. 2.8 +/- 0.8 mmHg; P < 0.01). After 24 h of TS, CVP had returned to control range while ECFV was reduced by 19%. CVP kinetics during 24 h of TS was not affected by either reduction (-20%) or augmentation (/35%) of the ECFV. The normalization of CVP is likely to be a consequence of ECFV reduction, which itself is reduced by increased urinary excretion of water and sodium. Second, recovery from TS was studied. Resumption of the horizontal position was shown to be associated with a significant increase of heart rate (HR) and a slight reduction of blood pressure (BP); there was an apparent delay between increased HR and reduced BP. This imbalance between HR and BP is compatible with CVD. A model of simulated orthostatism (SO) was developed to further investigate the responses of HR and BP. Interestingly, SO (90 degrees rotation) in the normal rat was associated with significant tachycardia and a slight increase of BP. This pattern remained stable for at least 3 h. In rats that were tail suspended for 48 h, episodes of hypotension and bradycardia (5 +/- 1 in 3 h) suggested a defect in adaptation to increased hydrostatic pressure. In conclusion, TS appears to be an appropriate model of CVD. Reduction process. Return to horizontal position in TS rats induced a tachycardia with minimal effects on BP; this pattern is close to that observed in humans assuming upright posture. SO in previously TS rats disclosed episodes of hypotension and bradycardia that deserve further investigation.