bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptidase modulation of noncholinergic vagal bronchoconstriction and airway microvascular leakage
Authors: Lotvall J. O. , Tokuyama K. , Lofdahl C. G. , Ullman A. , Barnes P. J. , Chung K. F.
Published: December 2017

We investigated whether inhibition of neutral endopeptidase 24.11 (NEP) and/or angiotensin-converting enzyme (ACE) modifies vagally induced nonadrenergic noncholinergic (NANC) airflow obstruction and airway microvascular leakage as measured by extravasation of Evans blue dye (intravenous) in anesthetized guinea pigs. We gave phosphoramidon to inhibit NEP and enalapril maleate or captopril to inhibit ACE. Animals pretreated with inhaled phosphoramidon (7.5 or 75 nmol), enalapril maleate (87 or 870 nmol), or captopril (350 nmol) reached higher peak lung resistance (RL) values (14.3 +/- 2.7, 15.7 +/- 3.8, 16.7 +/- 3.8, 11.4 +/- 1.6, and 24.6 +/- 3.5 cmH2O.ml-1.s, respectively) than saline-treated animals (5.9 +/- 1.1; P less than 0.05) after bilateral vagus nerve stimulation (5 Hz, 10 V, 10 ms, 150 s). Intravenous phosphoramidon (1 mg/kg), but not intravenous captopril (6 mg/kg), potentiated peak RL (22.9 +/- 6.9 and 7.1 +/- 1.5 cmH2O.ml-1.s, respectively). Vagal nerve stimulation (1 and 5 Hz) increased the extravasation of Evans blue dye in tracheobronchial tissues compared with sham-stimulated animals, but this was not potentiated by inhaled enzyme inhibitors or intravenous captopril. However, intravenous phosphoramidon significantly augmented the extravasation of Evans blue dye in main bronchi and intrapulmonary airways. We conclude that degradative enzymes regulate both NANC-induced airflow obstruction and airway microvascular leakage.
Skeletal muscle relaxation rate after fasting or hypocaloric feeding
Authors: Nishio M. L. , Jeejeebhoy K. N.
Published: December 2017

The effect of malnutrition on skeletal muscle relaxation is not entirely clear; some studies indicate no change and others a slowing of the relaxation rate. We investigated whether these different results were due to type of malnutrition, muscle fiber type composition, or the index used to express relaxation rate. The effect of a 2-day fast (16% body wt loss) or 1 wk of hypocaloric feeding (22.6% wt loss) on relaxation rates of soleus and extensor digitorum longus (EDL) muscles was studied in situ with the use of anesthetized adult Wistar rats. Relaxation rates were assessed for twitch contractions using half-relaxation times and exponential phase half-times and for tetanic contractions using exponential phase half-times. The rate of relaxation was unaffected by fasting, whereas hypocaloric feeding reduced relaxation rates after twitch and tetanic contractions in both soleus and EDL muscles. We conclude that slowing of skeletal muscle relaxation rate occurs after 1 wk of hypocaloric feeding but not after 2 days of fasting. The slowing is independent of muscle fiber composition, type of contraction, or the index used to express relaxation rate.
Analysis of responses to endothelins 1, 2, and 3 and sarafotoxin 6b in airways of the cat
Authors: Dyson M. C. , Kadowitz P. J.
Published: December 2017

Airway responses to endothelin (ET) 1, ET-2, ET-3, and sarafotoxin 6b (S6b) were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of ET-1 (0.11 nmol/kg) increased transpulmonary pressure (Ptp) and lung resistance (RL) and decreased dynamic compliance (Cdyn) in a dose-related manner. Airway responses to ET-1 were decreased significantly by sodium meclofenamate, a cyclooxygenase inhibitor, and by SKF 96148, a thromboxane receptor blocking agent. In terms of relative bronchoconstrictor activity, the thromboxane mimic, U-46619, was threefold more potent than ET-1 on a molar basis in increasing Ptp. ET-1 and ET-3 had similar bronchoconstrictor activity, and these peptides were less potent than ET-2 and S6b. Bronchoconstrictor responses to ET-2, ET-3, and S6b were also decreased significantly by meclofenamate and by thromboxane receptor blocking agents. The ET-1 precursor ET-1-(1–38) (big ET-1) caused a significant slowly developing increase in Ptp, RL, and aortic pressure (PAO) and a decrease in Cdyn, whereas a monocyclic ET-1 analogue and ET-1-(16–21) hexapeptide fragment had little or no activity in the airways. The present data indicate that ET-1, ET-2, ET-3, and S6b have significant bronchoconstrictor activity in the cat and that responses are dependent in part on the release of arachidonic acid and the formation of thromboxane A2. These data also suggest that big ET-1 is converted into a mature peptide in the cat and that ET-1-(16–21) hexapeptide fragment and a monocyclic ET-1 analogue have little if any bronchoconstrictor activity in the anesthetized cat.
Protection from hyperbaric oxidant stress by administration of buthionine sulfoximine
Authors: Komadina K. H. , Duncan C. A. , Bryan C. L. , Jenkinson S. G.
Published: December 2017

To explore the role of glutathione in protecting rats from hyperbaric hyperoxia, we administered buthionine sulfoximine (BSO) to block gamma-glutamyl cysteine synthase activity and decrease tissue glutathione synthesis. We then exposed these animals and their vehicle-treated matched controls to 100% oxygen at 4 ATA or room air at 1 ATA. After BSO treatment, glutathione concentrations in air-exposed controls decreased 62% in lung, 76% in liver, 28% in brain, and 62% in plasma. Paradoxically, BSO-treated rats were protected from hyperbaric hyperoxia. The BSO-treated animals seized significantly later and had a markedly prolonged time of survival compared with the vehicle-treated controls. We conclude that BSO treatment protects rats from hyperbaric hyperoxia, despite its effects of lowering plasma and tissue glutathione concentrations. This protection may be related to a direct effect of the compound in decreasing free radical-mediated tissue injury, increasing tissue antioxidant defenses, or increasing seizure threshold.
Pleural liquid pressure
Authors: Agostoni E. , D'Angelo E.
Published: December 2017

The knowledge of pleural liquid pressure (Pliq) is essential for understanding the mechanical coupling between lung and chest wall and the liquid exchanges of the pleural space. In the last decade, research in this field contributed new ideas and stimulating controversies but also caused some confusion. These aspects, along with the older contributions, are considered in this review, which is divided into three sections. The topics of the first section are 1) measurements of Pliq with different techniques in various mammals and various regions of the pleural space, 2) comparison of Pliq with the pressure exerted by the lung recoil (Ppl), and 3) vertical gradient of Pliq and downward flow of pleural liquid. In the second section the mechanisms absorbing liquid from the pleural space are analyzed: 1) Starling forces of the visceral pleura, 2) lymphatic drainage through the stomata of the parietal pleura, and 3) active transport of solutes. The third section deals with 1) measurements of pleural liquid thickness with two approaches in the costal region of various mammals and 2) mechanisms preventing a complete removal of pleural liquid and, thus, ensuring the lubrication.
Persistence of the Hering-Breuer reflex beyond the neonatal period
Authors: Rabbette P. S. , Costeloe K. L. , Stocks J.
Published: December 2017

There is conflicting evidence regarding the persistence of the Hering-Breuer reflex (HBR) beyond the 1st wk of life. This study was designed to assess the influence of postnatal age on the HBR. The airway occlusion technique was used to assess changes in respiratory timing during stimulation of the HBR in healthy full-term unsedated infants measured shortly after birth and at 6–8 wk of life. The strength of the HBR was assessed from the relative change in expiratory time (TE) after end-inspiratory occlusion compared with resting TE during spontaneous breathing. Paired studies were performed in 31 infants at approximately 2 days and 6 wk of age. There was a significant increase in TE during each occlusion in every infant irrespective of age at measurement. No maturational changes were observed. The increase in TE after end-inspiratory occlusion was 91.9 +/- 31.6% (SD) (range 38–158%) at approximately 2 days and 89.8 +/- 30.7% (range 44–175%) at approximately 6 wk. We conclude that the activity of the HBR during tidal breathing persists beyond the neonatal period and that there is no statistically significant change in its strength during the first 2 mo life in healthy infants during natural sleep.
High pressure modifies respiratory activity in isolated rat brain stem-spinal cord
Authors: Tarasiuk A. , Grossman Y.
Published: December 2017

Exposure to hyperbaric pressure causes a constellation of motor disturbances and ventilatory difficulties in animals and humans. The present experiments were designed to examine the effects of hyperbaric pressure on the rhythmic activity of the respiratory center in the absence of peripheral sensory afferents by using the isolated brain stem-spinal cord preparation from newborn rats. In addition, we examined the effect of pressure on the response of the respiratory center to sensory input from the trigeminal and vagus cranial nerves. Hyperbaric pressure significantly depressed the mean inspiratory drive (frequency X time integral of single electrical bursts) in C5 but not in C1 ventral roots. Pressure also reduced the amount of inhibition on the respiratory activity normally exerted by trigeminal and vagal nerve stimulation and in some cases reversed it to excitation. It is concluded that in the absence of sensory input, exposure to hyperbaric pressure depresses central respiratory activity. However, in an intact system, it may alter the balance between excitation and inhibition and render the system hyperexcitable to the same sensory input.
Regional distribution of blood flow within the diaphragm
Authors: Brancatisano A. , Amis T. C. , Tully A. , Kelly W. T. , Engel L. A.
Published: December 2017

We investigated the regional distribution of blood flow (Q) within the costal and crural portions of the diaphragm in a total of eight anesthetized supine mongrel dogs. Q was measured with 15-microns microspheres, radiolabeled with three different isotopes, injected into the left ventricle during spontaneous breathing (SB), inspiratory resistive loading (IR), and mechanical ventilation after paralysis (P). At necropsy, the costal and crural portions of each hemidiaphragm were arbitrarily subdivided along a sagittal plane into five to seven and three sections, respectively. During P, there was a dorsoventral Q gradient within the costal part of the diaphragm. During SB there was a fourfold increase in the gradient of Q. Furthermore, during IR, in which mouth pressures of -16 +/- 4 cmH2O were generated, there was a further increase in the gradient of Q. During both SB and IR, Q to the most ventral portion of the costal diaphragm was 26 +/- 6% less than the peak value. In two dogs, studied prone and supine, there was no difference in the Q gradients between the two postures. Over the dorsal 80% of the costal diaphragm there was also a dorsoventral gradient of muscle thickness, such that the most dorsal part was 54 +/- 2% (n = 5) that of the ventral portion. In contrast, there was no consistent gradient of Q or muscle thickness within the crural diaphragm. Our results demonstrate a topographical gravity-independent distribution of Q in the costal, but not the crural, diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS
Interactive effects of body posture and exercise training on maximal oxygen uptake
Authors: Ray C. A. , Cureton K. J.
Published: December 2017

To determine the effect of posture on maximal O2 uptake (VO2 max) and other cardiorespiratory adaptations to exercise training, 16 male subjects were trained using high-intensity interval and prolonged continuous cycling in either the supine or upright posture 40 min/day 4 days/wk for 8 wk and 7 male subjects served as non-training controls. VO2 max measured during upright cycling and supine cycling, respectively, increased significantly (P less than 0.05) by 16.1 +/- 3.4 and 22.9 +/- 3.4% in the supine training group (STG) and by 14.6 +/- 2.0 and 6.0 +/- 2.0% in the upright training group (UTG). The increase in VO2 max measured during supine cycling was significantly greater (P less than 0.05) in the STG than in the UTG. The increase in VO2 max in the UTG was significantly greater (P less than 0.05) when measured during upright exercise than during supine exercise. However, there was no significant difference in posture-specific VO2 max adaptations in the STG. A postural specificity was also evident in other maximal cardiorespiratory variables (ventilation, CO2 production, and respiratory exchange ratio). In the UTG, maximal heart rate decreased significantly (P less than 0.05) only during supine cycling; there was no significant difference in maximal heart rate after training in the STG. We conclude that posture affects maximal cardiorespiratory adaptations to cycle training. Additionally, supine training is more effective than upright training in increasing maximal cardiorespiratory responses measured during supine exercise, and the effects of supine training generalize to the upright posture to a greater extent than the effects of upright training generalize to the supine posture.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary surfactant will secure free airflow through a narrow tube
Authors: Liu M. Y. , Wang L. M. , Li E. , Enhorning G.
Published: December 2017

Well functioning pulmonary surfactant is necessary to ensure alveolar stability. It is proposed that surfactant is also required to keep the finest cylindrical airways open, thereby securing an unrestricted flow of air to and from the alveoli. If the surfactant is inadequate in quality or quality there is a risk that liquid will accumulate in the most marrow section of the airway and form a blocking column. To study that possibility special glass capillaries were used. The glass capillaries were heated and extended to make a short section very narrow. In the lumen of that section a minute volume (1 microliter) of liquid was deposited, which formed a blocking column. When pressure was raised on one side of the column, it forced the liquid to move away from the narrow section. Pressure dropped to zero as air could pass, and if the liquid column consisted of calf lung surfactant extract (CLSE), pressure remained at zero because a new liquid column did not form. If, on the other hand, the liquid column consisted of saline solution it would repeatedly reform as soon as it had been pressed out of the capillary's narrow section. The same occurred if the CLSE suspension forming the liquid column was very dilute or contained inhibiting proteins. These observations did not require that the capillary consisted of the material glass; they were also noted when the narrow tube was outlined by epithelium.
Influences of chemical sympathectomy and simulated weightlessness on male and female rats
Authors: Woodman C. R. , Stump C. S. , Stump J. A. , Sebastian L. A. , Rahman Z. , Tipton C. M.
Published: December 2017

Maximum oxygen consumption (VO2max) has been shown to be reduced after periods of simulated weightlessness. To assess the role of the sympathetic nervous system in these reductions, Sprague-Dawley rats were either chemically sympathectomized (SYMX) or injected with saline (SHAM) and assigned to head-down suspension (HDS), horizontal restraint with the hindlimbs weight bearing (HWB), or cage-control (CC) conditions. VO2max, run time (RT), and mechanical efficiency (ME) were measured before suspension and on days 7 and 14. Male and female SHAM HDS groups exhibited reduced measures of VO2max (12–13%) after 7 and 14 days, and this decrease was attenuated in the SYMX and HWB rats. HDS resulted in a significant reduction in RT (9–15%) in both the male and female rats, and ME was significantly reduced after HDS in male and female SYMX and male SHAM rats (23–33%) but not in the female SHAM rats. Lesser reductions in ME were observed in the HWB rats. HDS and HWB were associated with lower body, fat-free, and fat masses, which were similar in male and female rats as well as for the SHAM and SYMX conditions. In a related HDS experiment with normal rats, plasma norepinephrine and epinephrine were increased by 53 and 42% after 7 days, but only epinephrine returned to baseline after 14 days. It was concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. The mechanism(s) remains unclear at this time.
Mechanism of failure of recovery from hypoxic apnea by gasping in 17- to 23-day-old mice
Authors: Jacobi M. S. , Gershan W. M. , Thach B. T.
Published: December 2017

The mechanism of failure of autoresuscitation from hypoxic apnea in 17- to 23-day-old (weanling) Swiss Webster related/J mice was investigated by recording electrocardiogram (ECG) and ventilation in adult, weanling, and 11-day-old mice. Hypoxic apnea was induced with 97% N2–3% CO2. O2 (21% or 50% O2) or 97% N2–3% CO2 was given at the onset of apnea. The ECG showed no arrhythmias predictive of failure of autoresuscitation. The first indication of failure was a progressive fall in gasp volume (“run down”). This pattern also occurred in animals given continuous 97% N2–3% CO2 and was significantly different from that in mice that survived. Gasping duration in 97% N2 was longer in weanlings than adults but shorter than in 11 day olds. Respiratory and heart rate recovery were more rapid in adults than in weanlings. Although recovery in high O2 was more rapid, the survival rate was not increased. The lack of effect of high O2 on survival and the virtually identical pattern of gasping in mice dying in 97% N2 and air leads us to conclude that in mice that fail to autoresuscitate little or no O2 reaches the medullary respiratory centers. We speculate that this may be due to increased vulnerability of cardiac muscle to anoxia in 17- to 23-day-old mice, resulting in early and severe heart failure.
Coarse-graining spectral analysis: new method for studying heart rate variability
Authors: Yamamoto Y. , Hughson R. L.
Published: December 2017

Heart rate variability (HRV) spectra are typically analyzed for the components related to low- (less than 0.15 Hz) and high- (greater than 0.15 Hz) frequency variations. However, there are very-low-frequency components with periods up to hours in HRV signals, which might smear short-term spectra. We developed a method of spectral analysis suitable for selectively extracting very-low-frequency components, leaving intact the low- and high-frequency components of interest in HRV spectral analysis. Computer simulations showed that those low-frequency components were well characterized by fractional Brownian motions (FBMs). If the scale invariant, or self-similar, property of FBMs is considered a new time series (x′) was constructed by sampling only every other point (course graining) of the original time series (x). Evaluation of the cross-power spectra between these two (Sxx′) showed that the power of the FBM components was preserved, whereas that of the harmonic components vanished. Subtraction of magnitude of Sxx from the autopower spectra of the original sequence emphasized only the harmonic components. Application of this method to HRV spectral analyses indicated that it might enable one to observe more clearly the low- and high-frequency components characteristic of autonomic control of heart rate.
Cigarette smoke in lungs evokes reflex increase in tracheal submucosal gland secretion in dogs
Authors: Schultz H. D. , Davis B. , Coleridge H. M. , Coleridge J. C.
Published: December 2017

Stimulation of pulmonary C-fibers (PCs) by capsaicin and of rapidly adapting receptors (RARs) by reduced lung compliance reflexly increases airway submucosal gland secretion in dogs. Because both PCs and RARs are stimulated by cigarette smoke (nicotine being the primary stimulus), we performed experiments in anesthetized open-chest artificially ventilated dogs (with aortic nerves cut) to determine whether cigarette smoke reflexly stimulates airway secretion. We measured submucosal gland secretion by counting the hillocks in a 1.2-cm2 field of tracheal epithelium coated with tantalum dust. Secretion was stimulated by delivery of 40–320 ml smoke from high-nicotine cigarettes to the lower trachea, secretion rate increasing from 7.4 +/- 1.3 to 48.1 +/- 5.1 hillocks.cm-2.min-1. Results of cutting the pulmonary vagal branches or carotid sinus nerves or both indicated that the secretory response was initiated by stimulation of lower respiratory vagal afferents and augmented several seconds later by stimulation of carotid chemoreceptors. Results of cooling the cervical vagus nerves to 7 and 0 degrees C indicated that most of the vagally mediated increase in secretion was due to stimulation of afferent lung C-fibers.
Inspiratory timing of heart-lung transplant recipients during progressive hypercapnia
Authors: Kagawa F. T. , Duncan S. R. , Theodore J.
Published: December 2017

The relationship between tidal volume (VT) and inspiratory duration (TI) displays biphasic characteristics during progressive hypercapnia in humans: an initial phase in which VT increases while TI remains constant (region I) and a subsequent phase with reciprocal decreases of TI as VT continues to increase (region II). Region II behavior is generally attributed, albeit inferentially, to lung volume-mediated inflation inhibition (Breuer-Hering reflex). To investigate this phenomenon, we compared CO2 responses of 10 heart-lung transplant recipients (HL) with normal pulmonary function tests and 13 normal controls. Despite pulmonary denervation, the HL exhibited region II behavior identical to controls. In four additional HL with pulmonary restriction, there were comparative decreases of the region II slope (P less than 0.05), but the absolute VT where the phase change between regions occurred was indistinguishable from the other groups. We conclude that TI shortening in humans during progressive hypercapnia occurs in the absence of pulmonary reflexes. The consistency of the VT associated with phase changes, despite pulmonary denervation, suggests that the stimulus for this behavior is volume displacement of extra-pulmonary respiratory structures.
Ventilation during early and late rapid-eye-movement sleep in normal humans
Authors: Neilly J. B. , Gaipa E. A. , Maislin G. , Pack A. I.
Published: December 2017

Because successive rapid-eye-movement (REM) sleep periods in the night are longer in duration and have more phasic events, ventilation during late REM sleep might be more affected than in earlier episodes. Despite the increase in eye movement density (EMD) in late REM sleep, average minute ventilation was, however, not reduced compared with that in early REM sleep. Decreases in rib cage motion (mean inspiratory flow of the rib cage) in association with increasing EMD were offset by increments in respiratory frequency. Apart from expiratory time, there were no significant changes in the slopes of the relationships between EMD and specific ventilatory components, from early to late REM sleep periods. However, there was an increase in the number of episodes when ventilation was reduced during late REM sleep. Changes in ventilatory pattern during late REM sleep are due to changes in the underlying nature of REM sleep. The ventilatory response during eye movements is, however, subject specific. Some subjects exhibit large decrements in mean inspiratory flow of the rib cage and increments in respiratory frequency during bursts of eye movement, whereas other individuals demonstrate only small changes in these ventilatory parameters.
Myocardial function and energy substrate metabolism in the insulin-resistant JCR:LA corpulent rat
Authors: Lopaschuk G. D. , Russell J. C.
Published: December 2017

Alterations in myocardial energy substrate utilization contribute to the development of cardiomyopathic changes in insulin-dependent and non-insulin-dependent diabetic rats. Energy substrate utilization and contractile function, however, have not been characterized in insulin-resistant diabetes. In this study, we studied these parameters in the insulin-resistant obese JCR:LA-cp rat homozygous for the corpulent gene (cp/cp). Homozygous (+/+) or heterozygous (+/cp) lean non-insulin-resistant rats were used as controls. Isolated working hearts from cp/cp and lean control rats were perfused with Krebs-Henseleit buffer containing either 11 mM [U-14C]glucose and 0.4 mM palmitate or 11 mM glucose and 0.4 mM [1–14C]palmitate. Unlike control hearts, hearts from cp/cp rats were found to require high doses of insulin and Ca2+ concentrations of less than or equal to 1.75 mM to maintain mechanical function. In the presence of 2,000 microU/ml insulin, contractile function from cp/cp rat hearts was not depressed in the presence of either 1.25 or 1.75 mM Ca2+. Steady-state glucose oxidation rates in hearts perfused with 1.25 mM Ca2+ and 2,000 microU/ml insulin were 811 +/- 86 (SE) and 612 +/- 51 nmol.min-1.g dry wt-1 in cp/cp and control rats, respectively. Palmitate oxidation was 307 +/- 47 and 307 +/- 47 nmol.min-1.g dry wt-1 in cp/cp and lean control hearts, respectively. Under these perfusion conditions, 40% of myocardial ATP production was derived from glucose, whereas 60% was derived from palmitate in both cp/cp and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Thromboxane synthase inhibition and cardiopulmonary function during endotoxemia in sheep
Authors: Fujioka K. , Sugi K. , Isago T. , Flynn J. T. , Traber L. D. , Herndon D. N. , Traber D. L.
Published: December 2017

We studied the cardiopulmonary response to endotoxin (lipopolysaccharide, LPS) in sheep with and without the administration of a thromboxane synthase inhibitor, OKY-046. The animals were instrumented for crystalographic dimension analysis of the left ventricle (LV) and for measurement of LV, aortic, left atrial, and pulmonary arterial pressures and cardiac index, as well as lung lymph flow. They received 1.0 micrograms/kg of Escherichia coli LPS with (n = 8) and without (n = 8) OKY-046 (10 mg/kg bolus, then 10 micrograms.kg-1.min-1). OKY-046 prevented the increase of pulmonary arterial pressure and the decrease of cardiac index that occurred during the early phase of endotoxemia. Between 8 and 12 h after LPS, cardiac index increased from 6.8 +/- 0.7 to 8.9 +/- 0.51.min-1.m-2. Concomitantly, the end-systolic pressure-diameter relationship (ESPDR, sensitive myocardial contractility index) significantly decreased from 14.7 +/- 0.6 to 7.7 +/- 0.7. Other indexes of the LV contractility (+dP/dtmax) were also reduced. OKY-046 prevented the decreases of ESPDR and +dP/dtmax. OKY-046 also attenuated the increased lung lymph flow changes seen with LPS.
Intracranial self-stimulation motivates weight-lifting exercise in rats
Authors: Garner R. P. , Terracio L. , Borg T. K. , Buggy J.
Published: December 2017

The purpose of this study was to determine the feasibility of using a positive reinforcement protocol to motivate weight-lifting exercise in rats. Intracranial self-stimulation was used to induce weight-lifting exercise. Bipolar electrodes were implanted in the ventral tegmental area of rats, and the animals were trained to bar press on a continuous reinforcement schedule for electrical brain stimulation. Animals with response rates of 1,200–1,500 presses/h were then trained with a discriminative light stimulus to alternate between a normally positioned bar and an elevated bar that could be reached only by standing on the hindlimbs. The animals were fitted with a weighted jacket at a starting resistance of 5–10% of their body weight. Weight-training sessions were conducted 5 days/wk for 10 wk. Training consisted of 600 presses/session, alternating every 15 presses between the low and high bars. At the beginning of each subsequent week, the resistance was progressively increased, with some animals eventually training at resistances greater than 50% of their body weight. At the end of the training period, the rats were lifting over 550% of the starting weight. Gastrocnemius size and mean fiber diameter were increased in the weight-lifting animals. This model combines exercise with positive incentive and has the advantages of being relatively easy to implement and not producing any apparent physical or mental trauma in the animal.
Aldosterone and prolactin response to exercise in the heat in circumpubertal boys
Authors: Falk B. , Bar-Or O. , MacDougall J. D.
Published: December 2017

Thermoregulatory responses to exercise in the heat, especially sweating pattern, differ between children and adults. To determine whether such differences may be related to hormonal responses and to assess the possible association between this response and physical maturation, three groups of circumpubertal boys cycled at 50% of maximal O2 uptake (three 20-min bouts with 10 min of rest between bouts) in 42 degrees C at 20% relative humidity. On the basis of Tanner staging, 11 were prepubertal (PP), 12 midpubertal (MP), and 7 late pubertal (LP). Water ingestion was encouraged to minimize dehydration. Venous blood was sampled before and immediately after the session. Changes in heart rate, rectal temperature, and percent decrease in plasma volume did not differ among groups. There was no change in plasma osmolality in any of the groups. Resting testosterone concentrations were higher with increased level of physical maturity (PP = 0.4 +/- 0.1, MP = 8.2 +/- 1.9, LP = 13.8 +/- 1.2 nmol/l; P less than 0.05). In all groups, both aldosterone (ALD) and prolactin (PRL) markedly increased after exercise in the heat (ALD: PP = 161 +/- 40 vs. 1,289 +/- 263, MP = 173 +/- 47 vs. 1,245 +/- 153, LP = 250 +/- 76 vs. 1,681 +/- 400 pmol/l; PRL: PP = 8.1 +/- 1.2 vs. 24.9 +/- 4.2, MP = 8.8 +/- 1.0 vs. 22.0 +/- 8.9, LP = 8.4 +/- 0.8 vs. 39.0 +/- 3.6 micrograms/l; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypovolemic shock promotes neutrophil sequestration in lungs by a xanthine oxidase-related mechanism
Authors: Anderson B. O. , Moore E. E. , Moore F. A. , Leff J. A. , Terada L. S. , Harken A. H. , Repine J. E.
Published: December 2017

Our results suggest that xanthine oxidase (XO) contributes to lung neutrophil sequestration in hypovolemic shock. Catheterized rats subjected to shock by phlebotomy (approximately 30% blood loss) had decreased mean arterial blood pressures (P less than 0.05) and increased (P less than 0.05) lung myeloperoxidase (MPO) activities (indicative of lung neutrophil accumulation) compared with sham-treated normotensive rats. In contrast, rats depleted of lung and plasma XO activity by tungsten diet before phlebotomy had decreased (P less than 0.05) lung MPO activities compared with phlebotomized rats fed regular diets.
Neural control of the forearm cutaneous vasoconstrictor response to dynamic exercise
Authors: Friedman D. B. , Johnson J. M. , Mitchell J. H. , Secher N. H.
Published: December 2017

This study was designed to evaluate the relative importance of intended effort (“central command”) and of the absolute intensity of dynamic exercise to the cutaneous vasoconstrictor response to the onset of exercise in humans. Skin blood flow (laser-Doppler flowmetry) was measured from the forearm in six healthy individuals during 3-min periods of high- and low-intensity exercise with and without partial neuromuscular blockade. Cutaneous vascular conductance (CVC) was calculated from the ratio of skin blood flow to mean arterial pressure and expressed as a percent change from rest. A rating of perceived exertion (RPE) was expressed as a subjective measure of intended effort. Under control conditions, CVC decreased by 22% (median; range 7–42%, P less than 0.05) during high-intensity exercise [218 (186–268) W; RPE 16 (14–19) exertion units]. In contrast, during control low-intensity exercise [106 (88–128) W; RPE 10 (9–14) exertion units], during low-level exercise with curare [77 (54–98) W; RPE 13 (11–16) exertion units], and during maximal exercise with curare [106 (88–124) W; RPE 19 (18–20) exertion units], CVC did not change significantly. These results suggest that factors related to the activity of the exercising muscle and its metabolism rather than intended effort determine the cutaneous vasoconstrictor response to the initiation of intense dynamic exercise in humans.
Quantification of concentration changes in neonatal human cerebral oxidized cytochrome oxidase
Authors: Edwards A. D. , Brown G. C. , Cope M. , Wyatt J. S. , McCormick D. C. , Roth S. C. , Delpy D. T. , Reynolds E. O.
Published: December 2017

The oxygenation of cerebral cytochrome oxidase in vivo was investigated in eight newborn preterm infants. Near-infrared spectroscopy was used to quantify changes in the concentration of oxidized cytochrome oxidase ([CytO2]) observed during alterations in arterial oxygen saturation (SaO2) in the range of 85–99% and of carbon dioxide tension (PaCO2) in the range of 4.3–9.6 kPa. No relation was found between changes in SaO2 and [CytO2]. Alterations in PaCO2 were positively related both to changes in [CytO2] and total cerebral hemoglobin concentration [( Hb]t). The changes in [CytO2] ranged from 0.09 to 0.33 (median 0.21) mumol.l-1.kPa-1. The ratio [CytO2]/[Hb]t ranged from 0.06 to 0.12 (median 0.08). The relation of delta [CytO2] to the change in cerebral blood volume (delta CBV) was calculated: delta [CytO2]/delta CBV ranged from 0.09 to 0.18 (median 0.11) mumol/ml. These results define a fraction of cerebral cytochrome oxidase in the newborn infant that is oxidized after an increase in PaCO2 but demonstrate that a change in SaO2 in the range studied was not sufficient by itself to change [CytO2]. They differ from results of studies in adults; this may reflect significant differences between adult and neonatal brain.
Lung and chest wall mechanics in microgravity
Authors: Edyvean J. , Estenne M. , Paiva M. , Engel L. A.
Published: December 2017

We studied the effect of 15–20 s of weightlessness on lung, chest wall, and abdominal mechanics in five normal subjects inside an aircraft flying repeated parabolic trajectories. We measured flow at the mouth, thoracoabdominal and compartmental volume changes, and gastric pressure (Pga). In two subjects, esophageal pressures were measured as well, allowing for estimates of transdiaphragmatic pressure (Pdi). In all subjects functional residual capacity at 0 Gz decreased by 244 +/- 31 ml as a result of the inward displacement of the abdomen. End-expiratory Pga decreased from 6.8 +/- 0.8 cmH2O at 1 Gz to 2.5 +/- 0.3 cmH2O at Gz (P less than 0.005). Abdominal contribution to tidal volume increased from 0.33 +/- 0.05 to 0.51 +/- 0.04 at 0 Gz (P less than 0.001) but delta Pga showed no consistent change. Hence abdominal compliance increased from 43 +/- 9 to 70 +/- 10 ml/cmH2O (P less than 0.05). There was no consistent effect of Gz on tidal swings of Pdi, on pulmonary resistance and dynamic compliance, or on any of the timing parameters determining the temporal pattern of breathing. The results indicate that at 0 G respiratory mechanics are intermediate between those in the upright and supine postures at 1 G. In addition, analysis of end-expiratory pressures suggests that during weightlessness intra-abdominal pressure is zero, the diaphragm is passively tensed, and a residual small pleural pressure gradient may be present.
Pulmonary hypertension after postlavage lung injury in rabbits: possible role of polymorphonuclear leukocytes
Authors: Burger R. , Bryan A. C.
Published: December 2017

Previous studies showed that repeated lung lavage leads to a severe lung injury with very poor gas exchange, a substantial protein leak into the alveoli with hyaline membrane formation, pulmonary hypertension, and migration of granulocytes (PMN) into the alveolar spaces. Depletion of PMN leads to a better gas exchange and a markedly decreased protein leak with only scanty hyaline membranes. In this study we show that there is sustained pulmonary hypertension after the lung lavage, but in PMN-depleted rabbits there is no postlavage increase in pulmonary arterial pressure. Changing the shunt fraction by manipulating mean airway pressure still leads to a hypoxic vasoconstriction with increase of pulmonary arterial pressure. Thus, after lung lavage, pulmonary reactivity to hypoxia is still preserved. Comparisons between high-frequency ventilation and conventional mechanical ventilation at the same mean airway pressures showed that equal mean airway pressure in these two very different modes of ventilation do not translate into the same mean functional lung volumes.
In vivo neutrophil sequestration within lungs of humans is determined by in vitro "filterability"
Authors: Selby C. , Drost E. , Wraith P. K. , MacNee W.
Published: December 2017

Neutrophils are normally delayed in transit through the lung microcirculation, relative to the passage of erythrocytes. This sequestration contributes to a pulmonary pool of neutrophils that may relate to the relative inability of neutrophils to deform compared with erythrocytes when in transit in the pulmonary capillaries. A micropore membrane was used to model the human pulmonary microcirculation, in which cell deformability was measured as the pressure developed during filtration of the cells through the membrane at a constant flow. We demonstrated a significant correlation between in vitro deformability and in vivo lung sequestration of indium-111-labeled neutrophils in 10 normal subjects (r = 0.69, P less than 0.02). In eight patients with stable chronic obstructive pulmonary disease, this relationship was not significant (r = -0.2, P greater than 0.05). Furthermore, in a subject with microscopic pulmonary telangiectasia known to allow significant passage of 30-microns microspheres, neutrophils passed through the lungs without delay. Moreover, neutrophils from patients studied acutely with an exacerbation of chronic obstructive pulmonary disease were temporarily less deformable (P less than 0.01). These studies confirm that cell deformability is an important determinant of the normal neutrophil sequestration within the lungs. Changes in cell deformability may alter the extent of this sequestration.
Influence of SQ 30741 on thromboxane receptor-mediated responses in the feline pulmonary vascular bed
Authors: McMahon T. J. , Hood J. S. , Nossaman B. D. , Ibrahim I. N. , Feng C. J. , Kadowitz P. J.
Published: December 2017

The effects of SQ 30741, a thromboxane A2 (TxA2) receptor blocking agent, on responses to the TxA2 mimic, U-46619, were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 30741 in doses of 1–2 mg/kg iv markedly reduced vasoconstrictor responses to U-46619 without altering responses to prostaglandin (PG) F2 alpha or PGD2 and serotonin. SQ 30741 had no significant effect on mean vascular pressures in the cat, and the dose-response curve for U-46619 was shifted to the right in a parallel manner with a similar apparent maximal response. In addition to not altering responses to PGF2 alpha, PGD2 alpha, or serotonin, SQ 30741 (2 mg/kg iv) was without significant effect on pulmonary vasoconstrictor responses to the PGD2 metabolite 9 alpha, 11 beta-PGF2, norepinephrine, angiotensin II, BAY K 8644, endothelin 1, or endothelin 2. Although responses to vasoconstrictor agents, which act through a variety of mechanisms, were not altered, responses to the PG and TxA2 precursor, arachidonic acid, were reduced significantly. The duration of the TxA2 receptor blockade was approximately 30 and 75 min at the 1- and 2-mg/kg iv doses of the antagonist, respectively. The present data show that SQ 30741 selectively blocks TxA2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed. These data suggest that responses to arachidonic acid are due in large part to the formation of TxA2 and that discrete TxA2 receptors unrelated to receptors activated by PGD2 or PGF2 alpha are most likely located in resistance vessel elements in the feline pulmonary vascular bed.
N omega-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin
Authors: McMahon T. J. , Hood J. S. , Bellan J. A. , Kadowitz P. J.
Published: December 2017

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor (EDRF) production, on vascular tone and responses were investigated in the pulmonary vascular bed of the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was elevated with U-46619, intralobar injections of acetylcholine, bradykinin, sodium nitroprusside, isoproterenol, prostaglandin E1 (PGE1), lemakalim, and 8-bromo-guanosine 3′,5′-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intravenous administration of L-NAME elevated lobar arterial and systemic arterial pressures without altering left atrial pressure. When U-46619 was infused after L-NAME to raise lobar arterial pressure to levels similar to those attained during the control period, vasodilator responses to acetylcholine and bradykinin were reduced significantly, whereas responses to PGE1, lemakalim, and 8-bromo-cGMP were not altered, and responses to nitroprusside were increased. There was a small effect on the response to the highest dose of isoproterenol, and pressor responses to BAY K 8644 and angiotensin II were not altered. These results are consistent with the hypothesis that EDRF production may involve the formation of nitric oxide or a nitroso compound from L-arginine and that EDRF production may have a role in the regulation of tone and in the mediation of responses to acetylcholine and bradykinin in the pulmonary vascular bed of the cat.
Nasal and oral airway pressure-flow relationships
Authors: Wheatley J. R. , Amis T. C. , Engel L. A.
Published: December 2017

We examined the inspiratory and expiratory pressure-flow relationships of both the oral and nasal airways before and after exercise in normal upright subjects. With the use of a partitioned facemask, nasal resistance was measured using posterior rhinomanometry, and oral resistance was measured by recording transoral pressure during oral breathing. Both the nasal and oral pressure-flow relationships for inspiration and expiration were curvilinear and were well described by a power function of the form delta P = aVb (where P is pressure, V is flow, a and b are constants) (r2 = 0.96 +/- 0.01). The exponent b describes the curvilinearity of the pressure-flow curve and can be used to infer the flow regimen. At rest, the inspiratory nasal and oral curves suggested a similar degree of turbulence (b = 1.77 +/- 0.06 and 1.83 +/- 0.04, respectively). However, inspiratory flow regimens were inferred to be more turbulent than those during expiration both before and after exercise. After exercise, decreases in inspiratory nasal resistance at low flows were associated with a change in flow regimen from fully turbulent to orifice flow over the entire flow range. Thus the application of a power function to nasal and oral pressure-flow data permits representation of the whole relationship and allows insight into the nature of the flow regimens.
Nasal glandular secretory response to cholinergic stimulation in humans and guinea pigs
Authors: Gawin A. Z. , Emery B. E. , Baraniuk J. N. , Kaliner M. A.
Published: December 2017

A guinea pig model of nasal secretory responses was developed to assess the contributions of vascular permeability and glandular secretion responsible for the production of cholinergically stimulated nasal secretions. The nasal secretory responses to provocation with saline, methacholine, and atropine on the ipsilateral (challenged) side and contralateral (reflex) side were analyzed by measurement of total protein (Lowry method), guinea pig albumin (enzyme-linked immunosorbent assay), 125I-labeled bovine serum albumin after intravenous injection, and alkaline phosphatase enzyme activity in nasal fluid. Alkaline phosphatase was found to be localized to submucosal glands by zymography. Topical methacholine challenge increased the secretion of total protein, alkaline phosphatase activity, and albumin on the ipsilateral challenged side, whereas the percentage of total protein represented by albumin was not increased. This response was totally prevented by atropine pretreatment. Serial provocation with methacholine resulted in progressively reduced amounts of both the total protein and alkaline phosphatase in secretions. The observation that repeated challenges produced progressively smaller responses was also examined employing human nasal provocation. Repeating methacholine (25 mg) challenges four times at 10-min intervals in six human volunteers revealed that the initial challenge produced the largest response as reflected in total protein, albumin, lysozyme, lactoferrin, immunoglobulin (Ig) G, IgA, and secretory IgA secretion. When the constituents in secretions were analyzed in relationship to the total protein, the two vascular proteins, IgG and albumin, demonstrated the greatest decrements with repeated methacholine challenges. The glandular proteins, lactoferrin, lysozyme, and secretory IgA, either remained constant or increased in their relative proportion to total protein. Thus, cholinergic stimulation causes glandular secretion from both the guinea pig and human nasal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Permeability-surface area product and reflection coefficient of the parietal pleura in dogs
Authors: Negrini D. , Reed R. K. , Miserocchi G.
Published: December 2017

The parameters describing the permeability of the parietal pleura to liquid and total plasma proteins were measured in five anesthetized adult dogs. Small areas of parietal pleura (approximately 1 cm2) and the underlying endothoracic fascia were exposed through resection of the skin and the intercostal muscles. The portion of the thorax containing the pleural windows was removed from the chest and fixed over a bath of whole autologous plasma, the inner parietal pleural surface facing the bath. Small hemispheric Perspex capsules (surface area 0.28 cm2) connected to a pressure manometer were glued to the pleural windows; a subatmospheric pressure was set into the capsule chamber to create step hydraulic transpleural pressure gradients (delta P) ranging from 5 to 60 cmH2O. Transpleural liquid flows (Jv) and protein concentration of the capsular filtrate (Cfilt) and of the plasma bath were measured at each delta P. The transpleural protein flux (Js) at each delta P was calculated by multiplying Jv by the corresponding Cfilt. The hydraulic conductivity (Lp) of the parietal pleura was obtained from the slope of the Jv vs. delta P linear regression. The average Lp from 14 capsules was 9.06 +/- 4.06 (SD) microliters.h-1.cmH2O-1.cm-2. The mathematical treatment of the Js vs. Jv relationship allowed calculation of the unique Peclet number at the maximal diffusional protein flux and a corresponding osmotic permeability coefficient for plasma protein of 1 x 10(-5) +/- 0.97 x 10(-5) cm/s. The reflection coefficient calculated from the slope of the linear phase of the Js vs. Jv relationship was 0.11 +/- 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)