bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of exercise and food restriction on selected markers of the acute phase response in hamsters
Authors: Conn C. A. , Kozak W. E. , Tooten P. C. , Niewold T. A. , Borer K. T. , Kluger M. J.
Published: December 2017

Acute aerobic exercise has been shown to elicit physiological changes characteristic of the acute phase response (APR), a nonspecific host defense response. Regular evocation of these changes may prime the immune system to improve resistance to disease. Because food deprivation is associated with an impaired APR, food restriction may prevent these beneficial changes. We tested the hypotheses that voluntary exercise elicits an APR and that food restriction modifies this response in four groups of hamsters: ad libitum-fed sedentary, ad libitum-fed exercised, food-restricted sedentary, and food-restricted exercised. Five variables altered during an APR were examined: core temperature, serum iron, serum interleukin-6, serum amyloid A, and serum glucocorticoids measured by biotelemetry, colorimetric analysis, B-9 cell growth assay, indirect enzyme-linked immunosorbent assay, and radioimmunoassay, respectively. Blood was drawn during the hamsters' inactive period after 19–20 days of access to running wheels. Resting core temperature was elevated by exercise and depressed by food restriction (P < 0.01). Iron was depressed by food restriction (P < 0.01). Cortisol, but not corticosterone, was elevated by food restriction (P < 0.001). There were no significant differences among groups in interleukin-6 (P > 0.49) or serum amyloid A (P > 0.29). We conclude that there is little evidence that voluntary exercise or exercise combined with food restriction causes an APR in hamsters.
NG-nitro-L-arginine and phenylephrine have similar effects on the vascular waterfall in the canine hindlimb
Authors: Shrier I. , Magder S.
Published: December 2017

Hindlimb pressure-flow relationships are well characterized by modeling a vascular waterfall at the arteriolar level. Under these conditions, Q = (Pper - Pcrit)/Rart, where Q is blood flow, Pper is perfusion pressure, Pcrit is waterfall pressure, and Rart is the resistance upstream from the waterfall. To determine the effects of endothelium-derived relaxing factor (EDRF) on Pcrit, Rart, and venous resistance (Rv), we varied Pper in the canine hindlimb between 100 and 200 mmHg before and after NG-nitro-L-arginine infusion (L-NNA, an inhibitor of EDRF synthesis). Before L-NNA, Pcrit increased with increasing Pper. After L-NNA, Pcrit was higher at each Pper, and the increase in Pcrit with increases in Pper was greater than under control conditions. In contrast to Pcrit, Rart decreased with increasing Pper before L-NNA. After L-NNA, Rart was higher at each Pper and no longer decreased with increasing Pper. Rv was not affected by Pper under control conditions but decreased with increasing Pper after L-NNA. The pressure in the small venules at each Pper decreased after L-NNA. In a second group of animals, we infused phenylephrine to control for increased tone produced by L-NNA. Results were similar to those seen with L-NNA. In conclusion, blocking EDRF synthesis increases both Pcrit and Rart, but the same response was also obtained with phenylephrine.
Effect of fluoride on cardiopulmonary function and release of eicosanoids in pigs
Authors: Dodam J. R. , Olson N. C.
Published: December 2017

Fluoroaluminates are believed to stimulate guanine nucleotide-binding (G) proteins, leading to activation of effector enzymes and release of vasoactive mediators. As a model for G protein-induced cardiopulmonary dysfunction, we infused NaF (0.9 M in 0.9% NaCl at 15 microliters.kg-1.min-1 for 3 h i.v.) in the presence (n = 8) and absence (n = 4) of AlCl3 (0.6 microgram.kg-1.min-1) into pigs anesthetized with pentobarbital sodium. NaF, with or without AlCl3, induced progressive deterioration of cardiopulmonary function after 1 h of infusion. At 3 h, mean pulmonary arterial pressure, pulmonary vascular resistance (PVR), tracheal pressure, and plasma concentrations of thromboxane B2 (TxB2), 6-ketoprostaglandin F1 alpha, and prostaglandin F2 alpha were significantly (P < 0.05) increased to approximately 200, 520, 175, 759, 402, and 336%, respectively, of baseline values (0 h). At 3 h, cardiac index and arterial PO2 decreased 38% and 28 Torr, respectively, from baseline values. Although indomethacin blocked the NaF-induced increase in plasma TxB2 concentration, the cyclooxygenase inhibitor did not modify any cardiopulmonary parameter measured or calculated, except for a transient reduction in PVR at 2.5 h. In porcine whole blood treated with AlF4- (30 mM NaF + 10 microM AlCl3) in vitro for 0.5 h, TxB2 concentration increased to 649% of the control value. In porcine alveolar macrophages labeled with [3H]arachidonic acid, AlF4- (30 mM NaF + 10 microM AlCl3) induced release of radioactivity to 165, 539, and 573% of control values after 0.5, 1, and 2 h of incubation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Ventilatory inhomogeneity determined from multiple-breath washouts during sustained microgravity on Spacelab SLS-1
Authors: Prisk G. K. , Guy H. J. , Elliott A. R. , Paiva M. , West J. B.
Published: December 2017

We used multiple-breath N2 washouts (MBNW) to study the inhomogeneity of ventilation in four normal humans (mean age 42.5 yr) before, during, and after 9 days of exposure to microgravity on Spacelab Life Sciences-1. Subjects performed 20-breath MBNW at tidal volumes of approximately 700 ml and 12-breath MBNW at tidal volumes of approximately 1,250 ml. Six indexes of ventilatory inhomogeneity were derived from data from 1) distribution of specific ventilation (SV) from mixed-expired and 2) end-tidal N2, 3) change of slope of N2 washout (semilog plot) with time, 4) change of slope of normalized phase III of successive breaths, 5) anatomic dead space, and 6) Bohr dead space. Significant ventilatory inhomogeneity was seen in the standing position at normal gravity (1 G). When we compared standing 1 G with microgravity, the distributions of SV became slightly narrower, but the difference was not significant. Also, there were no significant changes in the change of slope of the N2 washout, change of normalized phase III slopes, or the anatomic and Bohr dead spaces. By contrast, transition from the standing to supine position in 1 G resulted in significantly broader distributions of SV (P < 0.05) and significantly greater changes in the changes in slope of the N2 washouts (P < 0.001), indicating more ventilatory inhomogeneity in that posture. Thus these techniques can detect relatively small changes in ventilatory inhomogeneity. We conclude that the primary determinants of ventilatory inhomogeneity during tidal breathing in the upright posture are not gravitational in origin.
Ventilation distribution and regional lung impedance during partial unilateral bronchial obstruction
Authors: Simon B. A. , Tsuzaki K. , Venegas J. G.
Published: December 2017

Significant degrees of main-stem bronchial obstruction may not have a detectable effect on ventilation distribution at normal breathing frequencies. We determined the effect of graded left main-stem bronchial obstruction (area reduction of 50 and 70%) on the distribution of tidal volume (VT) and mean lung volume (VL) using radioactive 13NN and two-dimensional planar positron imaging in six supine anesthetized tracheotomized dogs. Measurements were made during eucapnic high-frequency oscillatory ventilation at frequencies (f) of 0.2, 1, 5, and 10 Hz. Right and left lung respiratory system complex impedance (Z) values were assessed by simultaneous measurements of dynamic regional lung volume by positron imaging and carinal pressure. The results show a progressive shift of VT away from the obstruction at f > 1 Hz, with VT left-to-right (L/R) ratios of 0.9, 0.9, 0.58, and 0.46 at f of 0.2, 1, 5, and 10 Hz, respectively, for 70% obstruction. VT shifts with f for 50% obstruction were similar but of lesser magnitude. VL L/R ratio was 0.88 and did not change with f or obstruction. The real part of Z was frequency dependent and increased at low f independent of obstruction. The real part of Z L/R ratio increased with obstruction at 5 and 10 Hz. At low f there was a difference between left and right imaginary parts of Z due to the difference in VL. There was no significant change in the imaginary part of Z as a result of obstruction. We conclude that up to a 70% unilateral bronchial obstruction is not detectable by distribution of ventilation at f < or = 1 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)
Ozone toxicity in the rat. I. Effect of changes in ambient temperature on extrapulmonary physiological parameters
Authors: Watkinson W. P. , Wiester M. J. , Highfill J. W.
Published: December 2017

These studies examined the effects of exposure to near environmental levels of ozone (O3) on the unanesthetized unrestrained rat as well as the influence of changes in ambient temperature (Ta) on the observed responses. Male Fischer 344 rats were implanted with radiotelemetry transmitters that permitted continuous monitoring of electrocardiogram, heart rate, core body temperature (Tco), and activity. Telemetry animals (n = 4–5/group) were combined with nontelemetry animals to produce nine treatment groups (n = 44–50/group) composed of combinations of one of three O3 exposure regimens (0.0 ppm x 24 h/day, 0.5 ppm x 6 h/day, or 0.5 ppm x 23 h/day) paired with one of three Ta levels (10, 22, or 34 degrees C). The experimental protocol consisted of a Control Period (filtered air; 1 day), Treatment Period (O3; 5 days), and Recovery Period (filtered air; 7 days). At specific intervals during the experiment, subgroups (n = 6) of nontelemetry animals were randomly selected from each treatment group, anesthetized with urethan, and intubated, and their lungs were lavaged with warm saline. In general, results from the bronchoalveolar lavage procedure indicated that toxicity increased in magnitude and duration as the length of time of O3 exposure increased and the Ta decreased. Similarly, whereas minimal extrapulmonary effects were observed at an Ta of 34 degrees C, O3 exposures at Ta levels of 22 and 10 degrees C produced significant decreases in heart rate (160 and 210 beats/min, respectively), Tco (2.0 and 3.5 degrees C, respectively), and body weight (15 and 40 g, respectively). Decreases in these functional parameters reached their maxima over the first 2 exposure days and returned to control levels after the 3rd day of exposure. These data demonstrate the profound impact of Ta on Tco and other extrapulmonary parameters in the conscious unrestrained rat exposed to O3. Furthermore, these results suggest an integral role for both Tco and Ta in determination of the uptake of inhaled pollutants and modulation of the subsequent toxic effects and may have important implications with respect to the assessment of toxic risk.
Glucose kinetics during high-intensity exercise in endurance-trained and untrained humans
Authors: Coggan A. R. , Raguso C. A. , Williams B. D. , Sidossis L. S. , Gastaldelli A.
Published: December 2017

In humans, endurance training reduces the rates of glucose production and utilization during moderate-intensity exercise. It is uncertain, however, whether this is also true during high-intensity exercise. Accordingly, we studied eight endurance-trained cyclists and eight untrained subjects during 30 min of cycling at approximately 80% of maximal oxygen uptake (VO2max). Rates of glucose appearance (Ra) and disappearance (Rd) were determined using a primed, continuous infusion of [6,6–2H]glucose. Average glucose Ra during exercise did not differ in the trained and untrained subjects (34.3 +/- 3.6 vs. 36.0 +/- 1.7 mumol.min-1.kg-1; mean +/- SE; P, not significant). Plasma insulin, glucagon, norepinephrine, and epinephrine concentrations were also similar in the two groups. In contrast, glucose Rd during exercise was 19% lower in the trained compared with the untrained subjects (27.0 +/- 2.6 vs. 33.2 +/- 1.5 mumol.min-1.kg-1; P < 0.001). Consequently, during exercise, plasma glucose concentration rose significantly (P < 0.05) in the trained subjects but did not change in the untrained subjects. We conclude that utilization of plasma glucose is lower in trained subjects during high-intensity exercise, even when the exercise is performed at the same relative (and therefore a higher absolute) intensity as in the untrained state. Hyperglycemia in trained subjects during intense exercise appears to be due to this lower rate of glucose utilization rather than a higher rate of glucose production.
Activity of respiratory neurons during hypoxia in the chemodenervated cat
Authors: England S. J. , Melton J. E. , Douse M. A. , Duffin J.
Published: December 2017

Exposure of anesthetized paralyzed vagotomized peripherally chemodenervated cats to hypoxia results in initial depression and subsequent loss of the phrenic neurogram. To determine whether hypoxic respiratory depression results from the inhibition of respiratory premotor neurons by bulbospinal neurons of the Botzinger complex (Bot-E neurons), extracellular recordings were made of dorsal and ventral respiratory group bulbospinal inspiratory neurons and Bot-E neurons during acute hypoxic hypoxia. All neurons recorded decreased firing rate during hypoxia. Bot-E neurons became silent before the loss of phasic phrenic activity during hypoxia and commenced firing before or coincident with the return of the phrenic neurogram during reoxygenation. Inspiratory neurons ceased firing coincident with phrenic silence. Dorsal respiratory group and ventral respiratory group neurons that had a late onset of firing with respect to the phrenic neurogram during normoxia fired progressively earlier in inspiration during hypoxia, an effect that was reversed during reoxygenation. These data are consistent with inhibition and/or disfacilitation as the mechanism of hypoxic respiratory depression but suggest that Bot-E neurons are not the source of this inhibition.
Skin of the dorsal aspect of human hands and fingers possesses an active vasodilator system
Authors: Johnson J. M. , Pergola P. E. , Liao F. K. , Kellogg D. L. , Crandall C. G.
Published: December 2017

To test for an active vasodilator system in human hand and finger skin, seven subjects had a small area of dorsal hand, palm, or dorsal finger pretreated with bretylium (BT) to block adrenergic vasoconstriction. Skin blood flow was monitored at a BT-treated site, a comparable untreated site, and the forearm by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was evaluated from the ratio of blood flow to arterial pressure. Body cooling, to evaluate vasoconstrictor system blockade, caused CVC at untreated sites of forearm, palm, dorsal hand, and dorsal finger to fall by 45 +/- 4, 85 +/- 5, 51 +/- 9, and 63 +/- 7%, respectively (all P < 0.05). At BT-treated sites of palm, dorsal hand, and dorsal finger, reductions in CVC were only 13 +/- 3, 2 +/- 18, and 13 +/- 4%, respectively (dorsal hand not significant, others P < 0.05). With body heating, increases in CVC at untreated sites of forearm, palm, dorsal hand, and dorsal finger were 881 +/- 165, 779 +/- 368, 423 +/- 115, and 1,430 +/- 716%, respectively (all P < 0.05). At BT-treated sites of palm, dorsal hand, and dorsal finger, increases were 35 +/- 15, 342 +/- 107, and 343 +/- 34%, respectively (palm not significant, others P < 0.05). Increased CVC at the palm began after 1.2 +/- 0.2 min of heating, significantly earlier than forearm (11.8 +/- 2.5 min), dorsal hand (16.4 +/- 3.4 min), or dorsal finger (15.6 +/- 3.6 min), which did not differ significantly from one another.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine A2 receptors reverse ischemia-reperfusion lung injury independent of beta-receptors
Authors: Khimenko P. L. , Moore T. M. , Hill L. W. , Wilson P. S. , Coleman S. , Rizzo A. , Taylor A. E.
Published: December 2017

To evaluate the adenosine systems ability to reverse the endothelial damage produced by ischemia and reperfusion (I/R), we studied several different selective adenosine-receptor agonists and antagonists, a protein kinase A inhibitor, and a beta-adrenoreceptor antagonist in isolated buffer-perfused rat lungs. I/R (45 min/105 min) produced a sixfold increase in endothelial permeability as measured by the capillary filtration coefficient. Both a selective A2-receptor agonist (CGS-21680, 300 nM) and a beta-receptor agonist (isoproterenol, 10 microM) reversed the increased microvascular permeability. A nonselective adenosine-receptor antagonist (SPT, 20 microM) and a selective A1-receptor antagonist (DPCPX, 10 nM) had no effect on increased microvascular permeability. Also, isoproterenol and CGS-21680 reversed the damage being introduced after a selective A1-receptor agonist (CCPA, 100 nM). The nonspecific adenosine A1- and A2-receptor agonist NECA (12 nM) appeared to desensitize the A2 receptors and a protein kinase A inhibitor, adenosine-3′,5′-cyclic monophosphothioate (Rp-cAMPS, 100 microM), blocked the reversal of endothelial damage by isoproterenol or A2-receptor agonist. Propranolol (100 microM) blocked the effect of isoproterenol but not the effect of CGS-21680. From this study we conclude that A2-receptor activation reverses endothelial damage associated with I/R by a mechanism independent of beta-receptors or Gi protein. However, a protein kinase A-3′,5′,-cyclic adenosine monophosphate pathway is activated by both the adenosine systems and beta-receptor activation.
Effects of flow, perfusion pressure, and oxygen consumption on cardiac capillary exchange
Authors: Cousineau D. F. , Goresky C. A. , Rose C. P. , Simard A. , Schwab A. J.
Published: December 2017

The roles of blood flow, local oxygen consumption, and perfusion pressure on cardiac transcapillary exchange were characterized in closed-chest anesthetized dogs by use of the multiple-indicator dilution technique. Occlusion of the carotid arteries or injection of dipyridamole increased coronary flow to significantly higher values compared with a group of animals in a basal state obtained in a previous study. Carotid occlusion resulted in a significant increase in perfusion pressure and myocardial oxygen consumption, whereas these two variables were significantly reduced after dipyridamole. For the whole group of animals, the capillary permeability-surface area product for sucrose increased with coronary flow, which appeared to be the important controller for this microcirculatory exchange parameter. Perfusion pressure and myocardial oxygen consumption also regulated permeability-surface area product values, although to a lesser extent than flow. The heterogeneity of transit times in the capillaries was reduced at high coronary flow values, despite large differences in the cardiac utilization of oxygen. The data suggest that cardiac capillary exchange responds mostly to hemodynamic changes originating at the precapillary level.
Leukotriene B4 formation: human neutrophil-airway epithelial cell interactions
Authors: Zhou S. , Stark J. M. , Leikauf G. D.
Published: December 2017

Leukotriene B4 (LTB4) is a potent inflammatory mediator involved in the pathogenesis of many pulmonary diseases. Although the neutrophil is the predominant source of LTB4, other cells can also interact with neutrophils and increase LTB4 formation. In this study, we investigated whether human neutrophil-airway epithelial cell interactions can increase LTB4 formation. Neutrophils were cocultured with transformed airway epithelial cells (9HTEo- cells), and LTB4 and leukotriene A4 (LTA4) degradation product release was measured by high-performance liquid chromatography and ultraviolet spectrometry. When stimulated with the calcium ionophore A-23187, neutrophil-9HTEo- cell cocultures released more LTB4 and less LTA4 degradation products in a time- and dose-related manner than did neutrophils alone. This increase in LTB4 release involved the metabolism of neutrophil-derived LTA4 to LTB4 by 9HTEo- cells and was affected by the neutrophil-to-epithelial cell ratio. Enhanced LTB4 release required proximity between neutrophils and 9HTEo- cells but not specific cell-cell adhesion. Our data demonstrate that human neutrophil-airway epithelial cell interactions can increase LTB4 formation through transcellular arachidonic acid metabolism.
Effect of catecholamines on pulmonary circulation at elevated vascular tone
Authors: Barman S. A.
Published: December 2017

The effect of catecholamine stimulation on the longitudinal resistance and compliance distribution in the canine pulmonary vasculature was evaluated under control vascular tone and after vascular tone was elevated using the thromboxane analogue U-46619. The arterial-, venous-, and double-occlusion techniques were used to measure the segmental resistances and compliances in isolated dog lung blood perfused at constant flow. The results of this study indicate that at control vascular tone the catecholamines norepinephrine and epinephrine increase pulmonary vascular resistance and decrease pulmonary vascular compliance through alpha 1- and alpha 2-receptor-mediated stimulation with precapillary alpha 1- and alpha 2-receptors and postcapillary alpha 2-receptors interacting with precapillary and postcapillary beta 2-receptors. In addition, epinephrine appears to have a greater effect on beta 2-receptors than norepinephrine. When vascular tone was elevated, the effect of norepinephrine and epinephrine on pulmonary vascular resistance was not present, which may be due to the appearance of a more pronounced vasodilatory beta 2-receptor system and an attenuation of the alpha-mediated vasoconstrictor responses. In addition, neither catecholamine had any significant effect on pulmonary vascular compliance when vascular tone was raised. These data suggest that the adrenergic-receptor systems modulating pulmonary vascular resistance and compliance in the canine pulmonary circulation are altered when vascular tone is elevated. As a result, these altered pulmonary vascular responses may affect pulmonary capillary pressure, a major determinant of lung fluid balance.
Caffeine decreases malonyl-CoA in isolated perfused skeletal muscle of rats
Authors: Maclean P. S. , Winder W. W.
Published: December 2017

The regulation of acetyl-CoA carboxylase and malonyl-CoA levels in skeletal muscle may involve a calcium-dependent mechanism. To examine the effects of increased free sarcoplasmic calcium concentrations on malonyl-CoA in skeletal muscle, isolated hindlimbs of rats were perfused for 30 min with a medium containing bovine red blood cells, bovine serum albumin, 200 microU/ml insulin, and 10 mM glucose in Krebs-Henseleit buffer and caffeine at 0, 0.12, 0.5, or 3 mM. Malonyl-CoA decreased from control (no caffeine) values of 1.34 +/- 0.9 to 0.95 +/- 0.12 pmol/mg in gastrocnemius-plantaris muscles perfused with 0.12 and 0.5 mM caffeine and to 0.63 +/- 0.07 pmol/mg in the muscles perfused with 3 mM caffeine. Adenosine 3′,5′-cyclic monophosphate (cAMP) increased from 0.24 +/- 0.02 to 0.32 +/- 0.04 nmol/g, and AMP decreased from 83 +/- 8 to 53 +/- 3 nmol/g in response to 3 mM caffeine. Citrate and ATP were unaffected by caffeine. A decline in malonyl-CoA with 0.12 and 0.5 mM caffeine without an increase in cAMP supports the hypothesis that a calcium-dependent mechanisms of acetyl-CoA carboxylase and malonyl-CoA regulation exists, but a cAMP-dependent mechanism may also be involved with 3 mM caffeine.
Role of C fibers in physiological responses to ozone in rats
Authors: Jimba M. , Skornik W. A. , Killingsworth C. R. , Long N. C. , Brain J. D. , Shore S. A.
Published: December 2017

The purpose of this study was to evaluate the role of C fibers in airway responsiveness after exposure to ozone (O3) in rats. The role of C fibers in the decreases in heart rate (HR) and core body temperature (Tc) that occur after inhalation of O3 was also examined. Neonatal rats were treated with capsaicin (Cap) or the vehicle used to dissolve capsaicin (Veh). Cap has been shown to cause permanent destruction of C fibers. When they reached adulthood, conscious minimally restrained rats were exposed to 2 ppm O3 or to air for 3 h. Two hours after the cessation of exposure, rats were anesthetized and instrumented for the measurement of pulmonary mechanics and airway responsiveness to inhaled aerosolized methacholine. O3 had no effect on baseline pulmonary conductance (GL) in either Veh or Cap rats but did cause a decrease in dynamic compliance (Cdyn) in Cap rats (P < 0.05). In Cap rats, O3 exposure caused a marked increase in airway responsiveness; the doses of inhaled aerosolized methacholine required to decrease GL and Cdyn by 50% were 6.5-fold and 9.8-fold lower in O3-compared with air-exposed rats (P < 0.005). In contrast, in Veh rats, O3 did not alter responsiveness. During O3 exposure, there was a profound, almost 50%, decrease in HR as measured with implanted electrodes. A decrease in Tc (measured with a rectal probe) of approximately 2.5 degrees C also occurred during O3 exposure. There was no significant effect of Cap pretreatment on the magnitude of these O3-induced changes in HR and Tc. Our results are consistent with the hypothesis that C fibers act to inhibit the development of hyperresponsiveness elicited by O3 inhalation but do not contribute to O3-induced changes in HR or Tc.
Influence of spaceflight, hindlimb suspension, and venous occlusion on alpha 1-adrenoceptors in rat vena cava
Authors: Sayet I. , Neuilly G. , Mironneau J. , Mironneau C.
Published: December 2017

Effects of hindlimb suspension, spaceflight, and venous occlusion were examined in isolated strips from rat vena cava by using both [3H]prazosin-binding and contraction responses evoked by norepinephrine. Sensitivity to norepinephrine was decreased without modification of the maximal contractile response. Furthermore, the high K(+)-induced contractions were not affected, suggesting that there was no interference with voltage-dependent Ca2+ channels. The sensitivity of the norepinephrine-induced contraction to prazosin was decreased, and Scatchard analysis of [3H]prazosin binding indicated an increase in the dissociation constant without variation in maximal binding capacity. A similar increase in the dissociation constant was obtained in control rats after pretreatment with 3 microM norepinephrine or 0.1 microM phorbol 12,13-dibutyrate to desensitize the protein kinase C. This effect was completely abolished in the presence of GF-109203X, a selective inhibitor of protein kinase C. Taken together, these data indicate that altered gravity conditions induce a desensitization of alpha 1B-adrenoceptors depending on increased protein kinase C activity. This effect can be mimicked by venous occlusion and may be responsible for reduced contractile responses to norepinephrine.
Respiratory-related heart rate variability persists during central apnea in dogs: mechanisms and implications
Authors: Horner R. L. , Brooks D. , Kozar L. F. , Gan K. , Phillipson E. A.
Published: December 2017

The aim of this study was to determine the mechanism(s) responsible for the persistence of respiratory sinus arrhythmia (RSA) during central apnea. In five awake dogs, heart rate (HR) was recorded during constant mechanical ventilation (MV) and during central apneas produced by cessation of MV. For each of 10 control ventilator cycles before MV was stopped, instantaneous HR was plotted against the time from the onset of lung inflation; the fundamental and first harmonic of a sine wave (at the ventilator frequency) was then fitted to the HR data. For the control cycles, the mean r2 from the curve fits was 0.57 +/- 0.07, showing that a significant component of the HR variability was linked to the ventilator cycle. After MV was stopped, RSA persisted and only by the third "phantom" ventilator cycle during apnea had the degree of fit consistently decreased compared with control dogs (P < 0.02). The persistence of ventilator-linked RSA at the onset of central apnea supports the concept of a "memory" in the respiratory system. Toward the end of central apnea, HR variability reappeared and had the periodicity and rhythmic profile of RSA on 81% of occasions. The presence of RSA-like activity toward the end of central apnea suggests that subthreshold rhythmic respiratory-related activity may be present even before the onset of detectable lung volume changes.
Efficacy of drug regimen exceeds electrostimulation in treatment of avian muscular dystrophy
Authors: Hudecki M. S. , Povoski S. P. , Gregorio C. C. , Granchelli J. A. , Pollina C. M.
Published: December 2017

Autosomal-recessive dystrophic chickens were treated in three experimental groups with an intraperitoneal multicomponent drug mixture (50 mg/kg Ep475, 20 mg/kg Cinanserin, 10 mg/kg stanazolol, 100 mg/kg leucine, 0.1 mg/kg insulin, 100 mg/kg glucose, and 50 mg/kg carnitine), percutaneous high-frequency electrostimulation of the pectoralis muscle, or a combination of both drug and electrostimulation treatments. Therapeutic efficacy was determined in each group by measurements of strength, righting ability, and histomorphometric analyses of the pectoralis musculature. Drug treatment alone was found to significantly improve muscular strength, function, and relative myofiber necrosis compared with sham-injected controls. The efficacy of drug treatment was found to be equal to or better than singular electrostimulation treatment; there was no apparent additive effect of electrostimulation. As a result, these findings support the use of drug treatment as a useful nongenetic approach to the management of human muscular dystrophy where there is the potential risk of injury from exercise usage.
Epithelial modulation of afferent nerve endings: differential effects of amiloride on afferent subtypes
Authors: Ghosh T. K. , Van Scott M. R. , Mathew O. P.
Published: December 2017

Mechanisms underlying the differing chemosensitivity of laryngeal afferents have not been defined. The role of airway epithelium in transducing the chemical stimuli to neural signals was investigated by using Na(+)- and Cl(-)-channel inhibitors in anesthetized spontaneously breathing cats. Single-fiber action potentials were recorded from the peripheral cut end of the superior laryngeal nerve. Luminal application of amiloride (10(-4) M), an inhibitor of epithelial Na+ channels, reduced the responsiveness of non-respiratory-modulated endings (n = 25) to distilled water (65.76 +/- 5.77 vs. 50.67 +/- 5.13 Hz; P < 0.01). Water responsiveness of these endings was unaffected by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid and diphenylamine-2-carboxylate, two Cl(-)-channel blockers. Respiratory-modulated endings (water responsive, n = 8; water nonresponsive, n = 9) were unaffected by Na(+)- and Cl(-)-channel blockers. These results suggest that epithelial Na+ channels play a role in the modulation of non-respiratory-modulated laryngeal endings. The lack of an effect by amiloride on other subtypes may be due to differences in location or intrinsic properties of nerve endings. Cl- channels do not appear to play an important role in the modulation of laryngeal afferents targeted in this study.
Superoxide dismutase derivative reduces oxidative damage in skeletal muscle of rats during exhaustive exercise
Authors: Radak Z. , Asano K. , Inoue M. , Kizaki T. , Oh-Ishi S. , Suzuki K. , Taniguchi N. , Ohno H.
Published: December 2017

A superoxide dismutase derivative (SM-SOD) that circulates and is bound to albumin with a half-life of 6 h was injected intraperitoneally into rats before exhaustive treadmill running to study its antioxidant scavenging capacity in the plasma and soleus and tibialis muscles. The exercise induced a marked increase in xanthine oxidase activity in plasma and an increase in thiobarbituric acid-reactive substances in the plasma as well as in the soleus and tibialis muscles of nonadministered rats immediately after the exercise. The immunoreactive content and activity of both SOD isoenzymes (Cu,Zn-SOD and Mn-SOD) of the nonadministered rats increased in the soleus and tibialis muscles immediately after running. SM-SOD treatment definitely attenuated the degree of the increase in thiobarbituric acid-reactive substances and xanthine oxidase in all samples examined immediately after exercise. Glutathione peroxidase activity significantly increased in the soleus muscle of nonadministered rats 1 day after running, whereas catalase activity remained unchanged throughout the experimental period. These results suggest that a single bout of exhaustive exercise induces oxidative stress in skeletal muscle of rats and that this oxidative stress can be attenuated by exogenous SM-SOD.
Effects of nasal positive-pressure hyperventilation on the glottis in normal sleeping subjects
Authors: Jounieaux V. , Aubert G. , Dury M. , Delguste P. , Rodenstein D. O.
Published: December 2017

We have previously observed that, in normal awake subjects passively hyperventilated with intermittent positive-pressure ventilation delivered through nasal access (nIPPV), the glottis could interfere with the ventilation. We report on data obtained in the same subjects during stable sleep. In all cases, the glottis was continuously observed through a fiber-optic bronchoscope, and other indexes were also continuously recorded. Mechanical ventilation was progressively increased up to 30 l/min. We have observed during passive nIPPV in stable sleep that increases in delivered minute ventilation (VEd) resulted in progressive narrowing of the glottic aperture, with increases in inspiratory resistance and progressive reductions in the percentage of the delivered tidal volume effectively reaching the lungs. For a given level of VEd, comparisons showed that the glottis was significantly narrower during sleep than during wakefulness and that the glottis was significantly narrower during stage 2 than during stages 3/4 non-rapid-eye-movement sleep. Moreover, when CO2 is added to the inspired air, glottic aperture increased in five of nine trials without changes in sleep stage. We also observed a significant negative correlation between glottic width and the VED, independent of the CO2 level. We conclude that during nIPPV glottis narrowing results in a decrease in the proportion of the delivered tidal volume reaching the lungs.
Exercise training-induced changes in anterior pituitary gonadotrope of the female rat
Authors: Caston A. L. , Farrell P. A. , Deaver D. R.
Published: December 2017

Chronic exercise training may alter the hypothalamic-pituitary-ovarian axis by affecting gonadotropin secretion and structural indexes of the anterior pituitary gonadotropes. Young female Harlan Sprague-Dawley rats were randomly assigned to either a 12-wk intensive treadmill-running program (n = 16) or to a sedentary untrained group [untrained-proestrus (UTP), n = 16]. After training for 3 mo, animals were killed on proestrous morning, and individual pituitary glands were enzymatically dispersed into single-cell suspensions. Trained rats maintained either predominantly regular estrous cycles [trained-proestrus (TP), n = 11] or exhibited anestrous vaginal cytology [trained-anestrus (TA), n = 5]. At death, plasma estradiol concentrations for TP (57.4 +/- 6 pg/ml, mean +/- SE) and UTP (54.6 +/- 5 pg/ml) were similar. However, TA had plasma estradiol levels (2.7 +/- 0.2 pg/ml; P < 0.05) reflecting their anestrous status. Basal luteinizing hormone (LH) secretion (20-h static incubation) was significantly reduced in gonadotropes from TA (7.8 +/- 1.1 ng/pooled wells) compared with TP (13.6 +/- 1.6 ng/pooled wells) and UTP (12.6 +/- 1.0 ng/pooled wells). Immunofluorescence LH staining and cytoplasmic granularity were significantly lower within the TA gonadotrope population compared with those of TP and UTP rats. Evidence of impaired basal LH secretion, reduced gonadotrope LH-specific fluorescein content, and reduced gonadotrope cytoplasmic granularity in TA rats suggests that, concomitant with proposed changes in the central neural drive, there are important exercise training-induced alterations of the anterior pituitary gonadotrope that influence rats' estrous cycles and affect their reproductive status.
Endothelium-dependent vasodilation of proximal coronary arteries from exercise-trained pigs
Authors: Oltman C. L. , Parker J. L. , Laughlin M. H.
Published: December 2017

We recently reported that alpha-adrenergic vasoconstriction is blunted and adenosine-induced vasodilation is enhanced in proximal coronary arteries of exercise-trained miniature swine [C. L. Oltman, J. L. Parker, H. R. Adams, and M. H. Laughlin. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H372-H382, 1992]. The purpose of the present study was to determine whether this model of exercise training also alters endothelium-dependent vasodilator responses of proximal coronary arteries. Female Yucatan miniature swine were exercise trained (ET) on a motor-driven treadmill or were cage confined (Sed) for 13–20 wk. Exercise tolerance, heart weight-to-body weight ratios, and skeletal muscle oxidative capacity were all significantly greater in ET than in Sed animals. Vasodilator responses were evaluated in vitro by determining concentration-response curves by using vascular rings (3.5–4 mm in axial length) isolated from right and left coronary arteries. Vasorelaxation responses were determined, after tone had been produced with either 30 microM prostaglandin F2 alpha, 30 mM KCl, or 30 nM endothelin. Concentration-response curves were obtained to endothelium-dependent vasodilators including bradykinin (10(-9)-10(-6) M), substance P (10(-12)-10(-6) M), clonidine (10(-9)-10(-6) M), serotonin (10(-10)-10(-5) M), and the Ca2+ ionophore A-23187 (10(-10)-10(-6) M). Endothelium-independent vasodilator responses to sodium nitroprusside (10(-9)-10(-4) M) were not different between arteries from Sed and ET. Bradykinin, substance P, and A-23187 were potent vasodilators in arteries from both groups, whereas serotonin and clonidine did not consistently produce vasodilation.
Inhomogeneous activation of the parasternal intercostals during breathing
Authors: De Troyer A. , Legrand A.
Published: December 2017

Recent computations of the mechanical advantage of the canine intercostal muscles have suggested that the inspiratory advantage of the parasternal intercostals is not uniform. In the present studies, we have initially tested this hypothesis. Using a caliper and markers implanted in the costal cartilages, we have thus measured, in four supine paralyzed dogs, the length of the medial, middle, and lateral parasternal fibers at functional residual capacity and after a 1-liter mechanical inflation. With inflation, the medial fibers always shortened more than did the middle fibers (-9.8 +/- 0.8 vs. -6.0 +/- 0.8%; P < 0.001), whereas the lateral fibers remained virtually constant in length (-0.2 +/- 0.8%). This gradient of mechanical advantage agreed well with the gradient of orientation of the muscle fibers. Therefore, we have also recorded the electromyograms of the medial, middle, and lateral parasternal bundles during spontaneous breathing in nine anesthetized animals (20 interspaces); each activity was expressed as a percentage of the activity recorded during tetanic, supramaximal stimulation of the internal intercostal nerve (maximal activity). The medial bundle was invariably more active than was the middle bundle during resting breathing (57.3 +/- 3.3 vs. 25.5 +/- 3.4% of maximum; P < 0.001), and in 10 interspaces, medial activity consistently preceded middle activity at the onset of inspiration. These differences persisted during hypercapnia, during inspiratory resistive loading, as well as after phrenicotomy. Activity was never recorded from the lateral bundle.
Effects of neuromuscular blockade on fetal heart rate variability: a power spectrum analysis
Authors: Sibony O. , Fouillot J. P. , Luton D. , Oury J. F. , Blot P.
Published: December 2017

Spectral analysis of fetal heart rate variability allows quantitative determination of the main components that affect this variability. The physiological significance of these components is unclear; however, movements appear to contribute to variability. We studied six fetuses in which immobility required for in utero magnetic resonance or invasive fetal procedures was achieved by fetal intravascular injection of curare between 32 and 36 amenorrhea weeks. For each fetus, we compared spectral density parameters of heart rate variability. After curare administration, mean spectrum power was halved. We did not observe a larger significant decrease in any (very low, low, or high) frequency band. The other parameters of spectral analysis of variability were unaltered. Fetal movements accounted for a significant proportion of human fetal heart rate variability but did not constitute a unique frequency component.
Microdialyzed adenosine in nucleus tractus solitarii and ventilatory response to hypoxia in piglets
Authors: Yan S. , Laferriere A. , Zhang C. , Moss I. R.
Published: December 2017

Levels of adenosine, inosine, and hypoxanthine from the interstitial space at the nucleus tractus solitarii were measured by microdialysis in eight 20- to 25-day-old anesthetized spontaneously breathing piglets. Microdialyzed samples were collected every 30 min for 2 h after the insertion of the probe to ensure stability of purine levels and then during 30 min each of normoxia, hypoxia (10% O2–90% N2), and normoxia. The purines were separated by high-pressure liquid chromatography with ultraviolet detection and quantified at 254-nm wavelength. Tidal volume, breathing frequency, minute ventilation, mean arterial blood pressure, pH, and gas tensions were measured. Compared with control, adenosine levels during hypoxia increased by 40.7 +/- 5.5% and then tended to decline during the recovery from hypoxia, but the levels remained higher than in control. Ventilatory measures exhibited a modest biphasic pattern during hypoxia and resumed control values by 10 min after the removal of the hypoxia. The increased adenosine release during hypoxia provides additional evidence for the possible participation of adenosine in the central suppression of breathing during hypoxia.
Effect of negative intrathoracic pressure on left ventricular pressure dynamics and relaxation
Authors: Virolainen J. , Ventila M. , Turto H. , Kupari M.
Published: December 2017

To investigate the effect of a fall of intrathoracic pressure on left ventricular (LV) hemodynamics and relaxation, simultaneous micromanometric recordings of LV and aortic pressures were performed at rest and during two graded Mueller maneuvers in 16 patients undergoing cardiac catheterization for aortic valve stenosis (n = 8) or chest pain (n = 8). The reductions (means +/- SE) of airway pressure during the lesser and greater maneuvers were 26 +/- 1 and 42 +/- 1 mmHg, respectively. Simultaneously, LV isovolumic-developed pressure increased by 9 +/- 3 and 21 +/- 4 mmHg, respectively (P < 0.03 for both). During the greater maneuver, the individual changes of the time constant of LV isovolumic relaxation (tau) correlated with the changes of LV isovolumic-developed pressure (r = 0.73; P = 0.002). In patients with a > 20-mmHg rise in isovolumic-developed pressure, tau increased by 10.3 +/- 4.6 ms. By multiple-regression analysis, the change of tau was related directly to the change of isovolumic-developed pressure (standardized coefficient beta = 0.80; P = 0.001) and inversely related to the resting systolic LV-aortic pressure gradient (beta = -0.37; P = 0.050). The other hemodynamic changes were independent of aortic valve stenosis. In conclusion, during the Mueller maneuver, the LV isovolumic contraction load increases and tau lengthens, particularly with higher elevations of LV systolic load.
Myocardial oxygen extraction ratio is decreased during endotoxemia in pigs
Authors: Herbertson M. J. , Werner H. A. , Russell J. A. , Iversen K. , Walley K. R.
Published: December 2017

Why the myocardial oxygen extraction ratio (ERm) is decreased during septic shock in humans is unknown. Therefore, we calculated ERm in 15 anesthetized pigs by measuring arterial and coronary venous oxygen content. We measured myocardial lactate flux, myocardial contractility, and global myocardial blood flow and its distribution. After baseline measurements, animals received either saline (n = 6) or 50 micrograms/kg of endotoxin (n = 9). Measurements were repeated for 4 h. After endotoxin, ERm decreased from 67 +/- 12% at baseline to 36 +/- 10% (P < 0.01) at 1 h and 54 +/- 10% (P < 0.05) at 4 h, associated with an increased myocardial blood flow that was heterogeneous. Neither myocardial oxygen nor lactate consumption decreased in the endotoxin group, and changes in left ventricular contractility were not correlated with changes in ERm. We conclude that the decrease in ERm after endotoxin infusion is due to both increased blood flow and mismatching between myocardial oxygen delivery and demand. Impaired myocardial oxygen extraction capacity during sepsis did not cause global myocardial tissue hypoxia.
Respiratory system mechanics in mice measured by end-inflation occlusion
Authors: Ewart S. , Levitt R. , Mitzner W.
Published: December 2017

Characterization of pulmonary function parameters in mice will facilitate the dissection of genetic mechanisms underlying airway hyperresponsiveness. We evaluated acetylcholine (ACh)-induced respiratory system resistance (Rrs) and elastance (Ers) in A/J and C3H/HeJ mice and compared these results with the previously used airway pressure-time index (APTI). A low-dead-space ventilatory system was designed to ventilate anesthetized mice with constant inspiratory flow. The end-inflation occlusion method was used to measure Rrs and Ers at baseline and after intravenous ACh (12.5–75.0 micrograms/kg) challenge. ACh induced a dose-dependent rise in Rrs and Ers in A/J mice, whereas minimal changes were observed in C3H/HeJ mice. A/J mice had a higher baseline Rrs, yet the response to ACh was independent of baseline Rrs. Additionally, sequential ACh challenges led to augmented responses. Rrs, Ers, and APTI were strongly correlated, and each was useful to detect differences in interstrain cholinergic-induced airway responsiveness. The Rrs detected the smallest differences between the strains of mice studied.
Properties of postganglionic sympathetic fibers isolated from the right recurrent laryngeal nerve
Authors: Balkowiec A. , Szulczyk P.
Published: December 2017

The pattern of response of 45 single postganglionic sympathetic axons dissected from the right recurrent laryngeal nerve was examined in chloralose-anesthetized cats. Both vagoaortic nerves were cut, and both sinus nerves were left intact. Each neuron, based on the presence of cardiac and respiratory rhythmicities in its resting activity and reaction to systemic hypoxia (10% O2 in N2 for 2 min), was classified into one of three classes. Class I neurons (n = 29, 64%) were activated during systemic hypoxia and had a pronounced cardiac and inspiration-related rhythmicity in their resting activity. Class II neurons (n = 12,27%) were inhibited during systemic hypoxia, and their cardiac and respiratory rhythmicities were either negligible or totally absent. Class III neurons (n = 4,9%), similarly to class I, had a pronounced cardiac and inspiratory rhythmicity but were not affected by systemic hypoxia. The systemic hypoxia was always accompanied by an increase in blood pressure. We conclude that class I and possibly class III neurons innervate the arteries of upper airways. We also discuss the possibility that class II neurons are responsible for regulating the smooth muscles of upper airways.