bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced adipose tissue lipoprotein lipase activity in detrained rats: independent of changes in food intake
Authors: Lambert E. V. , Wooding G. , Lambert M. I. , Koeslag J. H. , Noakes T. D.
Published: December 2017

Short-term detraining has been characterized by increased body mass and rapid body fat accretion. However, detraining has also been associated with increased food intake, especially in rats genetically predisposed to obesity. Thus, it has been difficult to separate refeeding effects from alterations resulting from the cessation of exercise training. In the present study, the in vitro activity of adipose tissue lipoprotein lipase (ATLPL) was measured in freely running wheel-trained rats and rats that had stopped training for 1, 2, or 3 days or 1 or 2 wk, respectively. Heparin-releasable ATLPL activity was measured at rest and after acute exhaustive exercise. Feeding efficiency (change in body mass/kJ ingested energy), fat pad mass, and adipocyte size were also measured. The rate of weight gain in 1- and 2-wk detrained rats was significantly higher than that of sedentary control or trained rats (P < 0.05). Feeding efficiency was also higher in 1-wk detrained rats than in all other groups (P < 0.005). However, food energy intake was not different between trained rats, 1- and 2-wk detrained rats, or sedentary control rats. ATLPL activity in all groups was highest after acute exhaustive exercise. ATLPL activity in 1-wk detrained rats was nearly threefold higher compared with that in trained rats (P < 0.005) and was not different from that of sedentary control rats. These results suggest that the cessation of exercise training causes an enhanced capacity for lipogenesis independent of changes in food energy intake or the acute effects of the last bout of exercise.
Effect of inhaled budesonide on ozone-induced airway hyperresponsiveness and bronchoalveolar lavage cells in dogs
Authors: Stevens W. H. , Adelroth E. , Wattie J. , Woolley M. J. , Ellis R. , Dahlback M. , O'Byrne P. M.
Published: December 2017

Inhaled corticosteroids are known to reduce components of the airway inflammation characteristic of asthma and improve airway hyperresponsiveness. However, the effect of inhaled corticosteroids on ozone-induced airway responses is unknown. Eight dogs inhaled budesonide [2.74 +/- 0.25 (SE) mg/day] or lactose powder twice daily for 7 days before inhaling ozone (3 ppm for 30 min) or dry air. Acetylcholine airway responsiveness was measured before and 1 h after ozone, followed by a bronchoalveolar lavage (BAL). The response to acetylcholine was expressed as the concentration causing an increase in lung resistance of 5 cmH2O.l–1.s above baseline (acetylcholine provocation concentration). Budesonide pretreatment significantly attenuated the ozone-induced increase in pulmonary resistance (P = 0.003) and neutrophil influx into BAL (P = 0.001) and significantly reduced BAL eosinophils (P = 0.026). However, budesonide pretreatment had no significant effect on ozone-induced airway hyperresponsiveness. After budesonide, the acetylcholine provocative concentration fell from 5.96 mg/ml (%SE 1.46) before to 1.11 mg/ml (%SE 1.63) after ozone (P = 0.006). After lactose, the acetylcholine provocative concentration fell from 5.34 mg/ml (%SE 1.40) before to 0.50 mg/ml (%SE 1.85) after ozone (P = 0.001). Dry air inhalation did not cause airway hyperresponsiveness (P = 0.68). These results suggest that ozone-induced airway hyperresponsiveness is steroid resistant and that airway neutrophils or eosinophils are not important in its pathogenesis.
Effects of acute lung injury on dynamic tissue properties
Authors: Ingenito E. P. , Mark L. , Davison B.
Published: December 2017

The dynamic properties of lung tissue after acute injury (ALI) were characterized by studying parenchymal strips prepared from guinea pigs endobronchially treated with hydrochloric acid. Forty-eight-hour samples (10 x 4 x 4 mm) from control (C), acid-damaged (D), and uninvolved (U) lungs of treated animals had elastance and resistance measured in a perfused organ bath system during uniaxial length oscillation at a mean force of 750 mg over a 1.5 (0.1–3 Hz)-fold decade frequency range and 5-fold (1–5%) strain amplitude range. Results were interpreted using a quasi-linear viscoelastic model with tissue stress expressed as an exponential function of strain. Among C strips, elastance increased linearly with the logarithm of frequency, whereas resistance decreased hyperbolically with frequency; both were strain amplitude independent. In contrast, elastance among D strips was uniformly greater (P < 0.0001) and was inversely strain amplitude dependent (P < 0.01); resistance was markedly elevated (P < 0.0001) but decreased hyperbolically with frequency similar to C strips. Resistance and elastance changes among U strips were intermediate between those for D and C strips. Histological grading of cellular infiltration, alveolar septal thickening, and hemorrhage correlated with functional changes. The frequency and amplitude dependencies and magnitude changes for resistance and elastance were similar to those previously observed in intact dog lungs after ALI. These findings suggest that ALI can affect the rheological properties of lung parenchyma independently of surfactant and that changes in lung mechanics after ALI may, in part, be determined at the parenchymal level.
Effects of airway parasympathetic tone on responses to intravenous bronchoconstrictor agonists in rats
Authors: Sorkness R. , Clough J. , Lemanske R. F.
Published: December 2017

To test the hypothesis that parasympathetic airway tone may affect airway responsiveness, we measured bronchoconstrictor responses to intravenous bethanechol (BCh) in anesthetized vagotomized rats with and without background vagal nerve stimulation and developed a predictive model based on pharmacological additivity between endogenous and intravenous agonists. A high degree of agreement (r2 = 0.93) between the measured and predicted responses indicated that intravenous BCh and parasympathetic tone had bronchoconstrictor effects that were pharmacologically additive. An expansion of the additive model was used to determine that the percentage of decrease in respiratory system conductance (Grs) would be a measure of airway response independent of background parasympathetic tone. As predicted, the percentage of decrease in Grs after intravenous BCh was minimally affected by background vagal stimulation. However, the percentage of decrease in Grs was augmented by vagal stimulation for intravenous 5-hydroxytryptamine hydrochloride, a known parasympathetic neuromodulator, and for methacholine, an agonist with nicotinic as well as muscarinic activity (P < 0.02 for each agonist). We conclude that airway parasympathetic tone can be a source of variability for airway responsiveness when substances having neuromodulatory activity are involved in the provocative challenge.
Quantification of adult cerebral hemodynamics by near-infrared spectroscopy
Authors: Elwell C. E. , Cope M. , Edwards A. D. , Wyatt J. S. , Delpy D. T. , Reynolds E. O.
Published: December 2017

Near-infrared spectroscopy was used to measure global cerebral blood flow and volume in 10 healthy adult volunteers. High- and low-cerebral blood flow compartments were detected with mean flows for all 10 subjects of 59 +/- 21 (SD) and 11 +/- 4 ml.100 g-1.min-1, respectively. The mean cerebral blood volume of the group was 2.85 +/- 0.97 ml/100 g. Analysis of spontaneous changes in the cerebral concentrations of oxyhemoglobin and deoxyhemoglobin demonstrated strong correlations between respiratory rate and the oscillation frequency of cerebral oxyhemoglobin concentration (r = 0.99) and arterial oxygen saturation (SaO2) (r = 0.99). An estimate of the mean cerebral oxygen saturation for all subjects averaged 59.4 +/- 12.4% when their mean SaO2 was 91.8 +/- 2.4% (equivalent to 67.6 +/- 13.8% at a normoxic SaO2 of 98%). These results demonstrate that near-infrared spectroscopy can be used as a noninvasive bedside technique for both qualitative and quantitative evaluation of cerebral hemodynamics and oxygenation in adults.
Muscle chemoreflex alters vascular conductance in nonischemic exercising skeletal muscle
Authors: Mittelstadt S. W. , Bell L. B. , O'Hagan K. P. , Clifford P. S.
Published: December 2017

Previous studies have shown that the muscle chemoreflex causes an augmented blood pressure response to exercise and partially restores blood flow to ischemic muscle. The purpose of this study was to investigate the effects of the muscle chemoreflex on blood flow to nonischemic exercising skeletal muscle. During each experiment, dogs ran at 10 kph for 8–16 min and the muscle chemoreflex was evoked by reducing hindlimb blood flow at 4-min intervals (0–80%). Arterial blood pressure, hindlimb blood flow, forelimb blood flow, and forelimb vascular conductance were averaged over the last minute at each level of occlusion. Stimulation of the muscle chemoreflex caused increases in arterial blood pressure and forelimb blood flow and decreases in forelimb vascular conductance. The decrease in forelimb vascular conductance demonstrates that the muscle chemoreflex causes vasoconstriction in the nonischemic exercising forelimb. Despite the decrease in vascular conductance, the increased driving pressure caused by the pressor response was large enough to produce an increased forelimb blood flow.
Pentoxifylline inhibits basal glucose production in humans
Authors: Corssmit E. P. , Romijn J. A. , Endert E. , Sauerwein H. P.
Published: December 2017

Adenosine stimulates hepatic glucose production in vitro. To investigate whether pentoxifylline, a xanthine derivative that blocks the adenosine receptor, inhibits basal glucose production, we measured hepatic glucose production in eight healthy postabsorptive subjects on two occasions: during continuous infusion of pentoxifylline and, in a control study, during saline infusion. Glucose production was measured by primed continuous infusion of [3–3H]glucose. Pentoxifylline infusion resulted in an approximately 22 (volume of distribution for glucose 40 ml/kg) to approximately 46% (volume of distribution for glucose 165 ml/kg) decrease in basal glucose production within approximately 1 h (P < 0.05), whereas in the control experiment glucose production declined by only approximately 4% in this time interval (P < 0.03 pentoxifylline vs. control). There were no differences in concentrations of insulin, C peptide, glucagon, or catecholamines between the two experiments. Because pentoxifylline inhibited glucose production in the absence of any changes in concentrations of glucoregulatory hormones, we conclude that pentoxyifylline inhibits hepatic glucose production through other mechanisms, e.g., by blocking the adenosine receptor.
TNF potentiates PAF-induced pulmonary vasoconstriction in the rat: role of neutrophils and thromboxane A2
Authors: Chang S. W.
Published: December 2017

Both tumor necrosis factor (TNF) and platelet-activating factor (PAF) are released during sepsis and are important mediators of septic lung injury. I investigated the interactions of TNF and PAF on vasoactive responses in the pulmonary circulation. In isolated rat lungs perfused with a cell- and plasma-free physiological salt solution, PAF (0.01- and 0.1-micrograms boluses) caused transient dose-dependent pulmonary arterial and venous constrictions. In vivo pretreatment of the rats with TNF (0.02 or 0.2 mg/kg i.v.) 1 h before lung isolation increased lung myeloperoxidase activity and markedly enhanced PAF-induced pulmonary vasoconstriction without affecting the pressor responses to angiotensin II or hypoxia. In contrast, pretreatment with lipopolysaccharide (10 mg/kg), which increased lung myeloperoxidase to the same extent as TNF, caused only a modest enhancement of PAF-induced vasoconstriction associated with reduced pressor responses to angiotensin II and hypoxia. Ex vivo perfusion of isolated lungs with TNF for 1 h did not affect PAF vasoconstriction. The TNF-induced potentiation of PAF vasoconstriction was not altered by depletion of circulating neutrophils with vinblastine but was blocked by Dazmegrel, a thromboxane synthase inhibitor. Thus, TNF potentiates PAF-induced pulmonary vasoconstriction by an in vivo mechanism that is neutrophil independent but thromboxane dependent. This TNF-PAF interaction likely contributes to the development of pulmonary hypertension during sepsis.
Volume-homeostatic mechanisms in humans during graded water immersion
Authors: Larsen A. S. , Johansen L. B. , Stadeager C. , Warberg J. , Christensen N. J. , Norsk P.
Published: December 2017

The purpose of this experiment was to investigate whether a graded increase in cardiac distension induced by graded water immersion (WI) could be related to endocrine responses and renal sodium excretion (UNaV). On 3 separate days, nine healthy males were investigated in the upright seated position before, during, and after 3 h of WI to the midchest (CI) or to the neck (NI) or during control. Central venous pressure increased twice as much during NI as during CI. UNaV increased to the same extent during NI compared with CI, whereas urine flow rate, solute-free water clearance, and osmotic excretion increased more during the 2nd h of NI than during CI. During NI, the plasma concentration of atrial natriuretic peptide (ANP) increased twice as much as during CI. The plasma concentrations of aldosterone and norepinephrine were decreased in a similar manner during NI compared with CI. In conclusion, graded cardiac distension induced by graded WI and accompanied by a graded release of ANP was not accompanied by a graded increase in UNaV. Thus either a cardiac distension pressure of approximately one-half of that during NI is enough to induce a maximum UNaV during WI or other stimuli are important. Furthermore, aldosterone and norepinephrine are probably more important mediators of the natriuresis of WI in humans than is ANP.
Effect of chronic hypoxia on pulmonary vascular pressures in isolated lungs of newborn pigs
Authors: Fike C. D. , Kaplowitz M. R.
Published: December 2017

Our purposes were to determine whether chronic alveolar hypoxia altered pulmonary vascular pressures in lungs of newborn pigs, evaluate the contribution of smooth muscle tone to alterations in pulmonary vascular pressures, and examine whether chronic hypoxia altered pulmonary vascular reactivity to acute hypoxia. We kept 24- to 72-h-old pigs in chambers filled with room air (control) or 11–12% O2 (chronic hypoxia) for either 3–5 (short) or 10–12 (long) days. We used isolated lungs and applied micropuncture and vascular occlusion techniques to measure pressure in 10- to 30-microns-diam venules and inflow occlusion and outflow occlusion pressures before and after the addition of the smooth muscle dilator papaverine or before and after inflation of the lungs with a hypoxic gas mixture. For pigs in both the short and long groups, pulmonary arterial pressure was the only vascular pressure that was greater in chronically hypoxic than in control lungs. Increased smooth muscle tone was the primary source of the change in pulmonary arterial pressure with short hypoxia, whereas morphometric changes contributed to the change in pulmonary arterial pressure with long hypoxia. Exposure of newborn pigs to different lengths of alveolar hypoxia is a useful model to study postnatal pulmonary hypertension in newborns and infants.
Evaluation of the needle technique for producing an arteriovenous fistula
Authors: Huang M. , LeBlanc M. H. , Hester R. L.
Published: December 2017

The purpose of the present study were to evaluate the needle technique of creating an arteriovenous (a-v) fistula and to quantitatively determine the hemodynamic responses in rats with three different fistula sizes. The fistula was made in male Sprague-Dawley rats between the aorta and vena cava below the renal arteries by using 20-, 18-, and 16-gauge angiocath needles. Five weeks after a sham operation or creation of an a-v fistula, mean arterial blood pressure (MAP), right atrial pressure, shunt flow, cardiac index, systemic flow, individual organ flows, and heart weight were quantitatively determined. All flow measurements were made using radioactive microspheres. The flow to the lungs was used as a measure of shunt flow. The shunt flow in the 20-, 18-, and 16-gauge fistula animals was significantly increased from a value of 2 +/- 1% (SE) to 50.0 +/- 0.1, 78 +/- 3, and 76 +/- 3% of total cardiac output, respectively. Average cardiac index in the 20-, 18-, and 16-gauge fistula animals increased by 105, 270, and 250%, respectively, compared with control. Right atrial pressure and heart weight were increased in proportion to the size of the fistula. MAP in the control and 20-, 18-, and 16-gauge fistula animals was 122 +/- 5, 126 +/- 3, 118 +/- 3, and 111 +/- 4 mmHg, respectively. There were no significant differences in MAP or systemic flow among any of these groups. The calculated total peripheral resistance in all fistula groups was significantly decreased compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)
IMP metabolism in human skeletal muscle after exhaustive exercise
Authors: Tullson P. C. , Bangsbo J. , Hellsten Y. , Richter E. A.
Published: December 2017

This study addressed whether AMP deaminase (AMPD)myosin binding occurs with deamination during intense exercise in humans and the extent of purine loss from muscle during the initial minutes of recovery. Male subjects performed cycle exercise (265 +/- 2 W for 4.39 +/- 0.04 min) to stimulate muscle inosine 5'-monophosphate (IMP) formation. After exercise, blood flow to one leg was occluded. Muscle biopsies (vastus lateralis) were taken before and 3.6 +/- 0.2 min after exercise from the occluded leg and 0.7 +/- 0.0, 1.1 +/- 0.0, and 2.9 +/- 0.1 min postexercise in the nonoccluded leg. Exercise activated AMPD; at exhaustion IMP was 3.5 +/- 0.4 mmol/kg dry muscle. Before exercise, 16.0 +/- 1.6% of AMPD cosedimented with the myosin fraction; the extent of AMPD:myosin binding was unchanged by exercise. Inosine content increased about threefold during exercise and twofold more during recovery; by 2.9 min postexercise it was 0.43 +/- 0.02 mmol/kg dry muscle. IMP decreased 2.1 +/- 0.3 mmol/kg dry muscle with no change in total adenylates. Total purines declined significantly (P < 0.05) during the recovery period in the nonoccluded leg, consistent with a loss of purines to the circulation, whereas total purines were unchanged in the occluded leg. Regulation of muscle purine content is a dynamic process that must accommodate rapid changes due to degradation and efflux.
Rapid tracer lactate influx into canine skeletal muscle
Authors: Gladden L. B. , Crawford R. E. , Webster M. J. , Watt P. W.
Published: December 2017

This study evaluated the effects of various lactate transport inhibitors and competitors on rapid tracer lactate influx into the canine gastrocnemius-plantaris muscle (GP). GPs of 25 anesthetized dogs were perfused with red blood cell-free media in situ. At 0.9 mM lactate concentration ([La]), GP oxygen uptake (2.6 +/- 0.1 ml.kg-1.min-1) and net lactate output (-0.039 +/- 0.007 mmol.kg-1.min-1) were similar to values during blood perfusion. Rapid tracer lactate influx was inferred by a paired-tracer dilution method at nominal perfusate [La] values of 1, 5, 10, 25, and 50 mM. The maximal tracer influx rate (Umax) decreased significantly with each increase in unlabeled [La]. A saturation effect was suggested by the fact that percent inhibition of Umax began to reach a plateau at the higher unlabeled [La] values. The inhibition of Umax was 20.5 +/- 2.9% at 5 mM, 34.1 +/- 3.3% at 10 mM, 47.3 +/- 2.7% at 25 mM, and 56.1 +/- 2.8% at 50 mM [La]. Umax was also inhibited by various inhibitors/competitors of lactate transport as follows (% inhibition): 50 mM alpha-cyano-4-hydroxy-cinnamate (69.2 +/- 4.9%), 1.5 mM phloretin (25.4 +/- 5.5%), 0.1 mM 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (0.3 +/- 1.9%), 0.5 mM p-chloromercuribenzenesulfonic acid (72.9%), 0.5 mM furosemide (+ 2.8%), 25 mM pyruvate (52.4 +/- 2.9%), and 50 mM DL-lactate (50.2 +/- 4.0%). These experiments support the notion that lactate influx into canine skeletal muscle is a function of both a linear (possible diffusive) component and a Michaelis-Menten (carrier-mediated) component.
Model for a pump that drives circulation of pleural fluid
Authors: Butler J. P. , Huang J. , Loring S. H. , Lai-Fook S. J. , Wang P. M. , Wilson T. A.
Published: December 2017

Physical and mathematical models were used to study a mechanism that could maintain the layer of pleural fluid that covers the surface of the lung. The pleural space was modeled as a thin layer of viscous fluid lying between a membrane carrying tension (T), representing the lung, and a rigid wall, representing the chest wall. Flow of the fluid was driven by sliding between the membrane and wall. The physical model consisted of a cylindrical balloon with strings stretched along its surface. When the balloon was inflated inside a vertical circular cylinder containing a viscous fluid, the strings formed narrow vertical channels between broad regions in which the balloon pressed against the outer cylinder. The channels simulated the pleural space in the regions of lobar margins. Oscillatory rotation of the outer cylinder maintained a lubricating layer of fluid between the balloon and the cylinder. The thickness of the fluid layer (h), measured by fluorescence videomicroscopy, was larger for larger fluid viscosity (mu), larger sliding velocity (U), and smaller pressure difference (delta P) between the layer and the channel. A mathematical model of the flow in a horizontal section was analyzed, and numerical solutions were obtained for parameter values of mu, U, delta P, and T that matched those of the physical model. The computed results agreed reasonably well with the experimental results. Scaling laws yield the prediction that h is approximately (T/delta P)(microU/T)2/3. For physiological values of the parameters, the predicted value of h is approximately 10(-3) cm, in good agreement with the observed thickness of the pleural space.
Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle
Authors: Adams G. R. , Baldwin K. M.
Published: December 2017

This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid [creatine depletion juvenile (CDJ) group]. Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens [normal diet adult and creatine depletion adult (CDA) groups]. After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC distribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC transitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of animals to be used.
Arterial and arteriolar contributions to skeletal muscle functional hyperemia in spontaneously hypertensive rats
Authors: Lash J. M.
Published: December 2017

During contractions of the spinotrapezius muscle in spontaneously hypertensive rats (SHR), arteriolar dilation is of normal magnitude but tissue PO2 is significantly depressed relative to normotensive [Wistar-Kyoto (WKY)] rats. This study examined the possibility that this low PO2 results from suppressed dilation of the upstream arterial feed vessels and a limitation of muscle blood flow. Contraction-induced changes in vascular resistances (R) and conductances (G) were calculated for upstream (Rup, Gup), microvascular (Rst, Gst), and downstream (Rdown, Gdown) vascular segments from measurements of pressure and flow in the rostral feed artery and vein. Feed arteries were smaller in SHR than in WKY rats at rest and after contractions (rest, 63.0 +/- 2.6 vs. 86.0 +/- 4.8 microns; 2 Hz 84.0 +/- 4.5 vs. 111.0 +/- 7.3 microns; 8 Hz, 130.0 +/- 5.9 vs. 144.0 +/- 7.1 microns). However, relative increases [times control (xCT)] in diameter and flow were greater in SHR (8 Hz diam, 2.080 +/- 0.072 vs. 1.690 +/- 0.042 xCT; 8 Hz flow, 15.700 +/- 2.057 vs. 8.170 +/- 0.752 xCT). In both groups, Rup and Rst decreased 60–70 and 85–90% after 2- and 8-Hz contractions, respectively. However, segmental vascular conductances increased more in SHR than in WKY rats (8 Hz: Gup, 18.50 +/- 3.76 vs. 8.00 +/- 1.26 xCT; Gst, 19.90 +/- 3.73 vs. 10.10 +/- 0.96 xCT; Gdown, 8.80 +/- 1.70 vs. 5.50 +/- 0.88 xCT). Therefore, upstream arterial dilation is not suppressed during muscle contractions in SHR, and deficits in muscle blood flow and oxygen delivery cannot account for the abnormally low tissue PO2 observed during muscle contractions in SHR.
Intrapulmonary distribution of alveolar gas exchange during breath-hold diving in humans
Authors: Liner M. H. , Linnarsson D.
Published: December 2017

Expirograms for CO2 and O2 obtained immediately after 75-s breath holds (BHs) in thermoneutral conditions were studied in 10 subjects. BHs were performed at normal atmospheric pressure in dry condition (dry surface BH), at normal atmospheric pressure submerged (wet surface BH), and during a transient increase of ambient pressure to 3 atmospheres absolute submerged (wet BH dive). Cardiac index was estimated by means of impedance cardiography. Phase III (alveolar plateau) slopes for CO2 expirograms were lowest after wet surface BH. The greater slope observed after dry surface BH was attributed mainly to intrapulmonary perfusion heterogeneity and the greater slope seen after wet BH dive to continuing alveolar CO2 exchange during expiration. Cardiogenic oscillations in phase III (evaluated by spectral analysis) were largest after dry surface BH, much reduced by wet surface BH, and further reduced by wet BH dive. This was attributed to more even distribution of pulmonary perfusion during submersion and compression. Terminal changes of the expirograms (phase IV) revealed a less even interregional pulmonary distribution of CO2 and a more even distribution of O2 after wet BH dive compared with wet surface BH. This difference was attributed to improved apical pulmonary perfusion at depth during the wet BH dives.
K+ balance of the quadriceps muscle during dynamic exercise with and without beta-adrenoceptor blockade
Authors: Gullestad L. , Hallen J. , Sejersted O. M.
Published: December 2017

The effect of propranolol (0.15 mg/kg body wt) on K+ fluxes was investigated in seven healthy males performing 8-min two-legged knee-extension exercise at two different powers. K+ concentration was measured in the femoral vein by a K(+)-selective electrode, and leg blood flow was measured by the dye-dilution technique. During control bouts, rates of change in femoral venous K+ concentration were 38 +/- 10 and 53 +/- 8 mumol.l–1.s-1 at onset of exercise (K+ efflux) and -14 +/- 3 and -34 +/- 3 mumol.l–1.s-1 at cessation of exercise (K+ reuptake) at low and high powers, respectively. This mismatch between K+ efflux and reuptake rates fits with the steady-state K+ loss rate of 0.14 +/- 0.04 and 0.32 +/- 0.09 mmol/min. Propranolol raised K+ efflux rate, did not modify K+ reuptake rate or steady-state K+ loss, but caused transiently increased K+ loss rate at the onset of exercise, thus accentuating the rise of arterial K+ concentration. In conclusion, the continuous muscle K+ loss during steady-state exercise with a small muscle mass is not due to lack of catecholamine stimulation, but beta-adrenoceptor blockade increased the Na(+)-K+ pump lag so that the initial K+ loss at onset of exercise was increased.
Ventilatory responses to dead space and CO2 breathing under inspiratory resistive load
Authors: Sidney D. A. , Poon C. S.
Published: December 2017

To investigate how breathing is controlled during CO2 stimulation, steady-state ventilatory responses to rebreathing through a tube (DS) and inspiring a fixed PCO2 (INH) were compared in healthy human subjects. Tests were performed in hyperoxia with (IRL) and without (NL) an inspiratory resistive load (15 cmH2O.l–1.s at 1 l/s). The mean slope of the minute ventilation (VE)-end-tidal PCO2 relationship was significantly higher in DS-IRL than in INH-IRL [1.86 +/- 0.67 (SD) vs. 1.40 +/- 0.32 l.min-1.Torr-1, P < 0.01], and it was significantly different between INH-NL and INH-IRL (1.64 +/- 0.41 vs. 1.40 +/- 0.32 l.min-1.Torr-1, P < 0.05) but not between DS-NL and DS-IRL (1.85 +/- 0.72 vs. 1.86 +/- 0.67 l.min-1.Torr-1). The slope of the VE-tidal volume relationship was significantly lower in DS-NL than in INH-NL (19.6 +/- 3.8 vs. 21.2 +/- 5.1 min-1, P < 0.05), but other comparisons in breathing pattern between NL and IRL and between DS and INH failed to reach significance. We concluded that 1) alterations in alveolar PCO2 temporal profile by DS could induce changes in VE-end-tidal PCO2 sensitivity and ventilatory pattern, 2) these changes may be modified by increased mechanical impairment resulting from IRL, and 3) carotid chemoreceptor mediation is not necessary for the observed effects of DS.
Effect of fasting and refeeding on acetyl-CoA carboxylase in rat hindlimb muscle
Authors: Winder W. W. , MacLean P. S. , Lucas J. C. , Fernley J. E. , Trumble G. E.
Published: December 2017

Previous studies have demonstrated marked differences in liver acetyl-CoA carboxylase (ACC) activity between fasted rats and fasted rats refed with a fat-free diet. This study was designed to determine whether skeletal muscle ACC responds to dietary manipulation similarly to liver. Male Sprague-Dawley rats were fasted 48 h (F), fasted 48 h and refed fat-free diet for 48 h (R), or were fed normal rat chow ad libitum (A). Liver ACC, measured on resuspended ammonium sulfate precipitates of 48,000 g supernatants of tissue homogenates, was markedly decreased in F (77 +/- 6 nmol.g-1.min-1) and increased in R (562 +/- 37 nmol.g-1.min-1) rats compared with A rats (210 +/- 23 nmol.g-1.min-1). The citrate concentration required to cause half-maximal activation of liver ACC (K0.5) was 1.34 +/- 0.14 mM for F, 0.77 +/- 0.09 mM for R, and 0.87 +/- 0.09 mM for A. The quadriceps muscle, on the other hand, showed no difference in ACC activity or in the K0.5 for citrate activation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots confirmed the biochemical measurements, showing marked differences in the size of the protein bands in the +260,000 mol wt range in F vs. R liver ACC preparations but not in skeletal muscle ACC preparations. We conclude that skeletal muscle ACC is controlled by different mechanisms than those observed in liver.
Ventilation and carbon dioxide exchange in exercising horses: effect of inspired oxygen fraction
Authors: Pelletier N. , Leith D. E.
Published: December 2017

Thoroughbred horses (TB) have no ventilatory response to added CO2 during near-maximal exercise. To see whether that reflects mechanical limits to ventilation or the control of breathing, we examined the effects of varying inspired O2 fraction (0.16, 0.21, or 0.30) in five normal TB standing quietly and galloping at 10 and 14 m/s on a level treadmill. We measured gas exchange (O2 consumption and CO2 production) and ventilation with a flow-through mask system. We also measured PO2, PCO2, and O2 contents in arterial and mixed venous blood and calculated cardiac output by using the Fick equation. Low inspired O2 fraction (0.16 vs. 0.21) had significant effects in TB galloping at 14 m/s. Arterial PO2 then was 38 Torr compared with 56 Torr for horses on air. Tidal volume and minute ventilation were 20% greater than their corresponding values on air, which were 12 liters and 1,475 l/min, respectively, whereas respiratory frequency did not change. O2 consumption and CO2 production were unchanged, but alveolar ventilation was 6% greater, despite increased alveolar and physiological dead spaces, so arterial PCO2 was lower (45 vs. 50 Torr on air). Thus, hypoxia was an effective stimulus to breathing, and minute ventilation was not mechanically limited in TB breathing air at the speeds studied.
Ventilatory response to isocapnic hyperoxia
Authors: Becker H. , Polo O. , McNamara S. G. , Berthon-Jones M. , Sullivan C. E.
Published: December 2017

Breathing O2 for up to 1 h has been shown to either not influence or slightly increase (6–13%) minute ventilation. However, end-tidal PCO2 was not kept constant in these experiments. In nine healthy men, we studied the ventilatory, blood pressure, and heart rate responses to 30 min of normobaric hyperoxia (50% O2) at isocapnic conditions. Hyperoxia led to a 60% increase in mean minute ventilation (P = 0.002), largely due to an increase in mean tidal volume from 0.66 +/- 0.04 (SE) to 0.88 +/- 0.05 liter (P = 0.007). Fifteen minutes after the termination of hyperoxia, minute ventilation was still increased (P = 0.02) compared with baseline, although it was reduced compared with hyperoxia (P = 0.02). Arterial blood gas analyses in six subjects before and during hyperoxia showed an increase in arterial PO2 and O2 saturation but no change in arterial PCO2 or pH. Hyperoxia induced no changes in arterial blood pressure or heart rate. We conclude that 1) isocapnic hyperoxia stimulates respiration markedly, an effect that is approximately five times higher than previously measured; 2) the increase in ventilation induced by hyperoxia does not affect arterial blood pressure and heart rate; and 3) in experiments using hyperoxia, its effect on breathing and subsequently on PCO2 has to be taken into account.
Quantifying the potential of infant bedding to limit CO2 dispersal and factors affecting rebreathing in bedding
Authors: Kemp J. S. , Thach B. T.
Published: December 2017

Rebreathing may impair ventilation and lead to sudden death among sleeping infants. To estimate the potential for rebreathing imposed by an infant's sleep microenvironment, we developed a mechanical model to assess the rate of CO2 dispersal away from an infant's face. We compared the mechanical model results with changes in arterial blood gases of rabbits. The rabbits breathed into the same microenvironments used for the model studies. In the rabbits, rebreathing (documented by capnometry) caused hypercarbia and in some cases death. The mechanical model consisted of the mannequin head positioned as in the rabbit studies and connected to a 100-ml syringe filled with CO2. CO2 was washed out of the system using 30-ml “breaths” (rate = 15/min). The half times (t1/2) for CO2 dispersal served to quantify the rebreathing potential of 16 items of bedding. The t1/2 values correlated with increments in the rabbits' arterial PCO2 (r = 0.789). The threshold for the increase in the rabbits' arterial PCO2 corresponded to t1/2 values of > or = 18.7 s; the 90% point for lethality in the rabbit model was 28.1 s. The mechanical model was also used to show the independent effects of softness and porosity of bedding on its rebreathing potential. By describing the potential for rebreathing within bedding, the mechanical model should be useful in future quantitative studies of infants' respiratory adaptation to sleep microenvironments.
Diaphragm thickness heterogeneity at functional residual capacity and total lung capacity
Authors: Wait J. L. , Staworn D. , Poole D. C.
Published: December 2017

One of the determinants of muscular force is the number of myofibrils in parallel, which is approximated by thickness. To better understand the heterogeneity of diaphragm thickness, we quantified the interregional and radial patterns of thickness of nine canine diaphragms rapidly perfusion fixed in situ with glutaraldehyde at functional residual capacity (FRC) (n = 6) and total lung capacity (TLC) (n = 3). Thickness was determined gravimetrically from punch biopsies radiating from the central tendon to rib cage insertion in ventral, middle, and dorsal costal and crural regions. For comparison, the contralateral unfixed hemidiaphragm was sampled in the same fashion. The findings of this investigation include the following. 1) The costal diaphragm exhibits the same pattern of interregional heterogeneity at FRC, TLC, and in the freshly excised state. 2) The costal diaphragm is significantly thinner at FRC in situ (0.17 +/- 0.01 cm) than is the freshly excised contralateral diaphragm (0.21 +/- 0.01 cm; P < 0.05), whereas there is no significant difference between thickness at TLC and the freshly excised state. 3) There is significant, previously underscribed, radial tapering from the rib cage attachment (0.24 +/- 0.02) to the central tendon insertion (0.15 +/- 0.01 cm; P < 0.05) that is exaggerated at TLC. 4) With passive inflation from FRC to TLC, the greatest increase in thickness occurs close to the rib cage attachment for the ventral and medial costal regions but close to the central tendon in the dorsal and crural regions. We conclude that the diaphragm at FRC and TLC exhibits radial thickness heterogeneity that cannot be predicted from dimensions of the freshly excised diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. I. Theory and error analysis
Authors: Markham J. , McCarthy T. J. , Welch M. J. , Schuster D. P.
Published: December 2017

We developed a procedure for measuring pulmonary angiotensin-converting enzyme kinetics with fluorine-18 fluorocaptopril and positron emission tomography (PET). The method is based on the application of a compartmental receptor model that represents the kinetics of two species of ligand, presumably the trans and cis conformers of captopril. The input function was characterized and includes corrections for the labeled metabolites of fluorocaptopril. Application of the procedure to lung time-activity data obtained with PET produced estimates of kinetic parameters demonstrating fast kinetics for one conformer and slower kinetics for the other. Simulation studies were performed to evaluate the sensitivity of the estimated parameters to errors in the model assumptions and in measured values for variables required for analysis of the PET data. Estimates for two of the kinetic parameters, the amount of perfused unbound functional enzyme normalized to regional lung volume and the association rate constant for the trans conformer, were relatively stable even with large errors in the input data, varying < 30% from true values for all perturbations. Thus, the procedure produces reliable estimates of the kinetics of the trans conformer of captopril as well as theoretical curves that are close to the observed data.
Effects of high pressures of various gas mixtures on rat striatal dopamine detected in vivo by voltammetry
Authors: Rostain J. C. , Forni C.
Published: December 2017

This work was performed to study the effect of pressure of various gas breathing mixtures on dopaminergic activity in the striatum by in vivo differential pulse voltammetry using carbon multifiber electrodes chronically implanted in 23 freely moving rats. Compression (0.5 bar/min) in a helium-oxygen mixture induced an increase in striatal extracellular dopamine (DA) beginning at 10–20 bars and reaching 32% above precompression levels when arriving at 90 bars (n = 9). To demonstrate that this increase is dopaminergic, nine rats with right nigrostriatal pathway 6-hydroxydopamine lesions were compressed in the same conditions. In this case, the increase in DA did not occur in the right caudate nucleus but was recorded in the intact left caudate nucleus. To study the effects on DA increase of narcotic gases, which are known to reduce some high-pressure nervous syndrome symptoms, eight and six rats were compressed in helium-nitrogen-oxygen and hydrogen-helium-oxygen mixtures, respectively. They produced similar changes in striatal DA level in the same pressure range (23 and 20% increase, respectively, at the end of the compression). Consequently, the increase in striatal DA seems independent of the nature of the breathing mixture and seems related to the increase of pressure. The origin of this increase could be a pressure effect at the pre- or postsynaptic level.
Influence of spaceflight on the production of interleukin-3 and interleukin-6 by rat spleen and thymus cells
Authors: Miller E. S. , Koebel D. A. , Sonnenfeld G.
Published: December 2017

Six adult male Sprague-Dawley rats were flown on the 7-day US space shuttle mission STS-54. After flight, the spleen and thymus from each animal were assayed for the capacity to secrete the cytokines interleukin-3 (IL-3) and IL-6. Spleen and thymus cells (5 x 10(6)/ml) were incubated for 48 h in the presence of 5 micrograms/ml of concanavalin A or 2 micrograms/ml of bacterial lipopolysaccharide to stimulate the production of IL-3 and IL-6. IL-3 activity was measured using the IL-3/colony-stimulating-factor-dependent cell line 32D. IL-6 activity was measured using the IL-6-dependent cell line 7TD1. Spleen and thymus cells harvested from flown rats secreted significantly higher titers of biologically active IL-3 compared with ground control rats. Spaceflight significantly enhanced IL-6 production by thymus, but not spleen, cells. The results of this study demonstrate that spaceflight can enhance the production of certain cytokines by cells of the immune system.
Influence of isometric loading on biceps EMG dynamics as assessed by linear and nonlinear tools
Authors: Webber C. L. , Schmidt M. A. , Walsh J. M.
Published: December 2017

The summed electrical discharges generated by a contracting skeletal muscle constitute a dynamic system conveying electromyographic (EMG) information indicative of muscle physiological status. “Steady states” of activity can be achieved with light loads, but with heavy loads the dynamic system experiences continuous status transitions that culminate in task failure. The present study was designed to assess the applicability of two mathematical tools, one linear and the other nonlinear, in addressing the time course of EMG alterations under different loading challenges. Surface EMGs of the biceps brachii muscle were recorded from 14 healthy human volunteers during light and heavy loadings, and task failure occurred at varying times among the subjects. Digitized EMG signals were analyzed by linear spectral analysis (fast Fourier transform) and nonlinear recurrence-plot analysis. With light loading, computed variables from both analyses gave “quasi-steady-state” values over time, with recurrence-plot analysis having the higher variance. With heavy loading, the nonlinear variable (%determinism) increased sooner and exhibited larger changes from control values than decreases in the linear variable (spectral center frequency). Experimental results support the conclusion that both analyses can be combined to give a fuller assessment of the biceps EMG during light or heavy loading. Implications for the detection of muscular fatigue are discussed.
Reduced motor unit activation of muscle spindles and tendon organs in the immobilized cat hindlimb
Authors: Nordstrom M. A. , Enoka R. M. , Reinking R. M. , Callister R. C. , Stuart D. G.
Published: December 2017

Six weeks of limb immobilization of a healthy muscle (cat tibialis posterior) at a short length resulted in a significant reduction of mean fiber area for all fiber types (I, 71% of control; IIa, 77% of control; IIb, 79% of control), whereas fiber type proportions were unchanged. For motor units, there was a reduction in peak tetanic force (type slow > fast fatigue resistant > fast fatigable); an increase in the twitch-to-tetanus ratio for fast fatigue-resistant and slow units; and no effect on the twitch force, twitch time course, or fatigability. The reduction in peak force was greater than expected because of fiber atrophy in slow units. Immobilization had a minimal effect on muscle spindle afferent (Ia and spindle group II) responses to a ramp-and-hold stretch of the passive muscle. Tendon organ (Ib) afferents had an increased responsiveness to stretch after immobilization but only when the muscle was stretched from a short resting length. However, immobilization reduced the modulation of muscle afferent discharge in response to tetanic contractions of single motor units. The decline in responsiveness of spindles was a result of the reduced tetanic force of motor units. In contrast, tendon organs in immobilized muscle were twice as likely to convey no information on the contraction of a single motor unit and were more likely to be unloaded, suggesting that immobilization caused the functional denervation of some muscle fibers. Thus the responses of muscle spindles and tendon organs in immobilized muscle reflected atrophic changes in extrafusal fibers but did not provide evidence for substantial disturbance of receptor function.
Diaphragmatic microcirculation measured by laser-Doppler flowmetry in the rat
Authors: Chang H. Y. , Chen C. R. , Hussain S. N.
Published: December 2017

The applicability of laser-Doppler flowmetry (LDF) in measuring regional blood flow of the diaphragm (Qdi) was evaluated in anesthetized and mechanically ventilated rats. Specifically, we assessed the issues of the degree of tissue perfusion, spatial variations of Qdi signals, and the correlation between these signals and total Qdi. Qdi was detected from an area 1 mm in diameter and 0.5 mm in depth. With Ringer solution continuously suffusing the abdominal surface of the left hemidiaphragm, drugs were applied to the surface of the diaphragm at 1/100 of the flow rate of the suffusing fluid. In 13 rats, resting Qdi and the response of Qdi to a single concentration of adenosine (10(-4) M) remained unchanged over a 2-h period. Increasing adenosine concentrations (10(-9) to 10(-3) M) in eight rats elicited a progressive rise in Qdi. In six rats, the variability of Qdi in a given rat was assessed over five different sites at 2-mm intervals in a line on the diaphragm. A wide range of variability in Qdi was noticed among different sites. The depth of tissue penetration of LDF was little affected when a piece of freshly diaphragm was interposed between the probe and the perfused diaphragm, suggesting that LDF signals arise from complete penetration of the perfused diaphragm. Finally, significant linear relationships between mean Qdi and total Qdi were observed in all animals; however, the slopes of these relationships varied significantly between animals. In conclusion, LDF provides a stable and continuous method for monitoring regional microvascular diaphragmatic perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Prominence of myosin heavy chain hybrid fibers in soleus muscle of spinal cord-transected rats
Authors: Talmadge R. J. , Roy R. R. , Edgerton V. R.
Published: December 2017

The effect of a midthoracic spinal cord transection (ST) on myosin heavy chain (MHC) isoform expression in the rat soleus muscle was studied. Electrophoretic analyses demonstrated that 15 days after ST there were significant proportional increases in type IIx, decreases in type IIa, and no change in type I MHC composition. Thirty days after ST, some type IIb MHC was expressed, there were further proportional increases in type IIx, an increase in type IIa (compared with 15-day ST), and a decrease in type I MHC. At both time periods after ST, many fibers expressed multiple MHCs, as demonstrated by immunohistochemistry where a battery of monoclonal antibodies specific to MHC isoforms was used. Fibers were observed containing types I and II together or multiple type II MHC isoforms. These data suggest that the expression of the normal complement of MHC isoforms in the adult rat soleus muscle is dependent, in part, on normal neuromuscular activation.