bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracheal gas exchange: perfusion-related differences in inert gas elimination
Authors: Souders J. E. , George S. C. , Polissar N. L. , Swenson E. R. , Hlastala M. P.
Published: December 2017

Exchange of inert gases across the conducting airways has been demonstrated by using an isolated dog tracheal preparation and has been characterized by using a mathematical model (E. R. Swenson, H. T. Robertson, N. L. Polissar, M. E. Middaugh, and M. P. Hlastala, J. Appl. Physiol. 72: 1581–1588, 1992). Theory predicts that gas exchange is both diffusion and perfusion dependent, with gases with a higher blood-gas partition coefficient exchanging more efficiently. The present study evaluated the perfusion dependence of airway gas exchange in an in situ canine tracheal preparation. Eight dogs were studied under general anesthesia with the same isolated tracheal preparation. Tracheal perfusion (Q) was altered from control blood flow (Qo) by epinephrine or papaverine instilled into the trachea and was measured with fluorescent microspheres. Six inert gases of differing blood-gas partition coefficients were used to measure inert gas elimination. Gas exchange was quantified as excretion (E), equal to exhaled partial pressure divided by arterial partial pressure. Data were plotted as ln [E/(l-E)] vs. In (Q/Qo), and the slopes were determined by least squares. Excretion was a positive function of Q, and the magnitude of the response of each gas to changes in Q was similar and highly significant (P < or = 0.0002). These results confirm a substantial perfusion dependence of airway gas exchange.
Effects of muscle-to-electrode distance on the human diaphragm electromyogram
Authors: Beck J. , Sinderby C. , Weinberg J. , Grassino A.
Published: December 2017

It has been suggested that esophageal recordings of the diaphragm electromyogram (EMGdi) are influenced by changes in chest wall configuration. Whether the changes are of physiological or artifactual origin is unclear. For example, the distance between the esophageal electrode and the diaphragm is likely to alter with chest wall configuration and may lead to misinterpretations of EMGdi. The aims of this study were 1) to evaluate and quantify the effect of the muscle-to-electrode (ME) distance filter on EMGdi, as obtained with a multiple-array esophageal electrode, 2) to take advantage of the ME distance filter to locate the position of the diaphragm with respect to the electrode, and 3) to evaluate the influence of lung volume and chest wall configuration on EMGdi center frequency (CF) while controlling for the ME distance filter and signal quality. Five subjects performed six static contractions of the diaphragm at each of seven chest wall configurations, as evaluated by the method of K. Konno and J. Mead (J. Appl. Physiol. 22: 407–422, 1967). EMGdi was measured with seven pairs of electrodes mounted on an esophageal catheter. The pair of electrodes whose EMGdi power spectra were the least filtered by the ME distance was assumed to be closest to the diaphragm. The results of the study indicated that 1) EMGdi power spectra were strongly affected by the distance between the diaphragm and the electrodes. CF decreased by approximately 1 Hz/mm displacement away from the electrode pair closest to the diaphragm; and 2) no systematic relationship was found between changes in chest wall configuration and CF, when CF was measured from the electrode pair closest to the diaphragm. We conclude that the EMGdi CF can be reliably measured with a multiple-array esophageal electrode that covers the span of diaphragmatic excursion and by selecting the pair of electrodes that is the closest to the diaphragm.
Inhaled nitric oxide does not alter endotoxin-induced nitric oxide synthase activity during rat lung perfusion
Authors: Kurrek M. M. , Castillo L. , Bloch K. D. , Tannenbaum S. R. , Zapol W. M.
Published: December 2017

Nitric oxide (NO) has been demonstrated to decrease its own synthesis in tissue preparations. We tested the hypothesis that endogenous NO synthesis induced by lipopolysaccharides (LPS) would be decreased by exogenous NO during isolated lung perfusion. Rats were pretreated with either saline or LPS 48 h before lung harvest. Endogenous NO synthase activity was measured as conversion of L-[14C]-arginine to L-[14C]citrulline during 90 min of perfusion. NO (100 ppm) was added to the ventilating gas during perfusion of lungs from one group of control or LPS-treated rats. A second group of control or LPS-treated rats was exposed chronically to 100 ppm NO for the 48 h before lung harvest, in addition to receiving 100 ppm NO added to the ventilating gas during lung perfusion. We conclude that conversion of L-[14C]arginine to L-[14C]citrulline was minimal in control lungs and increased in response to LPS pretreatment. NO added to the ventilating gas for the 90 min of ex vivo perfusion did not alter the rate of L-[14C]citrulline production. In vivo exposure to 100 ppm NO for 48 h did not alter the induction of inducible NO synthase activity as measured during ex vivo lung perfusion. This indicates that inhaled NO does not exert negative-feedback inhibition on inducible NO synthase in the ex vivo rat lung.
Age alters regional distribution of blood flow during moderate-intensity exercise
Authors: Kenney W. L. , Ho C. W.
Published: December 2017

During dynamic exercise in warm environments, requisite increases in skin and active muscle blood flows are supported by increasing cardiac output (Qc) and redistributing flow away from splanchnic and renal circulations. To examine the effect of age on these responses, six young (Y; 26 +/- 2 yr) and six older (O; 64 +/- 2 yr) men performed upright cycle exercise at 35 and 60% of peak O2 consumption (VO2peak) in 22 and 36 degrees C environments. To further isolate age, the two age groups were closely matched for VO2peak, weight, surface area, and body composition. Measurements included heart rate, Qc (CO2 rebreathing), skin blood flow (from increases in forearm blood flow (venous occlusion plethysmography), splanchnic blood flow (indocyanine green dilution), renal blood flow (p-amino-hippurate clearance), and plasma norepinephrine concentration. There were no significant age differences in Qc; however, in both environments the O group maintained Qc at a higher stroke volume and lower heart rate. At 60% VO2peak, forearm blood flow was significantly lower in the O subjects in each environment. Splanchnic blood flow fell (by 12–14% in both groups) at the lower intensity, then decreased to a greater extent at 60% VO2peak in Y than in O subjects (e.g., -45 +/- 2 vs. -33 +/- 3% for the hot environment, P < 0.01). Renal blood flow was lower at rest in the O group, remained relatively constant at 35% VO2peak, then decreased by 20–25% in both groups at 60% VO2peak. At 60% VO2peak, 27 and 37% more total blood flow was redistributed away from these two circulations in the Y than in the O group at 22 and 36 degrees, respectively. It was concluded that the greater increase in skin blood flow in Y subjects is partially supported by a greater redistribution of blood flow away from splanchnic and renal vascular beds.
Effect of carotid chemoreceptor denervation on breathing during ventrolateral medullary cooling in goats
Authors: Pan L. G. , Forster H. V. , Ohtake P. J. , Lowry T. F. , Korducki M. J. , Forster A. L.
Published: December 2017

It has been postulated that the so-called area S of the ventrolateral medulla (VLM) integrates peripheral chemoreceptor activity; thus cooling-induced dysfunction of neurons in this VLM area should functionally eliminate carotid chemoreceptor stimulation of breathing. Accordingly, carotid chemoreceptor denervation (CBD) should not alter the breathing effects of VLM neuronal dysfunction. To test this hypothesis in awake goats, chronically implanted thermodes were used to cool the VLM and thereby cause reversible neuronal dysfunction in all or portions of VLM areas M and S. Within 5 s after initiation of cooling approximately 60–100% of areas M and S in (P < 0.05) uniformly over conditions of eupnea, hypercapnia, and hypoxia. Between 10 and 20 s of cooling, the reduction in VI was approximately 10% greater (P < 0.05) during hypercapnia than during eupnea and hypoxia. For the remaining 10 s of cooling and for approximately 1 min after cooling, VI increased to and above control for all conditions. For all conditions, CBD accentuated the depression of VI during cooling, causing VI to decrease (P < 0.05) 10–40% more than before CBD. After CBD, the greatest effect on VI of cooling was again during hypercapnia. Thus the carotid bodies in intact goats appear to sense blood gas errors caused during VLM cooling to minimize the decreases in VI. We conclude that the data from this study do not support the concept that the VLM integrates carotid chemoreceptor activity.
Effect of graded epinephrine infusion on blood lactate response to exercise
Authors: Turner M. J. , Howley E. T. , Tanaka H. , Ashraf M. , Bassett D. R. , Keefer D. J.
Published: December 2017

In an attempt to determine whether the lactate threshold (LT) is the result of a sudden increase in plasma epinephrine (Epi), eight healthy college-aged males (22.4 +/- 0.4 yr) were recruited to perform three cycle ergometer exercise tests. Each subject performed a graded exercise test (GXT) to determine LT, Epi threshold, and norepinephrine threshold (64.6 +/- 2.4, 62.5 +/- 2.4, and 60.8 +/- 4.3% peak oxygen uptake, respectively). Each subject also completed, in random order, two 30-min submaximal (20% peak oxygen uptake below LT) exercise tests. During one test, graded Epi infusions were carried out at rates of 0.02–0.12 micrograms.kg-1.min-1; the other served as a control test. Infusion resulted in plasma Epi concentrations similar to those observed during GXT. The increase in blood lactate with Epi infusion was significantly greater than that during the control test (3.0 +/- 0.3 vs. 1.4 +/- 0.1 mmol/l at minute 30) but did not approach levels exhibited during GXT. We suggest an interaction of the increasing plasma Epi with other factors may be responsible for the sudden increase in blood lactate during graded exercise.
Effects of physical conditioning on endogenous nitric oxide output during exercise
Authors: Maroun M. J. , Mehta S. , Turcotte R. , Cosio M. G. , Hussain S. N.
Published: December 2017

Nitric oxide (NO) has been detected in the expiratory air of normal animals and human subjects. Recent experiments revealed that expiratory NO production rises during exercise and correlates well with O2 consumption (VO2) and heart rate. Whether physical conditioning influences expiratory NO output production remains unclear. In this study, NO concentration in expired gas was measured in 18 healthy male volunteers subdivided into three groups (sedentary, intermediate, and athletic) on the basis of the subjects' state of physical conditioning. Measurements were taken at rest and during two steady-state exercise bouts on a bicycle ergometer designed to elicit VO2 of 1 and 2 l/min with the athletes performing an additional bout at VO2 of 4 l/min. In the sedentary and intermediate groups, expired NO concentrations declined significantly with increasing VO2. In contrast, expired NO levels declined only slightly with increasing VO2 in the athletes. At a VO2 of 2 l/min, expired NO concentrations were significantly higher in the athletes compared with values in the other groups. When correlated with minute ventilation (VE), expired NO concentrations declined linearly with the increase in VE in sedentary and intermediate groups but not in the athletes. Only the athletes had a significant linear increase in NO output (expired NO x VE) with increasing VO2 (P < 0.001). These results support the notion that physical conditioning increases expiratory NO output during exercise. We speculate that the rise in expiratory NO output in the athletes might be due to increased vascular and/or epithelial production of NO. Enhanced vascular NO production may be the result of increased shear stress and/or upregulation of endothelial NO synthase gene expression.
Muscle function and protein metabolism after initiation of eccentric contraction-induced injury
Authors: Lowe D. A. , Warren G. L. , Ingalls C. P. , Boorstein D. B. , Armstrong R. B.
Published: December 2017

This study was designed to determine the relationship between skeletal muscle function and protein metabolism after initiation of eccentric contraction-induced injury. Mouse anterior crural muscles were injured in vivo, and then either immediately or 3, 6, 24, 48, 72, 120, or 336 h after injury muscles were isolated and studied for indexes of muscle function, injury, phagocyte infiltration, and protein metabolism. A group of mice were administered anti-polymorphonuclear cell and anti-macrophage antisera in an attempt to reduce phagocytic infiltration into injured muscle. Force production in extensor digitorum longus muscles was reduced 55% immediately after injury induction and did not recover significantly until 120 h postinjury (28% below baseline). However, rates of protein degradation were not elevated until 48 h postinjury (60% above normal) and were not correlated with the changes in force production (r = -0.37; P = 0.24). Phagocytic infiltration was evident 24–120 h postinjury and was correlated with the elevated protein degradation rates (r = 0.75; P < 0.01). Protein synthesis rates began to increase approximately 48 h after injury was induced and were elevated by 83% 5 days postinjury. Fourteen days after injury, muscle protein degradation and synthesis rates had returned to normal, as well as specific force production, and phagocytic infiltration was not detected. However, muscle mass, protein content, and absolute force production were lower than normal. Antisera-treated mice were rendered neutropenic, but there was no difference in any variable measured between muscles from these mice and muscles from normal mice.
Erythropoietin levels with treatment of obstructive sleep apnea
Authors: Cahan C. , Decker M. J. , Arnold J. L. , Goldwasser E. , Strohl K. P.
Published: December 2017

The effect of nasal continuous positive pressure (CPAP) treatment on erythropoietin (EPO) was examined by measuring diurnal serum EPO levels before and twice (over the 3rd day and over 1 day on recall after > or = 1 mo of therapy) after initiation of treatment in 12 obstructive sleep apnea syndrome patients with normal hemoglobin, hematocrit, creatinine, blood urea nitrogen, and albumin levels. Over each study day, oxygen saturation was measured by an ambulatory pulse oximetry system. Patients spent 27 +/- 9% (SE) of time below oxygen saturation of 88% vs. 2.1 +/- 0.6% after initiation of nasal CPAP treatment (P < 0.01). The number of desaturation events per hour of sleep before nasal CPAP treatment was 62 +/- 6 vs. 9 +/- 2 with nasal CPAP (P < 0.01). EPO levels measured by radioimmunoassay were drawn every hour before and at 3 days (n = 9) and before and at recall (n = 0) after initiation of CPAP therapy. The mean serum EPO level was higher before treatment (61 +/- 14 mU/ml) than that at 3 days (38 +/- 10 mU/ml, P < 0.01) or at recall (32 +/- 7 mU/ml, P < 0.01). We conclude that nasal CPAP treatment of sleep-disordered breathing will reduce diurnal levels of EPO.
Lung cytokinetics after exposure to hypobaria and/or hypoxia and undernutrition in growing rats
Authors: Sekhon H. S. , Thurlbeck W. M.
Published: December 2017

We measured resting pulmonary gas exchange in eight subjects exposed to 9 or 14 days of microgravity (microG) during two Spacelab flights. Compared with preflight standing measurements, microG resulted in a significant reduction in tidal volume (15%) but an increase in respiratory frequency (9%). The increased frequency was caused chiefly by a reduction in expiratory time (10%), with a smaller decrease in inspiratory time (4%). Anatomic dead space (VDa) in microG was between preflight standing and supine values, consistent with the known changes in functional residual capacity. Physiological dead space (VDB) decreased in microG, and alveolar dead space (VDB-VDa) was significantly less in microG than in preflight standing (-30%) or supine (-15%), consistent with a more uniform topographic distribution of blood flow. The net result was that, although total ventilation fell, alveolar ventilation was unchanged in microG compared with standing in normal gravity (1 G). Expired vital capacity was increased (6%) compared with standing but only after the first few days of exposure to microG. There were no significant changes in O2 uptake, CO2 output, or end-tidal PO2 in microG compared with standing in 1 G. End-tidal PCO2 was unchanged on the 9-day flight but increased by 4.5 Torr on the 14-day flight where the PCO2 of the spacecraft atmosphere increased by 1–3 Torr. Cardiogenic oscillations in expired O2 and CO2 demonstrated the presence of residual ventilation-perfusion ratio (VA/Q) inequality. In addition, the change in intrabreath VA/Q during phase III of a long expiration was the same in microG as in preflight standing, indicating persisting VA/Q inequality and suggesting that during this portion of a prolonged exhalation the inequality in 1 G was not predominantly on a gravitationally induced topographic basis. However, the changes in PCO2 and VA/Q at the end of expiration after airway closure were consistent with a more uniform topographic distribution of gas exchange.
Multifrequency bioelectrical impedance estimates the distribution of body water
Authors: Cha K. , Chertow G. M. , Gonzalez J. , Lazarus J. M. , Wilmore D. W.
Published: December 2017

Multifrequency bioelectrical impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water in subjects with end-stage renal disease. The body's resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index (height2/resistance) determined at low frequency (5 kHz) correlated most closely with ECW (r = 0.886) using sodium bromide dilution as the standard of comparison. In contrast, the ratio of height squared to resistance determined at high frequency (500 kHz) correlated most closely with total body water (r = 0.974) using deuterium oxide dilution as the standard of comparison. The ratio of resistance at 500 kHz to resistance at 5 kHz was directly correlated (r = 0.767) with the ratio of ECW to total body water. Multifrequency bioelectrical impedance analysis may assist in the evaluation of body water distribution in endstage renal disease and other clinical disorders of fluid volume and/or distribution.
Phenyl biguanide does not inhibit locomotion in conscious rabbits
Authors: O'Hagan K. P. , Anderson R. S. , Bell L. B. , Mittelstadt S. W. , Clifford P. S.
Published: December 2017

Stimulation of cardiopulmonary vagal C fibers with phenyl biguanide (PBG) reflexly inhibits locomotion in addition to causing depression of blood pressure (BP), heart rate (HR), and respiration in cats and rats. We investigated whether PBG caused somatomotor inhibition during exercise in the rabbit, a species in which it is known that the hemodynamic and respiratory responses to PBG are mediated by cardiac rather than by pulmonary receptors. In eight New Zealand White rabbits, BP, HR, and hindlimb electromyographic (EMG) responses to 60 and 120 micrograms/kg PBG and saline vehicle were evaluated during two separate 3-min exercise bouts at 10 m/min at 0% grade. During exercise, 60 micrograms/kg PBG decreased BP (-27 +/- 4 mmHg) and HR (-95 +/- 16 beats/min) but did not inhibit locomotion as suggested by the EMG response (+112 +/- 8% of preinfusion EMG). Hemodynamic and EMG responses to 120 micrograms/kg PBG were similar to 60 micrograms/kg PBG. Saline infusion during exercise had no effect on HR, BP, or locomotion (+114 +/- 8% of preinfusion EMG). Locomotion is not inhibited by PBG in rabbits, which suggests that PBG-induced reflex somatomotor inhibition observed in other species is primarily mediated by pulmonary rather than by cardiac receptors.
Bone changes in 6-mo-old rats after head-down suspension and a reambulation period
Authors: Vico L. , Bourrin S. , Very J. M. , Radziszowska M. , Collet P. , Alexandre C.
Published: December 2017

In mature rats experiencing 14-day head-down suspension or 14-day head-down suspension followed by 28-day reambulation, the hindlimb long bones, humerus, and skull were removed for the determination of morphometry and bone mineral content (BMC) and density (BMD) with dual-energy X-ray absorptiometry, dry and ash weights, and calcium content. The bones of the animals in the control groups (killed at days 0, 14, and 42) had their own maturation rate. The body weights of suspended animals were lower than those of the control animals. Suspension does not appear to impair the long-bone elongation rate. However, the tibia of suspended rats exhibited a lower calcium content, ash weight, BMC, and BMD. Similar trends were observed in the femur. In the humerus, no significant change was observed. In the skull, the values of the suspended rats were similar to those of the control rats. At the end of the reambulation period, the body weights showed no difference between the control and experimental animals. The bone alterations were not completely reversible compared with their respective controls. In the tibia, BMC and BMD were always decreased. In the femur, trends toward low values were still visible. The skull showed a decrease in BMC and ash and dry weights. This unexpected finding suggested that importance of a rapid decrease in cephalad fluid shift at the time of desuspension. Finally, we showed that dual-energy X-ray absorptiometry measurement is sufficiently accurate to detect intergroup differences.
SDH and actomyosin ATPase activities of different fiber types in rat diaphragm muscle
Authors: Sieck G. C. , Zhan W. Z. , Prakash Y. S. , Daood M. J. , Watchko J. F.
Published: December 2017

In the rat diaphragm muscle, the histochemical classification of type I, IIa, IIb, or IIx fibers was correlated with myosin heavy chain (MHC) immunoreactivity. Expression of MHC isoforms in single dissected fibers was also assessed electrophoretically. Most fibers (approximately 86%) expressed a single MHC isoform, and when present, coexpression of MHC-2X and MHC-2B isoforms was most prevalent. Type I and IIa fibers were the smallest, type IIb fibers were the largest, and type IIx fibers were intermediate. Succinate dehydrogenase (SDH) and calcium-activated myosin adenosinetriphosphatase (actomyosin ATPase) activities were measured with quantitative histochemical procedures. Type I and IIa fibers had the highest SDH activities, followed in rank order by type IIx and IIb fibers. Type I fibers had the lowest actomyosin ATPase activity, followed in rank order by type IIa, IIx, and IIb fibers. Across all fibers, there was an inverse relationship between fiber SDH activity and cross-sectional area and a positive correlation between fiber actomyosin ATPase activity and cross-sectional area. The SDH and actomyosin ATPase activities of muscle fibers were also inversely correlated. These phenotypic differences in SDH and ATPase activities may be important in determining the contractile and fatigue properties of different fiber types in the rat diaphragm muscle.
HSP70 accumulation in tissues of heat-stressed rats is blunted with advancing age
Authors: Kregel K. C. , Moseley P. L. , Skidmore R. , Gutierrez J. A. , Guerriero V.
Published: December 2017

To determine whether aging results in reduced accumulation of the 70-kDa heat shock protein (HSP70) in response to a thermal challenge, experiments were conducted in conscious and freely moving mature (12-mo-old) and senescent (24-mo-old) male Fischer 344 rats. Rats were assigned to a euthermic control group or a nonexertionally heated group that was exposed to an ambient temperature of 42 degrees C until colonic temperature reached 41 degrees C. Samples were subsequently obtained from the liver and myocardium, and absolute levels of both the constitutive and inducible forms of HSP70 were quantitated. Heat-stressed rats had significantly elevated HSP70 levels in the liver compared with the euthermic groups. Post hoc comparisons revealed that heat stress elicited marked elevations in liver HSP70 in mature rats compared with age-matched control animals. In contrast, HSP70 values were unchanged in the senescent heated group vs. the control group. In the myocardium, heat stress produced marked increases in HSP70 levels in both the mature and senescent groups compared with age-matched control animals, with accumulation significantly blunted in the senescent vs. mature rats. Thus the increases in liver and myocardial HSP70 accumulation in response to nonexertional heat stress are attenuated with senescence. Because these proteins are postulated to protect cells from injury and enhance cellular recovery from heat stress, the data suggest that an aging organism has a reduced ability to properly maintain cellular function and integrity after a thermal challenge.
Respiratory response to positive inspiratory pressure in the cat: effects of CO2 and vagal integrity
Authors: Shams H. , Scheid P.
Published: December 2017

Effects of inspiratory pressure support (IPS) on respiration and activity of inspiratory muscles were tested in eight anesthetized cats by recording the diaphragmatic electromyogram (EMGdi) and respiratory variables at four levels of positive inspiratory airway pressure (5, 10, 15, and 20 cmH2O); onset of IPS was triggered by the inspiratory effort of the animal. When IPS was applied with room air (IPSAir) the respiratory frequency (f) was reduced compared with spontaneous breathing and the tidal volume (VT) was significantly increased, which resulted in a fall of arterial PCO2 (PaCO2) at IPS airway pressures (Paw) above 5 cmH2O. Despite this increase in VT, the amplitude of the integrated EMGdi (Adi) was reduced during IPS at all levels of Paw. When arterial hypocapnia is corrected by addition of CO2 to the inspirate, the values of VT at any given Paw were virtually identical with those during IPSAir, but IPS-mediated changes in f and Adi were smaller than those during IPSAir. IPS was also performed after bilateral vagotomy. Vagotomy itself caused VT and Adi to increase, and f to decrease, during spontaneous breathing. In comparison with the corresponding treatment before vagotomy, IPSAir led to a less severe reduction in Adi. As a result, VT was more enhanced and Paco2 was more reduced after vagotomy than before, both during spontaneous breathing and during IPSAir at all levels of Paw. When, however, isocapnia was restored with IPS with CO2 in the vagotomized animal, diaphragmatic activity and f became very similar to their values during spontaneous breathing, whereas VT remained elevated as a result of the high positive airway pressure. Our data suggest that in anesthetized cats IPS leads to a diminution of diaphragm activity and that this reduction can be entirely attributed to 1) the hypocapnia, resulting from increased VT, and 2) the stimulation of pulmonary vagal afferent fibers at positive airway pressure.
Effect of [Hb] on blood flow distribution and O2 transport in maximally working skeletal muscle
Authors: Kurdak S. S. , Grassi B. , Wagner P. D. , Hogan M. C.
Published: December 2017

We investigated whether the reduction in calculated muscle diffusion capacity for O2 (DmO2) previously shown to occur with lowered hemoglobin concentration ([Hb]) perfusion of maximally working muscle is related to changes in the blood flow distribution. If blood flow distribution is altered during low [Hb] conditions, the reduction in the calculated DmO2 may in fact be due to increasing heterogeneity and not to some other hemoglobin-related factor. Color-stained (15-microns-diam) microspheres were injected into the artery supplying maximally working isolated in situ dog gastrocnemius muscle (n = 6) while it was being perfused (flow controlled by pump perfusion) with whole blood at three different levels of [Hb] (14.1 +/- 0.5, 8.9 +/- 0.4, and 5.7 +/- 0.4 (SE) g/100 ml] in a blocked-order design. Muscle blood flow and arterial PO2 were not changed as [Hb] was altered. Maximal O2 uptake (11.8 +/- 1.3, 8.2 +/- 0.8, and 6.0 +/- 0.9 ml.100 g-1 min-1 for those [Hb] values, respectively) and the associated estimate of DmO2 (0.25 +/- 0.03, 0.18 +/- 0.03, and 0.15 +/- 0.03 ml.100 g-1.min-1.Torr-1) declined significantly (P < 0.05) with [Hb]. However, the dispersion of the blood flow distribution did not change significantly and, if anything, indicated less heterogeneity at lower [Hb] (coefficient of variation - 0.52 +/- 0.06, 0.46 +/- 0.05, and 0.43 +/- 0.03). These results suggest that in maximally working canine muscle in situ, when O2 delivery is reduced by lowering [Hb] (at constant blood flow), changes in blood flow distribution play no significant role in the reduction of maximal O2 uptake and calculated DmO2. The apparent increase in the resistance to O2 diffusion (i.e., reduction in the DmO2) during anemia may therefore be a result of increased red blood cell spacing in the capillary, slow chemical off-loading kinetics of O2 from Hb, or some other effect that remains to be determined.
Pulmonary oxygen toxicity in mice is characterized by alterations in ascorbate redox status
Authors: Rusakow L. S. , Han J. , Hayward M. A. , Griffith O. W.
Published: December 2017

Pulmonary oxygen toxicity results from disruption of the usual antioxidant defenses of the body. We therefore investigated whether mice that suffer from oxygen toxicity show significant alterations in the redox status of ascorbate, an important antioxidant, as reflected by changes in the relative amounts of its oxidized and reduced forms. Mice were exposed to air or hyperoxia (> 97% O2, 760 mmHg). After 5 days, plasma and saline-perfused lungs were removed and levels of ascorbate (AA), oxidized ascorbate [dehydroascorbate (DHAA)], and total ascorbate species ([AA+DHAA]) were determined by a sensitive and specific high-performance liquid chromatography assay; lungs were also assayed for total glutathione and glutathione disulfide (GSSG), an established marker of oxidative stress. We found that with hyperoxic exposure plasma AA increased by 32%, plasma DHAA increased substantially from previously undetectable levels, and the DHAA-to-[AA+DHAA] ratio increased. In contrast, in lung, [AA+DHAA] decreased by 41%. Plasma AA, DHAA, and [AA+DHAA] each correlated inversely with lung [AA+DHAA] and directly with lung GSSC. We conclude that alterations in plasma ascorbate redox status reflect pulmonary oxygen toxicity in mice. Our results suggest that further investigations are warranted to determine whether similar findings occur in humans and have clinical utility.
Exercise duration and thermoregulatory responses after whole body precooling
Authors: Lee D. T. , Haymes E. M.
Published: December 2017

Whole body precooling was hypothesized to reduce thermoregulatory and metabolic responses, thereby enhancing running time. Fourteen male runners completed two high-intensity running tests consisting of resting in 24 degrees C (normothermic condition; NC) or 5 degrees C (hypothermic condition; HC) for 30 min followed by 10–16 min of rest at 24 degrees C and then an exercise bout (24 degrees C) at 82% maximal aerobic capacity to exhaustion. Rectal temperature (Tre) before exercise was lower (by 0.37 degrees C; P < 0.005) and exercise duration was longer (by 121 +/- 24%; P < 0.05) in HC than in NC. Tre and mean skin (Tsk) and mean body (Tb) temperatures remained lower during HC (P < 0.01). Pre- and postexercise changes for Tsk, Tb, thermal gradient (Tre-Tsk), and heart rate (HR) were larger in HC than in NC (P < 0.05). Final Tre, Tre-Tsk, HR, and blood lactate were similar between HC and NC. During exercise, heat storage was greater (P < 0.01) in HC than in NC (173 +/- 46 and 143 +/- 38 W/m2, respectively) and subjects sweated more in NC than in HC (P < 0.01). O2 consumption was lower initially in HC than in NC (P < 0.05), but O2 pulse was not different. It was concluded that precooling results in greater exercise endurance with enhanced heat storage rate and less stress on metabolic and cardiovascular systems.
Short exposure to endotoxin increases the constriction induced by angiotensin II in rat aorta
Authors: Rasetti C. , Vicaut E.
Published: December 2017

The contraction elicited by angiotensin II (ANG II) was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 1 or 10 micrograms/ml Escherichia coli lipopolysaccharide endotoxin (LPS). This contraction was 18 and 71% greater for the two doses of LPS, respectively, than in unexposed control rings. In endothelium-denuded rings, the LPS-induced increase in contraction in response to ANG II was completely abolished. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that LPS interferes with this modulation. We found that the LPS-induced increase in contraction to ANG II was inhibited in the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) or the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548 (2 x 10(-7) M). Conversely, the LPS-induced increase in contraction in response to ANG II was not inhibited by the presence of dexamethasone (10(-6) M), which inhibits new protein synthesis. In addition, there was no loss of vasodilator response to the endothelium-dependent receptor agonist acetylcholine (10(-8)-10(-4) M) or in the constrictor responses to norepinephrine (10(-9)-10(-5) M) and KCl (20–100 mM). We conclude that short exposure to LPS produces a specific increase in the constrictor response to ANG II via mechanisms mediated by prostaglandin H2/thromboxane A2. This effect could be a LPS-induced shift in favor of constrictor prostanoids in the balance of dilator/constrictor prostanoids, the release of which is associated with stimulation by ANG II.
A multimode dynamometer for in vivo MRS studies of human skeletal muscle
Authors: Ryschon T. W. , Fowler M. D. , Arai A. A. , Wysong R. E. , Leighton S. B. , Clem TR Sr. , Balaban R. S.
Published: December 2017

The implementation of muscle ergometry during magnetic resonance spectroscopy and imaging is complicated by the restrictive dimensions of the magnet bore and the presence of a strong static magnetic field. We have developed a dynamometer that is compatible with these constraints. This device can provide resistance to voluntary muscle contraction during isometric, isokinetic concentric, and isokinetic eccentric muscle contractions. While controlling muscle contraction speed, the dynamometer simultaneously records muscle torque production at a 10-Hz sampling frequency to allow assessment of compliance and retrospective normalization of power output for the mass of active muscle. All parameters relevant to muscle contraction are selectable, including percentage of maximal voluntary contraction, velocity of muscle contraction, duty cycle, and range of motion for the contraction. This paper provides examples of 31P-magnetic resonance spectroscopic measurements during isokinetic concentric contractions of the ankle dorsiflexors, isokinetic eccentric contractions of the soleus, and isometric contractions of the soleus. Operation of the dynamometer has no adverse effects on the integrity of the 31P-magnetic resonance spectra at 4 T, permitting temporal resolution of the phosphocreatine resynthesis rate of approximately 1 spectrum/s. The unique capabilities of this dynamometer will facilitate studies into the metabolic response of working muscle in healthy and diseased populations.
Reproducibility of 24-h energy expenditure and macronutrient oxidation rates in an indirect calorimeter
Authors: White M. D. , Bouchard G. , Buemann B. , Almeras N. , Despres J. P. , Bouchard C. , Tremblay A.
Published: December 2017

The maintenance of weight and adipose tissue mass in humans appears to be related to a balance between the rates of oxidation and consumption of macronutrients; yet, little evidence is available on the reproducibility of 24-h macronutrient oxidation rates and how this relates to diet in the days preceding a chamber session. This study examined the reproducibility of 24-h macronutrient oxidation rates, 24-h energy expenditure (EE), and respiratory quotient (RQ) in 30 adults who ate their habitual diets before two 24-h whole body indirect calorimeter sessions. Results showed that the within-subject coefficients of variation (CVws) for 24-h EE and RQ were 2.8 and 2.6%, respectively. CVws for macronutrient oxidations ranged from approximately 15 to 25%. Means comparisons of 24-h EE, RQ, and macronutrient oxidation rates between sessions showed no significant differences, and all variables had significant positive intraclass correlation coefficients (P < 0.05). In conclusion, macronutrient oxidations all showed significant reproducibility for the group and a significant but lower reproducibility for individuals when habitual diet and activity preceded the experimental sessions.
Sleep in monozygotic twin pairs discordant for obesity
Authors: Kronholm E. , Aunola S. , Hyyppa M. T. , Kaitsaari M. , Koskenvuo M. , Mattlar C. E. , Ronnemaa T.
Published: December 2017

Nocturnal motor breathing and cardiac activity were recorded by using the static charge-sensitive bed, and sleep habits were studied by questionnaire in 24 pairs of monozygotic twins discordant for their body mass index; the mean intrapair difference between co-twins was 6.7 kg/m2. Intrapair differences in sleep characteristics between co-twins were related to intrapair differences in physiological and anthropometric characteristics. Two questions were tested. First, do monozygotic twins discordant for body mass index differ in sleep behavior? Second, if they do, are differences in sleep associated with nongenetic differences in the body weight and metabolism or with other environmental factors? Obese twins had higher nocturnal motor activity levels, less quiet sleep, and more habitual snoring than did their nonobese co-twins. Differences in sleep were associated with obesity-related factors. However, habitual snoring did not explain other intrapair differences in sleep. It was concluded that relatively moderate obesity is associated with disruption of physiological structure of sleep as measured by the static charge-sensitive bed method and that this disruption seems not to be associated with snoring or breathing disturbances.
Specific tension of human plantar flexors and dorsiflexors
Authors: Fukunaga T. , Roy R. R. , Shellock F. G. , Hodgson J. A. , Edgerton V. R.
Published: December 2017

Reported specific tension measurements for human skeletal muscle vary widely. This variability could be due, at least in part, to the determination of the physiological cross-sectional area (PCSA) of the muscles. In the present study, serial magnetic resonance images were taken every 10 mm along the lower leg of 8 male subjects to calculate the volume and subsequently the PCSAs of the individual muscles producing plantar flexor and dorsiflexor torques. Maximum plantar flexor and dorsiflexor voluntary isometric torques were determined at ankle joint angles of 90, 100, 110, and 120 degrees. Peak tendon force estimated from torque and moment arm measurements was more than fourfold higher in the plantar flexors (3,623 +/- 136 N) than in the dorsiflexors (832 +/- 19 N). PCSAs were about eight- and threefold higher than the anatomic cross-sectional areas at the level of maximum girth of the calf for the plantar flexor and dorsiflexor groups, respectively. Mean muscle volume and PCSA were 4.6 and 12 times larger in the plantar flexors compared with the dorsiflexors, respectively. The PCSAs of both plantar flexors (r = 0.92) and dorsiflexors (r = 0.80) were highly correlated with the tendon tension of the respective muscle groups. The maximum specific tension was more than twofold higher in dorsiflexors than in plantar flexors. These data suggest that factors other than PCSA contribute to the force output potential of ankle plantar flexors and dorsiflexors in humans.
Activation of pulmonary rapidly adapting receptors does not induce bronchoconstriction in dogs
Authors: Yu J. , Mink S.
Published: December 2017

Activation of pulmonary rapidly adapting receptors (RARs) is believed to constrict airways by a vagally mediated reflex. We tested this hypothesis in dogs anesthetized with sufentanil citrate. We ventilated both lungs separately at a positive end-expiratory pressure of 4 cmH2O. We stimulated RARs in one lung under three different conditions: 1) deflation of the lung; 2) decrease in lung compliance; and 3) aerosolization of methacholine. We monitored the airway pressure in the nonstimulated lung as an index for airway muscle tone and could not detect increases in the pressure swing under these conditions. On the other hand, electrical stimulation of the distal end of cervical vagus nerve increased the pressure swing bilaterally (ipsilateral dominant), suggesting that reflex response could be detected in our preparation. Moreover, deflation (or inflation) of either lung increased (or suppressed) diaphragmatic activity. The results indicate intact vagal afferents and central response in our preparation. We conclude that activation of RARs located below the carina does not induce bronchoconstriction by a centrally mediated reflex. If any effect is present, it appears to be small.
Modification of circadian body temperature rhythm during the luteal menstrual phase: role of melatonin
Authors: Cagnacci A. , Soldani R. , Laughlin G. A. , Yen S. S.
Published: December 2017

In women during early follicular phase (FP), the rise of melatonin at night accounts for 40% of the nocturnal core body temperature (Tc) decline. In seven normal-cycling women, the circadian rhythms of Tc and melatonin of the FP were compared with those of the luteal phase (LP). In addition, in both phases the Tc response to daytime melatonin administration was investigated. Melatonin levels were comparable during the two menstrual phases, but the nocturnal melatonin onset was delayed by 90 min in the LP (P < 0.01). This was accompanied by a delay of the nadir of the Tc circadian rhythm (P < 0.002), a 0.3 degrees C elevation (P < 0.005) of the mean 24-h value, and a 40% blunting (P < 0.002) of the amplitude. This attenuation of circadian Tc in LP women was replicated in two estrogen-treated hypogonadal women by the administration of medroxyprogesterone acetate. The daytime administration of melatonin (2.5 mg) decreased Tc during the FP (P < 0.01) but was ineffective in the LP. Present data indicate that in LP, in association with high progesterone levels, an attenuated and phase-delayed circadian Tc rhythm may, in part, be due to a reduced effect of melatonin.
Chronic inhaled nitric oxide: effects on pulmonary vascular endothelial function and pathology in rats
Authors: Roos C. M. , Frank D. U. , Xue C. , Johns R. A. , Rich G. F.
Published: December 2017

Nitric oxide (NO) is a potent endogenous vasodilator produced in endothelial cells. Inhaled NO selectively vasodilates the pulmonary circulation. We determined the effects of chronic inhaled NO on hypoxic pulmonary vascular remodeling and endothelium NO-dependent and -independent vasodilation during normoxic and hypoxic conditions in rats. Rats were exposed to 3 wk of normoxia (N), normoxia + 20 ppm inhaled NO (N+NO), chronic hypoxia with 10% normobaric oxygen (CH), or CH and 20 ppm inhaled NO (CH+NO). Inhaled NO decreased the number of muscular pulmonary arteries, the medial smooth muscle thickness, and the right ventricular hypertrophy associated with chronic hypoxia but had no effect on these parameters in normoxic rats. All groups were evaluated with isolated perfused lungs. The pulmonary artery pressure increased by the same amount in the CH and CH+NO rats compared with N rats. Inhibition of NO synthase with N omega-nitro-L-arginine methyl ester (L-NAME) caused greater pulmonary vasoconstriction in CH (19.2 +/- 3.7 mmHg) vs. N (7.8 +/- 3.0 mmHg) and less in CH+NO (9.1 +/- 0.8 mmHg) vs. CH rats. Bradykinin (3 micrograms) caused greater vasodilation in CH (76 +/- 12%) vs. N (29 +/- 5%) but significantly less in CH+NO (41 +/- 11%) vs. CH rats. Vasodilation with acute inhaled NO (40 ppm) was no different in CH vs. N rats but was lower in CH+NO (19 +/- 5%) vs. CH (34 +/- 6%) rats. This study demonstrates that chronic inhaled NO attenuates hypoxic pulmonary vascular remodeling. Furthermore, these results suggest that chronic inhaled NO decreases endothelium NO-dependent and -independent vasodilation.
Inducible nitric oxide synthase and vascular reactivity in rat thoracic aorta: effect of aminoguanidine
Authors: Scott J. A. , Machoun M. , McCormack D. G.
Published: December 2017

We tested the hypothesis that selective inhibition of the inducible form of nitric oxide (NO) synthase with aminoguanidine would prevent the loss of vascular contractility after exposure to endotoxin [lipopolysaccharide (LPS)]. Aortic rings were dissected from Sprague-Dawley rats, suspended in organ baths containing Krebs solution, and tested for vascular reactivity. Vessels incubated with LPS (1 microgram/ml) for 5 h exhibited a significant decrease in the maximal contractile response to phenylephrine. Aminoguanidine (100 microM) restored the maximal contractile response of LPS-treated vessels to the level of the control vessels. Aminoguanidine was approximately 250-fold less potent than NG-nitro-L-arginine methyl ester in inhibiting the constitutive NO synthase in vascular tissue as determined by its ability to further increase tone of submaximally contracted aortic rings. NO synthase activity was determined in vascular tissue incubated with and without LPS. Vessels incubated with LPS exhibited a marked increase in the levels of inducible NO synthase activity compared with control vessels. This increase was restored to control levels when tissue homogenates were incubated with aminoguanidine. We conclude that aminoguanidine is a selective concentration-dependent inhibitor of the inducible form of NO synthase and may be a useful probe to evaluate the role of inducible NO synthase in the abnormal vascular contractility characteristic of endotoxemia and sepsis.
Effects of prior exercise on pulmonary gas-exchange kinetics during high-intensity exercise in humans
Authors: Gerbino A. , Ward S. A. , Whipp B. J.
Published: December 2017

The effects of prior exercise on O2 uptake (VO2) kinetics during supra-lactate threshold (LT) cycling were assessed in 11 subjects. Protocols consisted of two consecutive 6-min work bouts separated by 0 W (6 min) with 1) both bouts sub-LT, 2) both bouts supra-LT, 3) bout 1 sub-LT and bout 2 supra-LT, and 4) bout 1 supra-LT and bout 2 sub-LT. Sub-LT VO2 kinetics were similar whether the prior bout was supra- or sub-LT. The VO2 kinetics for supra-LT work preceded by a sub-LT “warm-up” were similar to those for supra-LT work that was not preceded by exercise (O-W warm-up): the “partial”: O2 deficit averaged 2.64 vs. 2.57 liters, and the “effective” VO2 time constant averaged 56 vs. 65 s. Exercise responses (i.e., the change between O W and minute 6 of exercise) were unaffected for lactate concentration (4.58 vs. 4.50 meq/l), pH (-0.08 vs. -0.10), and CO2 output (VCO2; 2.65 vs. 2.49 l/min). However, when the supra-LT work was preceded by a supra-LT warm-up, VO2 kinetics were appreciably faster (O2 deficit = 1.82 liters, VO2 time constant = 37 s) relative to 0-W warm-up; the lactate (0.69 meq/l), pH (-0.01), and VCO2 (2.08 l/min) responses were smaller; and the effective VCO2 time constant was longer (58 vs. 43 s). The mechanism(s) that underlie this speeding of the VO2 kinetics cannot be firmly established, but we suggest that an improved muscle perfusion during the exercise may be involved consequent to the residual metabolic acidemia from the high-intensity warm-up.