bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of mixed venous PO2 and inspired O2 fraction on intrapulmonary shunt in patients with severe ARDS
Authors: Rossaint R. , Hahn S. M. , Pappert D. , Falke K. J. , Radermacher P.
Published: December 2017

In 12 patients undergoing extracorporeal membrane oxygenation for treatment of severe acute respiratory distress syndrome (ARDS), we examined the effects of independent variations in mixed venous oxygen tension (PvO2) and inspired oxygen fraction (FIO2) on the distribution of ventilation and perfusion as assessed by the multiple inert gas elimination technique. Reducing the oxygen concentration of the constant gas stream through the membrane lungs allowed us to decrease the PvO2 by approximately 20 Torr independently of variations in cardiac output and FIO2 as well as to augment FIO2 without influencing PvO2. The interventions did not induce any change in heart rate or systemic or pulmonary hemodynamics. In general, neither during mechanical ventilation at FIO2 of 0.6 nor during mechanical ventilation at FIO2 of 1.0 did the reduced PvO2 cause variations in the distribution of pulmonary blood flow in our patients with severe ARDS. Nevertheless, in individual patients, decreasing PvO2 or ventilation at FIO2 of 1.0 was associated with changes in intrapulmonary shunt. Therefore, we conclude that it is not possible to predict the influence of such interventions in pulmonary gas exchange in the individual patient suffering from ARDS. Differences in the regulation of the local distribution of blood flow caused by the disease itself might explain this phenomenon.
Modeling road-cycling performance
Authors: Olds T. S. , Norton K. I. , Lowe E. L. , Olive S. , Reay F. , Ly S.
Published: December 2017

This paper presents a complete set of equations for a “first principles” mathematical model of road-cycling performance, including corrections for the effect of winds, tire pressure and wheel radius, altitude, relative humidity, rotational kinetic energy, drafting, and changed drag. The relevant physiological, biophysical, and environmental variables were measured in 41 experienced cyclists completing a 26-km road time trial. The correlation between actual and predicted times was 0.89 (P < or = 0.0001), with a mean difference of 0.74 min (1.73% of mean performance time) and a mean absolute difference of 1.65 min (3.87%). Multiple simulations were performed where model inputs were randomly varied using a normal distribution about the measured values with a SD equivalent to the estimated day-to-day variability or technical error of measurement in each of the inputs. This analysis yielded 95% confidence limits for the predicted times. The model suggests that the main physiological factors contributing to road-cycling performance are maximal O2 consumption, fractional utilization of maximal O2 consumption, mechanical efficiency, and projected frontal area. The model is then applied to some practical problems in road cycling: the effect of drafting, the advantage of using smaller front wheels, the effects of added mass, the importance of rotational kinetic energy, the effect of changes in drag due to changes in bicycle configuration, the normalization of performances under different conditions, and the limits of human performance.
Attenuation of hyperoxic lung injury by the 21-aminosteroid U-74389G
Authors: Tasaka S. , Ishizaka A. , Urano T. , Sayama K. , Sakamaki F. , Nakamura H. , Terashima T. , Waki Y. , Soejima K. , Fujishima S. , et al.
Published: December 2017

Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We examined the effect of U-74389G on lung injury in guinea pigs during exposure to 90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed two series of experiments after exposure. In the first series, we measured the clearance rate of 99mTc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second series, pulmonary endothelial injury was estimated by using 28 guinea pigs divided into four experimental groups consisting of 1) control (n = 8), 2) AS alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series, we measured the wet-to-dry weight ratio (W/D) as an index of lung water and the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue samples was also assessed in the second series.(ABSTRACT TRUNCATED AT 250 WORDS)
Thermoregulatory responses of rats acclimated to heat given daily at a fixed time
Authors: Sugimoto N. , Shido O. , Sakurada S.
Published: December 2017

Body core temperature of rats acclimated to heat given daily at a fixed time falls during the previous heat exposure time. In the present study, thermoregulatory responses of heat-acclimated rats were examined during the specific period. Heat-acclimated rats were subjected to an ambient temperature of 32 degrees C for approximately 5 h in the first half or last half of the dark phase for 14 days while control rats were kept at 24 degrees C. Then the rats were placed in a direct calorimeter and were warmed for 30 min with an intraperitoneal electric heater. Measurements were made twice in the first and last halves of the dark phase. Body warming significantly increased body core temperature in all rats. In the heat-acclimated rats, heat production (M) was significantly depressed during the previous heat exposure time but not during the other period. Body warming had little effect on M in the control rats during either period. The results suggest that rats acclimated to heat given at a fixed time daily respond to an acute heat load with a pronounced reduction of M. However, such a response was observed only during the period when the rats had been previously exposed to heat.
Effects of acute and chronic exercise on skeletal muscle glucose transport in aged rats
Authors: Youngren J. F. , Barnard R. J.
Published: December 2017

The purpose of this study was to investigate the effects of acute and chronic exercise on skeletal muscle glucose transport in aged rats by using an isolated sarcolemmal membrane preparation. In 24-mo-old female Fischer 344 rats, a maximum dose of insulin increased glucose transport from 43 +/- 6 to 82 +/- 6 pmol.mg protein-1.15 s-1. A 45-min bout of exhaustive treadmill running increased glucose transport to the same maximum level (88 +/- 5 pmol.mg protein-1.15 s-1). Eight weeks of progressive exercise training resulted in a 65% increase in succinic dehydrogenase activity in hindlimb muscles and a 55% increase in total cellular GLUT-4 content. Despite these biochemical adaptations, there was no change in either basal or maximum insulin-stimulated glucose transport between control (43 +/- 6 and 82 +/- 6 pmol.mg protein-1.15 s-1, respectively) and trained (42 +/- 2 and 82 +/- 8 pmol.mg protein-1.15 s-1, respectively) animals. When hindlimb muscle succinate dehydrogenase activity and GLUT-4 content were compared for both the combined sedentary and trained groups, a significant correlation (r = 0.68) was obtained. This study demonstrates that the skeletal muscle glucose transport system of 24-mo-old rats is fully stimulated by acute exercise and that, although GLUT-4 levels are increased in aged animals after exercise training, this does not result in an enhancement of maximal insulin-stimulated glucose transport. Thus increases in GLUT-4 are not sufficient to improve muscle insulin responsiveness with training.
Tracheal epithelial damage alters tracer fluxes and effects of tracheal osmolaity in sheep in vivo
Authors: Wells U. M. , Woods A. J. , Hanafi Z. , Widdicombe J. G.
Published: December 2017

Tracheal osmolaity affects blood flow and the flux of a tracer, technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), from tracheal lumen to venous blood in anesthetized sheep. Hyperosmolar liquids increase blood flow and slightly decrease 99mTc-DTPA flux, whereas hyposmolar liquids have no effect on blood flow and greatly increase 99mTc-DTPA flux. We have now investigated whether epithelial damage induced by exposure of the tracheal lumen to a detergent (0.2% Triton X-100) alters these effects. A tracheal artery was perfused, and tracheal venous blood was collected. The initial tracheal volume was 12.8 +/- 0.7 ml. Triton X-100 greatly increased the permeability coefficient for 99mTc-DTPA from -2.1 x 10(-7) to -240 x 10(-7) cm/s. Hyperosmolar Krebs-Henseleit solution (KH; 739 +/- 6 mosmol/kg) increased arterial (+14.3%) and venous (+21.5%) flows and decreased 99mTc-DTPA output by 51.7%. Water flux into the lumen (+0.3 +/- 0.1 ml) was not significant, and the osmolality decreased by 99 +/- 9 mosmol/kg. Hyposmolar KH (124 +/- 2 mosmol/kg) had no effect on arterial and venous flows (-1.3% for both), and the increase in 99mTc-DTPA output (+8.3%) was small and not significant. The volume decreased by 0.4 +/- 0.1 ml, and the osmolaity increased by 36 +/- 4 mosmol/kg. Thus epithelial damage greatly increases the baseline permeability of the tracheal wall to 99mTc-DTPA. It does not alter the qualitative effects of hypersomolar KH on blood flow and 99mTc-DTPA output but does reduce the effect of hyposmolar KH on 99mTc-DTPA output. The latter effect may be a consequence of the reduced net water movement in response to non-isosmolar solutions after epithelial damage.
Activity of costal and crural diaphragm during progressive hypoxia or hypercapnia
Authors: Easton P. A. , Abe T. , Smith J. , Fitting J. W. , Guerraty A. , Grassino A. E.
Published: December 2017

Because costal and crural diaphragm segments have different functional characteristics, ventilatory stimulation with hypoxia or hypercapnia may elicit differential segmental function. We report measurements of diaphragm segmental length, shortening, and electromyogram (EMG) activity from 11 canines that were chronically implanted with sonomicrometry transducers and EMG electrodes and then studied a mean of 18 days postimplantation while awake and breathing spontaneously during CO2 rebreathing and progressive isocapnic hypoxia. Ventilatory responses to hypercapnia and progressive hypoxia were moderate at 1.13 +/- 0.31 (SD) 1. min-1. mm-1 arterial Pco2 and -0.98 +/- 0.51 l. min-1.%arterial O2 saturation-1. When tidal values for breathing pattern and segmental function were compared at matching tidal volumes that correspond to mean CO2 of 49.4 arterial Pco2 and 77% arterial O2 saturation, there was no significant difference in resting length, tidal shortening, or tidal EMG of costal or crural segments. Intrabreath profiles of flow, shortening, and EMG activity at matched tidal volumes showed that 1) inspiratory flow during hypoxia was significantly greater during early inspiration, 2) crural EMG activity preceded costal EMG activity in early inspiration during both hypercapnia and hypoxia, 3) both segments showed increased postinspiratory inspiratory activity with stimulated ventilation, and 4) postinspiratory shortening and EMG were greatest for the crural segment during hypoxia. These results suggest that costal and crural diaphragm segments exhibit differential function during chemical stimulation, especially during postinspiration.
Effect of lung volume on forced expiratory flows during rapid thoracoabdominal compression in infants
Authors: Hammer J. , Newth C. J.
Published: December 2017

The rapid thoracoabdominal compression (RTC) technique is commonly used in pulmonary function laboratories to assess flow-volume relationships in infants unable to produce a voluntary forced expiration maneuver. This technique produces forced expiratory flows over only a small lung volume segment (i.e., tidal volume). It has been argued that the RTC technique should be modified to measure flow-volume relationships over a larger portion of the vital capacity range to imitate the voluntary maximal forced expiratory maneuver obtained in older children and adults. We examined the effect of volume history on forced expiratory flows by generating forced expiratory flow-volume curves by RTC from well-defined inspiratory volumes delineated by inspiratory pressures of 10, 20, 30, and 40 cmH2O down to residual volume (i.e., the reference volume) in seven intubated and anesthetized infants with normal lungs [age 8.0 +/- 2.0 (SE) mo, weight 6.7 +/- 0.6 kg]. We compared maximal expiratory flows at isovolume points (25 and 10% of forced vital capacity) and found no significant differences in maximal isovolume flow rates measured from the different lung volumes. We conclude that there is no obvious need to initiate RTC from higher lung volumes if the technique is used for flow comparisons. However, compared with measurements of maximal flows at functional residual capacity by RTC from end-tidal inspiration, the initiation of RTC from a defined and reproducible inspiratory level appears to decrease the intrasubject variability of the maximal expiratory flows at low lung volumes.
Repeated exposure to 5 bar normoxic He-N2 changes cerebral blood flow distribution in rats
Authors: Bergo G. W. , Tyssebotn I.
Published: December 2017

The regional cerebral blood flow (rCBF), arterial pressure (AP), heart rate, respiratory frequency, and arterial acid-base chemistry were measured during control periods at 1 bar air and after 15 and 60 min at 5 bar normoxic He (4.0 bar)-N2 (0.8 bar) in two groups of awake habituated rats. Group 1 (10 control rats) were exposed 40 times while restrained for 1 h in the pressure chamber at 1 bar air. Group 2 (10 rats) were restrained and exposed 40 times to normoxic 5 bar He-N2 atmosphere in the pressure chamber for 45 min. During the control period, the systolic and mean AP levels were higher (P < 0.05), whereas the average CBF and nine rCBF values were lower in the preexposed group. During 5-bar exposure, the systolic AP rose significantly in both groups, whereas the mean AP remained at the control level or was reduced. The arterial O2, CO2, and HCO3 changed identically in both groups relative to hyperventilation. Generally, the total and local CBF values increased during the first 15 min in both groups and for 60 min in the preexposed rats. After 60 min of exposure, the flow returned toward the control level in most regions in both groups, whereas the flow was still elevated in the cerebellum and mesencephalon in the control rats and in the bulbus olfactorius, mesencephalon, medulla oblongata, spinal cord, and posterior part of cortex cerebri in preexposed animals. Hypothalamic rCBF in control rats was reduced after 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Myosin heavy chain composition in young and old rat skeletal muscle: effects of endurance exercise
Authors: Sullivan V. K. , Powers S. K. , Criswell D. S. , Tumer N. , Larochelle J. S. , Lowenthal D.
Published: December 2017

The objective of this study was to determine the effects of age and exercise on the myosin heavy chain (MHC) composition of skeletal muscle. Young (3 mo) and old (22 mo) female specific pathogen-free barrier-reared Fischer 344 rats were randomly assigned to young untrained or young trained and old untrained or old trained groups, respectively. Young trained and old trained animals performed endurance exercise training on a motorized treadmill for 8 wk. Succinate dehydrogenase activity and MHC isoforms were measured in the plantaris (Plan), lateral and medial gastrocnemius (Gast), and soleus (Sol) muscles. In sedentary animals, aging resulted in a decrease (P < 0.05) in type IIb MHC and an increase (P < 0.05) in type IIa MHC in both the Gast and Plan muscles. Also, aging resulted in a small but significant increase (approximately 4%; P < 0.05) in type I MHC in the Sol. Exercise training resulted in significant (P < 0.05) increases in Gast, Plan, and Sol succinate dehydrogenase activity in both young and old animals. Furthermore, exercise training resulted in a decrease (P < 0.05) in the percentage of type IIb MHC and an increase (P < 0.05) in the percentage of type IIa MHC in the Plan in both young and old animals. These data suggest that there is an age-related shift in locomotor muscle MHC isoforms from a faster to a slower isoform.
Skeletal muscle mitochondrial function studied by kinetic analysis of postexercise phosphocreatine resynthesis
Authors: Thompson C. H. , Kemp G. J. , Sanderson A. L. , Radda G. K.
Published: December 2017

To investigate mitochondrial regulation and its response to a defect in oxidative metabolism, we used 31P-magnetic resonance spectroscopy to study phosphocreatine (PCr) recovery in rat leg muscle after sciatic nerve stimulation at 1-4 Hz. We studied normal animals and animals with defective skeletal muscle mitochondrial function after experimental cardiac infarction. To analyze these data, we used three current theoretical approaches to the control of mitochondrial ATP synthesis, based on its hyperbolic relationship to cytosolic ADP concentration and on its linear relationships to PCr concentration and the free energy of ATP hydrolysis. The mitochondrial ADP concentration for one-half maximum rate of ATP synthesis appeared at least twice as high as the 30 microM expected from in vitro studies. According to all three approaches, the apparent maximum rate of ATP synthesis was independent of stimulation frequency and end-exercise pH and PCr and ADP concentrations and was reduced by approximately 50% after experimental cardiac infarction. Analysis of PCr recovery kinetics is a robust and practical way to study mitochondrial regulation and to quantify effective mitochondrial defects in vivo.
Lung and respiratory impedance at low frequency during mechanical ventilation in rabbits
Authors: Rotger M. , Peslin R. , Navajas D. , Farre R.
Published: December 2017

We have tested in eight rabbits the feasibility of measuring respiratory (Zrs) and lung (ZL) impedances in the low-frequency domain, including below the breathing frequency (fb), during conventional mechanical ventilation (CMV). The animals were tracheotomized and ventilated with a tidal volume (VT) of 20 ml at a fb of 1 Hz. The excitation signal was provided by a flow generator connected in parallel with the ventilator; it included six components ranging from 0.45 to 14.8 Hz, which met the neither-sum-nor-difference criterion of B. Suki and K. Lutchen (IEEE Trans. Biomed. Eng. 39: 1142-1151, 1992) to minimize the influence of nonlinearities. Zrs and ZL were also measured at the same mean lung volume and with the same excitation signal both during apnea and when the ventilator signal was replaced by a sine wave with the same VT and fb (SMV). The real parts (Re) of both Zrs and ZL, as well as the effective elastances, were significantly larger during apnea than during CMV and SMV over the whole frequency range. Re(Zrs) and Re(ZL) were similar during CMV and SMV above fb but they were lower during CMV at 0.45 Hz. The latter difference seems to be related to the presence of harmonics of fb and of additional frequency components due to pulse amplitude modulation. We conclude that, because of nonlinearities, it is feasible to measure Zrs and ZL during CMV only at and above fb.
Energy expenditure during antiorthostatic bed rest (simulated microgravity)
Authors: Gretebeck R. J. , Schoeller D. A. , Gibson E. K. , Lane H. W.
Published: December 2017

Few studies have addressed the interaction between energy balance and lean body mass in healthy subjects during spaceflight or its simulations. We used doubly labeled water to measure total energy expenditure (TEE) in nine healthy adult men during two 7-day periods, once before and once during a 10-day head-down bed-rest period. Mean TEE was 21% less during than before bed rest; however, neither basal (BEE) nor resting (REE) energy expenditures changed, implying that the lesser TEE resulted from a reduction in physical activity. During the bed-rest period, energy intake was 563 +/- 280 kcal/day higher than TEE (P < 0.05) but body weight, fluid balance, BEE, and REE did not change relative to before bed rest. However, the small but statistically significant increase in body fat (0.44 +/- 0.67 kg, P < 0.05) during the bed-rest period suggests that body weight alone does not accurately reflect changes in energy balance during antiorthostatic bed rest.
Modulation of ATP production by oxygen in obstructive lung disease as assessed by 31P-MRS
Authors: Mannix E. T. , Boska M. D. , Galassetti P. , Burton G. , Manfredi F. , Farber M. O.
Published: December 2017

Inadequate O2 supply may impair intramuscular oxidative metabolism and O2 availability may modulate ATP production within exercising muscle. Therefore, we studied ATP flux from anaerobic glycolysis, the creatine kinase reaction, and oxidative phosphorylation using 31P-magnetic resonance spectroscopy kinetic data collected during exercise. We examined six chronic obstructive pulmonary disease (COPD) patients with severe hypoxemia (group 1), seven COPD patients with mild hypoxemia (group 2), and seven healthy control subjects. Exercise (90-s isometric contraction of the gastrocnemius-soleus muscle group, 40% of max) was performed on room air for all subjects; for COPD patients, it was repeated during supplemental O2 at identical power outputs, with 60-min rest between the two sets. In group 1 (air vs. O2), oxidative phosphorylation ATP production was lower (P < 0.05), anaerobic glycolysis ATP production was higher (P < 0.05), and anaerobic glycolysis plus creatine kinase ATP production tended to be higher (P = 0.06). In group 2, no differences were observed across conditions. Assuming that mitochondrial size, density, function, and redox state were not affected by acute changes in the inspired O2 fraction, reduced O2 availability is the remaining factor that could have limited oxidative ATP production during hypoxemia. In conclusion, in severely hypoxemic COPD patients, O2 availability apparently limits intramuscular oxidative metabolism because acute hypoxemia increases anaerobic and decreases aerobic ATP production.
Adhesion molecules contribute to ischemia and reperfusion-induced injury in the isolated rat lung
Authors: Moore T. M. , Khimenko P. , Adkins W. K. , Miyasaka M. , Taylor A. E.
Published: December 2017

Leukocyte adherence to the endothelium after ischemia and reperfusion contributes to microvascular injury in most organs. The purpose of this study was to evaluate the leukocyte and endothelial cell adhesion molecules involved with ischemia-reperfusion (I/R)-induced pulmonary microvascular injury in the isolated rat lung. After 45 min of ischemia and 30 min of reperfusion, microvascular permeability was significantly increased and lung retention of leukocytes occurred. Pretreatment with monoclonal antibodies against the leukocyte adhesion molecule CD18 or the endothelial cell adhesion molecules intercellular adhesion molecule 1 and P-selectin significantly attenuated the I/R-induced permeability increase and lung sequestration of neutrophils, mononuclear leukocytes, and eosinophils. In contrast, immunoneutralization of the rat leukocyte adhesion molecule L-selectin neither protected against the I/R-induced permeability increase nor prevented lung sequestration of neutrophils and eosinophils. We conclude that leukocyte adherence in the pulmonary, microvasculature and subsequent permeability increase after I/R is dependent on the integrin CD18, its endothelial cell ligand intercellular adhesion molecule 1, and the endothelial cell rolling factor P-selectin but not the leukocyte rolling factor L-selectin.
Susceptibility to high-altitude pulmonary edema in Madison and Hilltop rats. I. Ventilation and fluid balance
Authors: Colice G. L. , Lee Y. J. , Chen J. , Du H. K. , Ramirez G. , Dietz J. , Ou L. C.
Published: December 2017

The pathogenesis of high-altitude pulmonary edema (HAPE) is not well understood. Ventilation and fluid-handling abnormalities at high altitude (HA) may play a role in HAPE. Because ventilatory and cardiopulmonary responses to chronic HA exposure in the Hilltop (H) strain of Sprague-Dawley rat are different from those in the Madison (M) strain, it was hypothesized that these strains would have different susceptibilities to developing HAPE. M and H rats were studied at sea level (SL) and in a hypobaric chamber after 9 and 12 h at a simulated altitude of 24,000 ft (barometric pressure = 295 mmHg) and 1, 12, and 24 h at a simulated altitude of 18,000 ft (barometric pressure = 380 mmHg). Both strains developed HAPE, but the M rat was more susceptible to HAPE, as demonstrated by a higher mortality rate from hemorrhagic pulmonary edema after 9 h at 24,000 ft and an earlier increase in lung water after exposure to 18,000 ft. Minute ventilation was similar in both strains at HA, but arterial PO2 was significantly higher in the M rat. Both strains had a significant decrease in fluid intake and negative sensible water balance at HA. No changes in plasma renin activity, aldosterone concentrations, antidiuretic hormone levels, and atrial natriuretic peptide levels were found at HA. The increased susceptibility of the M rat to HAPE is therefore not explained by ventilation or fluid-handling abnormalities.
Training in hypoxia vs. training in normoxia in high-altitude natives
Authors: Favier R. , Spielvogel H. , Desplanches D. , Ferretti G. , Kayser B. , Grunenfelder A. , Leuenberger M. , Tuscher L. , Caceres E. , Hoppeler H.
Published: December 2017

To determine the interactions between endurance training and hypoxia on maximal exercise performance, we performed a study on sedentary high-altitude natives who were trained in normoxia at the same relative (n = 10) or at the same absolute (n = 10) intensity of work as hypoxia-trained subjects (n = 10). The training-induced improvement of maximal oxygen uptake (VO2max) in hypoxia-trained subjects was similar to that obtained in normoxia-trained sea-level natives submitted to the same training protocol (H. Hoppeler, H. Howald, K. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. W. Weibel. J. Appl. Physiol. 59: 320–327, 1985). Training at the same absolute work intensity in the presence of increased oxygen delivery failed to provide a further increase in VO2max. VO2max was not improved to a greater extent by simultaneously increasing absolute work intensity and O2 delivery during the training sessions. In addition, training in normoxia is accompanied by an increased blood lactate accumulation during maximal exercise, leading to greater drops in arterial pH, bicarbonate concentration, and base excess. We conclude that, in high-altitude natives, 1) training at altitude does not provide any advantage over training at sea level for maximal aerobic capacity, whether assessed in chronic hypoxia or in acute normoxia; 2) VO2max improvement with training cannot be further enhanced by increasing O2 availability alone or in combination with an increased work intensity during the exercising sessions; and 3) training in normoxia in these subjects results in a reduced buffer capacity.
Metabolic and vascular effects of circulating endothelin-1 during moderately heavy prolonged exercise
Authors: Ahlborg G. , Weitzberg E. , Lundberg J.
Published: December 2017

The aims were to investigate 1) the effects of endothelin-1 (ET-1) during exercise and 2) the influence of exercise on arterial ET-1 levels. Six healthy subjects performed two exercises of 2 h duration at 50% of peak oxygen uptake preceded by intravenous infusion of physiological saline or ET-1 (4 pmol.kg-1.min-1). Blood specimens were taken from arterial and hepatic vein catheters. Arterial ET-1 rose 15-fold during the infusion. Splanchnic blood flow fell after ET-1 and remained lower than in control subjects during exercise (P < 0.001). Splanchnic glucose production was approximately 25% lower compared with control values during the whole exercise period (P < 0.01). Neither heart rate, arterial glucagon, insulin, catecholamines, renin, glucose, lactate, nor glycerol levels differed from control exercise values. The calculated gluconeogenesis from glycerol and lactate did not differ from the control values. ET-1 levels rose approximately twofold in the control exercise (P < 0.01) and in another group of seven subjects performing 1 h of exercise at 70% of peak oxygen uptake (P < 0.001). In conclusion, ET-1 levels increased during exercise without ET-1 administration. In addition, circulating ET-1 has a (direct or indirect) regulatory action on splanchnic blood flow and glucose metabolism during exercise (and possibly under pathophysiological conditions) in humans.
Right and left ventricular volumes and function after acute pulmonary hypertension in intact dogs
Authors: Dell'Italia L. J. , Pearce D. J. , Blackwell G. G. , Singleton H. R. , Bishop S. P. , Pohost G. M.
Published: December 2017

A canine model was developed to record right (RV) and left ventricular (LV) volumes and high-fidelity pressures during acute pulmonary hypertension without the need for major surgery. In this study, new methodology was applied to record high-fidelity RV and LV pressures during cinemagnetic resonance imaging of the heart before and after acute pulmonary hypertension in six anesthetized intact dogs in which the pericardium and thorax were never disturbed by any surgical procedure. After pulmonary embolus, RV systolic pressure increased from 27 + 2 (SD) to 43 +/- 8 mmHg (P < 0.01) as LV systolic pressure decreased (97 +/- 17 to 76 +/- 3 mmHg; P < 0.05). Stroke volume (26 +/- 7 to 21 +/- 5 ml; P < 0.05) and RV ejection fraction (45 +/- 9 to 28 +/- 3%; P < 0.01) decreased as LV ejection fraction was unchanged (50 +/- 5 to 52 +/- 5%; P = NS). LV end-diastolic pressure decreased from 11 +/- 4 to 7 +/- 3 mmHg (P < 0.05), and RV end-diastolic pressure increased from 6 +/- 3 to 11 +/- 3 mmHg (P < 0.01). RV end-diastolic volume increased from 57 +/- 14 to 75 +/- 20 ml (P < 0.01) as LV end-diastolic volumes decreased from 53 +/- 11 to 42 +/- 10 ml (P < 0.01), resulting in no change in total ventricular volume at end diastole (111 +/- 24 to 116 +/- 28 ml). The observed mean decrease of 4.0 mmHg and 11 ml in LV end-diastolic pressure and volume, respectively, was associated with no change in total ventricular volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of endothelial factors in active hyperemic responses in contracting canine muscle
Authors: King-Vanvlack C. E. , Curtis S. E. , Mewburn J. D. , Cain S. M. , Chapler C. K.
Published: December 2017

We investigated whether endothelium-derived relaxing factor (EDRF) and prostaglandins, which may be released under conditions of increased blood flow, contribute to the active hyperemia in contracting muscle of anesthetized dogs. The venous outflow from the left gastrocnemius muscle was isolated and measured. The tendon was cut and placed in a force transducer. One group served as a control (Con; n = 9); EDRF synthesis was inhibited using N omega-nitro-L-arginine methyl ester (L-NAME) in a second group (n = 9), and a third group (n = 7) received L-NAME and indomethacin (L-NAME+Indo) to inhibit prostaglandin synthesis. After resting measurements, the distal end of the cut sciatic nerve was stimulated to produce isometric contractions at 1, 2, 4, and 6 twitches/s for 6–8 min, separated by 25-min recovery periods. Blood flow and O2 uptake increased linearly from resting values of 11.8 +/- 2.4 and 0.3 +/- 0.05 ml.100 g-1.min-1, respectively, to maximal values of 84.2 +/- 5.1 and 11.1 +/- 0.7 ml.100 g-1.min-1 in the Con group; neither these values nor those for tension development were different from values observed at comparable contraction frequencies in the L-NAME and L-NAME+Indo groups. At rest, resistance was greater (P < 0.05) in both the L-NAME and L-NAME+Indo groups compared with Con, the highest value (P < 0.05) occurring in the L-NAME+Indo group. Muscle resistance decreased (P < 0.05) in all groups at all contraction frequencies; the values were not different among the three groups.
Effects of glutamine on the immune system: influence of muscular exercise and HIV infection
Authors: Rohde T. , Ullum H. , Rasmussen J. P. , Kristensen J. H. , Newsholme E. , Pedersen B. K.
Published: December 2017

Glutamine increased the proliferative response and the lymphokine-activated killer cell activity of blood mononuclear cells isolated from normal healthy subjects (n = 6) in a dose-dependent manner, with optimum at 0.3–1.0 mM. The relative fraction of CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells was not changed by glutamine at a concentration of 0.6 mM, except in the phytohemagglutinin-stimulated proliferation experiment where the fraction of CD4+, and therefore CD3+ cells, increased. The natural killer cell activity was not influenced by glutamine. Human immunodeficiency virus (HIV)-seropositive subjects (n = 8) who performed concentric bicycle exercise for 1 h at 75% of maximal O2 consumption had an overall lower phytohemagglutinin-stimulated proliferative response, compared with the HIV-seronegative control group (n = 7). The proliferation during exercise was lower in both the HIV-seropositive and the HIV-seronegative group. Addition of glutamine in vitro did not normalize the lower proliferation in the HIV-seropositive group or the attenuated proliferation seen during exercise in both groups.
Effect of unweighting on skeletal muscle use during exercise
Authors: Ploutz-Snyder L. L. , Tesch P. A. , Crittenden D. J. , Dudley G. A.
Published: December 2017

Exercise-induced spin-spin relaxation time (T2) shifts in magnetic resonance (MR) images were used to test the hypothesis that more muscle would be used to perform a given submaximal task after 5 wk of unweighting. Before and after unilateral lower limb suspension (ULLS), 7 subjects performed 5 sets of 10 unilateral concentric actions with the quadriceps femoris muscle group (QF) at each of 4 loads: 25, 40, 55, and 70% of maximum. T2-weighted MR images of the thigh were collected at rest and after each relative load. ULLS elicited a 20% decrease in strength of the left unweighted QF and a 14% decrease in average cross-sectional area (CSA) with no changes in the right weight-bearing QF. Average CSA of the left or right QF showing exercise-induced T2 shift increased as a function of exercise intensity both before and after ULLS. On average, 12 +/- 1, 15 +/- 2, 18 +/- 2, and 22 +/- 1 cm2 of either QF showed elevated T2 for the 25, 40, 55, and 70% loads, respectively, before ULLS. Average CSA of the left but not the right QF, showing elevated T2 after ULLS, was increased to 16 +/- 2, 23 +/- 3, 31 +/- 7, and 39 +/- 5 cm2, respectively. The results indicated that unweighting increased exercise-induced T2 shift in MR images, presumably due to greater muscle mass involvement in exercise after than before unweighting, suggesting a change in motor control.
Ventilatory and metabolic responses to hypoxia during moderate hypothermia in anesthetized rats
Authors: Frappell P. , Westwood K. , Maskrey M.
Published: December 2017

In resting euthermic mammals, hypoxia elicits a hyperventilation that results from a combination of hyperpnea and hypometabolism. Often accompanying the hypoxia-induced hypometabolism is a drop in body temperature. To separate the synergic effects of hypothermia per se from the direct effects of hypoxia on metabolic rate, ventilation (VE), and O2 consumption (VO2) were measured in anesthetized rats fitted with abdominal heat exchangers and maintained at either normothermic (37.5 degrees C) or hypothermic (35 degrees C) body temperatures while exposed to either normoxia or hypoxia (7% O2). Hypothermia induced parallel decreases in VE and VO2, thereby maintaining VE/VO2. Hypoxia resulted in a hyperventilation achieved with the same relative decrease in VO2 and increase in VE in both normothermic and hypothermic rats. The results suggest that 1) the changes in metabolic rate and VE during hypothermia reflect a direct effect of cold and, 2) because of similar levels of hypoxic hyperventilation in the hypothermic and normothermic rats, relative to metabolic rate, respiratory gain has not been depressed in hypothermic rats.
Acute systemic blood pressure elevation in obstructive and nonobstructive breath hold in primates
Authors: White S. G. , Fletcher E. C. , Miller C. C.
Published: December 2017

Phasic blood pressure (BP) response during obstructive apnea (OA) in human sleep has been previously described as consisting of a slow incremental increase in BP to the point of apnea termination followed by a rapid rise and then fall in BP at the resumption of respiration. This rise in BP has been attributed to postapneic augmentation of cardiac output resulting after release of the marked negative intrathoracic pressure (NIP) of obstructed inspiration. Via an endotracheal tube, we created obstructed and nonobstructed breath hold (apnea) in chloralose-anesthesized baboons consisting of fixed-duration (30, 45, and 60 s) single OAs (mechanical obstruction) and nonobstructive (paralysis, ventilator cessation) apneas of matched duration and arterial desaturation. Systemic BP was measured before apnea (T0), during the last 5 s of apnea (T1), and during the first 5 s after resumption of respiration (T2). Despite wide fluctuations in NIP and BP during the T0 to T1 phase of OA, BP elevation in OA and nonobstructive apnea at T0, T1, or T2 did not differ for any duration apnea. At the release of obstruction, when resolution of NIP changes could theoretically increase cardiac output and accentuate BP, there was no difference in T1 and T2 pressures between the two conditions. We conclude that in this anesthesized animal model, mechanical (NIP) changes do not play a major role in overall maximum BP response to OA. Because of physiological differences between natural sleep in humans and the anesthetized state in animals, care must be taken in extrapolating these results to human sleep apnea.
Changes in sympathoadrenal response to standing in humans after spaceflight
Authors: Whitson P. A. , Charles J. B. , Williams W. J. , Cintron N. M.
Published: December 2017

Plasma catecholamine levels and cardiovascular responses to standing were determined in astronauts before and after several Space Shuttle missions. Blood pressure, heart rate, and cardiac output were measured and blood samples for catecholamine analyses were drawn at the end of the supine and standing periods. Supine plasma norepinephrine and epinephrine concentrations increased 34 and 65%, respectively, on landing day compared with before flight. Standing on landing day resulted in a 65 and 91% increase in plasma norepinephrine and epinephrine, respectively. Supine and standing norepinephrine levels remained elevated 3 days after landing while epinephrine levels returned to preflight levels. On landing day, supine heart rate and systolic blood pressure increased 18 and 8.9%, respectively, and standing heart rate and diastolic blood pressure were elevated by 38 and 19%, respectively. On standing, stroke volume was decreased by 26% on landing day compared with before flight. Collectively, these data indicate that the decreased orthostatic function after spaceflight results largely from the decreased stroke volume. Possible mechanisms contributing to this condition are discussed.
Effect of posture, route of respiration, and negative pressure on palatal muscle activity in humans
Authors: Mortimore I. L. , Mathur R. , Douglas N. J.
Published: December 2017

Sleep apnea is worse in the supine posture and is associated with retropalatal airway narrowing or occlusion. We have, therefore, examined the effects of posture, negative pressure, and route of respiration on palatal muscle activity in 13 nonsnoring awake male subjects by using electromyography. Electromyographic activity of the levator palatini and palatoglossus was expressed as a percentage of maximum activity. Both the levator palatini (P = 0.002) and palatoglossus (P = 0.002) exhibited phasic inspiratory activity. Overall, posture did not affect the levator palatini (F = 1.58; P = 0.23) or palatoglossus (F = 0.98; P = 0.34) activity, but analysis by route of respiration showed the palatoglossus to be more active when the subjects were nose breathing supine (F = 6.64; P = 0.02). Levator palatini activity was lower when nose breathing was compared with mouth breathing in both the erect and supine postures (F = 6.67; P < 0.02). Nose breathing with the mouth held open caused an increase in palatoglossal activity (P = 0.04). Negative-pressure application (0 to -12.5 cmH2O) caused significant increases in levator palatini (P < 0.001) and palatoglossus (P < 0.001) activity, 100 ms after pressure stimulus, irrespective of route. However, the palatoglossus required significantly greater negative pressures to cause activation when applied via the nose compared with the mouth (P < 0.05). These observations indicate that the levator palatini and palatglossus have respiratory activity and are reflexly activated by negative pressure.
Acclimatization at high altitude in gradual and acute induction
Authors: Purkayastha S. S. , Ray U. S. , Arora B. S. , Chhabra P. C. , Thakur L. , Bandopadhyay P. , Selvamurthy W.
Published: December 2017

The study assessed physiological responses to induction to high altitude first to 3,500 m and then to 4,200 m and compared the time course of altitude acclimatization in two groups of male volunteers. The acutely inducted group was transported by aircraft (AI) to 3,500 m in 1 h, whereas the gradually inducted group was transported by road (RI) in 4 days. Baseline recordings of basal cardiovascular, respiratory, and blood gas variables were monitored at sea level as well as at 3,500 m on days 1, 3, 5, and 7. Blood gases were measured on day 10 also. After 15 days at 3,500 m, the subjects were inducted to 4,200 m by road, and measurements were repeated on days 1, 3, and 5, except blood gas variables, which were done on day 10 only. Acute mountain sickness symptoms were recorded throughout. The responses of RI were stable by day 3 of induction at 3,500 m, whereas it took 5 days for AI. Four days in transit for RI appear equivalent to 2 days at 3,500 m for AI. Acclimatization schedules of 3 and 5 days, respectively, for RI and AI are essential to avoid malacclimatization and/or high-altitude illness. Both groups took 3 days at 4,200 m to attain stability for achieving acclimatization.
Nasal pressure-volume relationships determined with acoustic rhinometry
Authors: Kesavanathan J. , Swift D. L. , Bascom R.
Published: December 2017

Partitioning of ventilation has been hypothesized to be related to nasal pressure-volume relationships, relationships that have been difficult to measure. Regional differences in nasal passage pressure-volume relationships are likely because the nasal valve and anterior turbinate are structurally different, but both are altered by agents that alter vascular tone. This study determined nasal volume-to-pressure ratio (NVPR) on six healthy nonsmoking subjects by measuring nasal volume by using acoustic rhinometry at pressures ranging between -14 and +14 cmH2O on 3 days: baseline, after intranasal decongestion (oxymetazoline), and congestion (histamine). NVPR was lower in the nasal valve (0.07 +/- 0.01 cm3/cmH2O) than in the anterior portion of the turbinates (0.29 +/- 0.05 cm3/cmH2O; P < 0.005). Oxymetazoline decongestion decreased NVPR in the nasal valve by 23% and NVPR in the anterior portion of the turbinates by 47%. Histamine did not alter NVPR at either site. Nasal resistance changes correlated with changes in nasal valve and anterior turbinate volume. In summary, regional differences in nasal pressure-volume relationships exist and changes occur with pharmacologically induced vascular decongestion.
ATP-sensitive K+ channels are not involved in ischemia-reperfusion lung endothelial injury
Authors: Khimenko P. L. , Moore T. M. , Taylor A. E.
Published: December 2017

The role of ATP-sensitive K+ channels (KATP) in ischemia and reperfusion (I/R) was studied in isolated rat lungs. I/R produced a sixfold increase in endothelial permeability as measured by the capillary filtration coefficient. Cromakalim (10 microM) given at 46 min after reperfusion reversed the filtration coefficient increase. This effect was not blocked by either a protein kinase A inhibitor (adenosine-3′,5′-cyclic monophosphothioate; 100 microM) or an adenosine antagonist [8-(p-sulfophenyl)-theophylline; 20 microM]. Cromakalim given before ischemia or at the beginning of reperfusion protected the endothelial barrier from injury. Glibenclamide (500 microM) given before the ischemic period, at the beginning of reperfusion, or 46 min after reperfusion did not alter the changes in microvascular permeability produced by I/R. Glibenclamide blocked the ability of cromakalim to reverse endothelial damage but not the ability of either isoproterenol (10 microM) or an adenosine A2-receptor agonist, CGS-21680 (300 nM). We conclude that opening of KATP channels does not produce endothelial injury in I/R. The activation of KATP channels can both protect against and reverse the endothelial damage associated with I/R. This novel mechanism(s) is independent from known pathways that employ cAMP-protein kinase system and adenosine.
During acute hypercapnia vasopressin inhibits an angiotensin drive to ventilation in conscious dogs
Authors: Walker J. K. , Jennings D. B.
Published: December 2017

Intravenous infusion of arginine vasopressin (AVP) depresses the slope of the ventilatory response to CO2 during acute hypercapnia. We therefore tested the hypothesis that AVP V1-receptor blockade would increase the slope of the ventilatory response to CO2. After a 20-min control period, an AVP V1-receptor antagonist (d(CH2)5[Tyr(Me)2]AVP) was injected into six conscious resting dogs. Thirty minutes after AVP V1-receptor blockade, dogs were exposed to sequential 20-min periods of 5 and 6.5% inspired CO2 in air. A second protocol (no AVP V1-receptor blockade) was conducted as a control. As predicted, AVP V1-receptor blockade enhanced ventilation during inhalation of 6.5% CO2 in association with an increased metabolic rate and increased plasma angiotensin II (ANG II). In eupneic dogs, stimulation of respiration by AVP V1-receptor blockade is mediated by ANG II. A third protocol with ANG II-receptor blockade (intravenous infusion of saralasin) combined with AVP V1-receptor blockade indicated that ANG II mediated the increase in metabolism and the augmented ventilation during inhalation of 6.5% CO2. We conclude that during acute hypercapnia of sufficient magnitude, and perhaps duration, AVP inhibits an ANG II-mediated stimulation of metabolism and respiration.
Effects of hypoxia and vascular tone on endothelium-dependent and -independent responses in developing lungs
Authors: Gordon J. B. , Martinez F. R. , O'Donnell D. C. , Tod M. L.
Published: December 2017

Both increases and decreases in endothelium-derived nitric oxide (EDNO) activity have been described in the developing pulmonary vasculature. We hypothesized that differences in baseline vasomotor tone and/or oxygen tension may contribute to this variability. Pulmonary arterial dose responses to endothelium-dependent and -independent vasodilators acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were measured in indomethacin-treated lungs of 1- to 2-day-old (2D) and 1-mo-old (1M) lambs. During 4% O2 ventilation, baseline pulmonary vascular resistance (PVR) and the dilator response to both ACh and SNP were greater in 2D lungs. However, when baseline PVR values were matched at both ages during either hypoxia or infusion of a thromboxane mimetic under normoxic conditions, developmental differences in ACh-induced vasodilation were minimal. Furthermore, hypoxia itself did not alter the responses to ACh in 2D lungs. In contrast, SNP caused greater vasodilation in 2D than in 1M lungs regardless of baseline PVR. These data and studies suggest that whereas high PVR enhances EDNO synthesis, responsiveness to ENDO decreases as synthesis of ENDO increases in developing lungs studied under basal conditions.