bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction
Authors: Smith T. C. , Marini J. J.
Published: December 2017

Positive end-expiratory pressure (PEEP) has generally been withheld from the treatment of patients with chronic airflow obstruction (CAO), in view of the risk of hyperinflation and lack of documented benefit. We studied 10 mechanically ventilated patients with exacerbated CAO and air trapping to determine the impact of PEEP on lung mechanics, alveolar pressure, and the work of breathing. PEEP levels of 5 and 10 cmH2O were applied to patients whose end-expiratory alveolar pressures were documented to be positive when breathing against ambient pressure (the auto-PEEP effect). All patients were studied under two conditions: every breath machine assisted (AMV) and every breath machine controlled (paralyzed, CMV). PEEP improved expiratory resistance without substantially increasing peak static pressure. Inspiratory resistance remained unchanged. The difference between the end-expiratory values of alveolar and central airway pressure narrowed as PEEP increased. Adding PEEP improved the effective triggering sensitivity of the ventilator, diminished ventilatory drive, and reduced the mechanical work of breathing during the machine-assisted ventilatory cycle. Our results indicate that low levels of PEEP may improve lung mechanics and reduce the effort required of mechanically ventilated patients with severe airflow obstruction, without substantially increasing the hazards of hyperinflation.
An assessment of nasal functions in control of breathing
Authors: Tanaka Y. , Morikawa T. , Honda Y.
Published: December 2017

Breathing pattern and steady-state CO2 ventilatory response during mouth breathing were compared with those during nose breathing in nine healthy adults. In addition, the effect of warming and humidification of the inspired air on the ventilatory response was observed during breathing through a mouthpiece. We found the following. 1) Dead space and airway resistance were significantly greater during nose than during mouth breathing. 2) The slope of CO2 ventilatory responses did not differ appreciably during the two types of breathing, but CO2 occlusion pressure response was significantly enhanced during nose breathing. 3) Inhalation of warm and humid air through a mouthpiece significantly depressed CO2 ventilation and occlusion pressure responses. These results fit our observation that end-tidal PCO2 was significantly higher during nose than during mouth breathing. It is suggested that a loss of nasal functions, such as during nasal obstruction, may result in lowering of CO2, fostering apneic spells during sleep.
Responses in muscle sympathetic activity to acute hypoxia in humans
Authors: Saito M. , Mano T. , Iwase S. , Koga K. , Abe H. , Yamazaki Y.
Published: December 2017

Responses in muscle sympathetic activity (MSA) to acute hypoxia were studied in 13 healthy male subjects under hypobaric hypoxic conditions at a simulated altitude of 4,000, 5,000, and 6,000 m. Efferent postganglionic MSA was recorded directly with a tungsten microelectrode inserted percutaneously into the tibial nerve. Heart rate (HR) and respiratory rate (RR) were counted respectively from the R wave of an electrocardiogram and from the respiratory tracing recorded by the strain-gauge method. The average values of the MSA burst rate and total activity of MSA (burst rate x mean burst amplitude) at 4,000, 5,000, and 6,000 m were 36.4 +/- 2.6, 39.1 +/- 3.1, and 40.2 +/- 4.2 (SE) bursts/min and 616 +/- 138, 794 +/- 190, and 764 +/- 227 arbitrary units, respectively. These values were significantly higher than the values of 27.1 +/- 2.9 bursts/min and 446 +/- 28 at sea level. HR increased significantly at altitudes, but RR did not show significant change. Under severe hypoxic conditions beyond 5,000 m, there were large interindividual differences in the MSA responsiveness to hypoxia. The results indicate that MSA is activated under hypoxia by stimulating the chemoreceptors. However, the central controlling mechanisms that would be affected by hypoxia may also influence the MSA responsiveness under severe hypoxia.
Erythrocyte deformability and segmental pulmonary vascular resistance: osmolarity and heat treatment
Authors: Hakim T. S.
Published: December 2017

The site and nature of change in resistance to blood flow in canine left lung lobe preparation after changes in blood viscosity were assessed by using the arterial and venous occlusion (AVO) technique and the vascular pressure-flow relationship. Blood viscosity was changed by erythrocyte (RBC) shrinkage and swelling with hypertonic and hypotonic NaCl solutions and by RBC membrane rigidification with heat treatment (49 degrees C for 1 h). The results show that although all three methods of changing blood viscosity increased the pulmonary vascular resistance (PVR) by 15-50%, the site and nature of the change in PVR were different in each case. The AVO data showed that the increase in PVR with heat treatment of RBC's was due entirely (100%) to increased resistance of the middle microvascular segment, whereas deviation from normal osmolarity potentiated the resistance in arterial, middle, and venous segments. By examining the effect of osmolarity in plasma-perfused lobes, it was possible to separate the increase in PVR due to changes in RBC deformability from those due to other factors. The increase in arterial and venous resistances with hypertonic solution was attributed in part (approximately 50%) to factors other than RBC's; however, the increase in middle resistance was entirely due to RBC crenation. The increase in arterial and venous resistances with hypotonic solutions was small and was apparently caused by factors other than RBC swelling, whereas the increase in middle resistance was partially (approximately 50%) due to RBC swelling and partially to other factors (e.g., endothelial cell hydration).(ABSTRACT TRUNCATED AT 250 WORDS)
Factors influencing hydrogen ion concentration in muscle after intense exercise
Authors: Kowalchuk J. M. , Heigenhauser G. J. , Lindinger M. I. , Sutton J. R. , Jones N. L.
Published: December 2017

To assess the importance of factors influencing the resolution of exercise-associated acidosis, measurements of acid-base variables were made in nine healthy subjects after 30 s of maximal exercise on an isokinetic cycle ergometer. Quadriceps muscle biopsies (n = 6) were taken at rest, immediately after exercise, and at 3.5 and 9.5 min of recovery; arterial and femoral venous blood were sampled (n = 3) over the same time. Intracellular and plasma inorganic strong ions were measured by neutron activation and ion-selective electrodes, respectively; lactate concentration ([La-]) was measured enzymatically, and plasma PCO2 and pH were measured by electrodes. Immediately after exercise, intracellular [La-] increased to 47 meq/l, almost fully accounting for a reduction in intracellular strong ion difference ([SID]) from 154 to 106 meq/l. At the same time, femoral venous PCO2 increased to 100 Torr and plasma [La-] to 9.7 meq/l; however, plasma [SID] did not change because of a concomitant increase in inorganic [SID] secondary to increases in [K+], [Na+], and [Ca2+]. During recovery, muscle [La-] fell to 26 meq/l by 9.5 min; [SID] remained low (101 and 114 meq/l at 3.5 and 9.5 min, respectively) due almost equally to the elevated [La-] (30 and 26 meq/l) and reductions in [K+] (from 142 meq/l at rest to 123 and 128 meq/l). Femoral venous PCO2 rose to 106 Torr at 0.5 min postexercise and fell to resting values at 9.5 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory sensation and pattern of respiratory muscle activation during diaphragm fatigue
Authors: Ward M. E. , Eidelman D. , Stubbing D. G. , Bellemare F. , Macklem P. T.
Published: December 2017

We have examined the relationship between respiratory effort sensation (modified Borg scale) and amplitude of the integrated surface electromyogram of the diaphragm (Edi, esophageal electrode), rib cage muscles (Erc), and sternomastoid muscle (Esm) during the development of diaphragm fatigue in five normal subjects. Three conditions were studied: run A: transdiaphragmatic pressure (Pdi), 65% Pdimax; esophageal pressure (Pes), 60% Pesmax; run B: Pdi, 50% Pdimax; Pes, 60% Pesmax; and run C: Pdi, 50% Pdimax; Pes, 20% Pesmax. During all runs there was a progressive rise in sensation, which was greater in runs A and B than in run C (P less than 0.05, analysis of variance). There was no difference between runs A and B. At the end of run C subjects did not report a maximal Borg score despite their inability to generate the target Pdi. The increase in sensory score with fatigue correlated highly with Esm/Esmmax and with Erc/Ercmax. There was no correlation between sensory score and Edi/Edimax. We conclude that the increase in respiratory effort sensation that accompanies diaphragm fatigue is not due to perception of increased diaphragmatic activation. It may reflect increased overall respiratory motor output not directed to the diaphragm.
Pulmonary vascular reactivity in hyperoxic pulmonary hypertension in the rat
Authors: Gore R. G. , Jones R.
Published: December 2017

Breathing 87% O2 for 7 days causes pulmonary vascular remodeling and pulmonary hypertension in the rat. In the isolated perfused lung of the normal and O2-exposed rat, change in pre- and postcapillary resistance was determined in response to challenge with angiotensin II (ANG II; 5, 25, and 50 micrograms) or histamine (0.5 and 1.0 microgram). In the hyperoxic lung both pre- and postcapillary resistance were increased at base line, although the latter less consistently so. In response to each agent precapillary resistance increased more than postcapillary resistance in the hyperoxic lung. In the normal lung pre- and postcapillary reactivity to histamine were similar but the latter was the greater in response to ANG II. In the hyperoxic lung only the pre- and postcapillary response to the first challenge of ANG II (5 micrograms) was greater than normal. The magnitude of the precapillary response was not related to the level of base-line resistance, and this response was significantly increased in a small number of hyperoxic lungs with base-line resistance in the normal range. Tachyphylaxis occurred after the first dose of ANG II. In the hyperoxic lung only the precapillary response to 0.5 micrograms histamine was greater than normal. We conclude that exposure to hyperoxia for 7 days causes an increase in pulmonary arterial reactivity. Furthermore, the alteration in reactivity is not caused by vascular restriction. We hypothesize that it is attributable to peripheral extension of smooth muscle in alveolar wall arteries.
Endotoxin-pretreated neutrophils increase pulmonary vascular permeability in dogs
Authors: Welsh C. H. , Lien D. C. , Worthen G. S. , Henson P. M. , Weil J. V.
Published: December 2017

Endotoxin causes pulmonary vascular neutrophil sequestration and injures the lung. Whether this is primarily due to a direct effect of endotoxin on the endothelium or is mediated by an action on the neutrophil is unclear. Canine neutrophils, isolated on plasma-Percoll gradients in vitro, were incubated with Salmonella enteriditis endotoxin, washed, and injected via wedged pulmonary arterial catheters into discrete lung zones of anesthetized dogs, whereas untreated neutrophils were administered into contralateral control lung zones. 113mIn-transferrin was administered intravenously 2 h before the animals were killed. Morphometry and extravascular protein accumulation were assessed at 4 h. Endotoxin treatment of neutrophils ex vivo induced a two- to three-fold increase in neutrophils in these lung zones (0.096 +/- 0.012 vs. 0.05 +/- 0.002 neutrophils/alveolar septal intercept, P less than 0.05). Extravascular-to-intravascular protein ratios in zones receiving endotoxin-treated neutrophils were significantly increased compared with control zones (0.146 +/- 0.02 vs. 0.079 +/- 0.02, P less than 0.05). Because complement fragments increase injury to endothelium in vitro, exogenous C5 fragments were administered to other dogs before administration of neutrophils but failed to significantly increase the extravascular protein signal (0.154 +/- 0.03 vs. 0.124 +/- 0.04). In summary, endotoxin treatment of neutrophils leads to neutrophil sequestration and increased pulmonary extravascular protein accumulation. C5 fragments failed to further enhance the protein accumulation. These data are consistent with an effect of endotoxin on the neutrophil to initiate neutrophil-endothelial interaction and subsequent lung injury.
Behavioral thermoregulation in mice subjected to high pressure
Authors: Macdonald A. G. , Marshall N. R. , Pertwee R. G.
Published: December 2017

Mice exposed to normoxic He and Ne at increased pressure and allowed to choose between a neutral and a cool environment showed a preference for the cooler environment. This behavior was apparent at 5.7 but not at 2.5 atm He. At 11.3 atm He and Ne, the behavior was associated with a similar reduction in the deep body temperature to a new steady level. The reduction in body temperature increased with pressure, up to 35 atm He, the maximum studied. Since the heat transfer of the He and Ne gas mixtures is different and both gases exert negligible anesthetic effects, the hydrostatic pressure most likely affects behavioral thermoregulation by affecting neuronal function.
Acoustic rhinometry: evaluation of nasal cavity geometry by acoustic reflection
Authors: Hilberg O. , Jackson A. C. , Swift D. L. , Pedersen O. F.
Published: December 2017

To study the geometry of the nasal cavity we applied an acoustic method (J. Appl. Physiol. 43: 523–536, 1977) providing an estimate of cross-sectional area as a function of distance. Acoustic areas in a model constructed from a human nasal cast, in the nasal cavity of a cadaver and in 10 normal subjects and two patients with well-defined afflictions of the nasal cavity, were compared with similar areas obtained by computerized tomography (CT) scans, a specially developed water displacement method, and anterior rhinomanometry. We found a coefficient of variation of the areas of less than 2% by the acoustic method compared with 15% for the rhinomanometric measurements. Acoustic areas correlated highly to similar areas obtained by CT scanning (r = 0.94) and by water displacement (r = 0.96). In two patients the acoustic method accurately outlined, respectively, a tumor in the nose and a septum deviation. It is concluded that this method provides an accurate method for measuring the geometry of the nasal cavity. It is easy to perform and is potentially useful for investigation of physiological and pathological changes in the nose.
Muscle glycogen availability and temperature regulation in humans
Authors: Martineau L. , Jacobs I.
Published: December 2017

The effects of intramuscular glycogen availability on human temperature regulation were studied in eight seminude subjects immersed in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each subject was immersed three times over a 3-wk period. Each immersion followed 2.5 days of a specific dietary and/or exercise regimen designed to elicit low (L), normal (N), or high (H) glycogen levels in large skeletal muscle groups. Muscle glycogen concentration was determined in biopsies taken from the vastus lateralis muscle before and after each immersion. Intramuscular glycogen concentration before the immersion was significantly different among the L, N, and H trials (P less than 0.01), averaging 247 +/- 15, 406 +/- 23, and 548 +/- 42 (SE) mmol glucose units.kg dry muscle-1, respectively. The calculated metabolic heat production during the first 30 min of immersion was significantly lower during L compared with N or H (P less than 0.05). The rate at which Tre decreased was more rapid during the L immersion than either N or H (P less than 0.05), and the time during the immersion at which Tre first began to decrease also appeared sooner during L than N or H. The results suggest that low skeletal muscle glycogen levels are associated with more rapid body cooling during water immersion in humans. Higher than normal muscle glycogen levels, however, do not increase cold tolerance.
Muscle glycogenolysis and H+ concentration during maximal intermittent cycling
Authors: Spriet L. L. , Lindinger M. I. , McKelvie R. S. , Heigenhauser G. J. , Jones N. L.
Published: December 2017

The relationships between muscle glycogenolysis, glycolysis, and H+ concentration were examined in eight subjects performing three 30-s bouts of maximal isokinetic cycling at 100 rpm. Bouts were separated by 4 min of rest, and muscle biopsies were obtained before and after bouts 2 and 3. Total work decreased from 20.5 +/- 0.7 kJ in bout 1 to 16.1 +/- 0.7 and 13.2 +/- 0.6 kJ in bouts 2 and 3. Glycogenolysis was 47.2 and 15.1 mmol glucosyl U/kg dry muscle during bouts 2 and 3, respectively. Lower accumulations of pathway intermediates in bout 3 confirmed a reduced glycolytic flux. In bout 3, the work done represented 82% of the work in bout 2, whereas glycogenolysis was only 32% of that in bout 2. Decreases in ATP and phosphocreatine contents were similar in the two bouts. Muscle [H+] increased from 195 +/- 12 to 274 +/- 19 nmol/l during bout 2, recovered to 226 +/- 8 nmol/l before bout 3, and increased to 315 +/- 24 nmol/l during bout 3. Muscle [H+] could not be predicted from lactate content, suggesting that ion fluxes are important in [H+] regulation in this exercise model. Low glycogenolysis in bout 3 may be due to an inhibitory effect of increased [H+] on glycogen phosphorylase activity. Alternately, reduced Ca2+ activation of fast-twitch fibers (including a possible H+ effect) may contribute to the low overall glycogenolysis. Total work in bout 3 is maintained by a greater reliance on slow-twitch fibers and oxidative metabolism.
Effect of training on the dose-response relationship for insulin action in men
Authors: Mikines K. J. , Sonne B. , Farrell P. A. , Tronier B. , Galbo H.
Published: December 2017

Seven endurance-trained subjects [maximal O2 consumption (VO2max) 64 +/- 1 (SE) ml.min-1.kg-1] were subjected to three sequential hyperinsulinemic euglycemic clamps 15 h after having performed their last training session (T). Results were compared with findings in seven untrained subjects (VO2max 44 +/- 2 ml.min-1.kg-1) studied both at rest (UT) and after 60 min of bicycle exercise at 150 W (UT-ex). In T and UT-ex compared with UT, sensitivity for insulin-mediated whole-body glucose uptake was higher [insulin concentrations eliciting half-maximal glucose uptake being 44 +/- 2 (T) and 43 +/- 4 (UT-ex) vs. 52 +/- 3 microU/ml (UT), P less than 0.05] and responsiveness was higher [13.4 +/- 1.2 (T) and 10.9 +/- 0.7 (UT-ex) vs. 9.5 +/- 0.7 mg.min-1.kg-1 (UT), P less than 0.05]. Furthermore, responsiveness was higher (P less than 0.05) in T than in UT-ex. Insulin-stimulated O2 uptake and maximal glucose oxidation rate were higher in T than in UT and UT-ex. Insulin-stimulated conversion or glucose to glycogen and muscle glycogen synthase was higher in T than in UT and UT-ex. However, glycogen storage in vastus lateralis muscle was found only in UT-ex. No change in any glucoregulatory hormone or metabolite could explain the increased insulin action in trained subjects. It is concluded that physical training induces an adaptive increase in insulin responsiveness of whole-body glucose uptake, which does not reflect increased glycogen deposition in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Dissociation of maximal O2 uptake from O2 delivery in canine gastrocnemius in situ
Authors: Hogan M. C. , Roca J. , West J. B. , Wagner P. D.
Published: December 2017

To test the hypothesis that maximal O2 uptake (VO2max) can be limited by O2 diffusion in the peripheral tissue, we kept O2 delivery [blood flow X arterial O2 content (CaO2)] to maximally contracting muscle equal between 1) low flow-high CaO2 and 2) high flow-low CaO2 conditions. The hypothesis predicts, because of differences in the capillary PO2 profile, that the former condition will result in both a higher VO2max and muscle effluent venous PO2 (PVO2). We studied the relations among VO2max, PVO2, and O2 delivery during maximal isometric contractions in isolated, in situ dog gastrocnemius muscle (n = 6) during these two conditions. O2 delivery was matched by varying arterial O2 partial pressure and adjusting flow to the muscle accordingly. A total of 18 matched O2 delivery pairs were obtained. As planned, O2 delivery was not significantly different between the two treatments. In contrast, VO2max was significantly higher [10.4 +/- 0.5 (SE) ml.100 g-1.min-1; P = 0.01], as was PVO2 (25 +/- 1 Torr; P less than 0.01) in the low flow-high CaO2 treatment compared with the high flow-low CaO2 treatment (9.1 +/- 0.4 ml.100 g-1.min-1 and 20 +/- 1 Torr, respectively). The rate of fatigue was greater in the high flow-low CaO2 condition, as was lactate output from the muscle and muscle lactate concentration. The results of this study show that VO2max is not uniquely dependent on O2 delivery and support the hypothesis that VO2max can be limited by peripheral tissue O2 diffusion.
Different hematologic responses to hypoxia in Sherpas and Quechua Indians
Authors: Winslow R. M. , Chapman K. W. , Gibson C. C. , Samaja M. , Monge C. C. , Goldwasser E. , Sherpa M. , Blume F. D. , Santolaya R.
Published: December 2017

Previous studies of the erythropoietic response to hypoxia in high-altitude natives suggest that the hematocrit and hemoglobin values in Himalayan natives (Sherpas) are lower than expected for the altitude, perhaps because of a genetic adaptation. However, differences in sampling techniques and experimental methods make comparisons difficult. Our studies were carried out to compare the erythropoietic response with the same altitude in age-matched natives of the Himalayas and Andes by the same experimental techniques. Healthy male subjects were selected in Ollague, Chile (n = 29, 27.3 +/- 5.9 yr) and in Khunde, Nepal (n = 30, 24.7 +/- 3.8 yr). Both of these villages are located at 3,700 m above sea level. Hematologic measurements confirmed lower hematocrit values in Nepal (48.4 +/- 4.5%) than in Chile (52.2 +/- 4.6%) (P less than 0.003). When subjects were matched for hematocrit, erythropoietin concentrations in Chile were higher than in Nepal (P less than 0.01). Detailed measurements of blood O2 affinity in Nepal showed no differences in shape or position of the O2 equilibrium curve between Sherpas and Western sojourners. Our results indicate that although Quechua Indians have higher hematocrits than Sherpas living at the same altitude, nevertheless they may be functionally anemic.
Supplemental oxygen reduces right ventricular hypertrophy in monocrotaline-injected rats
Authors: Hill N. S. , Jederlinic P. , Gagnon J.
Published: December 2017

We evaluated the possible contributory role of hypoxia in the development of monocrotaline-induced pulmonary hypertension. Male Sprague-Dawley rats were injected subcutaneously with monocrotaline (60 mg/kg) or saline in controls and were kept in oxygen-enriched (inspired O2 fraction of 0.35) or compressed air chambers. After 21 days, rats were anesthetized while spontaneously breathing room air, hemodynamic parameters and arterial blood gases were measured, and animals were killed. Right ventricular peak systolic pressures (RVPP), right ventricular-to-left ventricular plus septal weight ratios (RV/LV + S), hematocrits, lung dry weight-to-body weight ratios, and medial thickness of pulmonary arteries were significantly reduced in monocrotaline-injected rats exposed to mild hyperoxia compared with air. The air-exposed monocrotaline-injected rats had significantly more arterial hypoxemia than the other groups, and mild hyperoxia had no effect on any of the measured variables in saline-injected rats. To determine whether the effects of mild hyperoxia occurred early or late after monocrotaline injection, we moved separate groups of rats from air to mild hyperoxia and vice versa 10 days after monocrotaline injection. After 21 days, significant reductions in RVPP and RV/LV + S occurred only in rats exposed to mild hyperoxia during the latter 11 days after injection. Our findings suggest that hypoxia contributes to the development of pulmonary hypertension relatively late after monocrotaline injection in rats but that it does not influence the early injury.
Hypoxemia raises muscle sympathetic activity but not norepinephrine in resting humans
Authors: Rowell L. B. , Johnson D. G. , Chase P. B. , Comess K. A. , Seals D. R.
Published: December 2017

The experimental objective was to determine whether moderate to severe hypoxemia increases skeletal muscle sympathetic nervous activity (MSNA) in resting humans without increasing venous plasma concentrations of norepinephrine (NE) and epinephrine (E). In nine healthy subjects (20–34 yr), we measured MSNA (peroneal nerve), venous plasma levels of NE and E, arterial blood pressure, heart rate, and end-tidal O2 and CO2 before (control) and during breathing of 1) 12% O2 for 20 min, 2) 10% O2 for 20 min, and 3) 8% O2 for 10 min--in random order. MSNA increased above control in five, six, and all nine subjects during 12, 10, and 8% O2, respectively (P less than 0.01), but only after delays of 12 (12% O2) and 4 min (8 and 10% O2). MSNA (total activity) rose 83 +/- 20, 260 +/- 146, and 298 +/- 109% (SE) above control by the final minute of breathing 12, 10, and 8% O2, respectively. NE did not rise above control at any level of hypoxemia; E rose slightly (P less than 0.05) at one time only with both 10 and 8% O2. Individual changes in MSNA during hypoxemia were unrelated to elevations in heart rate or decrements in blood pressure and end-tidal CO2--neither of which always fell. We conclude that in contrast to some other sympathoexcitatory stimuli such as exercise or cold stress, moderate to severe hypoxemia increases leg MSNA without raising plasma NE in resting humans.
Rate of erythropoietin formation in humans in response to acute hypobaric hypoxia
Authors: Eckardt K. U. , Boutellier U. , Kurtz A. , Schopen M. , Koller E. A. , Bauer C.
Published: December 2017

This study was carried out to investigate the early changes in erythropoietin (EPO) formation in humans in response to hypoxia. Six volunteers were exposed to simulated altitudes of 3,000 and 4,000 m in a decompression chamber for 5.5 h. EPO was measured by radioimmunoassay in serum samples withdrawn every 30 min during altitude exposure and also in two subjects after termination of hypoxia (4,000 m). EPO levels during hypoxia were significantly elevated after 114 and 84 min (3,000 and 4,000 m), rising thereafter continuously for the period investigated. Mean values increased from 16.0 to 22.5 mU/ml (3,000 m) and from 16.7 to 28.0 mU/ml (4,000 m). This rise in EPO levels corresponds to 1.8-fold (3,000 m) and 3.0-fold (4,000 m) increases in the calculated production rate of the hormone. After termination of hypoxia, EPO levels continued to rise for approximately 1.5 h and after 3 h declined exponentially with an average half-life time of 5.2 h.
Extreme endurance training and fiber type adaptation in rat diaphragm
Authors: Green H. J. , Plyley M. J. , Smith D. M. , Kile J. G.
Published: December 2017

Extreme endurance training was used to investigate the adaptability of the rat diaphragm muscle fibers. During the final phase of the 14-wk training program, the animals were running for 240 min/day at an estimated requirement of 80% of pretraining maximal O2 consumption. Analysis of a sample of the costal diaphragm indicated that training resulted in a 34% reduction (P less than 0.05) in the percent distribution of type IIa fibers [27.7 +/- 1.1 vs. 18.3 +/- 2.6 (SE)] and a 15% increase (P less than 0.05) in the percent of type IIb fibers (40.0 +/- 1.2 vs. 46.1 +/- 2.4). No change (P greater than 0.05) was found in the distribution of the type I fibers (32.3 +/- 1.2 vs. 35.7 +/- 1.3). Oxidative potential as assessed with NADH-tetrazolium reductase and measured microphotometrically increased (P less than 0.05) by 19% in type I fibers but did not change in either the type IIa or type IIb fibers. No effect of training was found when a different oxidative marker, succinic dehydrogenase, was employed. Similarly glycolytic potential based on the activity of alpha-glycerophosphate dehydrogenase was not affected by training. Glycogen concentration was elevated by 60% (P less than 0.01) in type I fibers and 77% (P less than 0.01) in type IIb fibers with training but was not altered (P greater than 0.05) in type IIa fibers. Reductions (P less than 0.05) in fiber area ranging from 11 to 20% were observed in all fiber types as a result of training, whereas the number of capillaries per fiber remained static.(ABSTRACT TRUNCATED AT 250 WORDS)
Isoproterenol attenuates myosin phosphorylation and contraction of tracheal muscle
Authors: Obara K. , de Lanerolle P.
Published: December 2017

The effects of isoproterenol on isometric force, unloaded shortening velocity, and myosin phosphorylation were examined in thin muscle bundles (0.1–0.2 mm diam) dissected from lamb tracheal smooth muscle. Methacholine (10(-6) M) induced rapid increases in isometric force and in phosphorylation of the 20,000-Da myosin light chain. Myosin phosphorylation remained elevated during steady-state maintenance of isometric force. The shortening velocity peaked at 15 s after stimulation with methacholine and then declined to approximately 45% of the maximal value by 3 min. Isoproterenol pretreatment inhibited methacholine-stimulated myosin light chain phosphorylation, shortening velocity, and force during the early stages of force generation. However, the inhibitory effect of isoproterenol on force and myosin phosphorylation is proportionally greater than that on shortening velocity. Isoproterenol pretreatment also caused a rightward non-parallel shift in the methacholine dose-response curves for both isometric tension and myosin light chain phosphorylation. These data demonstrate that isoproterenol attenuates the contractile properties of airway smooth muscles by affecting the rate and extent of myosin light chain phosphorylation, perhaps through a mechanism that involves the synergistic interaction of myosin light chain kinase phosphorylation and Ca2+ metabolism.
Effects of undernutrition on diaphragm fiber size, SDH activity, and fatigue resistance
Authors: Sieck G. C. , Lewis M. I. , Blanco C. E.
Published: December 2017

The influence of prolonged nutritional deprivation on the succinate dehydrogenase (SDH) activity and cross-sectional areas of individual fibers in the rat diaphragm and deep portion of the medial gastrocnemius (MGr) muscles was determined. Fatigue resistance of the diaphragm was measured by means of an in vitro nerve-muscle strip preparation. Fiber SDH activity and cross-sectional area were quantified by means of an image processing system. Diaphragm fatigue resistance was significantly improved in the nutritionally deprived (ND) group. In both muscles, nutritional deprivation resulted in a significant decrease in fiber cross-sectional area (both type I and II), type II fibers showing greater atrophy. The SDH activities of type I and II fibers in the diaphragm were not affected by nutritional deprivation. This contrasted with a significant decrease in the SDH activity of both type I and II fibers in the MGr of ND animals. An assessment of the interrelationships between fiber atrophy and fiber SDH activity revealed a greater effect of malnutrition on those diaphragm type II fibers that had the lowest relative SDH activities and the largest cross-sectional areas. By comparison, the effect of malnutrition on type I and II fibers in the MGr was nonselective with regard to fiber SDH activity. We conclude that the enhanced diaphragm fatigue resistance in the ND animals does not result from an increase in the oxidative capacity of muscle fibers and is best explained by the pattern of diaphragm muscle fiber atrophy.
Effects of drug-induced pulmonary phospholipidosis on lung mechanics in rats
Authors: Camus P. , Joshi U. M. , Lockard V. G. , Petrini M. F. , Lentz D. L. , Mehendale H. M.
Published: December 2017

Chronic administration of amphiphilic drugs to rats induces pulmonary phospholipidosis (P), a disease characterized by accumulation of phospholipids and large foamy macrophages in alveolar spaces. We investigated whether P induced by chlorphentermine (CPH) causes changes in lung volumes and mechanics in this species. Groups of rats were fed CPH (50 mg.kg-1.day-1) for 1, 2, 3, 5, 9, and 14 wk. After each treatment period, lung volumes and mechanics were studied in the anesthetized, paralyzed, supine rat. Partial pressure-volume (PV) curves were developed at 3 and 6 ml above functional residual capacity (FRC; PV3, PV6), followed by maximal [up to total lung capacity (TLC)] PV curves. FRC was determined by saline displacement. Lungs were then fixed for histopathological examination. A subgroup of animals was allowed a recovery period of 6 wk, after the 9 wk of CPH administration. Pair-fed rats served as controls (CTR) at each time point. Lung weight increased in CPH-treated (CPH-T) rats from 1.5 +/- 0.2 (SD) g at week 1 to 5.8 +/- 1.4 g at week 14, reflecting the development of P. TLC, FRC, transpulmonary pressure at FRC, the shape of maximal PV curves, and static expiratory lung compliance computed from maximal PV data points did not change in CPH-T rats. However, partial PV curves of CPH-T lungs (particularly PV3) were shifted downward and to the right of those of CTR at 2, 3, 5, and 9 wk, indicating increased recoil pressure in phospholipidotic lungs at these time points.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of rehydration on atrial natriuretic peptide release during exercise in the heat
Authors: Follenius M. , Candas V. , Bothorel B. , Brandenberger G.
Published: December 2017

In an attempt to investigate their relationships with plasma volume (PV), heart rate (HR), and other hormonal systems, plasma atrial natriuretic peptide (ANP) levels were determined in response to exercise in the heat, associated with dehydration and rehydration with various fluids. Five normal subjects underwent four 3-h experiments, in a 36 degree C environment, in which 25-min exercise periods on a cycle ergometer at 90 W alternate with 5-min rest periods. Blood samples were collected hourly and ANP, arginine vasopressin (AVP), adrenocorticotropin (ACTH), and cortisol were analyzed in four experimental sessions: without fluid supplement (DH) and with progressive rehydration either with water (W), acid isotonic solution (AISO), or neutral isotonic solution (NISO). Exercise in the heat, accompanied by a decrease in PV and an increase in osmolality, elicited an increase of 28 +/- 1.6 pg/ml in plasma ANP, with concomitant increases in AVP (5.1 +/- 1.4 pg/ml), ACTH (49.6 +/- 12.3 pg/ml), and cortisol (8.4 +/- 2.0 micrograms/100 ml). Progressive rehydration maintained PV and blunted ANP, AVP, ACTH, and cortisol responses. These results demonstrate the importance of rehydration, during exercise in a warm environment, in preventing hormonal increases. They suggest that under our conditions, the PV changes and the inferred atrial pressure changes may not be the primary factors controlling ANP release, as under other physiological conditions. The exercise-related activation of pituitary and adrenals and the stimulation of HR counteract the influence of PV changes due to vascular fluid shifts.
Effect of saline infusion on body temperature and endurance during heavy exercise
Authors: Deschamps A. , Levy R. D. , Cosio M. G. , Marliss E. B. , Magder S.
Published: December 2017

We tested the hypothesis that volume infusion during strenuous exercise, by expanding blood volume, would allow better skin blood flow and better temperature homeostasis and thereby improve endurance time. Nine males exercised to exhaustion at 84.0 +/- 3.14% (SE) of maximum O2 consumption on a cycle ergometer in a double-blind randomized protocol with either no infusion (control) or an infusion of 0.9% NaCl (mean vol 1,280.3 +/- 107.3 ml). Blood samples and expired gases (breath-by-breath), as well as core and skin temperatures, were analyzed. Plasma volume decreased less during exercise with the infusion at 15 min (-13.7 +/- 1.4% control vs. -5.3 +/- 1.7% infusion, P less than 0.05) and at exhaustion (-13.6 +/- 1.2% vs. -1.3 +/- 2.2%, P less than 0.01). The improved fluid homeostasis was associated with a lower core temperature during exercise (39.0 +/- 0.2 degrees C for control and 38.5 +/- 0.2 degrees C for infusion at exhaustion, P less than 0.01) and lower heart rate (194.1 +/- 3.9 beats/min for control and 186.0 +/- 5.1 beats/min for infusion at exhaustion, P less than 0.05). However, endurance time did not differ between control and infusion (21.96 +/- 3.56 and 20.82 +/- 2.63 min, respectively), and neither did [H+], peak O2 uptake, and CO2 production, end-tidal partial pressure of CO2, blood lactate, or blood pressure. In conclusion, saline infusion increases heat dissipation and lowers core temperature during strenuous exercise but does not influence endurance time.
Variability of responses across training levels to maximal treadmill exercise
Authors: Kyle S. B. , Smoak B. L. , Douglass L. W. , Deuster P. A.
Published: December 2017

The variability of peak VO2 (ml/min, ml.kg-1.min-1), time on treadmill (TMILLTM), maximal heart rate (HRmax), respiratory exchange ratio at peak VO2 (Rmax), rate of respiration at peak VO2 (FREQ), and exercise-induced changes in plasma lactate concentration (LACDIF) was measured across three maximal treadmill runs in five highly trained, seven moderately trained, and five untrained males. No effect of training level on the variability of any of the parameters was found. Test-retest correlation coefficients for peak VO2 (r = 0.95, run 1 with run 2; r = 0.92, run 1 with run 3; r = 0.92, run 2 with run 3) were similar to previously reported values. Variance component distributions suggested that the underlying physiological mechanisms of response for peak VO2, TMILLTM, and HRmax were different from those of FREQ, Rmax, and LACDIF. Minimum detectable differences for peak VO2 (ml.kg-1.min-1, n = 5, minimum detectable within subject difference, 11.5%; minimum detectable among subject effects, 21.3%) indicated a need for careful attention to research design in future studies.
Contrasts in muscle and myofibers of elite male and female bodybuilders
Authors: Alway S. E. , Grumbt W. H. , Gonyea W. J. , Stray-Gundersen J.
Published: December 2017

Muscle cross-sectional area (CSA), fiber area, and fiber number were determined from the biceps brachii of eight elite male bodybuilders (MB) and five elite female bodybuilders (FB) who had similar training characteristics. Biceps CSA was obtained from computer tomographic scanning and corrected for noncontractile tissue. Biceps CSA was twofold greater in MB relative to FB and strongly correlated to lean body mass (R = 0.93). Biceps CSA expressed per kilogram lean body mass (LBM) or per centimeter body height (BH) was 35% greater in MB compared with FB. Most of the gender difference in muscle CSA was because of greater absolute mean fiber areas in MB (9,607 microns2) relative to FB (5,386 microns2); however, MB also had a significantly greater population of small type II fibers (less than 2,000 microns2) compared with FB. Type II fiber area/LBM averaged 1.6-fold greater in MB compared with FB; however, type I fiber area/LBM was similar between groups. Biceps CSA was positively correlated to fiber CSA (R = 0.75) and fiber number (R = 0.55). This suggests that adaptations to resistance training may be complex and involve fiber hypertrophy and fiber number (e.g., proliferation). Alternatively, since the muscle characteristics before training are not known, these apparent adaptations might be genetically determined attributes.
Measurement of sympathetic nerve activity in the unanesthetized rat
Authors: Fluckiger J. P. , Gremaud G. , Waeber B. , Kulik A. , Ichino A. , Nussberger J. , Brunner H. R.
Published: December 2017

A new system was developed in our laboratory to continuously monitor intra-arterial pressure, heart rate, and sympathetic nerve activity in unanesthetized rats. The animals were prepared 24 h before the start of the experiments. Sympathoneural traffic was measured at the level of splanchnic nerve. The amplitude of the spikes recorded at this level was utilized to express sympathetic nerve activity. The amplitude of the residual electroneurogram signal present 30 min after the rats were killed was 32 +/- 2 mV (mean +/- SE; n = 11). For analysis, these background values were subtracted from values determined in vivo. The nerve we studied contains postganglionic fibers, since electrical activity decreased in response to ganglionic blockade with pentolinium (1.25 mg/min iv for 4 min). The amplitude of spikes fell by 43 +/- 4% (n = 4). Sympathetic nerve activity was highly reproducible at a 24-h interval (104 +/- 26 vs. 111 +/- 27 mV for the amplitude of spikes; n = 11). Dose-response curves to the alpha 1-stimulant methoxamine and to bradykinin were established in four rats. The increase in blood pressure induced by methoxamine caused a dose-dependent fall in sympathetic nerve activity, whereas the blood pressure reduction resulting from bradykinin was associated with a dose-dependent activation of sympathetic drive. These data therefore indicate that it is possible with out system to accurately measure sympathetic nerve activity in the awake rat, together with intra-arterial pressure and heart rate.
Exercise intensity and glucose tolerance in trained and nontrained subjects
Authors: Young J. C. , Enslin J. , Kuca B.
Published: December 2017

The improved glucose tolerance and increased insulin sensitivity associated with regular exercise appear to be the result, in large part, of the residual effects of the last bout of exercise. To determine the effects of exercise intensity on this response, glucose tolerance and the insulin response to a glucose load were determined in seven well-trained male subjects [maximal O2 uptake (VO2max) = 58 ml.kg-1.min-1] and in seven nontrained male subjects (VO2max = 49 ml.kg-1.min-1) in the morning after an overnight fast 1) 40 h after the last training session (control), 2) 14 h after 40 min of exercise on a cycle ergometer at 40% VO2max, and 3) 14 h after 40 min of exercise at 80% VO2max. Subjects replicated their diets for 3 days before each test and ate a standard meal the evening before the oral glucose tolerance test. No differences in the 3-h insulin or glucose response were observed between the control trial and before exercise at either 40 or 80% VO2max in the trained subjects. In the nontrained subjects the plasma insulin response was decreased by 40% after a single bout of exercise at either 40 or 80% VO2max (7.0 X 10(3) vs. 5.0 X 10(3), P less than 0.05; 3.8 X 10(3) microU.ml-1.180 min-1, P less than 0.01). The insulin response after a single bout of exercise in the nontrained subjects was comparable with the insulin responses found in the trained subjects for the control and exercise trials.(ABSTRACT TRUNCATED AT 250 WORDS)
Serotonin increases excitability of rabbit C-fiber neurons by two distinct mechanisms
Authors: Christian E. P. , Taylor G. E. , Weinreich D.
Published: December 2017

Serotonin (5-HT) increases impulse activity in visceral afferent C-fibers in vivo. A 5-HT-induced membrane depolarization may partially account for this effect. Here, we examined the potential contribution of an additional mechanism to the 5-HT-mediated increase in impulse activity. Approximately 40% of rabbit visceral C-fiber neurons exhibit a protracted (greater than 3 s) spike afterhyperpolarization (AHPslow) that is a major determinant of repetitive firing properties in these neurons. Intracellular recording methods were applied to rabbit nodose ganglion neurons in vitro to assess whether 5-HT could increase excitability through effects on the AHPslow. Results revealed a concentration-dependent 5-HT-mediated depression of the AHPslow amplitude and duration that was accompanied by decreased accommodation of action potential firing. Experiments with 5-HT receptor antagonists further showed that this autacoid depressed the AHPslow through a different 5-HT receptor subtype than that subserving the 5-HT-induced depolarization. Thus the AHPslow represents a distinct locus where 5-HT can increase the impulse activity of these visceral C-fiber afferents.
Ten weeks of aerobic training do not affect lower body negative pressure responses
Authors: Lightfoot J. T. , Claytor R. P. , Torok D. J. , Journell T. W. , Fortney S. M.
Published: December 2017

Based mostly on cross-sectional data, it has been suggested that aerobic training may decrease lower body negative pressure (LBNP) tolerance through a hypothesized attenuation in both high- and low-pressure baroreflex gain. An experimental group (EXP) of eight male subjects [22.1 +/- 1.4 (SD) yr] underwent a 10-wk treadmill and cycle ergometer training program, which resulted in a 21% increase in maximal O2 uptake (VO2 max), 45.7 +/- 1.5 vs. 55.2 +/- 1.7 (SE) ml.kg-1.min-1; P less than 0.05]. A control group, (CON; n = 7; 27.3 +/- 5.7 yr), which did not undergo training, had no significant changes in VO2 max (49.4 +/- 3.3 vs. 48.8 +/- 3.2 ml.kg-1.min-1). Before and after training the EXP and CON groups participated in LBNP tolerance tests (terminated at presyncope) and neck pressure-suction testing (to describe the carotid sinus-heart rate baroreflex). LBNP tolerance, as defined by three different indexes, and carotid sinus-heart rate baroreflex gain were not altered in either group after training. Furthermore, there were no changes in LBNP heart rate, blood pressure, leg circumference, forearm blood flow, or forearm vascular resistance responses at any level of LBNP challenge after training. In conclusion, 10 wk of aerobic training did not change LBNP tolerance or alter the reflex cardiovascular compensatory mechanisms activated during LBNP.
Calcitonin gene-related peptide vasodilation of human pulmonary vessels
Authors: McCormack D. G. , Mak J. C. , Coupe M. O. , Barnes P. J.
Published: December 2017

Human calcitonin gene-related peptide (CGRP) is localized to sensory neurons in pulmonary vessels and is a potent vasodilator. We have characterized the effects of CGRP in human pulmonary vessels and localized the receptors for this peptide by autoradiography. Fresh human lung tissue was obtained from eight patients undergoing surgery and small (200–400 microns ID) pulmonary arteries and veins were dissected free of surrounding connective and pulmonary tissue. Pairs of vessels were studied and in one of each pair the endothelium was left intact and from the other of each pair the endothelium was removed by gentle abrasion. For functional studies arteries (n = 9) and veins (n = 9) were suspended in an organ bath, precontracted with 1 microM prostaglandin F2 alpha. CGRP (10 pM to 10 microM) was added in a cumulative manner. CGRP caused a dose-dependent relaxation of endothelium intact human pulmonary arteries and veins with log EC50 values of -8.01 +/- 0.35 and -8.70 +/- 0.40, respectively (not significant). Removal of the endothelium did not diminish the vasodilator potency of CGRP in either vessel. For autoradiographic studies, cryostat sections of the small human pulmonary vessels with or without endothelium were used. 125I-CGRP densely labeled CGRP receptors on vascular smooth muscle and endothelial removal did not have any effect on grain density. We concluded that CGRP is a potent vasodilator of human pulmonary arteries and veins that is not dependent on an intact endothelium. These functional studies correlate with the distribution of CGRP receptors as localized by autoradiography.