bluuebunny/crossref_metadata_2025 huggingface dataset:
Compensation of respiratory alkalosis induced after acclimation to simulated altitude
Authors: Gonzalez N. C. , Albrecht T. , Sullivan L. P. , Clancy R. L.
Published: December 2017

Conscious intact rats previously acclimated for 3 wk to barometric pressure of 370-380 Torr (3WHx) were made alkalotic for 3 h by a decrease in inspired O2 fraction from 0.10 to 0.075 at ambient barometric pressure (730-740 Torr). Controls were normoxic littermates (Nx) in which inspired O2 fraction was lowered from approximately 0.21 to 0.10 for 3 h. Arterial PCO2 decreased progressively and similarly in both groups (65-70% of control at 15 min). Initially, arterial pH increased less in 3WHx (0.09 +/- 0.004 vs. 0.15 +/- 0.008). As hypocapnia continued, delta[HCO3-]/delta pH (mmol.l-1.pH) became more negative in Nx, from -15.2 +/- 2.5 at 15 min to -37.0 +/- 2.9 at 3 h, indicating nonrespiratory compensation of alkalosis. In 3WHx, delta[HCO3-]/delta pH did not change during alkalosis. Cumulative renal excretion of base (mueq/100 g) during alkalosis increased by 73.2 +/- 11.1 in Nx and 25.4 +/- 7.3 in 3WHx. This difference was mainly due to a larger increase in HCO3- excretion in Nx. The data suggest that the smaller compensation of hypocapnic alkalosis in 3WHx is partly due to the smaller increase in renal base excretion. Because base availability limits renal base excretion, the smaller renal response of 3WHx may be secondary to the low plasma HCO3- concentration that accompanies altitude acclimation.
Theophylline minimally alters contractile properties of canine diaphragm in vitro
Authors: Derom E. , Janssens S. , De Bock V. , Decramer M.
Published: December 2017

We examined the effects of theophylline on contractile properties and high-frequency fatigue of canine diaphragm in vitro. Eighteen diaphragm muscle bundles were obtained from 10 anesthetized dogs and equilibrated in oxygenated Krebs solution to 100, 200, or 300 mg/l theophylline. These bundles were compared with 18 matched control bundles from the contralateral hemidiaphragm. No statistically significant differences in twitch tension, tetanic tension, twitch-to-tetanus ratio, time to peak tension, or half-relaxation time were observed. Concentrations of 300 mg/l theophylline, however, significantly (P less than 0.05) increased force production at 10 Hz by 32%. A similar tendency was present at lower concentrations and exhibited a clear dose-response behavior. High-frequency fatigue was similar in control and theophylline-treated bundles. We conclude that supratherapeutic in vitro concentrations of theophylline do not increase maximal tetanic tension and do not protect against muscle fatigue but potentiate relative force production at low stimulation frequencies. This relatively small effect cannot be explained by poor diffusion of the drug in the muscle bundle, because theophylline concentrations in the muscle bath and in the muscle bundle were virtually identical. Moreover, it remains unclear whether this potentially beneficial effect can be achieved at in vivo attainable serum concentrations.
Effects of carotid denervation and decerebration on ventilatory response to CO
Authors: Gautier H. , Bonora M. , Zaoui D.
Published: December 2017

To clarify the mechanisms involved in the ventilatory response to the inhalation of low concentrations of CO (0.18-0.22% in air), the roles of the arterial chemoreceptors and the forebrain structures have been investigated in unanesthetized adult cats. The ventilatory response was observed in conscious animals intact, after carotid denervation (CD), and after midcollicular decerebration. The results show that the initial small ventilatory depression was unaffected by CD but that the subsequent characteristic tachypnea was blunted after CD even after more prolonged exposure to CO. The CO tachypnea was not observed after decerebration, but a residual hyperventilation was noted with the higher concentration used. It may be concluded that carotid chemoreceptors do not mediate the CO tachypnea, which may then originate in suprapontine structures as shown by comparison of intact and decerebrate animals. The blunting of the tachypnea after CD may be caused by the relative hypercapnia observed in CD animals. The residual hyperventilation observed in decerebrate animals may be caused by central acidosis and/or some peripheral potentiation of chemoreceptor activity resulting from the decrease in arterial blood pressure that accompanied CO inhalation in decerebrate animals.
Ventilatory effect of acute pulmonary hypothermia
Authors: Giesbrecht G. G. , Younes M.
Published: December 2017

The isolated effect of cooling the pulmonary circulation on ventilation was quantified in nine anesthetized dogs. The right pulmonary artery (RPA) was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the RPA between, but not during, periods of cooling. Cooled blood boluses were injected into the RPA under conditions in which either bolus temperature (5-35 degrees C) or volume (0-1.5 ml/kg body wt) varied. Inspiratory time (TI), expiratory time (TE), breath duration (TT), and peak integrated activity (PEAK) were determined from diaphragm EMG. Results for five postinjection breaths were converted to a percent of the values from five preinjection breaths. There was a linear relationship between bolus temperature and TI [r = 0.61, slope (x) = 0.59%/degrees C, P less than 0.001), TE (r = 0.73, x = 1.43%/degrees C, P less than 0.001] as well as TT (r = 0.74, x = 1.10%/degrees C, P less than 0.001), whereas PEAK was unaffected (n = 9). When injection temperature was 5 degrees C, an inverse linear relationship existed between bolus volume and TI (r = 0.75, x = -15.2%.ml-1.kg-1, P less than 0.001) and TE (r = 0.78, x = -23.4%.ml-1.kg-1, P less than 0.001) (n = 4). In two dogs tested the effect of bolus injection was minimal at residual volume and progressively increased with lung volume. The effect of cold bolus injection was eliminated after right vagotomy in three dogs. Results indicate that cooling of some vagal receptor in the lung increases breathing frequency primarily by shortening TE.
Decreased free fraction of thyroid hormones after prolonged Antarctic residence
Authors: Reed H. L. , Brice D. , Shakir K. M. , Burman K. D. , D'Alesandro M. M. , O'Brian J. T.
Published: December 2017

We investigated the effects of Antarctic residence (AR) on serum thyroid hormone and cardiovascular responses to a 60-min standard cold air (0 degree C) test (SCAT). Serum total thyroxine (TT4) and serum total triiodothyronine (TT3), free T4 (FT4) and T3 (FT3), thyrotropin (TSH), and percent free fraction of T4 (%FT4) and T3 (%FT3) were measured in normal men (n = 15) before and after each of three SCATs. The SCAT was first carried out in California and then repeated after 24 and 44 wk AR. Mean arterial pressure (MAP) and sublingual oral temperature (Tor) were measured before and during each SCAT. The SCAT did not alter thyroid hormones before or after AR. The %FT4 decreased from 0.0334 +/- 0.0017 to 0.0295 +/- 0.0007% (P less than 0.002) with 44 wk AR but without a significant change in TT4 or FT4 for the same period. The %FT3 also decreased from 0.2812 +/- 0.0128 to 0.2458 +/- 0.0067% (P less than 0.005) after 44 wk AR. FT3 decreased (P less than 0.003) but TT3 and TSH were unchanged with 44 wk AR. The decrease in %FT4 and %FT3 may be theoretically accounted for by a 10% increase in either the capacity or the affinity of the serum binding proteins. The SCAT in California increased MAP and did not change Tor. After 44 wk AR, the SCAT no longer increased MAP but did lower Tor. The shift in the Tor and MAP response to the SCAT is consistent with the associated occurrence of cold adaptation during AR. We describe for the first time a decrease in the free fraction of both serum T3 and T4 present with extended polar residence and independent of a SCAT, further characterizing the recently reported “polar T3 syndrome.”
Effect of acute hypercapnia on limb muscle contractility in humans
Authors: Vianna L. G. , Koulouris N. , Lanigan C. , Moxham J.
Published: December 2017

The effect of acute hypercapnia on skeletal muscle contractility and relaxation rate was investigated. The contractile force of fresh and fatigued quadriceps femoris (QF) and adductor pollicis (AP) was studied in normal humans by use of electrical stimulation. Maximum relaxation rate from stimulated contractions was measured for both muscles. Acute hypercapnia led to a rapid substantial reduction of contraction force. The respiratory acidosis after 9% CO2 was breathed for 20 min [mean venous blood pH 7.26 and end-tidal PCO2 (PETCO2) 65.1 Torr] reduced 20- and 100-Hz stimulated contractions of QF to 72.8 +/- 4.4 and 80.0 +/- 5.1% of control values, respectively. After 8 and 9% CO2 were breathed for 12 min, AP forces at 20- and 50-Hz stimulation were also reduced. Twitch tension of AP was reduced by a mean of 25.5% when subjects breathed 9% CO2 for 12 min [mean arterialized venous blood pH (pHav) 7.25 and PETCO2 66 Torr]. Over the range of 5% (pHav 7.38 and PETCO2 47 Torr) to 9% CO2, there was a linear relationship between twitch tension loss and pHav, arterialized venous blood PCO2, and PETCO2. Acute respiratory acidosis (mean PETCO2 61 Torr) increased the severity of low-frequency fatigue after intermittent voluntary contractions of AP. At 20 min of recovery, twitch tension was 63.2 +/- 13.4 and 46.8 +/- 16.4% of control value after exercise breathing air and 8% CO2, respectively. Acute hypercapnia (mean PETCO2 65.1 and 60.5 Torr) did not alter the maximum relaxation rate from tetanic contractions of fresh QF and from twitch tensions of AP.
Exaggerated ANF response to exercise in middle-aged vs. young runners
Authors: Freund B. J. , Claybaugh J. R. , Hashiro G. M. , Buono M. , Chrisney S.
Published: December 2017

Hormonal, electrolyte, and renal responses were measured before, during, and after a marathon (42.2 km) in 14 runners: 8 young (Y) (mean age 27.8 yr) and 6 middle aged (MA) (mean aged 46.7 yr). No differences between groups in prerun values for heart rate (HR), plasma osmolality (OSM), antidiuretic hormone (ADH), aldosterone (ALDO), atrial natriuretic factor (ANF), or plasma renin activity (PRA) were found. Renal and urinary measurements were also similar between groups before the marathon. After 10 km of running, both groups had significant increases in HR, ALDO, ANF, and PRA, while OSM, Na+, and ADH remained unchanged from prerun values. The increase in plasma ANF concentrations at this point was significantly greater in the MA subjects compared with the Y (mean increase 104.1 vs. 42.8 pg/ml, respectively; P less than 0.01). Immediate postmarathon values for OSM, ADH, and Na+ were significantly higher than initial values in both groups, while HR, PRA, and ALDO continued to increase above the elevated levels found at 10 km. ANF values immediately postmarathon remained higher than prerun concentrations but were significantly reduced from those obtained at 10 km. In contrast, HR continued to rise until the completion of the run. These data are consistent with recent reports of an exaggerated ANF response in older subjects in response to central blood volume expansion.
Oral [13C]bicarbonate measurement of CO2 stores and dynamics in children and adults
Authors: Armon Y. , Cooper D. M. , Springer C. , Barstow T. J. , Rahimizadeh H. , Landaw E. , Epstein S.
Published: December 2017

During exercise, less additional CO2 is stored per kilogram body weight in children than in adults, suggesting that children have a smaller capacity to store metabolically produced CO2. To examine this, tracer doses of [13C]bicarbonate were administered orally to 10 children (8-12 yr) and 12 adults (25-40 yr) at rest. Washout of 13CO2 in breath was analyzed to estimate recovery of tracer, mean residence time (MRT), and size of CO2 stores. CO2 production (VCO2) was also measured breath by breath using gas exchange techniques. Recovery did not differ significantly between children [73 +/- 13% (SD)] and adults (71 +/- 9%). MRT was shorter in children (42 +/- 7 min) compared with adults (66 +/- 15 min, P less than 0.001). VCO2 per kilogram was higher in the children (5.4 +/- 0.9 ml.min-1.kg-1) compared with adults (3.1 +/- 0.5, P less than 0.0001). Tracer estimate of CO2 production was correlated to VCO2 (r = 0.86, P less than 0.0001) and when corrected for mean recovery accurately predicted the VCO2 to within 3 +/- 14%. There was no difference in the estimate of resting CO2 stores between children (222 +/- 52 ml CO2/kg) and adults (203 +/- 42 ml CO2/kg). We conclude that orally administered [13C]bicarbonate can be used to assess CO2 transport dynamics. The data do not support the hypothesis of lower CO2 stores under resting conditions in children.
High-intensity endurance training in 20- to 30- and 60- to 70-yr-old healthy men
Authors: Makrides L. , Heigenhauser G. J. , Jones N. L.
Published: December 2017

Factors contributing to maximal incremental and short-term exercise capacity were measured before and after 12 wk of high-intensity endurance training in 12 old (60-70 yr) and 10 young (20-30 yr) sedentary healthy males. Peak O2 uptake in incremental cycle ergometer exercise increased from 1.60 +/- 0.073 to 2.21 +/- 0.073 (SE) l/min (38% increase) in the old subjects and from 2.54 +/- 0.141 to 3.26 +/- 0.181 l/min (29%) in the young subjects. Peak cardiac output, estimated by extrapolation from a series of submaximal measurements by the CO2 rebreathing method, increased by 30% (from 12.7 to 16.5 l/min) in the old subjects, associated with a 6% increase (from 126 to 135 ml/l) in arteriovenous O2 difference; in the young subjects there were equal 14% increases in both variables (18.0 to 20.5 l/min and 140 to 159 ml/l, respectively). Submaximal mean arterial pressure and cardiac output were lower posttraining in the old subjects; total vascular conductance and cardiac stroke volume increased. Although peak power at the start of a short-term maximal isokinetic test did not change, total work accomplished in 30 s at a pedaling frequency of 110 revolutions/min increased in both groups, from 11.2 to 12.6 kJ and from 15.7 to 16.9 kJ in the old and young, respectively; fatigue during the 30-s test was less, and postexercise plasma lactate concentrations were lower. In older subjects, increases in aerobic power after high-intensity endurance training are at least as large as in younger subjects and are associated with increases in vascular conductance, maximal cardiac output, and stroke volume.
Catecholamine neurons in fetal brain: effects on breathing movements and electrocorticogram
Authors: Joseph S. A. , Walker D. W.
Published: December 2017

We investigated the effect of increasing the synaptic concentration of catecholamines released from central pathways on breathing movements and electrocortical (ECoG) activity in fetal sheep in utero. In 11 trials (9 fetuses) intravenous infusion of the noradrenergic uptake inhibitor desipramine (DMI) resulted in an initial increase in the incidence of breathing movements from 47.8 +/- 2.2%/h to a maximum of 77.9 +/- 5.5%/h (P less than 0.05) followed by a subsequent decrease to 18.8 +/- 2.7%/h (P less than 0.05), which was associated with a decrease in the incidence of low-voltage ECoG activity. Mean breath amplitude also increased after DMI infusion from 5.8 +/- 0.2 mmHg to a peak of 8.9 +/- 0.9 mmHg (P less than 0.05). In five fetuses, intravenous injection of the alpha 1-receptor antagonist prazosin 30 min after the start of the DMI infusion blocked the increase of breath amplitude observed when DMI was given alone. Intracisternal infusion of 6-hydroxydopamine (6-OHDA, which causes an initial displacement of transmitter stores followed by a neurotoxic action) in six fetuses caused an increase in mean breath amplitude from 6.6 +/- 0.3 mmHg (control) to 22.3 +/- 5.5 mmHg (P less than 0.05) and a prolonged episode of breathing movements (168.5 +/- 47.2 min). The incidence of low-voltage ECoG activity was also increased significantly. A second infusion of 6-OHDA, 2 days after the first, had no effect on breathing movements or ECoG activities. The two treatments with 6-OHDA also resulted in a significant reduction in the response to intravenous infusion of DMI, indicating that endogenous release of norepinephrine had been reduced by the neurotoxin. These results suggest that 1) there is normally some tonic release of norepinephrine from central pathways, but this release is insufficient to stimulate sustained fetal breathing, and 2) accumulation in the synaptic cleft of catecholamines from central neurons is able to stimulate fetal breathing and promote low-voltage ECoG activity. Possible mechanisms that normally limit the activity of central catecholamine pathways before birth are discussed.
Central action of tachykinins on activity of expiratory pumping muscles
Authors: Haxhiu M. A. , Cherniack N. S. , van Lunteren E.
Published: December 2017

The central effects of tachykinins (substance P, neurokinin A, and neurokinin B) on the distribution of the motor activity to rib cage and abdominal expiratory muscles were studied in anesthetized tracheotomized spontaneously breathing dogs and cats. Intracisternal application of substance P (11 dogs) in doses of 10(-5) to 10(-4) M caused diaphragm electrical activity to change insignificantly from 19.3 +/- 1.9 to 24.8 +/- 3.2 units (P greater than 0.05), produced a moderate increase of triangularis sterni activity from 12.6 +/- 2.2 to 19.2 +/- 2.2 units (P less than 0.05), and stimulated a large increase of transversus abdominis activity from 9.4 +/- 2.7 to 28.5 +/- 2.6 units (P less than 0.01). Comparable effects were seen with similar doses of neurokinin A (8 dogs) and neurokinin B (3 dogs) administered intracisternally. Local application of substance P to the ventral medullary surface (5 dogs and 4 cats) also caused expiratory muscle activity to increase more than diaphragm activity, and in addition transversus abdominis activity increased to a larger extent than triangularis sterni activity. Furthermore, administration of the substance P antagonist [D-Pro2,D-Trp7,9]-SP to the ventral medullary surface decreased respiratory motor output, with expiratory muscles activity being attenuated to a greater extent than diaphragm activity. Application of neurotensin and N-methyl-D-asparate to the ventral surface of the medulla produced responses similar to those observed as a result of central administration of tachykinin peptides. The results suggest that 1) mammalian tachykinins are involved in the regulation of thoracic and abdominal expiratory muscle activity, 2) these muscles manifest substantial differences in their electrical responses to excitatory neuropeptides acting centrally, and 3) inputs from modulatory neurons located in this vicinity of the ventral medullary surface seem to be distributed unevenly to different expiratory premotor and/or motoneurons.
Effect of vertical jumping on the medial gastrocnemius and soleus muscles of rats
Authors: Dooley P. C. , Bach T. M. , Luff A. R.
Published: December 2017

Ten rats were trained to perform approximately 30 jumps/day, 5 days/wk for at least 8 wk, from a force platform that enabled the number and height of jumps to be quantified. There was considerable variation in height jumped during an activity session both within and between rats. The two highest-jumping rats attained a displacement of center of mass of approximately 30 cm, estimated to be approximately 67% of the maximum attainable. The two lowest-jumping rats jumped to approximately 30% of the estimated maximum. The activity was described as "habitual activity" rather than "training" because there were no significant increases in the height of jumping by any rat over the period of activity. The isometric properties of medial gastrocnemius (MG) and soleus muscles were studied in terminal experiments on anesthetised rats. Five significant effects on MG were evoked by this pattern of exercise ("habituation"): 1) a 15-18% increase in force at frequencies of stimulation between 60 and 150 Hz and a 15% increase in maximum tetanic tension to 14.9 N, 2) a 3% increase in the maximum rate of rise of tetanic force to 3.4% of maximum tetanic tension per millisecond, 3) an increase in fatigability expressed as a smaller fatigue index in active rats (33%) than in controls (58%), 4) a decrease of 4% in the percentage of type IIa muscle fibers, and 5) an increase of 6% in the percentage of type II fibers that could not be classified with certainty as IIa or IIb.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung injury in a surfactant-deficient lung is modified by indomethacin
Authors: Burger R. , Fung D. , Bryan A. C.
Published: December 2017

Repetitive total lung lavage in adult rabbits leads to a reproducible severe surfactant-deficient lung injury. Hypoxemia requiring mechanical ventilation occurs, accompanied by a substantial pulmonary hypertension, a large intra-alveolar protein leak, peripheral neutropenia, and pathological features of marked neutrophil infiltration with extensive hyaline membrane formation. Pretreatment with indomethacin abolishes postlavage pulmonary hypertension, preserves a slightly better lung function with higher arterial PO2, and prevents the postlavage peripheral neutropenia found in untreated animals. Pretreatment with a thromboxane A2 receptor blocker (L 655,240, Merck Frosst, Canada) also completely attenuated pulmonary hypertension, providing evidence that thromboxane A2 mediates pulmonary arterial hypertension after lung lavage. However, specific thromboxane receptor blockade had no other long-lasting beneficial effects on the ongoing injury in this model.
Effects of training on reproductive tissue blood flow in exercising pregnant rats
Authors: Jones M. T. , Norton K. I. , Dengel D. R. , Armstrong R. B.
Published: December 2017

The purpose of this study were to investigate 1) whether treadmill training would attenuate the reduction in reproductive (RBF) and visceral tissue blood flow (VBF) that occurs during an acute bout of submaximal exercise (EX) in pregnant rats and 2) whether fetal number of fetal weight would be affected by training. One group (T) of female rats trained on a treadmill (10 degrees incline, 30 m/min) for 1 h/day 5 days/wk for 10 wk before becoming pregnant. A second group (UT) was run at the same speed and incline for 10 min/day 5 days/wk for 2 wk. T and UT rats were bred until pregnant. Skeletal muscle blood flow, RBF, and VBF were measured at pre-EX and at 1 and 10 min of EX (10 degrees incline, 30 m/min). No differences were observed before or during exercise between the two groups in RBF and VBF, heart rate, or mean arterial pressure. Both groups experienced decreases in VBF (except liver) and RBF from pre-EX to EX. In most muscles skeletal muscle blood flow increased for both groups from pre-EX to EX. Neither group experienced a change in mean arterial pressure from pre-EX to EX, but heart rate increased significantly for both groups. No differences were observed between groups in fetal number, fetal weight, or fetal resorptions. It was concluded that training does not significantly attenuate the reduction in RBF and VBF in pregnant rats that occurs during an acute bout of submaximal EX and that training does not affect fetal weight or fetal number.
Pulmonary arterial and venous constriction during hypoxia in 3- to 5-wk-old and adult ferrets
Authors: Raj J. U. , Hillyard R. , Kaapa P. , Gropper M. , Anderson J.
Published: December 2017

We have determined the sites of hypoxic vasoconstriction in ferret lungs. Lungs of five 3- to 5-wk-old and five adult ferrets were isolated and perfused with blood. Blood flow was adjusted initially to keep pulmonary arterial pressure at 20 cmH2O and left atrial and airway pressures at 6 and 8 cmH2O, respectively (zone 3). Once adjusted, flow was kept constant throughout the experiment. In each lung, pressures were measured in subpleural 20- to 50-microns-diam arterioles and venules with the micropipette servo-nulling method during normoxia (PO2 approximately 100 Torr) and hypoxia (PO2 less than 50 Torr). In normoxic adult ferret lungs, approximately 40% of total vascular resistance was in arteries, approximately 40% was in microvessels, and approximately 20% was in veins. With hypoxia, the total arteriovenous pressure drop increased by 68%. Arterial and venous pressure drops increased by 92 and 132%, respectively, with no change in microvascular pressure drop. In 3- to 5-wk-old ferret lungs, the vascular pressure profile during normoxia and the response to hypoxia were similar to those in adult lungs. We conclude that, in ferret lungs, arterial and venous resistances increase equally during hypoxia, resulting in increased microvascular pressures for fluid filtration.
Effect of voluntary vs. artificial activation on the relationship of muscle torque to speed
Authors: Dudley G. A. , Harris R. T. , Duvoisin M. R. , Hather B. M. , Buchanan P.
Published: December 2017

The speed-torque relationship of the right knee extensor muscle group was investigated in eight untrained subjects (28 +/- 2 yr old). Torque was measured at a specific knee angle during isokinetic concentric or eccentric actions at nine angular velocities (0.17-3.66 rad/s) and during isometric actions. Activation was by "maximal" voluntary effort or by transcutaneous tetanic electrical stimulation that induced an isometric torque equal to 60% (STIM 1) or 45% (STIM 2) of the voluntary isometric value. Torque increased (P less than 0.05) to 1.4 times isometric as the speed of eccentric actions increased to 1.57 rad/s for STIM 1 and STIM 2. Thereafter, increases in eccentric speed did not further increase torque. Torque did not increase (P greater than 0.05) above isometric for voluntary eccentric actions. As the speed of concentric actions increased from 0.00 to 3.66 rad/s, torque decreased (P less than 0.05) more (P less than 0.05) for both STIM 1 and STIM 2 (two-thirds) than for voluntary activation (one-half). As a result of these responses, torque changed three times as much (P less than 0.05) across speeds of concentric and eccentric actions with artificial (3.4-fold) than voluntary (1.1-fold) activation. The results indicate that with artificial activation the normalized speed-torque relationship of the knee extensors in situ is remarkably similar to that of isolated muscle. The relationship for voluntary activation, in contrast, suggests that the ability of the central nervous system to activate the knee extensors during maximal efforts depends on the speed and type of muscle action performed.
Pulmonary compliance: early assessment of evolving lung injury after onset of sepsis
Authors: Byrne K. , Cooper K. R. , Carey P. D. , Berlin A. , Sielaff T. D. , Blocher C. R. , Jenkins J. K. , Fisher B. J. , Hirsch J. I. , Tatum J. L. , et al.
Published: December 2017

We compared the sensitivity of dynamic (Cdyn) and static lung compliance (CL) with indicators of permeability injury in a model of septic porcine adult respiratory distress syndrome. Two groups of anesthetized ventilated swine (15-25 kg) were studied. Septic animals (Ps, n = 13) received Pseudomonas aeruginosa intravenously for 1 h, which resulted in severe adult respiratory distress syndrome. Controls (C, n = 13) received 0.9% NaCl. Cdyn, CL, bronchoalveolar lavage for protein estimation, and thermal cardiogreen extravascular lung water (EVLW) measurements were performed in seven C and eight Ps animals. Six C and five Ps animals underwent gamma camera measurement of lung-to-heart ratio (slope index) of 99Tc-labeled human serum albumin. Both Cdyn and CL decreased significantly (P less than 0.01) at 30 min and thereafter in Ps vs. C. EVLW, slope index, and bronchoalveolar protein content increased significantly (P less than 0.05) in Ps vs. C at 120, 150, and 300 min, respectively. Cdyn and CL decreased well before onset of permeability injury. These early changes may be due to release of vasoactive mediators and sequestration of neutrophils in the pulmonary capillaries and later to increases in EVLW. Measurement of Cdyn and CL represents an early means of assessing evolving lung injury in this acute septic porcine model.
Lymphocyte proliferation responses after exercise in men: fitness, intensity, and duration effects
Authors: MacNeil B. , Hoffman-Goetz L. , Kendall A. , Houston M. , Arumugam Y.
Published: December 2017

This study investigated the effects of intensity and duration of exercise on lymphocyte proliferation as a measure of immunologic function in men of defined fitness. Three fitness groups--low [maximal O2 uptake (VO2max) = 44.9 +/- 1.5 ml O2.kg-1.min-1 and sedentary], moderate (VO2max = 55.2 +/- 1.6 ml O2.kg-1.min-1 and recreationally active), and high (VO2max = 63.3 +/- 1.8 ml O2.kg-1.min-1 and endurance trained)--and a mixed control group (VO2max = 52.4 +/- 2.3 ml O2.kg-1.min-1) participated in the study. Subjects completed four randomly ordered cycle ergometer rides: ride 1, 30 min at 65% VO2max; ride 2, 60 min at 30% VO2max; ride 3, 60 min at 75% VO2max; and ride 4, 120 min at 65% VO2max. Blood samples were obtained at various times before and after the exercise sessions. Lymphocyte responses to the T cell mitogen concanavalin A were determined at each sample time through the incorporation of radiolabeled thymidine [( 3H]TdR). Despite differences in resting levels of [3H]TdR uptake, a consistent depression in mitogenesis was present 2 h after an exercise bout in all fitness groups. The magnitude of the reduction in T cell mitogenesis was not affected by an increase in exercise duration. A trend toward greater reduction was present in the highly fit group when exercise intensity was increased. The reduction in lymphocyte proliferation to the concanavalin A mitogen after exercise was a short-term phenomenon with recovery to resting (preexercise) values 24 h after cessation of the work bout. These data suggest that single sessions of submaximal exercise transiently reduce lymphocyte function in men and that this effect occurs irrespective of subject fitness level.
Relationship of fluid filtration to lung vascular pressure during edema
Authors: Ehrhart I. C. , Hofman W. F.
Published: December 2017

Effect of edema on the relationship between rate of fluid filtration and vascular pressure was studied in ventilated isolated dog lung lobes blood-perfused at constant flow. Constant rate of lobe weight gain (S), representing transvascular fluid flux, was obtained at different venous pressures (Pv) as Pv was increased stepwise from 2 to 40 and then similarly decreased from 40 to 2 Torr (n = 6). In another group (n = 6), edema was maximized by reversing the sequence of Pv change; S was obtained during similar Pv steps as Pv was decreased from 40 to 2 and then returned to 40 Torr. In both groups, delta S was disproportionately greater for delta Pv at higher Pv's, with S vs. Pv fit by an exponential curve (P less than 0.001). The exponential relationship was independent of lung hydration inasmuch as greater edema on the second limb of Pv change did not alter the curve (P greater than 0.05). At 144% weight gain, interstitial compliance was 55.5 +/- 26.8 ml.100 g-1.Torr-1 (n = 10). Interstitial pressure reportedly remains constant, i.e., fails to increase to further buffer fluid filtration, after transition of the lung interstitium from low to high compliance at approximately 40% lung weight gain. If so, then the exponential S vs. Pv relationship observed in the present study at elevated interstitial compliance does not appear related to tissue pressure-buffering effects.
Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis
Authors: DeLissio M. , Goodyear L. J. , Fuller S. , Krawitt E. L. , Devlin J. T.
Published: December 2017

We studied whole body and regional fuel metabolism before, during, and after 90 min of treadmill exercise at 50% of maximal aerobic capacity (VO2max) in four subjects with hepatic cirrhosis and in four normal volunteers. Rates of endogenous glucose production (EGP) were measured using D-[6–3H]glucose infusions and fuel oxidation using indirect calorimetry. In the basal state, cirrhotic subjects had similar rates of EGP compared with controls. Forearm release of alanine and lactate was significantly greater in cirrhotic subjects (P less than 0.05), suggesting increased basal rates of gluconeogenesis. During exercise, EGP increased 2- to 2.5-fold in control subjects (P less than 0.01) but did not increase in cirrhotic subjects. Despite lower glucose concentrations in cirrhotic subjects, progressive hypoglycemia did not occur during exercise, probably because cirrhotic subjects demonstrated increased plasma concentrations of fat-derived substrates and derived a greater percentage of total energy requirement from fat oxidation than did controls (P less than 0.05) and because forearm muscle glucose extraction was significantly lower in cirrhotic subjects compared with controls (0.5 vs. 3.6%, respectively; P less than 0.05). During recovery, control subjects demonstrated significant increases in EGP rates compared with both the basal and exercise periods, but cirrhotic subjects showed no increase. In conclusion, cirrhotic subjects failed to demonstrate the normal increase in EGP during and after exercise. Significant hypoglycemia during exercise did not occur, possibly because of the increased availability of fat-derived fuels, which may spare the requirement for circulating glucose as an oxidative fuel for exercising muscle tissues.
Hormonal interactions and renal function during mechanical ventilation and ANF infusion in humans
Authors: Andrivet P. , Adnot S. , Sanker S. , Chabrier P. E. , Macquin-Mavier I. , Braquet P. , Brun-Buisson C.
Published: December 2017

To investigate the influence of atrial natriuretic factor (ANF) on renal function during mechanical ventilation (MV), we examined the renal and hormonal responses to synthetic human ANF infusion in eight patients during MV with zero (ZEEP) or 10 cmH2O positive end-expiratory pressure (PEEP). Compared with ZEEP, MV with PEEP was associated with a reduction in diuresis (V) from 208 +/- 51 to 68 +/- 11 ml/h (P less than 0.02), in natriuresis (UNa) from 12.4 +/- 3.3 to 6.2 +/- 2.1 mmol/h (P less than 0.02), and in fractional excretion of sodium (FENa) from 1.07 +/- 0.02), 0.21 to 0.67 +/- 0.17% (P less than 0.02) and with an increase in plasma renin activity (PRA) from 4.83 +/- 1.53 to 7.85 +/- 3.02 ng.ml-1.h-1 (P less than 0.05). Plasma ANF levels markedly decreased during PEEP in four patients but showed only minor changes in the other four patients, and mean plasma ANF levels did not change (163 +/- 33 pg/ml during ZEEP and 126 +/- 30 pg/ml during PEEP). Glomerular filtration rate and renal plasma flow were unchanged. Infusion of ANF (5 ng.kg-1.min-1) during PEEP markedly increased V and UNa by 110 +/- 61 and 107 +/- 26%, respectively, whereas PRA decreased from 7.85 +/- 3.02 to 4.40 +/- 1.5 ng.ml-1.min-1 (P less than 0.05). In response to a 10 ng.kg-1.min-1 ANF infusion, V increased to 338 +/- 79 ml/h during ZEEP but only to 134 +/- 45 ml/h during PEEP (P less than 0.02), whereas UNa increased, respectively, to 23.8 +/- 5.3 and 11.3 +/- 3.3 mmol/h (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Chemical and postural influence on scalene and diaphragmatic activation in humans
Authors: Xie A. L. , Takasaki Y. , Popkin J. , Orr D. , Bradley T. D.
Published: December 2017

The electromyographic activity of the diaphragm (EMGdi) and scalene muscle (EMGsc) was studied in the supine and upright positions, respectively, during hyperoxic progressive hypercapnic rebreathing (HCVR) in five healthy males. End-expiratory esophageal pressure (EEPes) was quantified on a breath-to-breath basis as a reflection of altered end-expiratory lung volume. There was no significant difference in the slopes of EMGdi, expressed as a percentage of maximum at total lung capacity vs. minute volume of ventilation (VI), between the supine and upright positions [0.79 +/- 0.05 (SE) vs. 0.92 +/- 0.17, respectively]. In contrast, the slope of the regression line relating EMGsc to VI was steeper in the upright than in the supine position (0.69 +/- 0.05 vs. 0.35 +/- 0.04, respectively; P less than 0.005). Positive EEPes at comparable VI at the ends of HCVRs were of greater magnitude upright than supine (3.27 +/- 0.68 vs. 4.35 +/- 0.60 cmH2O, respectively, P less than 0.001). We conclude that altering posture has a greater effect on scalene and expiratory muscle activity than on diaphragmatic activity during hypercapnic stimulation.
Longitudinal analysis of lung function growth in healthy children and adolescents
Authors: Hopper J. L. , Hibbert M. E. , Macaskill G. T. , Phelan P. D. , Landau L. I.
Published: December 2017

Lung function and height in 242 8-yr-old and 299 12-yr-old children without known or suspected predisposition to lung disease were measured annually over 6 and 8 yr, respectively. Growth of forced expiratory volume in 1 s (FEV1), vital capacity, and expiratory flow after expiring 50% of vital capacity were statistically modeled by age and height by use of a multivariate normal model for longitudinal data. This method has the flexibility to fit an appropriate (not necessarily linear) mathematical description of average lung function while concurrently modeling the covariance between measures on the same individual. Differences in lung function growth between girls and boys, pre- and post-puberty, showed that girls had a steadier though less pronounced increase in lung function with height. In boys, before puberty there was deficit in lung volume relative to height (not evident in girls), which was compensated for by rapid growth after puberty. The standard error of FEV1 predictions based on current height and age were more than halved when measurements of FEV1, age, and height taken 1 yr before were incorporated. We found evidence for dysanaptic growth in childhood. Fitted models have application to early detection of departures from healthy lung function.
Carbohydrate metabolism during intense exercise when hyperglycemic
Authors: Coyle E. F. , Hamilton M. T. , Alonso J. G. , Montain S. J. , Ivy J. L.
Published: December 2017

The effects of hyperglycemia on muscle glycogen use and carbohydrate metabolism were evaluated in eight well-trained cyclists (average maximal O2 consumption 4.5 +/- 0.1 l/min) during 2 h of exercise at 73 +/- 2% of maximal O2 consumption. During the control trial (CT), plasma glucose concentration averaged 4.2 +/- 0.2 mM and plasma insulin remained between 6 and 9 microU/ml. During the hyperglycemic trial (HT), 20 g of glucose were infused intravenously after 8 min of exercise, after which a variable-rate infusion of 18% glucose was used to maintain plasma glucose at 10.8 +/- 0.4 mM throughout exercise. Plasma insulin remained low during the 1st h of HT, yet it increased significantly (to 16-24 microU/ml; P less than 0.05) during the 2nd h. The amount of muscle glycogen utilized in the vastus lateralis during exercise was similar during HT and CT (75 +/- 8 and 76 +/- 7 mmol/kg, respectively). As exercise duration increased, carbohydrate oxidation declined during CT but increased during HT. Consequently, after 2 h of exercise, carbohydrate oxidation was 40% higher during HT than during CT (P less than 0.01). The rate of glucose infusion required to maintain hyperglycemia (10 mM) remained very stable at 1.6 +/- 0.1 g/min during the 1st h. However, during the 2nd h of exercise, the rate of glucose infusion increased (P less than 0.01) to 2.6 +/- 0.1 g/min (37 mg.kg body wt-1.min-1) during the final 20 min of exercise. We conclude that hyperglycemia (i.e., 10 mM) in humans does not alter muscle glycogen use during 2 h of intense cycling.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of pneumonectomy on the remaining lung in dogs
Authors: Johnson R. L. , Cassidy S. S. , Grover R. , Ramanathan M. , Estrera A. , Reynolds R. C. , Epstein R. , Schutte J.
Published: December 2017

To determine the magnitude of functional compensation after pneumonectomy and whether compensation is related to maturity of the animal at the time of resection, we performed left pneumonectomy in either adult or 10-wk-old beagles. Studies were performed in adults 7-9 mo after surgery and in puppies 18-23 mo after surgery when the dogs reached full maturity. Results were compared with those in age- and sex-matched unoperated controls. Measurements included pressure-volume relationships, pulmonary hemodynamics, rebreathing studies of lung volume, diffusing capacity and its components, lung tissue volume, and pulmonary blood flow. Computerized-tomographic scans were performed in the puppy groups to determine changes in thoracic shape and size. Morphometric analysis of the lungs was performed under light microscopy. There was partial compensation for loss of one lung by functional improvement in the remaining lung. Compensation was greater in those pneumonectomized as puppies than as adults. Volume of the remaining lung was larger than predicted for a given transpulmonary pressure in both groups. Diffusing capacity, pulmonary capillary blood volume, and lung tissue volume were larger than expected for the normal right lung. After pneumonectomy, compliance of the rib cage was greater in puppies than in adults. Weight of the costal diaphragm was reduced in pneumonectomized puppies. Pulmonary hypertension at rest did not develop, and pulmonary vascular reactivity to hypoxia was unchanged after pneumonectomy in both groups. Significant correlations were obtained between physiological and morphometric measurements.
Arm blood flow at rest and during arm exercise
Authors: Ahlborg G. , Jensen-Urstad M.
Published: December 2017

To test the applicability of a dye-dilution method to quantitate total arm blood flow at rest and during arm exercise, indocyanine green was infused at a constant rate into the brachial artery. Eight subjects performed continuous 30-min arm exercises with an increase in intensity every 10 min (30, 60, and 90 W). The loads corresponded to 29 +/- 1, 48 +/- 2, and 78 +/- 4% (means +/- SE) of the maximal O2 uptake (VO2max 2.13 +/- 0.08 l/min) during arm exercise. VO2max during arm exercise was 61 +/- 1.7% of that during leg exercise. The dye concentration was analyzed in blood samples from three arm veins, two ipsi- and one contralateral, at shoulder level. Corresponding dye concentrations in both ipsilateral veins and a stable concentration difference between ipsi- and contralateral veins were achieved. Total arm blood flow was calculated to be 0.21 +/- 0.04 l/min at rest and 2.43 +/- 0.14 l/min at 90 W. Arm O2 uptake rose from 9 +/- 2 to 323 +/- 21 ml/min. Arm blood flow and O2 uptake each correlated linearly with both work load (r = 0.98) and pulmonary O2 uptake (r greater than or equal to 0.98). Mechanical efficiency for the arm and body was 34-44 and 16-19%, respectively. We conclude that arm blood flow can be determined by continuous infusion of indocyanine green.
Effects of feeding on muscle blood flow during prolonged exercise in miniature swine
Authors: McKirnan M. D. , Gray C. G. , White F. C.
Published: December 2017

Eight exercise-trained miniature swine were studied during prolonged treadmill runs (100 min) under fasting and preexercise feeding conditions. Each animal ran at identical external work loads that corresponded to 65% of the heart rate reserve (210-220 beats/min) for the two exercise bouts. Cardiac outputs and stroke volumes were higher and heart rates lower for fed than for fasting runs (P less than 0.05). Preexercise feeding did not alter oxygen consumption, core temperature, mean arterial pressure, and arterial-mixed venous oxygen difference during prolonged exercise; however, mixed venous lactate concentration was lower at end exercise than during fasting conditions (1.2 vs. 2.6 mM, P less than 0.05). Microsphere measurements of regional blood flow revealed significantly higher total gastrointestinal flow (23%) for fed than for fasting conditions. Throughout the exercise bout, blood flow to the biceps femoris, semitendinosus, and tibialis anterior muscles was lower in fed than in fasted nimals (P less than 0.05). Combined hindlimb muscle blood flow averaged 15 ml.min-1.100 g-1 (18%, P less than 0.05) lower under feeding than fasting run conditions. These findings provide further evidence that cardiovascular reflexes originate in the gut after feeding to increase cardiac output and redistribute a portion of the blood flow away from active muscle to the gastrointestinal tract during prolonged exercise.
Nonxenobiotic manipulation and sulfur precursor specificity of human endothelial cell glutathione
Authors: Cotgreave I. A. , Constantin-Teodosiu D. , Moldeus P.
Published: December 2017

Confluent human umbilical vein endothelial (HUVE) cells were readily (within 1 h) depleted of their glutathione (GSH) by diethylmaleate (0.1-1.0 mM), but dose-dependent cell detachment was noted. Buthionine sulfoximine (BSO, 25 microM) depleted cell GSH with sigmoidal kinetics, showing an initial half-life of depletion of 4-6 h and greater than 95% depletion by 48 h without morphological changes to the cells. However, BSO-dependent depletion of cell GSH was only partially reversible by cell washing and reincubation with complete medium. Likewise, incubation of the cells in sulfur-free medium depleted cell GSH again without morphological changes to the cells. However, unlike with BSO, these cells readily resynthesized GSH when resupplied with complete medium, fresh plasma, or whole blood, with a characteristic overloading of cell GSH (up to 200%) by 12 h. By use of the sulfur-free medium, it was shown that both cystine and cysteine are effective precursors to GSH synthesis in HUVE cells in culture and that cystine is the most likely precursor in vivo. During cystine-supported resynthesis of GSH, high levels of cysteine accumulated in the cells (up to 10% of total soluble free thiol). Physiologically relevant concentrations of extracellular GSH were not as effective as cystine or cysteine in stimulating GSH biosynthesis, whereas nonphysiologically high (mM) concentrations resulted in substantial elevation of GSH levels above those of control cells in a BSO-insensitive manner. These findings provide a simple methodology for the manipulation of HUVE cell GSH in studies of endothelial-specific oxidant toxicity and the sulfur dependence of the biochemistry and turnover of GSH in these human cells.
Changes of lung surfactant and pressure-volume curve in bleomycin-induced pulmonary fibrosis
Authors: Osanai K. , Takahashi K. , Sato S. , Iwabuchi K. , Ohtake K. , Sata M. , Yasui S.
Published: December 2017

We investigated whether alveolar surface force increased and participated in the lung pressure-volume relationship in bleomycin-induced pulmonary fibrosis in hamsters and, if so, whether lung surfactant was hampered in the lungs. On the air-filled pressure-volume curve, decreases of lung volume from control level were significantly higher at 3-8 cmH2O pressure on day 10 than on day 30. Because the change of lung tissue elasticity evaluated from the saline-filled pressure-volume curve was equal for the 2 days, the higher decrease of air volume on day 10 was due primarily to contribution of alveolar surface force. Pressure differences between deflation limbs of air-filled and saline-filled pressure-volume curves, which represented net alveolar surface force, were significantly higher at any lung volume between 50 and 90% total lung capacity on day 10, but almost no significance was observed on day 30. Phospholipid concentration in bronchoalveolar lavage fluid significantly decreased on day 10 but had improved by day 30. Analysis of phospholipid species in purified lung surfactant showed decreased fractions of disaturated phosphatidylcholine and phosphatidylglycerol on day 10. Surface-active properties of the surfactant, measured by a modified Wilhelmy balance, were remarkably hampered on day 10, but most of them had improved by day 30. We consider that the quantitative and functional abnormalities of lung surfactant have a part in the aggravation of lung mechanics in the acute phase of pulmonary fibrosis.