bluuebunny/crossref_metadata_2025 huggingface dataset:
Elimination rate of 65Zn as a measure of food intake: a validation study in the mouse (Mus sp.)
Authors: McLean J. A. , Speakman J. R.
Published: December 2017

We measured elimination of 65Zn in white mice (Mus musculus) using daily whole body counting. Thirteen male mice were randomly divided into three groups, each maintained at a different temperature. Each animal was labeled with 65Zn on day 0 and monitored over days 0–48 postinjection. Daily food intake and body masses of all the animals were measured. We evaluated the ability of derived components of the 65Zn elimination curves to predict food intake over different phases of the measurement period. Food intake was significantly different between temperature groups; temporal variation in food intake was not intercorrelated between groups. Whole body elimination of 65Zn involved a rapid decline over days 0–1, followed by a biexponential decline in counts over days 1–48. Components of the first phase of the biexponential elimination curve were not significantly related to food intake. The rate (k2) of isotope elimination in the second phase was significantly related to mean food intake over days 25–48, 13–24, and 37–48. Rate of turnover in the second phase of elimination, incorporating the variation in zinc body pool size (k2 x 1/N2), where N2 is the constant of the second phase of elimination, was the best predictor of food intake and accounted for 60% of the variability over days 37–48.
Effects of flow heterogeneity on the measurement of capillary exchange in the lung
Authors: Caruthers S. D. , Harris T. R. , Overholser K. A. , Pou N. A. , Parker R. E.
Published: December 2017

The effects of flow heterogeneity on the measurement of transcapillary escape of small molecules for perfused in situ sheep lungs were evaluated. Lungs were studied at five flows (1.5–5.0 l/min) ranging from zone 1 to zone 3 conditions. At each flow, multiple indicator-dilution curves were collected using 14C-labeled urea (U) or butanediol (B) as the diffusing tracer, and radiolabeled 15-microns microspheres were injected. The lungs were removed, dried, sectioned, weighed, and counted for microsphere radioactivity. Flow heterogeneity expressed as relative dispersion, decreased with increasing flow, from 0.838 +/- 0.179 (mean +/- SD, n = 8) to 0.447 +/- 0.119 (n = 6). We applied homogeneous flow models of capillary exchange to compute permeability-surface area product (PS) and a related parameter, D1/2S, for diffusing tracers. (D is effective diffusivity of capillary exchange.) PS and D1/2S increased to a maximum with increasing flow, but the ratio of D1/2SU to D1/2SB remained constant. A new model incorporating flow heterogeneity and recruitment (the variable recruitment model) was used. The variable recruitment model described the effects of flow on capillary recruitment, but incorporating heterogeneity into the computation did not alter D1/2S values from those computed assuming homogeneous flow.
Maximal vasodilation does not eliminate the vascular waterfall in the canine hindlimb
Authors: Shrier I. , Magder S.
Published: December 2017

Previous studies have shown that blood flow through skeletal muscle is regulated by changes in an arteriolar vascular waterfall [critical pressure (Pcrit)] and a proximal (arterial) resistance (Ra) element. To determine whether Pcrit still exists during maximal vasodilation, we pump perfused vascularly isolated canine hindlimbs. We set outflow pressure to zero and measured Pcrit, perfusion pressure (Pper), and regional elastic recoil pressure (Pcl; by a stop-flow technique) and calculated both Ra and venous resistance before and after maximal vasodilation with adenosine and nitroprusside. Pcrit was 56.4 +/- 5.1 mmHg before vasodilation and decreased to 11.0 +/- 0.6 mmHg after vasodilation, which was less than the downstream pressure in the venous compliant region (Pel). Therefore, Pcrit should not have affected flow at normal Pper levels under vasodilated conditions. However, we could still measure Pcrit because our technique allowed Pel to decline and Pcrit becomes apparent once Pel < Pcrit. With vasodilation, Ra decreased to < 8.1 +/- 2.6% and Rv decreased to 41 +/- 6% of control values. In contrast to the nonvasodilated vasculature, increases in venous pressure during maximal vasodilation caused immediate increases in Pper. This also suggests that the vascular waterfall is inactive under conditions of maximal vasodilation. We conclude that a small arteriolar Pcrit is still present in the maximally vasodilated hindlimb but is less than the downstream pressure and does not affect flow under these conditions.
Alveolar lining layer is thin and continuous: low-temperature scanning electron microscopy of rat lung
Authors: Bastacky J. , Lee C. Y. , Goerke J. , Koushafar H. , Yager D. , Kenaga L. , Speed T. P. , Chen Y. , Clements J. A.
Published: December 2017

The low-temperature electron microscope, which preserves aqueous structures as solid water at liquid nitrogen temperature, was used to image the alveolar lining layer, including surfactant and its aqueous subphase, of air-filled lungs frozen in anesthetized rats at 15-cmH2O transpulmonary pressure. Lining layer thickness was measured on cross fractures of walls of the outermost subpleural alveoli that could be solidified with metal mirror cryofixation at rates sufficient to limit ice crystal growth to 10 nm and prevent appreciable water movement. The thickness of the liquid layer averaged 0.14 micron over relatively flat portions of the alveolar walls, 0.89 micron at the alveolar wall junctions, and 0.09 micron over the protruding features (9 rats, 20 walls, 16 junctions, and 146 areas), for an area-weighted average thickness of 0.2 micron. The alveolar lining layer appears continuous, submerging epithelial cell microvilli and intercellular junctional ridges; varies from a few nanometers to several micrometers in thickness, and serves to smooth the alveolar air-liquid interface in lungs inflated to zone 1 or 2 conditions.
Repeated measurement of respiratory function and bronchoconstriction in unanesthetized mice
Authors: Hessel E. M. , Zwart A. , Oostveen E. , Van Oosterhout A. J. , Blyth D. I. , Nijkamp F. P.
Published: December 2017

A noninvasive forced oscillation technique was used to determine respiratory function in unanesthetized and spontaneously breathing mice. Pseudorandom noise pressure variations in a frequency range of 16–208 Hz were applied to the body surface, and the flow response was measured at the nose. From the pressure-flow relationship, respiratory transfer impedance was calculated. Study of intra-animal variability on a short- and a long-term basis revealed that the real part of respiratory transfer impedance was reproducible within 9%. The imaginary part appeared less reproducible (within 22%). Furthermore, bronchoconstrictive responses were investigated and analyzed by evaluation of respiratory resistance as measured at 16 Hz (Rrs16). During the first 15 min after ovalbumin challenge in ovalbumin-sensitized mice, Rrs16 was significantly increased [49 +/- 7% (SE)]. Inhalation of methacholine in untreated mice induced an increase in Rrs16 of 75 +/- 16% (SE). In saline-challenged animals, no significant changes were observed. This method enables evaluation of long-term respiratory function in mice and appeared to be a sensitive measure for bronchoconstriction.
Human intramuscular temperature and heat flow transients at rest
Authors: Binzoni T. , Hiltbrand E. , Kayser B. , Ferretti G. , Terrier F.
Published: December 2017

A general model for heat exchange, comprising the major models in the literature, was developed. Temperature changes as a function of space and time were determined in six resting humans (age 32.7 +/- 4.5 yr) during temperature transients by magnetic resonance imaging (MRI), so that the exact solution of the model was obtained. These results allowed application of the model, e.g., the analysis of transient muscle heat flow changes, which could not be assessed by previous steady-state analyses. A microthermocouple was inserted in muscle vastus lateralis 2–3 cm below the skin surface. The measured temperature was used for calibrating the pixel intensity of a temporal series of transaxial magnetic resonance images obtained with a spin echo sequence around the microthermocouple position. After muscle temperature was increased by immersion in a controlled water bath, MRI acquisition was performed while muscle temperature was decreasing. Temperature maps relative to space and time inside a homogeneous region of interest were reconstructed by neural networks, showing specific temperature patterns. Subsequently calculated heat flows (with negative sign) appeared to increase linearly as temperature decreased, until a maximum was attained at a critical temperature, below which dramatic consistent heat flow changes were found. In conclusion, MRI is indeed a powerful technique, useful to study the determinants of muscle temperature and heat flow changes in space and time.
A model analysis of asymmetrical response of pulmonary VO2 during incremental and decremental ramp exercise
Authors: Niizeki K. , Takahashi T. , Miyamoto Y.
Published: December 2017

The responses of gas exchange and ventilatory variables exhibit obvious asymmetry between the incremental and decremental phases of trapezoidal ramp exercise (29). Computer simulation was performed to explore the possible mechanisms producing this asymmetry of pulmonary O2 uptake (VO2) dynamics. The model consisted of three compartments (the lungs, the exercising muscles, and the other organs and tissues), which were perfused by respective regional circulations. Exercise was simulated by increasing the pulmonary blood flow (Q) and the muscle. VO2 in proportion to work rate. The dynamic responses of Q and the muscle VO2 were assumed to obey first-order linear kinetics. The ratio of blood flow in the muscle compartment to total cardiac output was assumed to increase linearly with work rate. Our simulation demonstrated that the muscle blood flow and mixed venous O2 content exhibited significant asymmetry between the incremental and decremental phases of exercise. The model suggested that the asymmetry of VO2 between incremental and decremental ramp exercise was dependent on the redistribution ratio of blood flow to the working muscles. The validity of the model was then evaluated by comparing the simulated results with experimental data obtained.
Electrical stimulation of leg muscles increases tibial trabecular bone formation in unloaded rats
Authors: Zerath E. , Canon F. , Guezennec C. Y. , Holy X. , Renault S. , Andre C.
Published: December 2017

Rat head-down hindlimb suspension (HS) has been shown to induce hindlimb cancellous bone loss. As HS is known to associate unloading with progressive disappearance of hindlimb muscle contractions, we investigated whether persisting muscle motion could modify suspension-induced bone disorders or even prevent them. Chronic electrical stimulation (ES) was applied to leg muscles of rats during 3-wk hindlimb suspension, the lack of support for hindlimbs maintaining a hypodynamic situation. The histomorphometric characteristics of the proximal tibial metaphysis were analyzed. At the end of this protocol of combined suspension and stimulation, trabecular bone loss remained similar to that of nonstimulated HS animals. However, trabecular bone cell activity parameters showed greater bone formation after muscle stimulation in unloaded animals, with significantly increased osteoblastic, osteoid, and mineralizing surfaces. In addition, periosteal mineral apposition rate and cancellous bone formation rate, markedly decreased by suspension, were not significantly different in suspended stimulated compared with normal loaded animals. This enhanced formation activity could be related to persistence of muscle activity, as shown by partial preservation of muscle mass. However, direct electrical effects on bone cannot be excluded. Thus, despite muscle stimulation, with enhanced bone formation, isolated suppression of hypokinesia has not been able to counteract bone effects of unloading. This finding supports the hypothesis of the importance of mechanical loading to maintain bone architecture.
Motor unit discharge behavior in older adults during maximal-effort contractions
Authors: Kamen G. , Sison S. V. , Du C. C. , Patten C.
Published: December 2017

A reduction in maximal force production is a common observation in older individuals. In an effort to determine whether aging is accompanied by reductions in central motoneuron drive limiting motor performance, motor unit discharge records were obtained from seven young (21–33 yr) and seven older (> 67 yr) adults. Informed consent was obtained from all subjects. The task required the subject to perform a maximal abduction of the second digit under isometric conditions. Motor unit potentials in the first dorsal interosseous were monitored by using a selective four-wire needle electrode and identified off-line with the aid of a Dantec electromyograph. The maximal discharge rate in the older adults (31.1 impulses/s) was significantly smaller (P < 0.05) than that in the younger subjects (50.9 impulses/s). These findings suggest that reductions in maximal force capability in older adults are partially due to an impaired ability to fully drive the surviving motor units.
Effect of intensity and energy expenditure on postexercise insulin responses in women
Authors: Ben-Ezra V. , Jankowski C. , Kendrick K. , Nichols D.
Published: December 2017

The purposes of the study were to compare insulin responses after rest and exercise of two different intensities and equal total energy expenditure and to examine these responses in normoglycemic women. Twenty-four untrained women (age 23.4 +/- 0.9 yr) completed three randomly assigned treatments over the course of a 3- to 4-wk period: rest, 40% maximal oxygen consumption x 87 min (Low), and 70% maximal oxygen consumption x 50 min (High). Total energy expenditure was 1,821 +/- 61 and 1,692 +/- 59 kJ, heart rate was 119 +/- 2 and 163 +/- 2 beats/min, and oxygen consumption was 17.1 and 27.2 ml.kg-1.min-1 for Low and High, respectively. Fifteen to 17 h posttreatment and 12 h postprandial, each subject drank a 75-g glucose solution (oral glucose tolerance test). Blood samples were drawn before and at 30, 60, 90, 120, and 150 min after ingestion and were analyzed for glucose and insulin. Glucose areas and responses at the same time points across treatments were similar. Area under the insulin curve was significantly lower (P < 0.05) after High (51,864 +/- 3,780 pM x min) compared with rest (61,009 +/- 4,425 pM x min), but Low (59,191 +/- 5,307 pM x min) was not different from either rest or High. The insulin level at the 120-min time point was significantly (P < 0.01) lower after High (290.8 pM) compared with rest (391.7 pM). On the basis of these results, exercise-related changes in insulin responses are more dependent on exercise intensity than on energy expenditure in untrained women.
Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats
Authors: Chen S. J. , Chen Y. F. , Meng Q. C. , Durand J. , Dicarlo V. S. , Oparil S.
Published: December 2017

The current study examined the effects of bosentan, an orally active antagonist of endothelin-A and -B receptors, on the development and maintenance of hypoxia (10% O2)-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with bosentan (100 mg.kg-1.day-1, 1 gavage/day for 2 days) completely blocked the pulmonary vasoconstrictor response to acute hypoxia. Chronic bosentan treatment (100 mg.kg-1.day-1 po in the food) instituted 48 h before hypoxic exposure prevented the subsequent development of pulmonary hypertension, attenuated the associated right heart hypertrophy, and prevented the remodeling of small (50–100 microns) pulmonary arteries without altering systemic arterial pressure. Institution of bosentan treatment (for 4 wk) after 2 wk of hypoxia produced a significant reversal of established hypoxia-induced pulmonary hypertension (from 36 +/- 1 to 25 +/- 1 mmHg), right heart hypertrophy, and pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous endothelin-1 plays a major role in hypoxic pulmonary vasoconstriction and/or hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that endothelin-receptor blockade may be useful in the treatment of hypoxic pulmonary hypertension humans.
Aging among elite distance runners: a 22-yr longitudinal study
Authors: Trappe S. W. , Costill D. L. , Vukovich M. D. , Jones J. , Melham T.
Published: December 2017

The purpose of this study was to assess the physiological responses of former elite distance runners during submaximal and maximal exercise after a mean period of 22 yr. Fifty-three men were initially tested (T1) in the late 1960s and early 1970s when they were all highly trained and competitive. For the current evaluation (T2), these men were classified as highly trained (HT; n = 10), fitness trained (FT; n = 18), untrained (UT; n = 15), and fit older (FO; n = 10), depending on their continued level of training and age. The mean (+/- SE) age for the HT, FT, and UT men during T2 was similar (46.5 +/- 1.6 yr), whereas the FO men were significantly (P < 0.05) older (68.4 +/- 2.7 yr). All groups experienced a significant decrease (P < 0.05) in maximal O2 uptake (VO2 max) from T1 to T2. However, this decrease was related to the amount of training between evaluations. The HT men had the smallest reduction (6% per decade) in VO2 max (from 68.8 to 59.2 ml.g-1.min-1). The FT men's VO2 max was approximately 10% lower per decade (from 64.1 to 48.9 ml.kg-1.min-1), whereas an approximately 15% decrease per decade was observed for the UT (from 70.7 to 46.7 ml.kg-1.min-1) and FO (from 60.3 to 40.7 ml.kg-1.min-1) men, despite the continued training of the FO men. Energy requirements for a standardized run at 12 km/run were similar from T1 to T2 for the HT and FT men, whereas the UT men required an increased (P < 0.05) O2 uptake (40.3-41.8 l/min), ventilation (53.7-72.7 l/min), and heart rate (127-142 beats/min). The perceived effort and %VO2 max for this submaximal run were greater during T2 for all groups, which was related to the decline in VO2 max. These longitudinal data indicate that after more than two decades the physiological capacities of these aging runners are compromised, regardless of training. These data also confirm previous cross-sectional findings that aerobic capacity of highly trained middle-aged men declines approximately 5-7% per decade.
Effort and volume dependence of forced-deflation flow-volume relationships in intubated infants
Authors: Hammer J. , Newth C. J.
Published: December 2017

The application of negative pressure to the airway opening [called the forced-deflation (FD) technique] allows the examination of maximal expiratory flow-volume curves in intubated infants who are unable to generate a voluntary maximal expiratory maneuver. We explored the questions of effort and volume dependence of flows generated by FD in 18 intubated, sedated, and paralyzed infants [age 10.6 +/- 2.0 (SE) mo; weight 7.2 +/- 0.7 kg] with normal lungs. Effort dependence was assessed by isovolume pressure-flow curves that were constructed in 10 infants from repeated FD maneuvers from total lung capacity (defined as +40 cmH2O) by varying airway opening pressures from 0 (barometric pressure) to -100 cmH2O at intervals of 20 cmH2O. The effect of volume history was assessed by initiating FD maneuvers from different inspiratory volumes delineated by the inspiratory pressures +10, +20, +30, and +40 cmH2O. We compared maximal expiratory flows at isovolume points [50, 25, and 10% forced vital capacity (FVC) of the standard +40/-40 cmH2O FD maneuver] and found that flow limitation consistently occurred in all infants at and below 25% FVC with -40 cmH2O or greater airway opening pressure. We found no significant influence of volume history on maximal flows at and below 25% FVC. Under well-controlled study conditions, we demonstrated excellent reproducibility of maximal expiratory flows at low lung volumes, analogous to those of voluntary forced expiratory maneuvers in adults and older children. This information may be helpful in setting standards for performance and interpretation of FD maneuvers in intubated infants.
Disparity between tidal and static volumes of immature lungs treated with reconstituted surfactants
Authors: Kobayashi T. , Li W. Z. , Tashiro K. , Takahashi R. , Waseda Y. , Yamamoto K. , Suzuki Y.
Published: December 2017

We biologically assessed functions of several reconstituted surfactants with the same minimum surface tension (2-3 mN/m) as “complete” porcine pulmonary surfactant (natural surfactant) but with longer surface adsorption times. Administration of natural surfactant (adsorption time 0.29 s) into the lungs of surfactant-deficient immature rabbits brought a tidal volume of 16.1 +/- 4.4 (SD) ml/kg during mechanical ventilation with 40 breaths/min and 20 cmH2O insufflation pressure. In static pressure-volume recordings, these animals showed a lung volume of 62.4 +/- 9.7 ml/kg at 30 cmH2O airway pressure and maintained 55% of this volume when the pressure decreased to 5 cmH2O. With two reconstituted surfactants consisting of synthetic lipids or isolated lipids from porcine lungs plus surfactant-associated hydrophobic proteins (adsorption times 0.57 and 0.78 s, respectively), tidal volumes were < 38% of that with natural surfactant (P < 0.05), but static pressure-volume recordings were not different. Care is therefore needed in estimating the in vivo function of surfactant preparations from minimum surface tension or static pressure-volume measurements.
Effects of surfactant on the in vivo alveolar surface-to-volume ratio
Authors: Miyazawa N. , Suzuki S. , Akahori T. , Okubo T.
Published: December 2017

To investigate how pulmonary surfactant influences alveolar structure in vivo, we examined the alveolar surface area-to-lung volume (S/V) ratio of the lung parenchyma of a live dog by light-scattering stereology before and after saline lavage. We measured the backscattered light pattern produced by applying a laser beam to the pleural surface of a ventilated animal and obtained the S/V [equivalent to the inverse of the optical mean free path (lambda)]. After saline lavage, V at transpulmonary pressure (P) of 30 cmH2O (defined as total lung capacity) decreased by 11.1 +/- 3.1% (SD) and the P-V curve shifted to a lower V. The lambda-V curve was shifted to a higher lambda and to a lower V after saline lavage. S/V decreased after saline lavage (lambda increased by 38 +/- 27% on the deflation limb at a V of 80% of control total lung capacity). The alveolar surface tension increased after saline lavage, and the increase in surface tension was greater on inflation than on deflation. We conclude that depletion of pulmonary surfactant increases the alveolar surface tension in vivo, resulting in a decrease in S/V.
Age-related increases in diaphragmatic maximal shortening velocity
Authors: Powers S. K. , Criswell D. , Herb R. A. , Demirel H. , Dodd S.
Published: December 2017

Recent evidence demonstrates that aging results in an increase in fast (type IIB) myosin heavy chain (MHC) in the rat diaphragm. It is unknown whether this age-related change in fast MHC influences the diaphragmatic maximal shortening velocity (Vmax). Therefore, we tested the hypothesis that aging is associated with an increase in the diaphragmatic Vmax and that the increase in the Vmax is highly correlated with the percentage of type IIb MHC. In vitro contractile properties were measured with costal diaphragm strips obtained from young (4 mo old; n = 8) and (old 24 mo old; n = 8) male Fischer-344 rats. Diaphragmatic maximal tetanic specific force production was 14.5% lower in the old compared with the young animals (23.0 +/- 0.4 vs. 19.7 +/- 0.8 N/cm2; P < 0.05). In contrast, the diaphragmatic Vmax was significantly higher in the old compared with the young animals (5.5 +/- 0.1 vs. 4.4 +/- 0.3 lengths/s; P < 0.05). Although the percent type IIb MHC was significantly higher (approximately +14%; P < 0.05) in the old compared with the young animals, the correlation between Vmax and percent type IIb MHC was relatively low (r = 0.50; P = 0.05). These data support the hypothesis that an age-related increase in diaphragmatic Vmax occurs; however, factors in addition to type IIb MHC are involved in regulating diaphragmatic Vmax. Interestingly, although aging resulted in a decrease in diaphragmatic maximal specific force production, power output at all muscle loads was maintained in the old animals due to the increase in diaphragmatic shortening velocity.
Peak blood lactate and blood lactate vs. workload during acclimatization to 5,050 m and in deacclimatization
Authors: Grassi B. , Marzorati M. , Kayser B. , Bordini M. , Colombini A. , Conti M. , Marconi C. , Cerretelli P.
Published: December 2017

Peak blood lactate ([Labl]peak) and blood lactate concentration ([Labl]) vs. workload (W) relationships during acclimatization to altitude and in the deacclimatization were evaluated in 10 Caucasian lowlanders at sea level (SL0); after approximately 1 wk (Alt1wk), 3 wk (Alt3wk), and 5 wk (Alt5wk) at 5,050 m; and weekly during the first 5 wk after return to sea level (SL1wk-SL5wk). Incremental bicycle ergometer exercises (30 W added every 4 min up to exhaustion) were performed. At Alt1wk and at Alt5wk, the experiments were repeated in hypobaric normoxia (Alt1wk-O2 and Alt5wk-O2). [Labl] was determined at rest and during the last approximately 30 s of each W. [Labl]peak was taken as the highest [Labl] during recovery. Acid-base status (pH and concentration of HCO-3 in arterialized capillary blood) was determined at rest. Mean [Labl]peak values were 11.5 (SL0), 8.0 (Alt1wk), 6.4 (Alt3wk), 6.3 (Alt5wk), 8.0 (SL1wk), 9.4 (SL2wk), 10.8 (SL3wk), 11.3 (SL4wk), and 11.6 (SL5wk) mM. At Alt1wk-O2 and Alt5wk-O2, peak W increased, compared with Alt1wk and Alt5wk, whereas no changes were observed for [Labl]peak. [Labl] vs. W was shifted to the left (i.e., higher [Labl] values were found for the same W) at Alt1wk compared with SL0 and partially shifted back to the right (i.e., lower [Labl] values were found for the same W) at Alt3wk and Alt5wk. At Alt1wk-O2 and Alt5wk-O2, [Labl] vs. W values were superimposed on that at SL0. At SL1wk-SL5wk, [Labl] vs. W values were shifted to the right compared with that at SL0. At Alt1wk, a condition of respiratory alkalosis was found, which was only partially compensated for during acclimatization. At SL1wk, the acid-base status was back to normal. We conclude that 1) the reduced [Labl]peak at altitude is still present for 2-3 wk after return from altitude; is not attributable to reduced peak W nor to hypoxia per se, nor to a reduced buffer capacity; alternatively, it could be related to some central determinants of fatigue. 2) The [Labl] vs. W leftward shift at altitude was due to hypoxia per se. 3) The factor(s) responsible for the [Labl] vs. W partial rightward shift during acclimatization could still be effective during the first weeks after return to sea level.
Role of hematocrit in the recruitment of pulmonary diffusing capacity: comparison of human and dog
Authors: Wu E. Y. , Ramanathan M. , Hsia C. C.
Published: December 2017

In dogs, maximal O2 uptake (VO2max) per kilogram of body weight is two- to threefold that in humans; the difference cannot be explained solely by differences in structural features between species. We compared the functional recruitment of pulmonary diffusing capacity (DLCO) during exercise in dogs with that in humans to determine whether pulmonary gas exchange is matched to VO2max or the size of the lungs and to define the potential role of exercise-induced polycythemia in producing the superior aerobic capacity of the dogs. We compared the relationships of DLCO, membrane diffusing capacity (DMCO), and pulmonary capillary blood volume (Vc) with respect to pulmonary blood flow (Qc) by a rebreathing method during steady-state exercise in adult male human subjects and in conditioned adult male foxhounds. The slopes and intercepts of the relationships of DLCO and DMCO to Qc are significantly greater in dogs than in humans; the slopes of the relationship of Vc to Qc are similar. In dogs diffusive pulmonary gas transport is matched to the higher VO2max. The enhanced recruitment of DLCO and DMCO in dogs during exercise could potentially be explained entirely by the exercise-induced polycythemia, which is seen in dogs but not in humans.
Technique for repetitive recording from fetal respiratory neurons
Authors: Ioffe S. , Jansen A. H. , Chernick V.
Published: December 2017

We developed a new method for repetitive recording of medullary neurons in fetal sheep in situ. The technique involves chronically fixing the fetal head to the flank of the ewe by way of a Teflon plate that has a removable window. This window allows direct access of a recording electrode to the floor of the fourth ventricle of the fetus. In four of six fetuses, repetitive recordings lasting 3-4 h were possible for up to 6 days. By operating on younger fetuses and with care, this time span could be extended. This novel method should be useful in the future for extracellular and intracellular recordings of neurons in the developing fetus without disturbing the fetal state and for the study of putative neurotransmitters during development with iontophoretic techniques.
Effects of a single bout of exercise on glucose effectiveness
Authors: Higaki Y. , Kagawa T. , Fujitani J. , Kiyonaga A. , Shindo M. , Taniguchi A. , Nakai Y. , Tokuyama K. , Suzuki M. , Tanaka H.
Published: December 2017

The effects of a single bout of exercise on glucose effectiveness (SG) and insulin sensitivity (SI) in 22 sedentary subjects were estimated with a minimal model approach. The intravenous glucose tolerance test (IVGTT) was performed 1) 11 h after an exercise bout on a cycle ergometer at the lactate threshold level (mild exercise) for 60 min, 2) 11 h after an exercise bout at the 4 mM lactate level (hard exercise) for 36 +/- 1 min, 3) 11 h after an exhaustive-exercise bout (exhaustive exercise) for 96 +/- 7 min, or 4) without any prior exercise (control). Only the exhaustive exercise increased the glucose disappearance constant (2.69 +/- 0.28 vs. 2.05 +/- 0.13%/min; P < 0.05) and SI (15.0 +/- 2.0 vs. 10.3 +/- 0.9 x 10(-5) min/pM: P < 0.05) in comparison with the control condition. The SG and SG at zero insulin (GEZI) were not affected by any exercise condition. However, a marked individual difference in GEZI emerged after the exhaustive exercise and could be divided into two subgroups: one decreased in GEZI (0.014 +/- 0.001 vs. 0.007 +/- 0.001 min-1) and the other increased in GEZI (0.014 +/- 0.001 vs. 0.021 +/- 0.003 min-1). The former subgroup was accompanied by elevated levels of plasma creatine kinase (100 +/- 16 vs. 598 +/- 315 IU/l; P < 0.05) and myoglobin (Mb; 46 +/- 4 vs. 126 +/- 47 ng/ml; P < 0.05), whereas the latter subgroup showed no significant change in creatinine kinase (99 +/- 10 vs. 128 +/- 9 IU/l; P = 0.05) and Mb (50 +/- 7 vs. 51 +/- 4 ng/ml; P = 0.05). In both subgroups, SI was similarly increased after the exhaustive exercise. These results thus suggest that a single bout of exercise that results in muscle damage or changes in muscle permeability, as reflected in the increased creatine kinase and Mb levels, decreases GEZI, whereas exhaustive exercise without such alterations increases GEZI.
Flow-dependent influence of high-O2-affinity erythrocytes on peak VO2 in exercising muscle in situ
Authors: Kohzuki H. , Enoki Y. , Matsumura K. , Sakata S. , Shimizu S.
Published: December 2017

To evaluate the influence of a high-O2 affinity of the erythrocyte and of flow rate on muscle's ability to extract O2 and develop force, we perfused dog gastrocnemius contracting isometrically at 4 Hz with normal-O2-affinity perfusate or high-O2-affinity perfusate at high and moderate flows (200 and 100 ml . min-1 . 100g-1, respectively). High-O2-affinity perfusate was prepared by incubating human citrate-phosphate-dextrose-stored erythrocytes with buffered saline containing cyanate (4 degrees C, 18 h) and normal-affinity perfusate by storing 2,3-diphosphoglycerate-rejuvenated erythrocytes in the same solution without cyanate. PO2 when blood is half oxygenated was 30.6 Torr for normal perfusate and 18.1 Torr for high-affinity perfusate. During 4-Hz stimulation, the tension developed by the muscle increased incrementally (positive staircase) to reach a peak value after 1.2-1.6 min for the normal perfusate and 0.6-0.7 min for the high-affinity perfusate (P < 0.05). The rate of decline during the early fatigue (measured from the onset of tension decline to 3 min) with high-affinity perfusate was significantly faster than it was with normal perfusate (P < 0.05). These findings suggest that both the staircase effect and the early fatigue are related to O2 availability, which is restricted when erythrocytes have a high O2 affinity. The peak O2 uptake values measured at 3 and 5 min were significantly lower (by 14-24%) with high-affinity perfusate than with normal perfusate at a given level of O2 delivery (arterial O2 content x flow) (P < 0.05). PO2 of venous effluent was proportionally related to peak O2 uptake. The present results indicate that neither blood flow nor O2 delivery is the sole determinant of the muscle's ability to extract O2.
Soleus fiber force and maximal shortening velocity after non-weight bearing with intermittent activity
Authors: Widrick J. J. , Bangart J. J. , Karhanek M. , Fitts R. H.
Published: December 2017

This study examined the effectiveness of intermittent weight bearing (IWB) as a countermeasure to non-weight-bearing (NWB)-induced alterations in soleus type I fiber force (in mN), tension (Po; force per fiber cross-sectional area in kN/m-2), and maximal unloaded shortening velocity (Vo, in fiber lengths/s). Adult rats were assigned to one of the following groups: normal weight bearing (WB), 14 days of hindlimb NWB (NWB group), and 14 days of hindlimb NWB with IWB treatments (IWB group). The IWB treatment consisted of four 10-min periods of standing WB each day. Single, chemically permeabilized soleus fiber segments were mounted between a force transducer and position motor and were studied at maximal Ca2+ activation, after which type I fiber myosin heavy-chain composition was confirmed by sodium dodecyl sufate-polyacrylamide gel electrophoresis. NWB resulted in a loss in relative soleus mass (-45%), with type I fibers displaying reductions in diameter (-28%) and peak isometric force (-55%) and an increase in Vo (+33%). In addition, NWB induced a 16% reduction in type I fiber Po, a 41% reduction in type I fiber peak elastic modulus [Eo, defined as (delta force/delta length) x (fiber length/fiber cross-sectional area] and a significant increase in the Po/Eo ratio. In contrast to NWB, IWB reduced the loss of relative soleus mass (by 22%) and attenuated alterations in type I fiber diameter (by 36%), peak force (by 29%), and Vo (by 48%) but had no significant effect on Po, Eo, or Po/Eo. These results indicate that a modest restoration of WB activity during 14 days of NWB is sufficient to attenuate type I fiber atrophy and to partially restore type I peak isometric force and Vo to WB levels. However, the NWB-induced reductions in Po and Eo, which we hypothesize to be due to a decline in the number and stiffness of cross bridges, respectively, are considerably less responsive to this countermeasure treatment.
Muscle O2 uptake kinetics in humans: implications for metabolic control
Authors: Grassi B. , Poole D. C. , Richardson R. S. , Knight D. R. , Erickson B. K. , Wagner P. D.
Published: December 2017

Muscle O2 uptake (VO2) kinetics in response to an augmented energetic requirement (on-transition) has never been directly determined in humans. We have developed a constant-infusion thermodilution technique that allowed rapid measurements of leg blood flow (Qleg) and, in conjunction with frequent serial measurement of arteriovenous O2 content difference across the leg [(Ca - Cv)O2leg], permitted the determination of the VO2 of the leg (VO2leg) at 3- to 4-s time intervals. VO2leg kinetics during the on-transition was taken as a close approximation of muscle VO2 (VO2mus) kinetics. Alveolar VO2 (VO2A), Qleg, leg O2 delivery [(Q.CaO2leg)], (Ca - Cv)O2leg, and VO2leg kinetics were determined in six trained subjects [age 22.8 +/- 4.4 (SD) yr; maximal O2 uptake 59.1 +/- 5.3 ml.kg-1.min-1] during the transition from unloaded pedaling to a workload (loaded pedaling; LP) (183 +/- 20 W) well below the previously determined ventilatory threshold. For all variables, two distinct phases were recognized. During the first 10-15 s of loaded pedaling (phase I), VO2A, Qleg, and (Q.CaO2)leg increased rapidly, whereas VO2leg increased only slightly and (Ca - Cv)O2leg actually decreased. After phase I, all variables showed a monoexponential increase (phase II), with similar time courses [slightly faster for (Ca - CV)O2leg]. In a consideration of both phases, the half times of the responses among variables were not significantly different: 25.5 +/- 2.6 s for VO2A, 26.6 +/- 7.6 s for Qleg, 26.9 +/- 8.3 s for (Q.CaO2leg, 23.5 +/- 1.3 s for (Ca - Cv)O2leg, and 27.9 +/- 5.7 s for VO2leg. We conclude that during the on-transition the kinetics of VO2A and VO2leg, as measured by these methods, are similar. The analysis of the early phase (first 10-15 s) of the on-transition indicates that bulk delivery of O2 to the working muscles is not limiting VO2leg kinetics. However, the present results cannot discriminate between maldistribution of blood flow/VO2 vs. inertia the intracellular oxidative machinery as the limiting factor.
Respiratory resistance by end-inspiratory occlusion and forced oscillations in intubated patients
Authors: Beydon L. , Malassine P. , Lorino A. M. , Mariette C. , Bonnet F. , Harf A. , Lorino H.
Published: December 2017

Measurement of respiratory impedance by the forced oscillation technique (FOT) in intubated patients requires corrections for the flow-dependent resistance, inertance, and air compression inside the endotracheal tube (ETT). Recently, we published a method to correct respiratory impedance for the mechanical contribution of the ETT. To validate this correction, we compared the respiratory resistance obtained with this method (Rfo) to the intrinsic (Rmin) and total resistances (RT) measured by the airway-occlusion technique (OCT) in 16 intubated sedated paralyzed ventilated patients. The FOT was applied at functional residual capacity in the 4- to 32-Hz frequency range, whereas the OCT was performed at the end of a normal constant-flow inspiration. Rmin corrected with Rfo measured at 16 and 32 Hz [Rfo(16) = 1.10 x Rmin + 0.10 cmH2O.s.l-1, r = 0.96, P < 0.001; Rfo(32) = 0.93 x Rmin + 0.72 cmH2O.s.l-1, r = 0.97, P < 0.001]. RT corrected with Rfo at 4 Hz [Rfo(4) = 1.11 x RT - 1.48 cmH2O.s.l-1; = 0.92; P < 0.001]. We conclude that the FOT improved by correction for the behavior of the ETT is in good agreement with the OCT in intubated patients.
Cardiomyoplasty: degeneration of the assisting skeletal muscle
Authors: Ianuzzo C. D. , Ianuzzo S. E. , Carson N. , Feild M. , Locke M. , Gu J. , Anderson W. A. , Klabunde R. E.
Published: December 2017

This study determined effects of surgical dissection and chronic stimulation on degeneration of the latissimus dorsi muscle (LDM), the muscle used for contractile assistance in cardiomyoplasty. LDMs from 10 goats were allocated into four groups: N-LDM (normal), D-LDM (dissected muscle and collateral vessels ligated, muscle remained in original anatomic location), S-LDM (electrically stimulated for 65-75 days), and DS-LDM (dissected and stimulated). S-LDM had nearly a complete transformation to type I fibers throughout the lengths of the muscle. Both groups of dissected muscles (D-LDM and DS-LDM) showed lesser transformation and significant damage. Type I myosin heavy chain and citrate synthase activity were less in the distal compared with the proximal LDM. Morphology of the N-LDM and S-LDM was normal, whereas dramatic morphological abnormalities were observed in the D-LDM and DS-LDM, including lipid-containing ghostlike fibers, atrophied and hypertrophied fibers within the same fascicle. In conclusion, muscle degeneration associated with the cardiomyoplasty procedure was caused by surgical dissection, which was exacerbated by chronic stimulation but was not caused by stimulation alone.
Augmented hypoxic cerebral vasodilation in men during 5 days at 3,810 m altitude
Authors: Jensen J. B. , Sperling B. , Severinghaus J. W. , Lassen N. A.
Published: December 2017

The fractional increase in cerebral blood flow (CBF) velocity (VCBF) from the control value with 5-min steps of isocapnic hypoxia and hyperoxic hypercapnia was measured by transcranial Doppler in six sea-level native men before and during a 5-day sojourn at 3,810 m altitude to determine whether cerebral vasoreactivity to low arterial O2 saturation (SaO2) gradually increased [as does the hypoxic ventilatory response (HVR)] or diminished (adapted, in concert with known slow fall of CBF) at altitude. A control resting PCO2 value was chosen each day during preliminary hyperoxia to set ventilation at 140 ml.kg-1.min-1 for this and the parallel HVR study, attempting to establish control cerebrospinal fluid (CSF) and brain extracellular fluid pH values unaltered by acclimatization. The relationship of CBF to SaO2 was nonlinear, steepening at a lower SaO2. A hyperbolic equation was used to describe hypoxic cerebrovascular reactivity: fractional VCBF = x[60/ (SaO2-40)-1], where X is the fractional increase of VCBF at 70%.X rose from 0.346 +/- 0.104 (SD) at sea level to 0.463 +/- 0.084 on altitude day 5 (P < 0.05 by paired t-test, justified by the a priori experimental plan). For comparison with CO2 sensitivity, from these X values, we estimate the rise in CBF in response to a 1% fall in SaO2 at 80% to be 1.30% at sea level and 1.74% after 5 days at altitude. CBF sensitivity to increased end-tidal PCO2 rose from 4.01 +/- 0.62%/Torr at sea level to 5.12 +/- 0.79%/Torr on day 5 (P < 0.05), as expected, at the lower PCO2 due to the logarithmic relationship of PCO2 to CSF pH. This change was not significant after correction to log PCO2. We conclude that the cerebral vascular response to acute isocapnic hypoxia may increase during acclimatization at high altitude. The mechanism is unknown but is presumably unrelated to the parallel carotid chemosensitization that, in these subjects, increased the HVR by 60% in the same 5-day period from 0.91 +/- 0.38 to 1.46 +/- 0.59 l.min-1.% fall in SaO2-1).
L-type Ca2+ channel and Na+/Ca2+ exchange inhibitors reduce Ca2+ accumulation in reperfused skeletal muscle
Authors: Welsh D. G. , Lindinger M. I.
Published: December 2017

It is known that extracellular Ca2+ accumulates within skeletal muscle after prolonged periods of ischemia and reperfusion. In this study, we determined whether the L-type Ca2+ channel and the Na+/Ca2+ exchanger mediated Ca2+ influx and whether Ca2+ accumulation limited the metabolic and contractile recovery of reperfused skeletal muscle. Contracting rat hindlimbs (1-Hz twitch) exposed to 40 min of no-flow ischemia were reperfused with diltiazem (500 microM) or 3,4-dichlorobenzamil (300 microM) to block the Na+/Ca2+ exchanger and/or the L-type Ca2+ channel. High inhibitor concentrations were used to counter the binding of diltiazem and 3,4-dichlorobenzamil to albumin and red blood cells. Muscle Ca2+ accumulation, contractile function, and energy metabolism were assessed by measuring intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, twitch tension, and high-energy phosphagens [ATP, total adenine nucleotides (TAN) and phosphocreatine (PCr)]. Compared with control reperfusion, diltiazem and 3,4-dichlorobenzamil reduced Ca2+ influx and attenuated the rise in [Ca2+]i in the fast-oxidative glycolytic plantaris (Pl) and the fast-glycolytic white gastrocnemius (WG). The inhibitor-induced decrease in Ca2+ influx was 1.5- to 2-fold greater with 3,4-dichlorobenzamil than with diltiazem. Coinciding with the reduced Ca2+ accumulation, diltiazem and 3,4-dichlorobenzamil enhanced the resynthesis of ATP (Pl and WG), PCr (Pl and WG), and TAN (Pl) compared with control reperfusion. 3,4-Dichlorobenzamil also augmented twitch-tension recovery. We conclude that Ca2+ accumulation during reperfusion 1) arises from L-type Ca2+ channel and Na+/Ca2+ exchange activation; and 2) impairs the metabolic and contractile recovery of skeletal muscle.
Differential respiratory activity of four abdominal muscles in humans
Authors: Abe T. , Kusuhara N. , Yoshimura N. , Tomita T. , Easton P. A.
Published: December 2017

Together the abdominal muscles contribute significantly to ventilation under some conditions, but there is little information regarding individual recruitment and timing of activation of the four abdominal muscles in humans. Fine-wire electrodes were inserted under direct vision guided by high-resolution ultra-sound into the rectus abdominis (Rectus), external oblique (Extern), internal oblique (Intern), and transversus abdominis (Transv) in nine awake healthy subjects. Airflow, end-tidal CO2, and moving-average EMG signals were recorded during 1) supine resting and CO2-stimulated ventilation and 2) resting ventilation in the standing position. During resting supine breathing, Transv showed significant phasic EMG activity during expiration. As posture changed from supine to standing, phasic activity during resting ventilation was greatest in Transv, with lesser activity in Intern and Extern, while Rectus remained inactive. As CO2 began to increase, Transv was activated first, followed by Intern, the Extern, and finally Rectus. With moderate CO2 stimulation, Transv and Intern were more active than was Extern and Rectus remained least active. EMG activities in the expiratory muscles after cessation of expiratory flow (postexpiratory expiratory activity) and in expiratory muscle activity preceding expiratory flow were observed consistently during supine stimulated ventilation and standing resting ventilation. These activities before and after expiratory airflow were prominent with stimulated ventilation during a substantial portion of inspiration, suggesting dual control of inspiratory pump action by both inspiratory and expiratory muscles, which provide acceleration and braking actions, respectively. These results suggest that in awake humans 1) during resting ventilation, expiration is an active process; 2) abdominal muscles are activated differentially; 3) Transv is the most active, Intern and Extern are intermediate, and Rectus is the least active expiratory muscle; and 4) during stimulated ventilation, inspiratory and expiratory muscles contribute dually to inspiratory pump action.
Anatomic dead space in infants and children
Authors: Numa A. H. , Newth C. J.
Published: December 2017

In adults, anatomic dead space is 2.2 ml/kg. Because of the relatively large head size of infants and children, we hypothesized that extrathoracic and, therefore, total dead space would be relatively larger in pediatric subjects. Extrathoracic dead space was measured by a "water displacement" technique in 40 patients aged 7 days to 14.2 yr who were intubated with cuffed endotracheal tubes. Intrathoracic dead space was measured by continuous analysis of end-tidal and mixed-expired PCO2 and minute ventilation in 10 patients, aged 18 days to 14.7 yr. Extrathoracic dead space per kilogram decreased exponentially with increasing age, ranging from 2.3 ml/kg in early infancy to 0.8 ml/kg in children older than 6 yr. Mean intrathoracic anatomic dead space was 1.03 ml/kg and was not related to age. The following relationship between total anatomic dead space (DStotal; in ml/kg) and age (in yr) is derived: DStotal = 3.28 - 0.56 [ln(1 + Age)], with r = 0.95 and P = 0.0001. Anatomic dead space is age dependent and is > 3 ml/kg in early infancy.