bluuebunny/crossref_metadata_2025 huggingface dataset:
Human muscle fatigue after glycogen depletion: a 31P magnetic resonance study
Authors: Bertocci L. A. , Fleckenstein J. L. , Antonio J.
Published: December 2017

To differentiate the effects of high energy phosphates, pH, and [H2PO4-] on skeletal muscle fatigue, intracellular acidosis during handgrip exercise was attenuated by prolonged submaximal exercise. Healthy human subjects (n = 6) performed 5-min bouts of maximal rhythmic handgrip (RHG) before (CONTROL) and after prolonged (60-min) handgrip exercise (ATTEN-EX) designed to attenuate lactic acidosis in active muscle by partially depleting muscle glycogen. Concentrations of free intracellular phosphocreatine ([PCr]), adenosine triphosphate ([ATP]), and orthophosphate ([P(i)]) and pH were measured by 31P nuclear magnetic resonance spectroscopy and used to calculate adenosine diphosphate [ADP], [H2PO4-], and [HPO4(2-)]. Handgrip force output was measured with a dynamometer, and fatigue was determined by loss of maximal contractile force. After ATTEN-EX, the normal exercise-induced muscle acidosis was reduced. At peak CONTROL RHG, pH fell to 6.3 +/- 0.1 (SE) and muscle fatigue was correlated with [PCr] (r = 0.83), [P(i)] (r = 0.82), and [H2PO4-] (r = 0.81); [ADP] was 22.0 +/- 5.7 mumol/kg. At peak RHG after ATTEN-EX, pH was 6.9 +/- 0.1 and [ADP] was 116.1 +/- 18.2 mumol/kg, although [PCr] and [P(i)] were not different from CONTROL RHG (P greater than 0.05). After ATTEN-EX, fatigue correlated most closely with [ADP] (r = 0.84). The data indicate that skeletal muscle fatigue 1) is multifactorial, 2) can occur without decreased pH or increased [H2PO4-], and 3) is correlated with [ADP] after exercise-induced glycogen depletion.
A comparative study of postpneumonectomy compensatory lung response in growing male and female rats
Authors: Sekhon H. S. , Thurlbeck W. M.
Published: December 2017

Postpneumonectomy compensatory lung response and normal lung growth in the early postnatal period were studied in male and female rats. Four-week-old litter-matched male and female Sprague-Dawley rats were subjected to left pneumonectomy or sham operation and followed for 3 wk. In both sexes after pneumonectomy, lung weight (WL), lung volume (VL), alveolar surface area (Sw), total alveolar number (N(at)), and the amount of DNA and protein increased significantly. In both males and females, WL, VL, and Sw matched those of both lungs of the sham-operated group, but N(at) and the amount of DNA and protein did not. Female pneumonectomy and sham-operated rats were smaller in body weight than males. Absolute WL, VL, Sw, N(at), and the amount of DNA and protein were significantly lower, but specific parameters (per unit body weight) were significantly greater in females than in males. After pneumonectomy, the postcaval lobe increased most in volume (70 and 73% in males and females, respectively). Mean linear intercept and mean chord length of alveoli increased, and the number of alveoli per unit volume decreased more in the postcaval and middle lobes than in upper and lower lobes in both sexes. Postpneumonectomy, loss of elastic lung recoil was observed in females. We conclude that, in certain aspects (WL, VL), compensatory growth matched both lungs of controls, but in others (biochemical, morphometric) it did not. There was evidence of alveolar multiplication, but the dominant effect was enlargement of air spaces.(ABSTRACT TRUNCATED AT 250 WORDS)
Intrinsic PEEP monitored in the ventilated ARDS patient with a mathematical method
Authors: Eberhard L. , Guttmann J. , Wolff G. , Bertschmann W. , Minzer A. , Kohl H. J. , Zeravik J. , Adolph M. , Eckart J.
Published: December 2017

Under mechanical volume-controlled ventilation, the intensive care patient can develop intrinsic positive end-expiratory pressure (iPEEP); that is, the passive expiration is terminated by the following inspiration before the alveolar pressure comes to its physical equilibrium value. We present a mathematical method to estimate this alveolar dynamic iPEEP breath by breath, without the need of a maneuver. We tested it in paralyzed patients ventilated for adult respiratory distress syndrome after multiple trauma and/or sepsis, and we compared the results obtained with the new mathematical method with those from the occlusion method introduced by Pepe and Marini. The results agreed well (median difference of 0.8 mbar in 201 investigations in 12 patients). However, the mathematically determined values, representing dynamic iPEEP, are systematically slightly smaller than those measured by the occlusion maneuver. A variation of expiratory time suggests that this difference might be due to mechanical time-constant inhomogeneity, viscoelastic processes, or other mechanisms showing time dependence.
Effects of series compliance on twitches superimposed on voluntary contractions
Authors: Loring S. H. , Hershenson M. B.
Published: December 2017

The activation of skeletal muscle during voluntary isometric contraction has been assessed by measuring the increase in force caused by a superimposed maximal shock to the motor nerve (the twitch-interpolation technique). When the muscle is held isometric, the increase in force with stimulation (superimposed twitch force) decreases with increasing voluntary force, and a line fit through the data can be extrapolated to maximal voluntary force at the zero twitch force axis. In a previous paper we questioned the applicability of this technique in situations where a high series compliance allows the muscle to shorten during the superimposed twitch. To explore effects of series compliance, we measured force of the adductor pollicis during voluntary isometric contractions with noncompliant and compliant loading devices. With the compliant loading device, superimposed twitch force was systematically less than with the noncompliant device, and the plot of superimposed twitch force vs. voluntary force was often concave upward, preventing easy extrapolation to maximal voluntary force. These findings are consistent with force-velocity characteristics of muscle and suggest that twitch-interpolation data must be interpreted with caution when the muscle is not held isometric during the superimposed twitch.
Role of neutrophil elastase in allergen-induced lysozyme secretion in the dog trachea
Authors: Tabachnik E. , Schuster A. , Gold W. M. , Nadel J. A.
Published: December 2017

To test our hypothesis that neutrophil elastase plays a role in airway hypersecretion associated with the allergic late-phase response, using an isolated tracheal segment system in vivo and measuring lysozyme activity in the perfusate of the lumen as a marker of submucosal gland secretion over 8 h, we studied the response of five allergic dogs to ragweed. The dogs were exposed on separate occasions to specific allergen, to allergen vehicle, and to allergen in the presence of a selective neutrophil elastase inhibitor, ICI 200,355. Allergen exposure caused a marked increase in lysozyme secretion that was significantly increased at 4, 6, and 8 h compared with controls and ICI 200,355-treated dogs. Neutrophil elastase appeared in the perfusate after allergen exposure and was positively correlated with lysozyme secretion at 8 h. These findings suggest that neutrophil elastase plays an important role as a secretagogue in the allergic late-phase response.
Analyses of plasma for metabolic and hormonal changes in rats flown aboard COSMOS 2044
Authors: Merrill A. H. , Wang E. , Mullins R. E. , Grindeland R. E. , Popova I. A.
Published: December 2017

Plasma samples from rats flown aboard COS-MOS 2044 were analyzed for the levels of key metabolites, electrolytes, enzymes, and hormones. The major differences between the flight group and the synchronous control were elevations in glucose, cholesterol, phosphate, creatinine, blood urea nitrogen, lactate dehydrogenase, and aspartate amino-transferase and decreased levels of thyroxine. Most of these differences were not mimicked by tail suspension of ground-based rats; however, both flight and suspended rats exhibited inhibited testosterone secretion. Corticosterone, immunoreactive growth hormone, and prolactin showed inconsistent differences from the various control groups, suggesting that the levels of these hormones were not due to actual or simulated microgravity.
Pituitary oxytocin and vasopressin content of rats flown on COSMOS 2044
Authors: Keil L. , Evans J. , Grindeland R. , Krasnov I.
Published: December 2017

Preliminary studies in rats (COSMOS 1887) suggested that levels of posterior pituitary hormones were reduced by exposure to spaceflight. To confirm these preliminary findings, we obtained pituitary tissue from rats flown for 14 days on COSMOS 2044. Posterior pituitary content of oxytocin (OT) and vasopressin (VP) were measured in these tissues as well as those from ground-based controls. The synchronous control group had feeding and lighting schedules synchronized to those in the spacecraft and were maintained in flight-type cages. Another group was housed in vivarium cages; a third group was tail suspended (T), a method used to stimulate microgravity. Flight rats showed an average reduction of 27% (P less than 0.05) in pituitary OT and VP compared with the three control groups. When hormone content was expressed in terms of pituitary protein (micrograms hormone/mg protein), the average decrease in OT and VP for the flight animals ranged from 20 to 33% (P less than 0.05) compared with the various control groups. Reduced levels of pituitary OT and VP were similar to preliminary measurements from the COSMOS 1887 mission and appear to result from exposure to spaceflight. These data suggest that changes in the rate of hormone secretion or synthesis may have occurred during exposure to microgravity.
Effect of spaceflight on natural killer cell activity
Authors: Rykova M. P. , Sonnenfeld G. , Lesnyak A. T. , Taylor G. R. , Meshkov D. O. , Mandel A. D. , Medvedev A. E. , Berry W. D. , Fuchs B. B. , Konstantinova I. V.
Published: December 2017

The effects of spaceflight on immune cell function were determined in rats flown on COSMOS 2044. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. The ability of natural killer cells to lyse two different target cell lines was determined. Spleen and bone marrow cells obtained from flight rats showed significantly inhibited cytotoxicity for YAC-1 target cells compared with cells from synchronous control rats. This could have been due to exposure of the rats to microgravity. Antiorthostatic suspension did not affect the level of cytotoxicity from spleen cells of suspended rats for YAC-1 cells. On the other hand, cells from rats flown in space showed no significant differences from vivarium and synchronous control rats in cytotoxicity for K-562 target cells. Binding of natural killer cells to K-562 target cells was unaffected by spaceflight. Antiorthostatic suspension resulted in higher levels of cytotoxicity from spleen cells for 51Cr-labeled K-562 cells. The results indicate differential effects of spaceflight on function of natural killer cells. This shows that spaceflight has selective effects on the immune response.
PAF antagonists inhibit pulmonary vascular remodeling induced by hypobaric hypoxia in rats
Authors: Ono S. , Westcott J. Y. , Voelkel N. F.
Published: December 2017

Chronic hypoxia causes pulmonary hypertension and pulmonary vascular remodeling in rats. Because platelet-activating factor (PAF) levels increase in lung lavage fluid and in plasma from chronically hypoxic rats, we examined the effect of two specific, structurally unrelated PAF antagonists, WEB 2170 and BN 50739, on hypoxia-induced pulmonary vascular remodeling. Treatment with either agent reduced hypoxia-induced pulmonary hypertension and right ventricular hypertrophy at 3 wk of hypoxic exposure (simulated altitude 5,100 m) but did not affect cobalt (CoCl2)-induced pulmonary hypertension. The PAF antagonists had no effect on the hematocrit of normoxic or chronically hypoxic rats or CoCl2-treated rats. Hypoxia-induced pulmonary hypertension was associated with an increase in the vessel wall thickness of the muscular arteries and reduction in the number of peripheral arterioles. In WEB 2170-treated rats, these changes were significantly less severe than those observed in untreated chronically hypoxic rats. PAF receptor blockade had no acute hemodynamic effects; i.e., it did not affect pulmonary arterial pressure or cardiac output nor did it affect the magnitude of acute hypoxic pulmonary vasoconstriction in awake normoxic or chronically hypoxic rats. Isolated lungs from chronically hypoxic rats showed a pressor response to the chemotactic tripeptide N-formyl-Met-Leu-Phe (fMLP) and an increase in the number of leukocytes lavaged from the pulmonary circulation. In vivo treatment with WEB 2170 significantly reduced the fMLP-induced pressor response compared with that observed in isolated lungs from untreated chronically hypoxic rats. These results suggest that PAF contributes to the development of chronic pulmonary hypertension induced by chronic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Relationship between body and leg VO2 during maximal cycle ergometry
Authors: Knight D. R. , Poole D. C. , Schaffartzik W. , Guy H. J. , Prediletto R. , Hogan M. C. , Wagner P. D.
Published: December 2017

It is not known whether the asymptotic behavior of whole body O2 consumption (VO2) at maximal work rates (WR) is explained by similar behavior of VO2 in the exercising legs. To resolve this question, simultaneous measurements of body and leg VO2 were made at submaximal and maximal levels of effort breathing normoxic and hypoxic gases in seven trained male cyclists (maximal VO2, 64.7 +/- 2.7 ml O2.min-1.kg-1), each of whom demonstrated a reproducible VO2-WR asymptote during fatiguing incremental cycle ergometry. Left leg blood flow was measured by constant-infusion thermodilution, and total leg VO2 was calculated as the product of twice leg flow and radial arterial-femoral venous O2 concentration difference. The VO2-WR relationships determined at submaximal WR′s were extrapolated to maximal WR as a basis for assessing the body and leg VO2 responses. The differences between measured and extrapolated maximal VO2 were 235 +/- 45 (body) and 203 +/- 70 (leg) ml O2/min (not significantly different). Plateauing of leg VO2 was associated with, and explained by, plateauing of both leg blood flow and O2 extraction and hence of leg VO2. We conclude that the asymptotic behavior of whole body VO2 at maximal WRs is a direct reflection of the VO2 profile at the exercising legs.
Fatigability and blood flow in the rat gastrocnemius-plantaris-soleus after hindlimb suspension
Authors: McDonald K. S. , Delp M. D. , Fitts R. H.
Published: December 2017

The purpose of this study was to test the hypothesis that hindlimb suspension increases the fatigability of the soleus during intense contractile activity and determine whether the increased fatigue is associated with a reduced muscle blood flow. Cage-control (C) and 15-day hindlimb-suspended (HS) rats were anesthetized, and either the gastrocnemius-plantaris-soleus (G-P-S) muscle group or the soleus was stimulated (100 Hz, 100-ms trains at 120/min) for 10 min in situ. In the G-P-S preparation, blood flow was measured with radiolabeled microspheres before and at 2 and 10 min of contractile activity. The G-P-S fatigued markedly at this stimulation frequency, and the differences between C and HS animals were not significant until the 9th min of contractile activity. In contrast, the stimulation resulted in faster rates and significantly larger amounts of fatigue in the soleus from HS than from C animals. The atrophied soleus showed significant differences by 1 min of stimulation (C = 70 +/- 1% vs. HS = 57 +/- 2% of peak train force) and remained different at 10 min (C = 64 +/- 4% vs. HS = 45 +/- 2% peak train force). Relative blood flow to the soleus was similar between groups before and during contractile activity (rest: C = 20 +/- 3 vs. HS = 12 +/- 3; 2 min: C = 128 +/- 6 vs. HS = 118 +/- 4; 10 min: C = 123 +/- 11 vs. HS = 105 +/- 11 ml.min-1.100 g-1). In conclusion, these results established that 15 days of HS increased the fatigability of the soleus, but the effect was not caused by a reduced muscle blood flow.
Effects of high-frequency pressure waves applied to upper airway on respiration in central apnea
Authors: Henke K. G. , Sullivan C. E.
Published: December 2017

We examined the effects of high-frequency (30-Hz) low-pressure oscillations on respiration in nine patients with central sleep apnea. All patients were studied during sleep and wore a nasal mask through which the oscillations were applied. All tests were performed during periods of repetitive central apneas. Respiratory efforts were monitored from the airflow and calibrated Respitrace signals. After several cycles of apnea were monitored, the oscillatory pressures were applied for brief periods (less than 5 s) at the midpoint of the central apneas. All trials in which arousal occurred were discarded, leaving a total of 106 trials in the nine patients. High-frequency oscillation of the upper airway stimulated respiratory effort(s) in 68% of all trials (72 of 106). Apnea length was significantly shortened in four of the nine patients. In one patient with a tracheostomy, the stimulus applied to his isolated upper airway evoked respiratory efforts during central apnea in 13 of 15 trials. We conclude that high-frequency oscillatory pressures applied to the upper airway can stimulate respiratory efforts during central apnea. This response may be mediated by upper airway receptors involved in nonrespiratory airway defense reflexes and may have implications in the treatment of patients with central sleep apnea.
Relationship among running mileage, bone density, and serum testosterone in male runners
Authors: MacDougall J. D. , Webber C. E. , Martin J. , Ormerod S. , Chesley A. , Younglai E. V. , Gordon C. L. , Blimkie C. J.
Published: December 2017

Our purpose was to investigate the relationship between running volume and bone mineral mass in adult male runners. Whole body and regional bone mineral density were determined by dual-photon absorptiometry in 22 sedentary controls and 53 runners who were selected according to their running mileage to fall into a 5- to 10-, 15- to 20-, 25- to 30-, 40- to 55-, or 60- to 75-mile/wk group. All groups were of similar age (20–45 yr) and nutritional status, as determined by 7-day food records. Regional sites for bone density measurements included the trunk, spine, pelvis, thighs, and lower legs. In addition, serum total testosterone was determined in each subject and computed tomography scans were made of the lower legs in 34 subjects to assess bone cross-sectional area. No significant differences were detected for bone density measurements with the exception of the lower legs where it was significantly (P less than 0.05) greater for the 15- to 20-mile/wk group than for the control and 5- to 10-mile/wk groups. With mileage greater than 20 miles/wk, bone density of the lower legs showed no further increase and, in fact, tended to decrease, so that for the 60- to 75-mile/wk group it was similar to that of the controls. Cross-sectional area of the tibia and fibula when normalized to body weight tended to be greater as weekly mileage increased and was significantly greater in the 40- to 55-mile/wk runners than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Oxygen cost of resistive-loaded breathing in quadriplegia
Authors: Manning H. , McCool F. D. , Scharf S. M. , Garshick E. , Brown R.
Published: December 2017

We hypothesized that, in quadriplegia, chest wall distortion would increase the energy cost of ventilation. To assess this, we measured the oxygen cost of breathing (VO2 resp) and changes in chest wall configuration during inspiratory resistive-loaded breathing tasks in five quadriplegic and five normal subjects. Each subject performed three breathing tasks that spanned a range of work rates (Wtot). Configurational changes of the abdomen and upper, lower, and transverse rib cage were assessed with magnetometers. We found that 1) in both groups, VO2resp increased linearly with Wtot over the range of tasks performed, 2) the mean slope of the regression line of VO2resp vs. Wtot was greater for quadriplegic than for normal subjects (3.7 +/- 0.8 vs. 2.0 +/- 0.7 ml O2/J, P less than 0.01), 3) efficiency of breathing (Wtot/VO2resp) was less for quadriplegic than for normal subjects (1.9 +/- 0.6 vs. 3.5 +/- 1.4%, P less than 0.001), 4) during inhalation, upper and lower rib cages behaved similarly in the two groups, but the quadriplegic subjects had a decrease in transverse rib cage and a much greater increase in abdomen than normal subjects, and 5) functional residual capacity decreased in normal but not in quadriplegic subjects during the breathing tasks. We conclude that the lesser efficiency of breathing in quadriplegia may be related to the elastic work of chest wall distortion, shorter mean operational diaphragm length, and possibly differences between normal and quadriplegic subjects in mechanical advantage of available inspiratory muscles.
Ventilatory and metabolic responses to cold and hypoxia in intact and carotid body-denervated rats
Authors: Gautier H. , Bonora M.
Published: December 2017

The effects of hypoxia on thermoregulation and ventilatory control were studied in conscious rats before and after carotid denervation (CD). Measurements of metabolic rate (VO2), ventilation (V), shivering intensity (SI), and colonic temperature (Tc) were made in groups of eight rats subjected to three protocols. In protocols 1 and 2, at ambient temperature (Ta) of 25 and 5 degrees C, respectively, rats were exposed to normoxia and hypoxia [inspired O2 fraction (FIO2) 0.13–0.11]. In protocol 3, Ta was decreased from 25 to 5 degrees C in 30-min steps of 5 degrees C. Recordings were made in normoxia and hypoxia (FIO2 0.12). The results show that in both intact and CD rats 1) in normoxia, cold exposure increased VO2, V, and SI, and these increases were proportional to the decrease in Ta; 2) hypoxia induced only a transient decrease in SI, and, for a given Ta, VO2 was reduced whereas V and SI were increased; and 3) in CD rats, V increased less during cold exposure in both normoxia and hypoxia; VO2 and Tc were more depressed during hypoxia. It is concluded that 1) the interaction between Ta and FIO2 in the control of V is partly dependent on the carotid body afferents, 2) shivering thermogenesis may be transiently affected by hypoxia independently of the carotid body afferents, and 3) nonshivering thermogenesis may be directly inhibited by hypoxia, especially during cold exposure.
Aerosol bolus dispersion and convective mixing in human and dog lungs and physical models
Authors: Rosenthal F. S. , Blanchard J. D. , Anderson P. J.
Published: December 2017

The dispersion of aerosol boluses in the lung is a probe for convective mixing and has been proposed as a marker for abnormal lung function. To better understand the factors underlying this phenomenon, aerosol dispersion was compared in human subjects, dogs, and various physical models. In all systems, dispersion increased with the volumetric penetration of the aerosol bolus. The rate of this increase was 83% greater in humans compared with dogs. Dispersion in dogs was close to that in a packed bed with beads of 2.5 mm. Aerosol dispersion decreased with increasing flow rate in human subjects. An artificial larynx inserted into the straight tube caused a 33% increase in dispersion. In humans, aerosol dispersion was significantly correlated with forced expired flow between 25 and 75% of vital capacity. A 2-s pause between inspiration and expiration increased dispersion 23–58% in three isolated dog lungs but did not affect dispersion in the packed bed. The data suggest that lung geometry, flow rate, particle mobility, and the larynx all significantly affect aerosol dispersion by influencing the reversibility of aerosol transport between inspiration and expiration.
Mechanical constraints on exercise hyperpnea in endurance athletes
Authors: Johnson B. D. , Saupe K. W. , Dempsey J. A.
Published: December 2017

We determined how close highly trained athletes [n = 8; maximal oxygen consumption (VO2max) = 73 +/- 1 ml.kg-1.min-1] came to their mechanical limits for generating expiratory airflow and inspiratory pleural pressure during maximal short-term exercise. Mechanical limits to expiratory flow were assessed at rest by measuring, over a range of lung volumes, the pleural pressures beyond which no further increases in flow rate are observed (Pmaxe). The capacity to generate inspiratory pressure (Pcapi) was also measured at rest over a range of lung volumes and flow rates. During progressive exercise, tidal pleural pressure-volume loops were measured and plotted relative to Pmaxe and Pcapi at the measured end-expiratory lung volume. During maximal exercise, expiratory flow limitation was reached over 27–76% of tidal volume, peak tidal inspiratory pressure reached an average of 89% of Pcapi, and end-inspiratory lung volume averaged 86% of total lung capacity. Mechanical limits to ventilation (VE) were generally reached coincident with the achievement of VO2max; the greater the ventilatory response, the greater was the degree of mechanical limitation. Mean arterial blood gases measured during maximal exercise showed a moderate hyperventilation (arterial PCO2 = 35.8 Torr, alveolar PO2 = 110 Torr), a widened alveolar-to-arterial gas pressure difference (32 Torr), and variable degrees of hypoxemia (arterial PO2 = 78 Torr, range 65–83 Torr). Increasing the stimulus to breathe during maximal exercise by inducing either hypercapnia (end-tidal PCO2 = 65 Torr) or hypoxemia (saturation = 75%) failed to increase VE, inspiratory pressure, or expiratory pressure. We conclude that during maximal exercise, highly trained individuals often reach the mechanical limits of the lung and respiratory muscle for producing alveolar ventilation. This level of ventilation is achieved at a considerable metabolic cost but with a mechanically optimal pattern of breathing and respiratory muscle recruitment and without sacrifice of a significant alveolar hyperventilation.
ACE inhibition facilitates sodium and water excretion during PEEP in conscious volume-expanded dogs
Authors: Kaczmarczyk G. , Rossaint R. , Altmann C. , Falke K. , Mohnhaupt R. , Reinhardt H. W.
Published: December 2017

Increased activity of the renin-angiotensin system may be involved in sodium and water retention during controlled mechanical ventilation (CMV) with positive end-expiratory pressure (PEEP). We therefore evaluated renal, hemodynamic, and hormonal effects of an acute angiotensin-converting enzyme inhibition (ACEI) during PEEP and extracellular volume expansion in five trained chronically tracheotomized dogs. Three protocols were performed: control, 4 h spontaneous breathing with continuous positive mean airway pressure (Paw) of 4 cmH2O (CPAP 4); CMV 20, CPAP for 1st h, CMV with 20 cmH2O Paw for 2 h (2nd and 3rd h), and 1 h of CPAP (4th h); and CMV20-ACEI, ACEI (Ramipril, 2 mg/kg body wt) followed by the same protocol as in CMV 20. During control, sodium excretion (UNaV) and urine volume (V) increased continuously to 56.2 +/- 2.7 (SE) mumol.min-1.kg body wt-1 and 482 +/- 23 microliters.min-1.kg body wt-1, respectively. UNaV and V increased less during PEEP in CMV 20 and CMV 20-ACEI. However, significantly more sodium and water were retained in CMV 20 than in CMV 20-ACEI (2.3 +/- 0.3 vs. 1.0 +/- 0.3 mmol/kg body wt, and 20 +/- 3 vs. 11 +/- 2 ml/kg body wt) because of a decrease of glomerular filtration rate and fractional UNaV in CMV 20. Heart rate did not change in control, CMV 20, or CMV 20-ACEI. Mean arterial pressure increased during control by 13 mmHg, did not change during CMV 20, and was decreased by 7 mmHg in CMV 20-ACEI.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute hemorrhage in dogs: construction and validation of models to quantify blood loss
Authors: Waisman Y. , Eichacker P. Q. , Banks S. M. , Hoffman W. D. , MacVittie T. J. , Natanson C.
Published: December 2017

We examined the ability of commonly used clinical parameters to quantify acute hemorrhage in dogs. Eight animals were bled 40 ml/kg body wt over 100 min. Ten hemodynamic and 20 blood laboratory parameters were obtained every 10 min to construct, with use of linear regression analysis, models that quantify blood loss. During model construction, the best indicator of quantity of hemorrhage was arterial base deficit [ABD; coefficient of variation (CV) 35%]. This model was more accurate (P < 0.05) than 27 others (CV range 43 to 63%) and similar to systolic (CV 40%) and mean (CV 40%) arterial pressures. In validation studies in 10 additional animals, our best models based on ABD and systolic and mean arterial pressures each unexpectedly showed a significant (P < 0.05) decrease in accuracy (CV 86, 57, and 60%, respectively) attributable to large baseline (before hemorrhage) variability among animals. To eliminate this variability, models based on changes from baseline measurements were investigated. The best predictor of change in blood volume was change in ABD (CV 27%). This model was significantly (P < 0.05) more accurate than any of 27 others (CV range 36 to 65%) and similar to change in venous base deficit and venous pH (each CV 31%). When validated, acid-base models such as ABD, venous pH, and arterial bicarbonate were the best predictors of volume change (CV range 28 to 40%). With the use of multivariate analysis, pairwise combinations of single parameter models (n = 465) improved prediction errors only minimally. In summary, most commonly used hemodynamic and blood indexes could not be validated as accurate measurements in quantifying hemorrhage. In contrast, changes in acid-base parameters were validated as moderately accurate predictors of blood volume changes and therefore may have utility in the assessment of patients with ongoing hemorrhage.
Centrally administered ouabain aggravates central sleep apneas
Authors: Sato T. , Tadokoro M. , Kaba H. , Saito H. , Seto K. , Takatsuji H.
Published: December 2017

The presence of endogenous digitalis-like factors in the central nervous system suggests their functional significance in the central nervous system. Three-day infusions of three-stepped doses of the digitalis agent ouabain (1–100 ng.kg body wt-1.h-1) into the lateral cerebral ventricle of freely moving rats caused a dose-dependent increase in the number of central-apneic episodes during rapid-eye-movement sleep without affecting the time spent in rapid-eye-movement sleep or basic respiratory rate. These results suggest that endogenous digitalis-like factors may be involved in the genesis of central sleep apneas.
Response time, autonomic mediation, and reversibility of hyperoxic bradycardia in conscious dogs
Authors: Lodato R. F. , Jubran A.
Published: December 2017

Normobaric hyperoxia decreases heart rate (HR) in humans and animals. This study explored the mechanisms of hyperoxic bradycardia by examining its response time, autonomic neural mediation, and reversibility in conscious dogs. Five trained mongrel dogs breathed from a mask as the inspired gas was alternated between air and O2 for multiple cycles, and continuous time series records of HR and oxyhemoglobin saturation were recorded on a digital computer and analyzed by the technique of ensemble averaging. Hyperoxia decreased HR by 9% (P < 0.001), but only gradually, requiring 5 min to reach steady state. This delay was much longer than the time required for hyperoxic respiratory depression (10–20 s), a response known to be mediated by chemoreceptor reflexes. The bradycardia was sustained for > or = 30 min. On return to normoxia, HR gradually returned toward, but failed to reach, the baseline HR, suggesting incomplete reversibility of the response. However, in control experiments without hyperoxic challenge, HR showed a slow continuous downward trend that was sufficient to account for the apparent incomplete reversibility of hyperoxic bradycardia. Hyperoxic bradycardia was unaffected by beta-adrenergic blockade but was completely prevented by muscarinic cholinergic blockade. We conclude that 1) hyperoxia-induced bradycardia in conscious dogs is mediated by efferents of the vagus nerve; 2) its afferent pathway remains unknown, but its long response time suggests mechanisms other than chemoreceptor reflexes or other known neural reflexes; and 3) it is completely reversible.
Thyroarytenoid muscle activity in sleep apneas
Authors: Insalaco G. , Kuna S. T. , Catania G. , Marrone O. , Costanza B. M. , Bellia V. , Bonsignore G.
Published: December 2017

In normal subjects the thyroarytenoid muscle (TA), a vocal cord adductor, has phasic expiratory activity during wakefulness that disappears during non-rapid-eye-movement (NREM) sleep. Fiber-optic studies have reported absent or irregular vocal cord movements during obstructive apneas and vocal cord adduction during central apneas. This study was designed to investigate TA activity during NREM sleep in 14 subjects with sleep apnea by means of intramuscular wire electrodes. During central apneas, which were recorded in three subjects, continuous TA activity was observed. During obstructive apneas, which were recorded in all subjects, two different patterns of TA activity were observed: 1) absence of any activity until arousal and 2) phasic activity throughout the apnea. The first pattern was detected in six subjects, whereas both patterns were observed in the remaining eight subjects. No correlation was found between obstructive apnea characteristics and presence or absence of TA activity. In all subjects TA underwent a marked activation during arousal. While nasal continuous positive airway pressure was applied during NREM sleep TA activity was always absent. The persistence of TA activity during central apneas suggests that they may represent an extreme prolongation of neural expiratory discharge. We speculate that a variable interaction of different stimuli acting during obstructive apnea may activate TA, which, in turn, may contribute to glottic narrowing.
Medullary respiratory neuronal activity during augmented breaths in intact unanesthetized cats
Authors: Orem J. , Trotter R. H.
Published: December 2017

In intact unanesthetized cats, we studied the behavior of five medullary respiratory cell types during augmented breaths: 1) decrementing, 2) augmenting, and 3) late-onset inspiratory cells and 4) decrementing and 5) augmenting expiratory cells. Certain features of their behavior were inconsistent with either their proposed role in rhythmogenesis or the proposed nature of augmented breaths. For example, decrementing inspiratory cells switched to an augmenting pattern during the second part of the augmented breath. This behavior is inconsistent with mechanisms proposed to account for their decrementing pattern and with their postulated inhibitory actions on augmenting inspiratory cells, which are intensely active at the same time. In addition, augmenting expiratory cells discharged intensely at the end of inspiration and then throughout expiration, indicating that their discharge profiles (and, therefore, their inhibitory actions) are more labile than previously assumed. The behavior of inspiratory cells gave mixed evidence of the idea that the augmented breath comprises two inspiratory phases: decrementing and late-onset inspiratory cells discharged in two bursts during the inspiratory phase, but other inspiratory cells discharged without interruption throughout it. These results reveal that current theories do not account for the behavior of medullary respiratory cells during augmented breaths.
Does body temperature mediate anxiolytic effects of acute exercise?
Authors: Youngstedt S. D. , Dishman R. K. , Cureton K. J. , Peacock L. J.
Published: December 2017

We tested the thermogenic hypothesis that reductions in blood pressure and self-reported state anxiety and altered brain electrocortical (electroencephalographic, EEG) activity after acute exercise are due to increased body temperature. Eleven fit [cycle peak O2 consumption (VO2peak) = 57 +/- 5.8 ml.kg-1 x min-1] males (26 +/- 5.8 yr) were randomly assigned to four 20-min conditions in a within-subjects counterbalanced design: 1) thermoneutral (32–35 degrees C) or 2) cold (18–23 degrees C) cycling at 70% VO2peak, 3) passive warm water exposure (39–41 degrees C), and 4) quiet rest (60 dB below ambient; 22 +/- 1 degrees C). All exercise testing was conducted in shoulder-deep water. Esophageal temperature increased equally during thermoneutral cycling (+1.45 +/- 0.05 degrees C) and passive heating (+1.51 +/- 0.06 degrees C), was blunted during cold cycling (+0.40 +/- 0.12 degrees C), and was unchanged at rest. Mean radial arterial pressure (MAP), self-reported state anxiety (State-Trait Anxiety Inventory, STAI), and spontaneous occipital (O1 + O2) and photostimulated temporal (T5 + T6) surface EEG activity (10–20 system) in theta (4–8 Hz), alpha (9–13 Hz), and beta (14–40 Hz) frequency bands were assessed 5 min pre- and 10–15 and 20–25 min postcondition and analyzed in 4- (condition) by-3 (time) repeated-measures analysis of variance (P < 0.05). Results showed a condition-by-time interaction for MAP, which decreased from pre- to 15 min postcondition for thermoneutral cycling (81 +/- 2 to 73 +/- 2.7 mmHg) and passive heating (86 +/- 2.5 to 74 +/- 1.4 mmHg) and persisted at 25 min postcondition.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronically instrumented rat model for hemodynamic studies of both pulmonary and systemic circulations
Authors: Sardella G. L. , Ou L. C.
Published: December 2017

We developed a chronic rat preparation in which a flow probe is placed around the ascending aorta and arterial catheters are implanted in the systemic and pulmonary circulations. This preparation was used to continuously monitor cardiac output (CO), systemic arterial pressure (Psa), and pulmonary arterial pressure (Ppa). More than 80% of the instrumented animals appeared healthy and continued to gain weight for longer than 2 wk. Stable CO, Psa, and Ppa were observed throughout this period. The effects of angiotensin II and hypoxia on the systemic and pulmonary circulations were studied, and possible adverse effects on the heart of long-term implantation of the flow probe were examined. This rat model provides a physiological small-animal preparation for short- and long-term hemodynamic and therapeutic studies on both the systemic and pulmonary circulations.
Acute hormonal responses to two different fatiguing heavy-resistance protocols in male athletes
Authors: Hakkinen K. , Pakarinen A.
Published: December 2017

To examine endogenous hormonal responses to heavy-resistance exercise, ten male strength athletes performed two fatiguing but different types of sessions on separate days. In session A the loads for the leg extensor muscles in the squat-lift exercise were maximal so that the subjects performed 20 sets at 1 repetition maximum (RM) (20 x 1 RM x 100%), whereas during session B the loads were submaximal (70%) but the subjects performed each of the 10 sets until the RM (i.e., 10 repetitions/set or 10 x 10 x 70%). The recovery time between the sets was always 3 min. A decrease of 10.3 +/- 4.7% (P < 0.001) occurred in the squat-lift in 1 RM during session A, whereas session B led to a decrease of 24.6 +/- 18.9% (P < 0.001) in 10 RM. Increases in the concentrations of serum total and free testosterone (P < 0.05 and 0.05, respectively), cortisol (P < 0.001), and growth hormone (GH, P < 0.001) were observed during session B, whereas the corresponding changes during session A were statistically insignificant except for the relatively slight increase (P < 0.01) in serum GH level. The significant (P < 0.001) increase in blood lactate concentration during the two sessions correlated significantly (P < 0.01) with the increase in serum GH concentration. The morning values of serum testosterone and free testosterone were significantly (P < 0.05–0.001) lowered on the 1st and 2nd rest days after the sessions.(ABSTRACT TRUNCATED AT 250 WORDS)
Portable electrical stimulator for use in small animals
Authors: Takahashi M. , Rana A. , Hood D. A.
Published: December 2017

The detailed electronic configuration of a lightweight (7 g) battery-operated portable electrical stimulator unit is described. It has proven useful for the study of the effects of chronic stimulation on skeletal muscle in small animals (i.e., the rat). The unit requires wavelengths in the infrared region for activation. This allows for remote triggering of the stimulator and permits it to function reliably even when animals are housed in rooms illuminated by fluorescent lamps. Unique to the system is the inclusion of a visual indicator of unit function (light-emitting diode), thus providing a convenient means of monitoring unit activation. The stimulator unit described has proven to be highly reliable and very useful for the study of alterations in gene expression in muscle subject to chronic use (M. Takahashi and D. A. Hood, J. Appl. Physiol. 74: 934–941, 1993).
Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise
Authors: Kanter M. M. , Nolte L. A. , Holloszy J. O.
Published: December 2017

We studied the effects of ingesting an antioxidant vitamin mixture for 6 wk on breath pentane and serum malondialdehyde (MDA) levels before and after exercise. Twenty young (mean age 25.0 +/- 2.9 yr) healthy males were randomly assigned to either an antioxidant vitamin group (daily doses of 592 mg of alpha-tocopherol equivalents, 1,000 mg of ascorbic acid, and 30 mg of beta-carotene) or a placebo group. Exercise consisted of 30 min of treadmill running at 60% of maximal O2 consumption (VO2max) followed by 5 min of running at a pace that elicited approximately 90% of VO2max. Blood and breath samples were collected immediately after the two exercise bouts. The antioxidant supplement did not prevent the exercise-induced increase in lipid peroxidation, as reflected by the rate of pentane production and the increase in serum MDA concentration. However, ingestion of the antioxidant vitamins did result in significantly lower resting and postexercise levels of expired pentane and serum MDA. We conclude that taking ascorbate, alpha-tocopherol, and beta-carotene in the amounts used in this study serves to lower markers of lipid peroxidation at rest and after exercise but does not prevent the exercise-induced increase in oxidative stress.
How changes in the serial distribution of bronchoconstriction affect lung mechanics
Authors: Robatto F. M. , Simard S. , Ludwig M. S.
Published: December 2017

It is generally accepted that methacholine (MCh) acts predominantly on the central airways and histamine (H) acts on the lung periphery. We hypothesized therefore that lung mechanics would be affected differently by H and MCh aerosols. In 12 anesthetized paralyzed open-chest mongrel dogs, we obtained MCh (0.1–30 mg/ml, n = 6) and H (0.1–30 mg/ml, n = 6) concentration-response curves. The alveolar capsule technique was used to partition lung resistance (RL) into airway (Raw) and tissue (Rti) components. The degree of mechanical heterogeneity across the lung was assessed by computing the coefficient of variation for five alveolar pressures during relaxed expirations. RL increased 823 +/- 202% after H and 992 +/- 219% after MCh. Rti increased 784 +/- 192% after H and 1,014 +/- 279% after MCh. Raw increased 1,098 +/- 297% after H and 1,275 +/- 332% after MCh. Elastance increased 342 +/- 53% after H and 423 +/- 88% after MCh. The coefficient of variation increased 279 +/- 65% after H and 252 +/- 55% after MCh. The patterns of change were similar throughout the H and MCh concentration-response curves. We conclude that H and MCh have comparable effects on lung mechanics and that the degree and pattern of heterogeneity inside the lung after constriction are the same regardless of the agent used. These data support the hypothesis that H and MCh have some similar direct effect on the lung parenchyma. Parenchymal deformation after MCh-induced central airway constriction alone would be unlikely to explain increases in Rti of this magnitude or changes in lung mechanics so similar to those induced by H.
Endogenous production of superoxide by rabbit lungs: effects of hypoxia or metabolic inhibitors
Authors: Paky A. , Michael J. R. , Burke-Wolin T. M. , Wolin M. S. , Gurtner G. H.
Published: December 2017

We find spontaneous light emission from isolated Krebs-Henseleit-perfused rabbit lungs when the light-emitting super-oxide trap lucigenin is added to the perfusate. Lucigenin light emission appears to be specific for superoxide anion, because light emission from the lung caused by a superoxide-generating system is abolished by superoxide dismutase but not by catalase or dimethylthiourea. We also studied the relative sensitivity of lucigenin photoemission to superoxide and to H2O2 in vitro. Lucigenin photoemission is three to four orders of magnitude more sensitive to superoxide than to H2O2 and probably cannot detect H2O2 in concentrations thought to occur in biological systems. Basal lucigenin photoemission by the lung is oxygen dependent, because severe hypoxia completely inhibits light emission. Superoxide dismutase reduces basal photoemission by 50%, and administration of the low-molecular-weight superoxide scavenger 4,5-dihydroxy-1,3-benzene disulfonic acid (tiron) inhibits basal photoemission by approximately 90%. These observations suggest that endogenous superoxide production is primarily intracellular and that approximately half of the superoxide reaches the extracellular space. Superoxide transport may involve anion channels, because the anion channel blocker 4,4′diisothiocyanostilbene2,2′disulfonic acid increases photoemission, suggesting intracellular accumulation of superoxide. A cytochrome P-450 inhibitor, SKF 525A, or the mitochondrial transport inhibitor antimycin decreased basal photoemission by approximately 50%, suggesting that cytochrome P-450-mediated reactions and perhaps mitochondrial function contribute to basal superoxide production in the isolated perfused lung. Endogenous superoxide production may be important in regulation of pulmonary vascular reactivity and may contribute to the pathogenesis of lung reperfusion injury.
Total cerebral blood volume calculated from a model of [99mTc]pertechnetate distribution in the head
Authors: Keyeux A. , Ochrymowicz-Bemelmans D. , Van Eyll C. , Charlier A. A.
Published: December 2017

A method for calculation of the blood volume from the internal carotid and vertebral arteries to the internal jugular veins [total cerebral blood volume (TCBV)] was validated. This was achieved noninvasively in anesthetized rats from the time-activity curve recorded over the head after [99mTc]pertechnetate (Tc) intravenous bolus injection. Tc had the advantage over many other tracers in that it rapidly and evenly distributed in blood cells and plasma. Tc was found to behave in the head according to a two-parallel-compartment model containing a fast cerebral compartment and a slow extracerebral compartment. This model was mathematically described by a sum of two lagged normal density curves (LNDC) that fitted the head curve adequately. Responses of the LNDC parameters to flow and volume variations were first tested on a hydraulic setup. TCBV was calculated from the LNDC parameters of the cerebral fast compartment and the simultaneously determined cardiac output. In normocapnic rats, TCBV amounted to 49 +/- 7 (SD) microliters/g, distributed approximately two-thirds in the extra-parenchymal and one-third in the intraparenchymal cerebral vasculatures.