bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of pulmonary blood flow in postpneumonectomy lung growth
Authors: McBride J. T. , Kirchner K. K. , Russ G. , Finkelstein J.
Published: December 2017

To study the influence of blood flow on postpneumonectomy lung growth, we banded the left caudal lobe pulmonary artery of eight ferrets in such a way that blood flow to the caudal lobe did not increase when the right lung was excised 1 wk later. The fraction of the cardiac output received by the right lung before pneumonectomy was therefore directed entirely to the left cranial lobe. Three weeks after pneumonectomy the weight, volume, and protein and DNA contents of the two lobes of the left lung were measured and compared with those of five unoperated animals and eight animals after right pneumonectomy alone. Although its perfusion did not increase after pneumonectomy, the left caudal lobe of banded animals participated in compensatory growth, increasing in weight and protein and DNA contents. Although the cranial lobe of banded animals received 25% more of the cardiac output than the same lobe in pneumonectomized animals, cranial lobe volume and protein and DNA contents in the two groups were similar. Caudal lobes were smaller in banded than in simple pneumonectomized animals and tended to contain less protein, whereas the cranial lobes tended to be heavier. We conclude that increased pulmonary perfusion is not necessary for compensatory lung growth in adult ferrets, but it may modify this response.
Muscle temperature, contractile speed, and motoneuron firing rates during human voluntary contractions
Authors: Bigland-Ritchie B. , Thomas C. K. , Rice C. L. , Howarth J. V. , Woods J. J.
Published: December 2017

A study was made of motoneuron firing rates and mechanical contractile parameters during maximum voluntary contraction of human hand muscles. A comparison of muscles that had been fatigued after a 60-s maximum voluntary contraction (MVC) with muscles that were cooled by approximately 5 degrees C showed that the contractile properties, in particular the rates of contraction and relaxation, were similarly affected in both conditions. In contrast, the motoneuron firing rate was affected differently by the two treatments. In the case of the fatigued muscles the motoneuron firing rate was reduced by 36%, as was expected from previous studies, but in the case of the cooled muscles, there was no significant change in the motoneuron firing rate. We conclude that the reflex reduction in the motoneuron firing rate seen in the fatigued muscle is not triggered directly by a change in the mechanical properties of the muscle.
13CO2 washout dynamics during intermittent exercise in children and adults
Authors: Zanconato S. , Cooper D. M. , Barstow T. J. , Landaw E.
Published: December 2017

To test the hypothesis that children store less CO2 than adults during exercise, we measured breath 13CO2 washout dynamics after oral bolus of [13C]bicarbonate in nine children [8 +/- 1 (SD) yr, 4 boys] and nine (28 +/- 6 yr, 5 males) adults. Gas exchange [O2 uptake and CO2 production (Vco2)] was measured breath by breath during rest and during light (80% of the anaerobic threshold) intermittent exercise. Breath samples were obtained for subsequent analysis of 13CO2 by isotope ratio mass spectrometry. The tracer estimate of Vco2 was highly correlated to Vco2 measured by gas exchange (r = 0.97, P < 0.0001). The mean residence time was shorter in children (50 +/- 5 min) compared with adults (69 +/- 7 min, P < 0.0001) at rest and during exercise (children, 35 +/- 7 min; adults, 50 +/- 11 min, P < 0.001). The estimate of stored CO2 (using mean Vco2 measured by gas exchange and mean residence time derived from tracer washout) was not statistically different at rest between children (254 +/- 36 ml/kg) and adults (232 +/- 37 ml/kg). During exercise, CO2 stores in the adults (304 +/- 46 ml/kg) were significantly increased over rest (P < 0.001), but there was no increase in children (mean exercise value, 254 +/- 38 ml/kg). These data support the hypothesis that CO2 distribution in response to exercise changes during the growth period.
Inhibitory NANC nerves in human tracheal smooth muscle: a quest for the neurotransmitter
Authors: Belvisi M. G. , Stretton C. D. , Miura M. , Verleden G. M. , Tadjkarimi S. , Yacoub M. H. , Barnes P. J.
Published: December 2017

Inhibitory nonadrenergic noncholinergic (i-NANC) nerves are the only neural bronchodilator pathway in human airways. Possible candidates for the neurotransmitter include vasoactive intestinal peptide (VIP) and nitric oxide (NO) and purines such as ATP. We have investigated the potential role of these neurotransmitters. Phosphoramidon (10(-5) M) significantly potentiated relaxations to low doses of VIP with no effect on i-NANC responses. Relaxations induced by VIp were abolished with alpha-chymotrypsin (2 U/ml), but i-NANC responses were unaffected. Reactive blue 2 had no effect on i-NANC neural responses, indicating that endogenous ATP was not involved. The NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 10(-4) M) produced a concentration-dependent inhibition of the i-NANC response, producing almost complete inhibition at every frequency studied (0.5–40 Hz), whereas L-NG-monomethyl arginine was effective only at low stimulation frequencies. The inhibitory effect of L-NAME was partially reversed by L- but not D-arginine, and D-NAME was without effect. These results suggest that in human tracheal segments the neural bronchodilator response is mediated by NO, and there is no functional evidence for implicating VIP in this response.
Effects of varied air velocity on sweating and evaporative rates during exercise
Authors: Adams W. C. , Mack G. W. , Langhans G. W. , Nadel E. R.
Published: December 2017

This study was designed to determine the extent to which changes in the evaporative power of the environment (Emax) affect sweating and evaporative rates. Six male subjects undertook four 60-min bouts of cycle ergometer exercise at 56% maximal O2 uptake (VO2max).Emax was varied by differences in ambient temperature and airflow; two exercise bouts took place at 24 degrees C and two at 35 degrees C, with air velocity at < 0.2 and 3.0 m/s in both. Total sweat production was estimated from body weight loss, whereas whole body evaporative rate was measured continuously from a Potter beam balance. Body core temperature was measured continuously from a thermocouple in the esophagus (T(es)), with mean skin temperature (Tsk) computed each minute from thermocouples at eight sites. Total body sweat loss was significantly greater (P < 0.05) in the 0.2- than in the 3.0-m/s condition at both 24 and 35 degrees C. Tsk was higher (P < 0.05) in the still-air conditions at both temperatures, but final T(es) was significantly higher (P < 0.05) in still air only in the 35 degrees C environment. Thus the reduced Emax in still air caused a greater heat storage, thereby stimulating a greater total sweat loss. However, in part because of reduced skin wettedness, the slope of the sweat rate-to-T(es) relation at 35 degrees C in the 3.0-m/s condition was 118% that at 0.2 m/s (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Dynamic response of the isolated passive rat diaphragm strip
Authors: Navajas D. , Mijailovich S. , Glass G. M. , Stamenovic D. , Fredberg J. J.
Published: December 2017

To further our understanding of the mechanisms underlying chest wall mechanics, we investigated the dynamic response of the isolated passive rat diaphragm strip. Stress adaptation of the tissue was measured from 0.05 to 60 s after subjecting the strips to strain steps of normalized strain amplitudes from 0.005 to 0.04. The tissue resistance (R), elastance (E), and hysteresivity (eta) were measured in the same range of amplitudes by sinusoidally straining the strip at frequencies from 0.03125 to 10 Hz. The stress (T) depended exponentially on the strain (epsilon) and relaxed and recovered linearly with the logarithm of time. E increased linearly with the logarithm of frequency and decreased with increasing amplitude. R fell hyperbolically with frequency and showed an amplitude dependence similar to that of E. To interpret the strong nonlinear behavior, we extended the viscoelastic model of Hildebrandt (J. Appl. Physiol. 28: 365–372, 1970) to include an exponential stress-strain relationship. Accordingly, the step response was described by T - Tr = Tr(e alpha delta epsilon - 1)(1 - gamma log t), where delta epsilon is the strain amplitude, Tr is the initial operating stress, alpha is a measure of the stress-strain nonlinearity, and gamma is the rate of stress adaptation. The oscillatory response of the model was computed by applying Fung's quasi-linear viscoelastic theory. This quasi-linear viscoelastic model fitted the step and oscillatory data fairly well but only if alpha depended negatively on delta epsilon, as might be expected in a plastic material.
Energetics of walking and running: insights from simulated reduced-gravity experiments
Authors: Farley C. T. , McMahon T. A.
Published: December 2017

On Earth, a person uses about one-half as much energy to walk a mile as to run a mile. On another planet with lower gravity, would walking still be more economical than running? When people carry weights while they walk or run, energetic cost increases in proportion to the added load. It would seem to follow that if gravity were reduced, energetic cost would decrease in proportion to body weight in both gaits. However, we find that under simulated reduced gravity, the rate of energy consumption decreases in proportion to body weight during running but not during walking. When gravity is reduced by 75%, the rate of energy consumption is reduced by 72% during running but only by 33% during walking. Because reducing gravity decreases the energetic cost much more for running than for walking, walking is not the cheapest way to travel a mile at low levels of gravity. These results suggest that the link between the mechanics of locomotion and energetic cost is fundamentally different for walking and for running.
Abdominal muscle activation by respiratory stimuli in conscious dogs
Authors: Yasuma F. , Kimoff R. J. , Kozar L. F. , England S. J. , Bradley T. D. , Phillipson E. A.
Published: December 2017

The responses of the diaphragm, external oblique, and transversus abdominis muscles to hyperoxic hypercapnia and isocapnic hypoxia were studied in four awake dogs to test the hypothesis that central and peripheral chemoreceptor inputs result in different patterns of respiratory muscle activation. The dogs were trained to lie quietly in place, and electromyographic (EMG) discharges of the diaphragm (EMGdi), external oblique (EMGeo), and transversus abdominis (EMGta) were recorded from chronically implanted electrodes. Both hypercapnia and hypoxia recruited EMGeo and EMGta activity, but at comparable levels of minute volume of ventilation the EMG activity of the abdominal muscles was greater during hypercapnia than during hypoxia. However the two chemical stimuli also resulted in different tidal volume (VT) and respiratory frequency responses at any given minute volume of ventilation. When EMG activity was reanalyzed as a function of VT, EMGeo and EMGta were the same for a given VT whether induced by hypercapnia or hypoxia, but EMGdi was consistently greater during hypoxia than during hypercapnia. When the vagus nerves were blocked by cooling exteriorized cervical vagal loops, all abdominal muscle EMG activity was abolished. The findings support the concept that stimulation of the central and peripheral chemoreceptors results in asymmetric activation of the inspiratory and expiratory respiratory muscles. The findings also indicate that afferent vagal stimuli play an important facilitatory role in activation of the abdominal expiratory muscles.
Pulmonary impedance and right ventricular-vascular coupling during coronary angioplasty
Authors: Kussmaul W. G. , Wieland J. , Altschuler J. , Laskey W. K.
Published: December 2017

Right ventricular ejection may be modified by alterations in pulmonary vascular properties during acute pulmonary hypertension. Pulmonary artery impedance and reflection properties were analyzed during coronary angioplasty in nine patients with single-vessel disease involving the left anterior descending artery by use of high-fidelity catheter recordings of pulmonary pressure and flow made before angioplasty balloon inflation and at peak ischemia. Acute pulmonary hypertension in this resting model resulted in a significant decrease in pulmonary vascular resistance (142 +/- 54 to 92 +/- 64 dyn.s.cm-5, P < 0.05), increase in low-frequency impedance (67 +/- 36 to 101 +/- 43 dyn.s.cm-5, P < 0.05), and no change in high-frequency (characteristic) impedance (38 +/- 14 to 41 +/- 13 dyn.s.cm-5). Pulmonary wave reflection amplitudes were increased, and the amount of hydraulic power expended per unit of net forward flow significantly increased (3.1 +/- 0.7 to 4.3 +/- 0.7 mW.ml-1.s-1, P < 0.001). These findings indicate that, during acute pulmonary hypertension in humans, 1) recruitment of additional resistance vessels can occur, 2) pulsatile pulmonary artery properties are significantly altered, and 3) right ventricular power output requirements are increased. Because episodic pulmonary hypertension occurs frequently in coronary artery disease, these changes may help explain eventual right ventricular hypertrophy or failure.
Thromboxane contributes to pulmonary hypertension in ischemia-reperfusion lung injury
Authors: Zamora C. A. , Baron D. A. , Heffner J. E.
Published: December 2017

Exposure of isolated perfused rabbit lungs (IPL) to ischemia-reperfusion causes a transient increase in pulmonary arterial (PA) pressure at the onset of reperfusion. Because thromboxane A2 (TxA2) is a potent vasoconstrictor, we hypothesized that it may contribute to the ischemia-reperfusion-induced pressor response. To evaluate this hypothesis, we exposed IPL perfused with a cell-free solution to 40 min of warm ischemia followed by reperfusion and measured perfusate immunoreactive thromboxane B2 (iTxB2) and 6-ketoprostaglandin F1 alpha (i6-keto-PGF1 alpha). We observed that ischemia-reperfusion IPL compared with controls had an increase in PA pressure (40.2 +/- 4.8 vs. 9.3 +/- 0.3 mmHg, P < 0.05), lung edema (29.3 +/- 6.3 vs. -0.2 +/- 0.2 g, P < 0.05), iTxB2 perfusate levels (155 +/- 22 vs. < 50 pg/ml, P < 0.05), and i6-keto-PGF1 alpha (436 +/- 33 vs. 61 +/- 16 pg/ml, P < 0.05). In ischemia-reperfusion IPL, infusion of SQ 29548 (10(-6) M), a specific TxA2/prostaglandin H2 receptor antagonist, attenuated the PA pressor response and the degree of edema. We conclude that pulmonary hypertension associated with ischemia-reperfusion results in part from pulmonary release of TxA2. Furthermore, TxA2 directly through membrane effects or indirectly through hydrostatic mechanisms increases the severity of ischemia-reperfusion-induced lung edema.
Acute effect of cigarette smoke on breathing is attenuated by chronic smoking in rats
Authors: Swanny A. , Morton R. F. , Lee L. Y.
Published: December 2017

To determine whether the irritant effect of cigarette smoke on breathing was affected by chronic exposure to smoke, two groups of sixteen young male Sprague-Dawley rats were exposed daily to fresh cigarette smoke (treated group) or air (control group) for 4–8 wk. Acute ventilatory response to cigarette smoke (50% concn, 6 ml volume) inhaled via a tracheal cannula was then studied under anesthesia and compared between the two groups. Inhalation of either cigarette smoke or gas phase smoke induced an immediate and transient apnea or bradypnea that was completely abolished by bilateral vagotomy in both groups, suggesting the involvement of vagal bronchopulmonary afferents. However, the apneic response was markedly attenuated in the treated group. Inhalation of cigarette smoke, but not the gas phase smoke, also induced a delayed tachypneic response after the initial apnea. The tachypneic response was again significantly smaller in treated rats, and this difference between the two groups was eliminated after vagotomy. On the basis of these results, we suggest that a reduced stimulatory effect on vagal bronchopulmonary sensory receptors was responsible for the attenuated ventilatory responses to smoke observed in treated rats.
Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice
Authors: MacNeil B. , Hoffman-Goetz L.
Published: December 2017

This study investigated the influence of 9 wk of chronic exercise on natural cytotoxicity in male C3H mice. Both in vivo cytotoxicity (pulmonary vasculature) and in vitro cytotoxicity (spleen) were determined for voluntary (wheel running; n = 30) and forced (treadmill running, 15 m/min, 30 min/day; n = 30) exercise protocols. A sedentary control group (n = 30) and a treadmill control group (5 m/min, 5 min/day; n = 30) were also included. After 9 wk of chronic exercise, submaximal exercise O2 uptake was reduced in the wheel-running group relative to that in sedentary or treadmill-trained mice. Maximal citrate synthase activity of soleus muscle was higher in treadmill-trained group compared with that in sedentary or wheel-running mice. Chronic exercise consistently reduced percent retention of CIRAS 3 tumor cells in the lungs of treadmill- (15.3 +/- 1.4) and wheel- (17.9 +/- 1.4) trained mice below that of sedentary (29.5 +/- 2.7) and treadmill control (25.8 +/- 1.8) groups (P < 0.001). Injection of anti-asialo GM1 (ASGM1) antibody increased tumor cell retention in the lungs for all groups but did not alter the differences between activity conditions. In vitro cytotoxicity was enhanced in treadmill- and wheel-trained mice relative to that in sedentary controls but was not elevated in the treadmill control group. Anti-ASGM1 injection eliminated in vitro cytotoxicity for all groups. Chronic exercise slightly increased the frequency of ASGM1-positive splenocytes in treadmill-trained mice only. These results indicate that chronic exercise enhances natural cytotoxic mechanisms in vivo and in vitro and that this enhancement is present for both forced and voluntary exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of respiration on heart rate and blood pressure fluctuations
Authors: Novak V. , Novak P. , de Champlain J. , Le Blanc A. R. , Martin R. , Nadeau R.
Published: December 2017

The dynamics of the respiratory and cardiovascular systems were studied by continuously slowing respiration from 0.46 to 0.05 Hz. The time-frequency distribution and global spectral analysis were used to assess the R-R interval (R-R) and the systolic and diastolic blood pressure fluctuations in 16 healthy subjects. During rest, the nonrespiratory-to-respiratory frequency ratios were not affected by occasional slow breathing, whereas the low- (0.01–0.15 Hz) to high- (0.15–0.3 Hz) frequency indexes for blood pressure were increased (P < 0.05). The respiratory fluctuations in R-R and the systolic and diastolic pressures were paced over the 0.46- to 0.05-Hz range. As respiration slowed to 0.07–0.09 Hz, the frequency content of the respiration and cardiovascular variables increased sharply and nonlinearly to a maximum that exceeded values at higher frequencies (P < 0.001). The nonrespiratory frequency content remained stable in the 0.01- to 0.05-Hz range and did not significantly differ from that at rest. In contrast, the nonstable 0.05- to 0.1-Hz component was suppressed. A slow 0.012- to 0.017-Hz rhythm modulated respiration and hemodynamic fluctuations at both respiratory and nonrespiratory frequencies. The study indicated that respiration input should be considered in the interpretation of global spectra. Furthermore the time-frequency distributions demonstrated that a close nonlinear coupling exists between the respiratory and cardiovascular systems.
Autonomic control of heart rate during physical exercise and fractal dimension of heart rate variability
Authors: Nakamura Y. , Yamamoto Y. , Muraoka I.
Published: December 2017

The objectives of the present study were to investigate autonomic nervous system influence on heart rate during physical exercise and to examine the relationship between the fractal component in heart rate variability (HRV) and the system's response. Ten subjects performed incremental exercise on a cycle ergometer, consisting of a 5-min warm-up period followed by a ramp protocol, with work rate increasing at a rate of 2.0 W/min until exhaustion. During exercise, alveolar gas exchange, plasma norepinephrine (NE) and epinephrine (E) responses, and beat-to-beat HRV were monitored. HRV data were analyzed by "coarse-graining spectral analysis" (Y. Yamamoto and R. L. Hughson. J. Appl. Physiol. 71: 1143–1150, 1991) to break down their total power (Pt) into harmonic and nonharmonic (fractal) components. The harmonic component was further divided into low-frequency (0.0–0.15 Hz) and high-frequency (0.15–0.8 Hz) components, from which low-frequency and high-frequency power (Pl and Ph, respectively) were calculated. Parasympathetic (PNS) and sympathetic (SNS) nervous system activity indicators were evaluated by Ph/Pt and Pl/Ph, respectively. From the fractal component, the fractal dimension (DF) and the spectral exponent (beta) were calculated. The PNS indicator decreased significantly (P < 0.05) when exercise intensity exceeded 50% of peak oxygen uptake (VO2 peak). Conversely, the SNS indicator initially increased at 50–60% VO2peak (P < 0.05) and further increased significantly (P < 0.05) at > 60% VO2peak when there were also more pronounced increases in NE and E.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct measurement of capillary blood pressure in the human lip
Authors: Parazynski S. E. , Tucker B. J. , Aratow M. , Crenshaw A. , Hargens A. R.
Published: December 2017

In this study, we developed and tested a new procedure for measuring microcirculatory blood pressures above heart level in humans. Capillary and postcapillary venule blood pressures were measured directly in 13 human subjects by use of the servo-nulling micropressure technique adapted for micropuncture of lip capillaries. Pressure waveforms were recorded in 40 separate capillary vessels and 14 separate postcapillary venules over periods ranging from 5 to 64 s. Localization and determination of capillary and postcapillary vessels were ascertained anatomically before pressure measurements. Capillary pressure was 33.2 +/- 1.5 (SE) mmHg in lips of subjects seated upright. Repeated micropunctures of the same vessel gave an average coefficient of variation of 0.072. Postcapillary venule pressure was 18.9 +/- 1.6 mmHg. This procedure produces a direct and reproducible means of measuring microvascular blood pressures in a vascular bed above heart level in humans.
Impact of frequency range and input impedance on airway-tissue separation implied from transfer impedance
Authors: Lutchen K. R. , Everett J. R. , Jackson A. C.
Published: December 2017

In humans, application of the DuBois (DuBois et al. J. Appl. Physiol. 8: 587–594, 1956) six-element model to respiratory transfer impedance (Ztr) data has been proposed as a means to noninvasively estimate airway and tissue properties. This approach requires prior knowledge of alveolar gas compressibility (Cg). With input impedance (Zin), prior knowledge of Cg is not required, but the data do not support a reliable separation of airway from tissue properties. In this study, we investigated the separation of airway and tissue properties when Ztr and Zin data are measured and analyzed simultaneously over a larger frequency range than usual. In 10 healthy adults, we measured Ztr and Zin from 2 to 64 Hz. Zin was measured using both the standard approach with oscillations directly into the airway opening (Zst) and the head generator approach (Zhg) with oscillations applied around the head. With Ztr data alone, we found that the airway resistance and inertance estimates were reliable with only 2- to 32-Hz data and were unaffected by including the additional 32- to 64-Hz data. Conversely, the estimates of tissue resistance and inertance were highly unreliable unless the 32- to 64-Hz data are included. Because of enhanced sensitivity of Ztr to Cg from 32 to 64 Hz, inaccuracies in the assigned Cg will distort the estimated tissue but not airway properties. The Ztr-based parameters predicted Zhg data far better than Zst data, which is consistent with Zhg data being less influenced by upper airway shunting over this frequency range. There was no apparent advantage to combining Ztr and Zhg data during parameter estimation. With Cg unfixed, the estimated Cg was 50–100% higher than expected from an independent measurement of functional residual capacity. These results confirm that Ztr alone can provide a reliable distinction of lumped respiratory airway and tissue properties that are little influenced by upper airway wall shunting but only if 2- to 64-Hz data are analyzed. This distinction, however, requires an accurate prior measurement of Cg, and this requirement cannot be removed by combining Ztr and Zin data.
Effects of long-term continuous respiratory resistive loading on rat diaphragm function and structure
Authors: Prezant D. J. , Aldrich T. K. , Richner B. , Gentry E. I. , Valentine D. E. , Nagashima H. , Cahill J.
Published: December 2017

The effects of long-term (24- to 28-wk) continuous respiratory resistive loading on diaphragm mass, contractility, fatigue, and fiber types were studied in male rats. Increased respiratory resistance was produced by extratracheal banding, and results were compared with sham-operated pair-fed controls. At the time the animals were killed, banded tracheal segment internal diameter was reduced by 57% of control values. Diaphragm surface area and muscle mass (normalized for body mass) increased by 19% of control values. Isometric diaphragm contractility and fatigue resistance indexes were measured using an in vitro diaphragm costal strip preparation at 37 degrees C. Twitch and tetanic stimulations were evoked using direct stimulation. Compared with controls, baseline tensions (normalized for diaphragm cross-sectional area) were significantly decreased at low frequencies. Fatigue resistance (endurance) indexes were significantly increased at all frequencies. These findings were consistent with observed increases in number and cross-sectional area of type I (low-tension high-endurance) fibers. We conclude that the diaphragm adapts to chronic long-term resistive loads by sacrificing peak tensions for an increase in endurance capacity.
Site and mechanical conditions for failure of skeletal muscle in experimental strain injuries
Authors: Tidball J. G. , Salem G. , Zernicke R.
Published: December 2017

Failure in muscle strain injuries has been reported to occur within the muscle belly, at the myotendinous junction, or within muscle near the myotendinous junction. The goal of this investigation was to determine by electron-microscopic examination the site of lesion in whole muscle strained to failure. In addition, site and conditions for failure of stimulated and unstimulated muscle were compared. Frog semitendinosus myotendinous units with intact tendon-bone junctions were strained at physiological strain rates to failure. All failures occurred at or near the proximal myotendinous junction in both stimulated and unstimulated muscle. Stimulated muscle required approximately 30% more force and approximately 110% more energy to reach failure. Electron-microscopic examination of longitudinal sections of small bundles of fibers showed that unstimulated muscle failed within the muscle near the myotendinous junction. Failure occurred in a single transverse plane of each cell within Z disks. Other Z disks near the failure site displayed strains of several hundred percent. Stimulated muscle failed within the lamina lucida at the myotendinous junction in most fibers. No Z-disk strain was observed in those fibers. We conclude that the site of failure in muscle strain injuries varies with the state of activation of the cell at the time of injury. Furthermore, the data show that the breaking strength of the Z disk varied with muscle stimulation and indicate the existence of two load-bearing systems in parallel within Z disks.
Tissue resistance and the contractile state of lung parenchyma
Authors: Fredberg J. J. , Bunk D. , Ingenito E. , Shore S. A.
Published: December 2017

When challenged with a contractile agonist in increasing graded concentrations, lung parenchymal tissue assumes a sequence of mechanical states. That sequence is mapped here. Isolated lung parenchymal strips from male Hartley guinea pigs were mounted in a bath containing Krebs solution at 37 degrees C, aerated with 95% O2–5% CO2. One end was attached to a force transducer and the other to a servo-controlled lever arm. After stress adaptation, sinusoidal length oscillations (1% strain at 0.31 Hz) yielded force-length loops from which we computed induced changes in active tension (F), tissue stiffness (E), and hysteresivity (eta) (J. J. Fredberg and D. Stamenovic. J. Appl. Physiol. 67:2408–2419, 1989). Changes of tissue resistance (R) were, by definition, governed by those of eta and E. Histamine (10(-6) -10(-3) M), prostaglandin D2 (10(-5) -10(-4) M), and prostaglandin F2 alpha (10(-5) -10(-4) M) caused dose-related increases of F, eta, and E. Plotting induced changes of E vs. those of F revealed a unique relationship that was identical for these as well as a wider panel of contractile agonists; changes of E and F were closely associated. However, plotting induced changes of E vs. those of eta revealed relationships that differed distinctly between agonists; changes of eta were dissociated from those of F and E. This latter observation demonstrated the existence of distinct mechanical states that differed according to the specific agonist by which the tissue was stimulated. In producing agonist-induced changes in R, changes of E were of equal or greater importance compared with those of eta. We conclude that guinea pig lung parenchyma, viewed as an integrated physiological tissue system, exhibits different kinds as well as varying intensities of mechanical response according to the specific agonist present in the cellular microenvironment. These differences in contractile state reveal themselves principally in the hysteretic nature of the tissue.
Adenosine prevents PMA-induced lung injury via an A2 receptor mechanism
Authors: Adkins W. K. , Barnard J. W. , Moore T. M. , Allison R. C. , Prasad V. R. , Taylor A. E.
Published: December 2017

Previous studies indicate that adenosine attenuates phorbol myristate acetate-(PMA) induced canine lung injury, but the mechanism has not been explained. To evaluate adenosine's protective mechanism, isolated and blood-perfused dog lungs were challenged by PMA (50 micrograms) under control conditions and after both pre- and post-treatment with adenosine and pretreatment with 2-chloro-N6-cyclopentyladenosine (CCPA), 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS 21680C), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; PD-116948), or isoproterenol. Injury was assessed by measurement of the capillary filtration coefficient (Kf,c), and pulmonary vascular resistance was measured. PMA increased the Kf,c (0.170 +/- 0.015 to 1.030 +/- 0.167 ml.min-1.cmH2O-1.100 g lung wet wt-1) and the total pulmonary vascular resistance (18.2 +/- 3.8 to 110.2 +/- 60.8 cmH2O.l-1.min.100 g lung wet wt). Pretreatment with adenosine, A2 agonist, A1 antagonist, and isoproterenol blocked the increase in Kf,c induced by PMA. These agents also slightly attenuated the resistance increase induced by PMA, with the exception of the A1 antagonist, which completely prevented the resistance increase (24.3 +/- 7.8 to 23.4 +/- 8.1 cmH2O.l-1.min.100 g lung wet wt). The A1 agonist also slightly attenuated the increase in Kf,c (0.174 +/- 0.022 to 0.486 +/- 0.128 ml.min-1.cmH2O-1.100 g lung wet wt-1) and did not affect the resistance increase. Posttreatment with adenosine did not significantly affect the changes induced by PMA. These data show that PMA-induced increases in capillary permeability in the isolated blood-perfused dog lung can be blocked by pretreatment with adenosine, which binds the adenosine A2 receptors.
31P-NMR spectroscopy of isolated perfused rat lung
Authors: Hayashi Y. , Inubushi T. , Nioka S. , Forster R. E.
Published: December 2017

We obtained 202.5-MHz 31P-nuclear magnetic resonance (NMR) spectra of isolated perfused rat lungs, degassed and inflated, and of lung extract. The spectra included those of ATP, ADP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters, phosphodiesters, and a broad component due to the membrane phospholipids. The line width at one-half peak height for beta-ATP was 1.0 ppm for the degassed lung and 1.2 ppm for the inflated lung. This suggests that the air-water interfaces in inflated lung, which produce proton NMR line broadening, do not act prominently in 31P-NMR spectroscopy. In a degassed lung, when perfusion was stopped for up to 30 min, PCr and ATP peaks decreased progressively with time while Pi and phosphomonoester peaks increased. On return of flow, these changes reversed. The intracellular pH values calculated from the difference in magnetic field between PCr and Pi peaks of inflated and degassed lungs were 7.16 +/- 0.10 (SD; n = 4) and 6.99 +/- 0.10 (n = 4), respectively. The change of intracellular pH caused by 30 min of ischemia was -0.2 pH units. Our findings indicate that air-water interfaces should not broaden lung 31P peaks in vivo.
Aortic baroreflex control of heart rate during hypertensive stimuli: effect of fitness
Authors: Shi X. , Andresen J. M. , Potts J. T. , Foresman B. H. , Stern S. A. , Raven P. B.
Published: December 2017

We examined the aortic baroreflex control of heart rate (HR) in seven healthy young men of average fitness (AF) and seven of high fitness (HF). The fitness level was determined by maximal oxygen uptake (AF = 42.9 +/- 1.1, HF = 62.3 +/- 1.8 ml.kg-1.min-1). Aortic baroreflex control of HR was determined during a steady-state increase of mean arterial pressure (MAP; AF, +15.0 +/- 2.1 and HF, +18.3 +/- 0.8 mmHg) with phenylephrine (PE) infusion combined with positive neck pressure (NP; AF, 18 +/- 2.0 and HF, 20 +/- 0.8 mmHg) to counteract the increased carotid sinus pressure and with low levels of lower body negative pressure to counteract the increased central venous pressure. There was no group difference in the increased MAP or NP, nor was there stage difference in MAP within either group during PE infusion. However, the isolated cardiac-aortic baroreflex gains (i.e., delta HR/delta MAP) were significantly less in the HF (0.16 +/- 0.02 and 0.14 +/- 0.03 beats.min-1.mmHg-1) than in the AF (0.52 +/- 0.08 and 0.59 +/- 0.07 beats.min-1.mmHg-1) subjects at PE + NP and PE + NP + lower body negative pressure. We concluded that during steady-state increases in MAP, the sensitivity of aortic baroreflex control of HR was significantly less in the HF than in the AF subjects.
Airway smooth muscle shortening in excised canine lung lobes
Authors: Okazawa M. , Bai T. R. , Wiggs B. R. , Pare P. D.
Published: December 2017

To estimate the importance of lung parenchymal airway interdependence in attenuating airway narrowing, airway smooth muscle shortening in response to nebulized carbachol was measured in excised canine lung lobes and compared with the calculated load applied by lung elastic recoil. Pulmonary resistance of matched right and left upper lobes of five dogs was measured in a pressure-compensated volume plethysmograph by forced oscillation (6 Hz) before and after administration of an aerosol of carbachol (250 mg/ml) or saline. Matched lobes were studied at transpulmonary pressures (PL) of 5, 7, 10, 12, and 15 cmH2O. The lungs were then fixed at that PL by pulmonary arterial perfusion with formaldehyde, and cross sections of multiple airways from each lobe (n = 275) were examined by use of morphometric techniques to measure luminal area and smooth muscle length. By use of the saline lobe as a control, percentage of muscle shortening and decrease in airway lumen area caused by carbachol could be calculated. Passive and active smooth muscle stresses in each airway were calculated from PL and the calculated change in peribronchial pressure for a given change in airway diameter. The increase in pulmonary resistance and average smooth muscle shortening after administration of carbachol was greater in lobes held at lower PL. There was marked variation in narrowing between airways within a lobe: smooth muscle shortening ranged between 0 and 65% but averaged < 45% at all levels of PL.(ABSTRACT TRUNCATED AT 250 WORDS)
PDC activity and acetyl group accumulation in skeletal muscle during isometric contraction
Authors: Constantin-Teodosiu D. , Cederblad G. , Hultman E.
Published: December 2017

The activity of pyruvate dehydrogenase complex (PDC) was studied in the human quadriceps femoris muscle during isometric contraction induced by intermittent electrical stimulation at 20 Hz. Muscle biopsy samples were obtained at rest and after 10, 20, and 46 contractions. The active form of PDC (PDCa) increased from a mean value of 26% of the total PDC at rest to mean values of 46, 78, and 80%, respectively. Muscle biopsy samples were also obtained at rest, after 46 contractions with limb blood flow intact or occluded, and after 2 min of oxidative recovery. In another experiment, muscle biopsy samples were obtained at rest, after 10 min of resting ischemia, and after 46 contractions with limb blood flow occluded. The transformation of PDC to PDCa was nearly complete, regardless of whether the blood flow was intact or occluded. However, the accumulation of acetyl groups observed during stimulation with intact blood flow was abolished when the blood flow was occluded. The absence of NADH oxidation during anoxia had no effect on the contraction-induced transformation of PDC to PDCa, but it inhibited the flux through the enzyme reaction.
Effects of eccentric and concentric exercise on muscle glycogen replenishment
Authors: Doyle J. A. , Sherman W. M. , Strauss R. L.
Published: December 2017

Eccentric contractions appear to reduce muscle glycogen replenishment during the 1- to 10-day period after exercise. The main purpose of this study was to determine whether consuming a large amount of carbohydrate (1.6 g.kg-1.h-1) during the 4 h after glycogen-reducing exercise would produce different patterns of glycogen replenishment in human muscle that had undergone either eccentric or concentric contractions approximately 2 or 48 h earlier. Subjects cycled for 75 min and undertook interval exercise to deplete glycogen on days 1 and 3. After cycling exercise on day 1 only, subjects performed 10 sets of 10 repetitions of either concentric or eccentric contractions in opposite legs. During the 4 h after exercise, subjects consumed 0.4 g carbohydrate/kg body wt every 15 min. Biopsies were obtained immediately before the feedings and 4 h later, and blood was sampled every 15 min. For days 1 and 3 combined, total integrated areas for the glucose and insulin response curves averaged 1,683 mumol.ml-1.240 min-1 and 21,450 microU.ml-1.240 min-1, respectively. For days 1 and 3 combined, muscle glycogen replenishment after concentric exercise averaged 10 mmol.kg-1.h-1. On day 1 glycogen replenishment was similar for subjects performing either concentric or eccentric contractions. On day 3, however, glycogen replenishment was 25% lower (P < 0.05) in muscle that had undertaken eccentric contractions 48 h earlier than in concentrically exercised muscle. In conclusion, glycogen replenishment can be stimulated to a high rate when a large amount of carbohydrate is consumed after glycogen-depleting concentric exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Leukocyte CD18 monoclonal antibody worsens endotoxemia and cardiovascular injury in canines with septic shock
Authors: Eichacker P. Q. , Hoffman W. D. , Farese A. , Danner R. L. , Suffredini A. F. , Waisman Y. , Banks S. M. , Mouginis T. , Wilson L. , Rothlein R. , et al.
Published: December 2017

We investigated the effects of a murine monoclonal antibody directed against the canine leukocyte CD11/18 adhesion complex (MAb R15.7) in a canine model of septic shock. Awake 2-yr-old purpose-bred beagles were studied 7 days before and 1, 2, 4, and 10 days after intraperitoneal placement of an Escherichia coli-infected fibrin clot. Starting 12 h before clot placement, animals received 0.5–1 mg/kg iv every 12 h (4 doses total) of either MAb R15.7 (MAb group, n = 8) or, as controls, murine serum protein (n = 8). After infected clot placement, all animals received antibiotic (ceftriaxne, 100 mg.kg-1.day-1 for 4 days). Two of eight control animals and four of eight MAb animals died (P = 0.4). During the first 8 h after clot placement, MAb animals, compared with control animals, had greater (P < 0.06) increases in serum endotoxin levels and higher (P < 0.05) neutrophil counts. Day 1 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) central venous pressure and arterial pH and increased (P < 0.05) arterial lactate. Day 2 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) cardiac index and mean arterial pressure. In summary, MAb R15.7, although associated with increased neutrophil counts, worsened serum endotoxemia, acidosis, and cardiovascular function in this canine model of septic shock. These data suggest that in septic shock, antibody directed against this leukocyte membrane protein complex may be harmful, possibly via impairment of normal leukocyte function.
Capillary filtration coefficients using laser densitometry and gravimetry in isolated dog lungs
Authors: Parker J. C. , Prasad R. , Allison R. A. , Wojchiechowski W. V. , Martin S. L.
Published: December 2017

We compared pulmonary capillary filtration coefficients (Kf,c) using measurements of transcapillary filtration rates based on laser densitometry of perfusate hematocrit changes (Jy,l) and gravimetric measurement of the rate of lobe weight gain (delta Wt/delta t) after an increase in capillary pressure (Pc) in isolated autologous blood-perfused dog lungs. Although the lobe weight increased at a rate that decreased with time, the densitometric filtration rate was relatively constant over time. Kf,c values were calculated in milliliters per minute per centimeter water per 100 g from filtration rates obtained by 1) extrapolation of the delta Wt/delta t from 3 to 10 min back to time 0 [Kf,c(0)], 2) use of the slope of the line fitted to the delta Wt/delta t and Jv,l values obtained after three stepwise increases in Pc [Kf,c(slope)], and 3) use of delta Wt/delta t and Jv,l values obtained 10, 20, and 30 min after either a constant 30-min or three 10-min stepwise increases in Pc [Kf,c(t)]. The mean Kf,c(0) values ranged from 0.171 +/- 0.024 to 0.188 +/- 0.070 and were not significantly different between vascular pressure states. These Kf,c(0) values were significantly higher than all gravimetric or densitometric Kf,c(t) or Kf,c(slope) values that ranged from 0.037 to 0.100. Kf,c(t) values were not statistically different from each other by use of either method, but the gravimetric Kf,c(slope) was significantly higher than the densitometric value. Therefore, extrapolated Kf,c(0) probably overestimates endothelial barrier Kf,c because of persistent vascular stress relaxation after a vascular pressure increase. Adjustment of tissue Starling forces may occur rapidly after an increase in filtration pressure.
Quantitative EMG analysis in soleus and plantaris during hindlimb suspension and recovery
Authors: Blewett C. , Elder G. C.
Published: December 2017

Activity levels in rat soleus (SOL) and plantaris (PL) were quantitated electromyographically during control (6 days), hindlimb suspension (HS, 28 days), and recovery (6 days). The number and amplitude of "turns" were determined in each muscle from the complex interference pattern every 2 min for 40 days. Each muscle was sampled for 500 ms consecutively, providing 12 s.2 min-1 x muscle-1 of actual data. Changes in activity were assessed by differences in the total number of turns each 24 h, expressed as a percentage of control. Daily intervals of low (< 5,000 turns/2 min) and high activity (> 30,000 turns/2 min) were determined. The number of turns was significantly reduced throughout HS, to just 39% (SOL) and 35% (PL) of control levels on day 28. Low-activity periods increased significantly during HS while high-activity periods disappeared. During recovery, the number of turns increased to control levels in SOL and to 80–90% of control levels in PL. Large differences in activity observed between the dark and light cycles in control muscles were absent during HS and recovery. Similarly, cyclical periods of low and high activity were common during the control period but disappeared during HS and only partly returned during recovery. In conclusion, not only were activity levels significantly reduced in both SOL and PL during HS, but also the patterns of activity were changed.
Uteroplacental blood flow at rest and during exercise in late-gestation conscious rats
Authors: Dowell R. T. , Kauer C. D.
Published: December 2017

The present studies were conducted to achieve three specific aims. First, techniques and procedures were developed to allow tissue and organ blood flow measurements by radioactive microsphere methodology in the conscious female rat. Second, technical aspects of the methodology were evaluated with emphasis on potential uteroplacental shunting of microspheres in the late-gestational period. Third, the above techniques and procedures were utilized to assess uteroplacental blood flow at rest and during exercise in conscious pregnant rats during the late stages of gestation, i.e., days 15, 19, and 22 of pregnancy. Results established the validity of tracer blood flow technical assumptions, and no significant increase in arteriovenous shunting of 15-microns microspheres either as pregnancy progressed or during superimposed exercise in near-term pregnant animals was detected. During the stages of pregnancy studied, cardiac output was enhanced approximately 20% near term. Marked and progressive increases in uterine blood flow were noted both in milliliters per minute and as percentage of cardiac output. Preferential placental perfusion during late-stage gestation was indicated by increased tissue flow (7 +/- 1, 84 +/- 12, 232 +/- 32 ml.min-1 x 100 g-1), increased percent cardiac output (1.7 +/- 0.1, 5.1 +/- 0.7, 11.0 +/- 1.7% cardiac output), and increased percent uterine blood flow (10 +/- 1, 59 +/- 3, 87 +/- 2% uterine flow) at days 15, 19, and 22 of gestation, respectively. Progressive maternal body weight increase during gestation enhanced exercise work intensity, as shown by heart rate and cardiac output at the end of 30 min of treadmill running at 8.5 m/min, 0% incline.
Renal hemodynamics, tubular function, and response to low-dose dopamine during acute hypoxia in humans
Authors: Olsen N. V. , Hansen J. M. , Kanstrup I. L. , Richalet J. P. , Leyssac P. P.
Published: December 2017

Renal function was investigated in eight normal subjects before and during infusion of dopamine (3 micrograms.kg-1 x min-1) at sea level (SL) and at high altitude (HA, 4,350 m). Lithium clearance (CLi) was used as an index of proximal tubular outflow. HA significantly increased arterial pressure, heart rate, and plasma norepinephrine. Effective renal plasma flow (ERPF) decreased at HA by 10% (P < 0.05), but glomerular filtration rate (GFR), CLi, sodium clearance (CNa), and urine flow remained unchanged compared with SL. Dopamine at SL and HA increased ERPF by 47% (P < 0.001) and 30% (P < 0.01), respectively, but the increase at HA was smaller than that at SL (P < 0.05). Dopamine increased GFR only at SL. CLi and CNa increased by 29% (P < 0.001) and 108% (P < 0.001) at SL and by 23% (P < 0.01) and 108% (P < 0.001) at HA. Whereas dopamine at SL increased urine flow by 46% (P < 0.01), this response was abolished at HA, and free water clearance decreased (P < 0.05). The decreased ERPF at HA suggests a constriction of the renal arterioles secondary to increased adrenergic nervous activity. Although the effect of dopamine on ERPF was attenuated in hypoxia, dopamine-induced increases in CLi and CNa remained unaltered, suggesting that natriuresis in both environments was secondary to an increased outflow from the proximal tubules. The absence of a diuretic response to dopamine at HA seemed to be caused by an effect on distal tubular function.