bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of the latissimus dorsi muscle and respiratory function
Authors: Orozco-Levi M. , Gea J. , Sauleda J. , Corominas J. M. , Minguella J. , Aran X. , Broquetas J. M.
Published: December 2017

The aim of this study was to evaluate whether respiratory function influences the structure of the latissimus dorsi muscle (LD). Twelve patients (58 +/- 10 yr) undergoing thoracotomy were studied. Lung and respiratory muscle function were evaluated before surgery. Patients showed a forced expired volume in 1 s (FEV1) of 67 +/- 16% of the reference value, an FEV1-forced vital capacity ratio of 69 +/- 9%, a maximal inspiratory pressure of 101 +/- 21% of the reference value, and a tension-time index of the diaphragm (TTdi) of 0.04 +/- 0.02. When patients were exposed to 8% CO2 breathing, TTdi increased to 0.06 +/- 0.03 (P < 0.05). The structural analysis of LD showed that 51 +/- 5% of the fibers were type I. The diameter was 56 +/- 9 microns for type I fibers and 61 +/- 9 microns for type II fibers, whereas the hypertrophy factor was 87 +/- 94 and 172 +/- 208 for type I and II fibers, respectively. Interestingly, the histogram distribution of the LD fibers was unimodal in two of the three individuals with normal lung function and bimodal (additional mode of hypertrophic fibers) in seven of the nine patients with chronic obstructive pulmonary disease. An inverse relationship was found between the %FEV1-forced vital capacity ratio and both the diameter of the fibers (type I: r = -0.773, P < 0.005; type II: r = -0.590, P < 0.05) and the hypertrophy factors (type I: r = -0.647, P < 0.05; type II: r = -0.575, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary venous congestion augments respiratory motoneuronal responses to cigarette smoke in rabbit
Authors: Bonham A. C. , Ravi K. , Wilson C. G. , Zhang Z. , Kappagoda C. T.
Published: December 2017

We examined the effects of cigarette smoke inhaled during subthreshold pulmonary venous congestion(sPVC) on phrenic nerve (PN) and unit activity in the ventral respiratory group in rabbits. sPVC was achieved by inflating a balloon in the left atrium. Inhalation of low-nicotine cigarette smoke produced initial prolonged bursts in 34 (19 bulbospinal) out of 43 inspiratory (I) cells and in PN. Smoke decreased the activity of 29 out of 36 expiratory (E) cells (27 of 32 early E and 2 of 4 late E). The prolonged PN bursts occasionally progressed to doublets superimposed over regularly occurring PN bursts. sPVC augmented the smoke effects: I cells displayed greater increases in spikes/burst (27 vs. 12%; P = 0.02) and burst duration (42 vs. 20%; P = 0.02) and greater decreases in interburst interval (34 vs. 10%; P < 0.02); PN displayed greater increases in I time (40 vs. 27%; P < 0.05), greater decreases in E time (18 vs. 26%; P < 0.05), and a greater incidence and duration of time of PN doublets (29 +/- 9 vs. 9 +/- 4 s; P < 0.03); E cells displayed greater decreases in spikes/burst (43 vs. 29%; P = 0.01) and burst durations (35 vs. 18%; P < 0.01). Smoke-induced respiratory changes may be exaggerated during sPVC.
K+ and Lac- distribution in humans during and after high-intensity exercise: role in muscle fatigue attenuation?
Authors: Lindinger M. I. , McKelvie R. S. , Heigenhauser G. J.
Published: December 2017

This review describes processes for the distribution of K+ ([K+]) and lactate concentrations ([Lac-]) that are released from contracting muscle at high rates during high-intensity exercise. This results in increased interstitial and venous [K+] and [Lac-] in contracting muscle. Large and rapid increases in plasma [K+] and [Lac-] result in the transport of these ions into red blood cells (RBCs). These ions are distributed to noncontracting tissues within both the plasma and RBC compartments of blood. The extraction of K+ and Lac- from the circulation by noncontracting tissue serves to markedly attenuate exercise-induced increases in plasma [K+] and [Lac-]. This apparent regulation of the plasma compartment by noncontracting tissues helps to maintain favorable concentration gradients for the net movement of [K+] and [Lac-] into the venous side of the microcirculation from interstitial fluids of contracting muscle. This provides conditions that 1) reduce the increase in interstitial [K+], thereby decreasing the magnitude and rate of sarcolemmal depolarization, and 2) favor the sarcolemmal transport of Lac- from within contracting muscle cells, thereby regulating intracellular osmolality and H+ concentration. On cessation of exercise, net K+ uptake by recovering muscle is rapid, with 90–95% recovery of intracellular [K+] within 3.5 min, indicating a very high rate of Na+-K+ pump activity. The K+ extracted by noncontracting tissues during exercise may be slowly released during recovery. During the initial minutes of recovery, recovering muscle continues to release Lac- into the circulation, and noncontracting tissues continue to extract Lac- for up to 30 min. The uptake of Lac- by noncontracting tissues results in elevated intracellular [Lac-]. There is no evidence that Lac- extracted by noncontracting tissues is subsequently released; it is probably metabolized within these cells. We conclude that the uptake of K+ and Lac- by RBCs and noncontracting tissues regulates ion homeostasis within plasma and the interstitial and intracellular compartments of contracting muscle. The regulatory processes help to maintain the function of active muscles by delaying the onset of fatigue during exercise and to restore homeostasis during recovery.
Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women
Authors: Fleg J. L. , O'Connor F. , Gerstenblith G. , Becker L. C. , Clulow J. , Schulman S. P. , Lakatta E. G.
Published: December 2017

To examine whether age differentially modifies the physiological response to exercise in men and women, we performed gated radionuclide ventriculography with measurement of left ventricular volumes at rest and during peak upright cycle exercise in 200 rigorously screened healthy sedentary volunteers (121 men and 79 women) aged 22–86 yr from the Baltimore Longitudinal Study of Aging. At rest in the sitting position, age-associated declines in heart rate (HR) and increases in systolic blood pressure occurred in both sexes. Whereas resting cardiac index (CI) and total systemic vascular resistance (TSVR) in men did not vary with age, in women resting CI decreased 16% and TSVR increased 46% over the six-decade age span. Men, but not women, demonstrated an age-associated increase of approximately 20% in sitting end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and stroke volume index over this age span. Peak cycle work rate declined with age approximately 40% in both sexes, but at any age it was greater in men than in women even after normalization for body weight. At peak effort, ejection fraction (EF), HR, and CI were reduced similarly with age while ESVI and TSVR were increased in both sexes; EDVI increased 35% with age and stroke work index (SWI) rose 19% in men, but neither was related to age in women; and stroke volume index did not vary with age in either sex. When hemodynamics were expressed as the change from rest to peak effort as an index of cardiovascular reserve function, both sexes demonstrated age-associated increases in EDVI and ESVI and reductions in EF, HR, and CI. However, the exercise-induced reduction in ESVI and the increases in EF, CI, and SWI from rest were greater in men than in women. Thus, age and gender each have a significant impact on the cardiac response to exhaustive upright cycle exercise.
Modification of conditioned apneas in rats: evidence for cortical involvement
Authors: Thomas A. J. , Friedman L. , MacKenzie C. N. , Strohl K. P.
Published: December 2017

Apneic patterns in breathing can be classically conditioned in rats by brief neonatal exposures to hypoxia, noise, and petting during sleep (A. J. Thomas, W. Austin, L. Friedman, and K. P. Strohl, J. Appl. Physiol. 73: 1530–1536, 1992); thus animals may acquire apneic patterns by exposure to not only respiratory but also nonrespiratory stimuli. We hypothesized that conditioned apneas in these animals can be reduced or abolished by presentation of counterconditioning stimuli, which would prevent the respiratory controller from being influenced by nonrespiratory stimuli and affecting breathing rhythmicity. In five female rats conditioned during neonatal life to exhibit apneic breathing during adulthood and in five female unconditioned control rats, the effect of a brief quiet repetitive auditory stimulus (white noise, 50 Hz, 30 dB) presented for periods of 20 min on and 20 min off was assessed. In conditioned apneic rats, white noise reduced the frequencies of apneas by approximately 79% (P < 0.01) but did not alter the number of apneas in unconditioned control rats. In either group, white noise had no effect on the number of apneas preceded by a sigh. In a second experiment, the effect of Equithesin anesthetic was examined in five female conditioned apneic rats. In contrast to the white noise effect, not only apneic breathing but also apneas preceded by a sign were completely abolished by anesthesia (P < 0.0001). These findings suggest a role for counterconditioning and cortical influences on respiratory rhythm in the adult mammal.
Partitioning of pulmonary function in rabbits during cholinergic stimulation
Authors: Fuller S. D. , Freed A. N.
Published: December 2017

Our goal was to partition whole lung resistance (RL) and cholinergic reactivity in rabbits into central airway, peripheral airway, and alveolar tissue (Rt) resistances by using forced oscillation (2 Hz), a retrograde catheter, and an alveolar capsule. Central and peripheral airway resistances accounted for approximately 80% of the baseline RL. However, immediately after acetylcholine challenge, Rt was negative. Bilateral vagal stimulation made Rt negative when the capsule was located on the left lung and not on the right lung. Stimulating either vagus produced a negative Rt in the lung ipsilateral to the stimulated nerve. Partial occlusion of the right main-stem bronchus with a balloon also made Rt negative. These results suggest that heterogeneous airflow exists at the level of the alveolar capsule during bronchoconstriction. Phase relationships between tracheal flow and retrograde catheter pressure suggest that flow at the level of the catheter was homogeneous. Thus, using only tracheal and retrograde catheter pressures, we repartitioned RL into its central airway and peripheral lung components. We conclude that cholinergic reactivity resides predominantly in the peripheral lung and that its peripheral location may be due largely to the development of heterogeneous airflow in peripheral airways.
Arms are different from legs: mechanics and energetics of human hand-running
Authors: Glasheen J. W. , McMahon T. A.
Published: December 2017

To determine whether nonlocomotor limbs (arms) differ from locomotor limbs (legs), we trained human subjects to run on their hands while supporting a fraction of their body weight. We wanted to know whether the low cost of force production and the speed-independent limb stiffness of locomotor limbs were characteristics associated with locomotion or were inherent properties of all limbs. We found that the limb stiffness of the human arm increases by 135% over less than a fourfold range in peak vertical force. In contrast, human legs and a variety of other mammalian locomotor limbs maintain a constant stiffness, regardless of speed and loading, for normal running. In addition, we explored the energetics of locomotion in hand-running. The economy of force generation (in J/N) is invariant with speed, as is found in legged locomotion. However, our results show that the metabolic cost of force generation while running on human arms is four to five times greater than the cost of force generation for the locomotor limbs of running quadrupeds.
Exercise-induced cardiac hypertrophy is associated with an increased myocardial compliance
Authors: Woodiwiss A. J. , Norton G. R.
Published: December 2017

Left ventricular (LV) chamber and myocardial wall compliance were investigated in rats with exercise-induced cardiac hypertrophy. Voluntary exercise training was performed on running wheels. After 16 wk of exercise training, cardiac performance was measured in anesthetized open-chest ventilated rats. LV end-diastolic performance was calculated from both short-axis external diameter and long-axis segmental length measurements. Exercise-trained rats developed significant LV hypertrophy (1.03 +/- 0.02 g) compared with control rats (0.91 +/- 0.03 g; P < 0.01). The physiological hypertrophy was associated with an increased LV wall thickness-to-internal radius ratio consistent with a concentric geometry. LV end-diastolic stiffness (slope of the linearized LV end-diastolic pressure-strain relationship) was decreased in both the short (P < 0.02) and long (P < 0.02) axis of LV as a result of exercise training. The LV end-diastolic chamber stiffness (slope of the linearized LV end-diastolic pressure-volume relationship) was also decreased in the exercised group (P < 0.05). The decreased chamber stiffness occurred as a consequence of a decrease in the regional myocardial wall elastic stiffness (slope of the linearized LV end-diastolic stress-strain relationship; P < 0.05). Thus an increased LV wall thickness as a result of exercise-induced LV hypertrophy is associated with an enhanced ventricular chamber compliance, which in turn is attributed to a decrease in the diastolic stiffness of the myocardial wall.
Maximal accumulated oxygen deficit in thoroughbred horses
Authors: Eaton M. D. , Evans D. L. , Hodgson D. R. , Rose R. J.
Published: December 2017

Thoroughbred horses have a high aerobic capacity, approximately twice that of elite human athletes. Whereas the aerobic capacity of horses can be accurately measured, there have been no measurements of anaerobic capacity. The aim of this study was to determine whether maximal accumulated O2 deficit (MAOD) could be measured in horses and used as an estimate of anaerobic capacity, as in human athletes. Six fit Thoroughbred horses were used with the exercise protocol utilizing a treadmill set at a 10% incline. O2 uptake VO2 was measured via an open-flow system for seven submaximal speeds (3–9 m/s), and maximal VO2 (135 +/- 3 ml.kg-1.min-1) was determined. The horses performed three tests at 105 and 125% and six tests at 115% of maximal VO2. The MAOD test was performed with the treadmill accelerated rapidly from 1.5 m/s (mean acceleration time 8 s) to the calculated speed (11–14 m/s). VO2 was measured every 10 or 15 s, and the test ended when the horse no longer kept pace with the treadmill. The mean run times were 165, 98, and 57 s for intensities of 105, 115, and 125% maximal VO2. The mean MAOD values were 31 +/- 2, 30 +/- 1, and 32 +/- 2 (SE) ml O2 eq/kg for the three intensities (P > 0.05). The proportion of energy derived from aerobic and anaerobic sources was calculated from the difference between calculated O2 demand and the VO2 curve. There was no correlation between MAOD and maximal VO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Hering-Breuer reflex and respiratory rate: a biased association
Authors: Gagliardi L. , Rusconi F.
Published: December 2017

The Hering-Breuer reflex (HBR) plays an important role in the regulation of respiratory timing in infancy. Some investigators have noted that HBR is stronger when the respiratory rate (RR) is faster. However, this finding may be due to a spurious correlation, since one of the variables (expiratory time) used to calculate both HBR and RR is the same. We investigated this hypothesis with Monte Carlo (simulation) studies by using uncorrelated random numbers to calculate RR and HBR and found a strong spurious correlation (r = 0.7) between HBR and RR, i.e., subjects with higher RR had a stronger HBR. These results were confirmed algebraically, and the formula for the expected value of the correlation coefficient [E(r)] was derived. E(r) was always >0; it was 0.707 when no prolongation of inspiration occurred and was larger in the presence of a prolongation; when HBR strength was 100%, E(r) = 0.89, and when it was 200%, E(r) = 0.94. The expected value of the slope of the regression line of HBR on RR was found to be directly proportional to expiratory time during occlusion. As faster RRs produce stronger HBRs, any variable associated with RR, i.e., age, length, and weight, may influence HBR. This can lead to inconclusive or biased results in studies of the maturation of HBR with age and can confound comparisons across groups that do not have the same RR.
Mechanisms of myocardial hypercarbic acidosis during cardiac arrest
Authors: Johnson B. A. , Weil M. H. , Tang W. , Noc M. , McKee D. , McCandless D.
Published: December 2017

During the global myocardial ischemia of cardiac arrest and during regional myocardial ischemia due to local impairment of coronary blood flow, intramyocardial carbon dioxide tensions (Pmco2) of ischemic myocardium increase to levels exceeding 400 Torr. The mechanism of such myocardial hypercarbic acidosis is as yet incompletely understood, specifically whether these increases in Pmco2 are due to increased oxidative metabolism, decreased CO2 removal, or buffering of metabolic acids. We therefore measured Pmco2 and the total CO2 content of rat hearts harvested before, during, and after resuscitation from cardiac arrest. Pmco2 significantly increased from an average of 63 to 209 Torr during a 4-min interval of untreated ventricular fibrillation. This was associated with concurrent decreases in intracellular pH from an average of 7.03 to 6.02 units. The total CO2 content of the myocardium simultaneously decreased from 17.0 to 16.5 mmol/kg. Accordingly, increases in Pmco2 and [H+] were observed in the absence of increases in the total CO2 content and therefore the calculated myocardial bicarbonate. These observations in the rat model implicate buffering of metabolic acids by bicarbonate rather than increases in CO2 production or decreases in CO2 removal as the predominant mechanism accounting for myocardial hypercarbia.
Contribution of diaphragmatic power output to exercise-induced diaphragm fatigue
Authors: Babcock M. A. , Pegelow D. F. , McClaran S. R. , Suman O. E. , Dempsey J. A.
Published: December 2017

n nine normal humans we compared the effects on diaphragm fatigue of whole body exercise to exhaustion (86–93% of maximal O2 uptake for 13.2 +/- 2.0 min) to voluntary increases in the tidal integral of transdiaphragmatic pressure (integral of Pdi) while at rest at the same magnitude and frequency and for the same duration as those during exercise. After the endurance exercise, we found a consistent and significant fall (-26 +/- 2.9%, range -19.2 to -41.0%) in the Pdi response to supramaximal bilateral phrenic nerve stimulation at all stimulation frequencies (1, 10, and 20 Hz). Integral of Pdi.fB (where fB is breathing frequency) achieved during exercise averaged 509 +/- 81.0 cmH2O/min (range 304.0–957.0 cmH2O/min). At rest, voluntary production of integral of Pdi.fB, which was < 550–600 cmH2O/min (approximately 4 times the resting eupenic integral of Pdi.fB or 60–70% of Pdi capacity), did not result in significant diaphragmatic fatigue, whereas sustained voluntary production of integral of Pdi.fB in excess of these threshold values usually did result in significant fatigue. Thus, with few exceptions (5 of 23 tests) the ventilatory requirements of whole body endurance exercise demanded a level of integral of Pdi.fB that, by itself, was not fatiguing. The rested first dorsal interosseous muscle showed no fatigue in response to supramaximal ulnar nerve stimulation after whole body exercise. We postulate that the effects of locomotor muscle activity, such as competition for blood flow distribution and/or extracellular fluid acidosis, in conjunction with a contracting diaphragm account for most of the exercise-induced diaphragm fatigue.
Anaerobic threshold and respiratory compensation in pregnant women
Authors: Lotgering F. K. , Struijk P. C. , van Doorn M. B. , Spinnewijn W. E. , Wallenburg H. C.
Published: December 2017

In an effort to explore why CO2 output (VCO2) at peak exercise is lower during pregnancy than postpartum despite little change in the peak O2 uptake (VO2), we determined the VCO2/VO2 relationship during rapidly incremental exercise and estimated the anaerobic threshold (AT) and the respiratory compensation (RC) point. We measured heart rate, VO2, VCO2, and minute ventilation (VE) at rest and during cycle exercise tests with rapidly increasing exercise intensities until maximal effort in 33 volunteers at 16-, 25-, and 35-wk gestation and postpartum. Through modification of the V-slope method, we estimated the AT and RC point for each test by nonlinear regression analysis in a three-dimensional space (defined by VE, VO2, and VCO2) for a line assumed to have two breakpoints; we found a good fit for all tests. The AT and RC points were found at exercise intensities of approximately 50 and 80% peak VO2, respectively, with no significant differences between test periods. VE was significantly higher during pregnancy than during postpartum at rest and throughout incremental exercise. A lower peak VCO2 relative to peak VO2 during pregnancy compared with postpartum was reflected by a more shallow slope of VCO2 vs. VO2 above the AT point. This suggests that during pregnancy the buffering of lactic acid is reduced.
Pharyngeal narrowing/occlusion during central sleep apnea
Authors: Badr M. S. , Toiber F. , Skatrud J. B. , Dempsey J.
Published: December 2017

We hypothesized that subatmospheric intraluminal pressure is not required for pharyngeal occlusion during sleep. Six normal subjects and six subjects with sleep apnea or hypopnea (SAH) were studied during non-rapid-eye-movement sleep. Pharyngeal patency was determined by using fiber-optic nasopharyngoscopy during spontaneous central sleep apnea (n = 4) and induced hypocapnic central apnea via nasal mechanical ventilation (n = 10). Complete pharyngeal occlusion occurred in 146 of 160 spontaneously occurring central apneas in patients with central sleep apnea syndrome. During induced hypocapnic central apnea, gradual progressive pharyngeal narrowing occurred. More pronounced narrowing was noted at the velopharynx relative to the oropharynx and in subjects with SAH relative to normals. Complete pharyngeal occlusion frequently occurred in subjects with SAH (31 of 44 apneas) but rarely occurred in normals (3 of 25 apneas). Resumption of inspiratory effort was associated with persistent narrowing or complete occlusion unless electroencephalogram signs of arousal were noted. Thus pharyngeal cross-sectional area is reduced during central apnea in the absence of inspiratory effort. Velopharyngeal narrowing consistently occurs during induced hypocapnic central apnea even in normal subjects. Complete pharyngeal occlusion occurs during spontaneous or induced central apnea in patients with SAH. We conclude that subatmospheric intraluminal pressure is not required for pharyngeal occlusion to occur. Pharyngeal narrowing or occlusion during central apnea may be due to passive collapse or active constriction.
Skeletal muscle phosphofructokinase activity examined under physiological conditions in vitro
Authors: Peters S. J. , Spriet L. L.
Published: December 2017

The in vitro activity of skeletal muscle phosphofructokinase (PFK) was determined over the full physiological range of citrate concentrations. Enzyme aggregation was enhanced with a crowding agent, as the regulatory properties of PFK are altered with dilution. Cuvette conditions simulated concentrations of effectors and substrates during rest, moderate aerobic exercise, and intense aerobic exercise in human skeletal muscle. Citrate inhibition was not eliminated with enhanced enzyme aggregation, but activity was improved at all citrate concentrations. Maximal PFK activity with no citrate present was 0.27 +/- 0.01 mumol.min-1.mg-1 protein with resting effectors and 1.64 +/- 0.07 and 7.15 +/- 0.52 mumol.min-1.mg-1 protein with moderate aerobic and intense aerobic effector levels, respectively. Under resting conditions, PFK activity decreased to 49% of maximal when citrate was increased from 0 to 0.15 mM and only a small further inhibition to 43% occurred at 0.5 mM. Citrate was a less potent inhibitor under both exercise conditions with the sharpest decline to 72–77% of maximal activity at 0.15 mM followed by a slower decline to 65–70 and 53% activity at 0.25 and 0.5 mM citrate, respectively. The present in vitro measurements predict that alterations in citrate around concentrations normally reported in resting and exercising muscle would have little effect on flux through PFK. Therefore, the generally accepted concept that citrate is a potent inhibitor of PFK in all physiological situations has been exaggerated.
Control of expiratory time in conscious humans
Authors: Rafferty G. F. , Evans J. , Gardner W. N.
Published: December 2017

Combinations of 17 normal awake humans breathed mildly hyperoxic and hypercapnic gas mixtures via a pneumotachograph into an open circuit. Respiratory pattern was measured for each breath in real time by computer. Use of computer-controlled auditory feedback at a constant end-tidal PCO2 (PETCO2) allowed prolonged changes of 1) inspiratory time (TI) at constant inspired tidal volume (VTI), 2) VTI up and down in repeated steps at constant TI, and 3) expiratory time (TE) at constant VTI. The remaining variables were free to be determined by the subjects' automatic respiratory control mechanisms. We showed that TE changed in parallel with the change in TI despite constant VTI, TE did not change in response to step changes in VTI at constant TI, and large changes in TE had no influence on the subsequent TI, but VTI increased slightly as TE lengthened despite clamping. Time for expiratory flow (TE--end-expiratory pause) changed in parallel with TE in all protocols. Thus, in conscious humans, inspiratory timing has a direct influence on expiratory timing, independent of volume change and chemical drive, but expiratory timing has no influence on the inspiratory timing of the subsequent breath but has a small influence on volume.
Dilatory effects of upper airway muscle contraction induced by electrical stimulation in awake humans
Authors: Schnall R. P. , Pillar G. , Kelsen S. G. , Oliven A.
Published: December 2017

During sleep, diminished activity of upper airway dilator muscles (UADMs) is believed to increase upper airway (UAW) resistance and ultimately cause collapse of the UAW. In anesthetized dogs, electrically induced UADM contraction reduces UAW resistance and collapsibility. In this study, we measured the effects of electrically induced contraction of UADMs on pharyngeal resistance (Rph) in seven awake healthy subjects. UAW partial occlusion was achieved by applying external pressure to the submental hyoid region, leading to increased Rph. Transmucosal electrical stimulation (ES) of the base of the tongue was used to preferentially stimulate the genioglossus muscle. Transcutaneous ES using submental and paralaryngeal electrodes were used to preferentially stimulate the geniohyoid and the sternohyoid and sternothyroid muscles, respectively. During the unobstructed state, Rph averaged 6.11 +/- 0.48 cmH2O.l-1.s, and ES produced minimal resistance changes for all stimulation sites tested. In contrast, during the application of external pressure, when Rph was raised to an average of 190 +/- 14% of the baseline value, sublingual ES reduced resistance from 11.67 +/- 1.90 to 6.77 +/- 1.30 cmH2O.l-1.s (P < 0.01). ES at the other sites during the raised Rph state produced only minor statistically insignificant changes in Rph, even when combined submental and paralaryngeal ES was applied. Likewise, only sublingual ES produced measurable anterior movement of the tongue. We conclude that when Rph is raised by exogenous means, sublingual transmucosal ES effectively reduces Rph in awake humans.
Endothelial barrier resistance in multiple organs after septic and nonseptic challenges in the rat
Authors: Deng X. , Wang X. , Andersson R.
Published: December 2017

Local variations in endothelial permeability, hypothesized to play a role in the development of multiple-organ injury, were measured by 125I-labeled human serum albumin flux and leakage index in rats with a variety of challenges. The albumin flux significantly increased in the peritoneum, pancreas, stomach, and liver in acute pancreatitis; in the peritoneum and liver in abdominal sepsis; in the spleen, proximal small intestine, colon, liver, lungs, heart, and muscle in bacteremia; in the kidneys, liver, lungs, heart, brain, and muscle in endotoxemia; and in the peritoneum, proximal small intestine, colon, kidneys, liver, and heart after bradykinin administration. A redistribution of the tissue blood content, measured by 51Cr-labeled red blood cells, was noted. An increased albumin leakage index, assaying endothelial permeability considering local hemodynamic alterations, was noted in various organs in the different experimental groups. Thus septic and nonseptic challenges induce endothelial barrier injury. The endothelial resistance appears to be organ and/or tissue dependent and associated with a redistribution of blood.
Voluntary control of breathing does not alter vagal modulation of heart rate
Authors: Patwardhan A. R. , Evans J. M. , Bruce E. N. , Eckberg D. L. , Knapp C. F.
Published: December 2017

Variations in respiratory pattern influence the heart rate spectrum. It has been suggested, hence, that metronomic respiration should be used to correctly assess vagal modulation of heart rate by using spectral analysis. On the other hand, breathing to a metronome has been reported to increase heart rate spectral power in the high- or respiratory frequency region; this finding has led to the suggestion that metronomic respiration enhances vagal tone or alters vagal modulation of heart rate. To investigate whether metronomic breathing complicates the interpretation of heart rate spectra by altering vagal modulation, we recorded the electrocardiogram and respiration from eight volunteers during three breathing trials of 10 min each: 1) spontaneous breathing (mean rate of 14.4 breaths/min); 2) breathing to a metronome at the rate of 15, 18, and 21 breaths/min for 2, 6, and 2 min, respectively; and 3) breathing to a metronome at the rate of 18 breaths/min for 10 min. Data were also collected from eight volunteers who breathed spontaneously for 20 min and breathed metronomically at each subject's mean spontaneous breathing frequency for 20 min. Results from the three 10-min breathing trials showed that heart rate power in the respiratory frequency region was smaller during metronomic breathing than during spontaneous breathing. This decrease could be explained fully by the higher breathing frequencies used during trials 2 and 3 of metronomic breathing. When the subjects breathed metronomically at each subject's mean breathing frequency, the heart rate powers during metronomic breathing were similar to those during spontaneous breathing. Our results suggest that vagal modulation of heart rate is not altered and vagal tone is not enhanced during metronomic breathing.
A beta 2-adrenergic agonist inhibits dry air-induced injury in canine peripheral airways
Authors: Omori C. , Schofield B. H. , Mitzner W. , Freed A. N.
Published: December 2017

We examined the effects of a beta 2-agonist on dry air-induced injury in canine peripheral airways. Dry air-induced bronchoconstriction (AIB) was assessed by measuring peripheral airway resistance in anesthetized dogs. Salbutamol reduced AIB by approximately 75% compared with control values. Colloidal carbon was used to detect bronchovascular leakage in contralateral sublobar segments that were pretreated with saline or salbutamol. About 87% of the perimeter of bronchi was damaged after dry air challenge in saline-treated segments. Salbutamol reduced mucosal damage by approximately 30% (P < 0.05). The mucosa of bronchioles was not injured. The average goblet-to-ciliated cell ratio (which reflects mucosal perturbation) in bronchi decreased from 0.38 in control bronchi to 0.15 in challenged bronchi, and this effect was also evident in bronchioles. Salbutamol did not affect this decrement. Dry air challenge also caused degranulation of mast cells located below damaged mucosa, dilation of bronchial vessels, and leakage from capillaries and venules located below normal ciliated and damaged mucosa of bronchi. Thus, we conclude that salbutamol attenuates epithelial damage and AIB but fails to inhibit mast cell degranulation and vascular hyperpermeability.
Cigarette smoke-induced bronchoconstriction: cholinergic mechanisms, tachykinins, and cyclooxygenase products
Authors: Hong J. L. , Rodger I. W. , Lee L. Y.
Published: December 2017

The mechanisms underlying cigarette smoke-induced bronchoconstriction were studied by using selective blockade of muscarinic acetylcholine receptors, neurokinin receptors and production of eicosanoids of the cyclooxygenase pathway in anesthetized guinea pigs. Inhalation of three breaths of cigarette smoke (University of Kentucky research series 2R1; 2.45 mg of nicotine and 35.3 mg of tar per cigarette) reproducibly induced an immediate bronchoconstriction; total pulmonary resistance increased from 0.24 +/- 0.02 to 1.44 +/- 0.21 cmH2O.ml-1.s (P < 0.01) and dynamic lung compliance decreased from 0.53 +/- 0.03 to 0.39 +/- 0.06 ml/cmH2O (P < 0.05) in 10–15 breaths after the smoke inhalation. Atropine pretreatment (50 micrograms/kg i.v.) prevented the immediate decrease in dynamic lung compliance and reduced the immediate increase in total pulmonary resistance by approximately 55%. The atropine-resistant bronchoconstriction occurring immediately after smoke inhalation was completely blocked by a pretreatment with a combination of CP-99994 (0.3 mg/kg i.v.) and SR-489668 (0.3 mg/kg i.v.), the antagonists of neurokinin-1 and neurokinin-2 receptors, respectively. However, a delayed and sustained bronchoconstriction still persisted and reached a plateau in 45–55 breaths after smoke inhalation challenge. This delayed response was completely prevented by pretreatment with indomethacin (5 mg/kg i.v.). We conclude that the smoke-induced bronchoconstriction in guinea pigs consists of an early phase induced by both a cholinergic reflex and tachykinin release, probably evoked by the activation of bronchopulmonary C fibers, and a late phase caused by the action of arachidonic acid metabolite(s) of the cyclooxygenase pathway.
Effects of hypercapnia on ECoG and oxidative metabolism in neonatal dog brain
Authors: Yoshioka H. , Miyake H. , Smith D. S. , Chance B. , Sawada T. , Nioka S.
Published: December 2017

The effects of hypercapnia on cerebral electrical activity and mitochondrial oxidative phosphorylation were studied in the anesthetized neonatal dog by using the electrocorticogram (ECoG) and 31P-magnetic resonance spectroscopy. Three levels of hypercapnia with arterial PCO2 values of approximately 70, 100, and 140 Torr reduced the intracellular pH of the brain from 7.11 to 6.99, 6.87, and 6.76, respectively. These levels of hypercapnia also reduced ADP concentration ([ADP]) from 21.5 to 18.1, 14.8, and 12.9 microM as well as the average ECoG power output by 20, 30, and 40%. A Michaelis-Menten relationship for the mitochondrial respiratory enzymes was fitted with [ADP] and the change in the average ECoG. The result suggests that mitochondrial respiration is regulated by [ADP] and that the in vivo Michaelis-Menten constant for ADP was 21 microM, a value close to the in vitro value. The mitochondrial maximal reaction velocity was reduced by only 10% during hypercapnia and showed no relationship with the degree of acidosis, suggesting that mitochondrial respiratory enzymes are not responsible for the inhibition of the brain electrical activity.
Neuromechanical regulation of respiratory motor output in ventilator-dependent C1-C3 quadriplegics
Authors: Simon P. M. , Leevers A. M. , Murty J. L. , Skatrud J. B. , Dempsey J. A.
Published: December 2017

To evaluate the role of phrenic and sternocleidomastoid afferents as alternate sources of inhibitory feedback during mechanical ventilation, we studied five C2-C3 quadriplegics with sensory denervation of the rib cage and diaphragm, six C1-C2 quadriplegics with additional loss of sensory feedback from the neck muscles, and seven normal subjects. We compared the return of inspiratory muscle activity [the recruitment threshold (PCO2RT)] during mechanical ventilation between subject groups after stepwise increases in end-tidal PCO2 (PETCO2) either by increasing the inspired fraction of CO2 (FICO2), decreasing tidal volume (VT; 50 ml/min), or decreasing frequency (f; 1 breath/2 min). Normal subjects were mechanically hyperventilated via a nasal mask until inspiratory activity was undetectable. Efferent input to the sternocleidomastoid was intact at both levels of spinal cord injury, but phasic activity was not evident at the quadriplegics' baseline resting ventilation. The PCO2RT was defined as the level of PETCO2 at which phasic activity of the diaphragm in normal subjects and of the sternocleidomastoid in C1-C2 and C2-C3 quadriplegics recurred. The mean PCO2RT (in response to raising PETCO2 via increased FICO2 while maintaining a high VT and f) was not significantly different (P = 0.6) between normal subjects (43 +/- 3 Torr) and C2-C3 quadriplegics (38 +/- 5 Torr). Both subject groups demonstrated a frequency- and volume-related inhibition, as evidenced by a substantially lower PCO2RT when PETCO2 was raised by reducing either VT or f. In contrast to the C2-C3 quadriplegics, the C1-C2 quadriplegics responded with a similar PCO2RT among the three different mechanical ventilation trials, independent of whether PETCO2 was raised with high VT and f, with reduced VT, or with reduced f. We conclude that feedback from at least some part of the chest wall is required to produce a volume- and frequency-dependent inhibition of inspiratory muscle activity observed during mechanical ventilation.
Pattern of recovery from diaphragmatic fatigue over 24 hours
Authors: Laghi F. , D'Alfonso N. , Tobin M. J.
Published: December 2017

The rate of recovery from diaphragmatic fatigue beyond 1 h is unknown. To investigate this question, we studied 12 healthy subjects and measured transdiaphragmatic twitch pressure (Pditw) using magnetic stimulation of the phrenic nerves. Measurements were obtained at baseline and after a fatigue protocol consisting of inspiratory resistive loading in which the subjects generated 60% of maximal transdiaphragmatic pressure until task failure. At baseline, Pditw was 38.9 +/- 1.1 (SE) cmH2O and fell to 25.1 +/- 0.6 cmH2O 10 min after the conclusion of the fatigue protocol (P < 0.01). Pditw increased to 27.6 +/- 0.9, 31.6 +/- 1.1, and 32.7 +/- 1.2 cmH2O 1, 8 and 24 h, respectively, after the conclusion of the fatigue protocol; the 24-h value was significantly lower than baseline (P < 0.01). The nadir in Pditw after the protocol was delayed by 10 min. In separate experiments, we showed that this delay was probably due to the development of twitch potentiation as a result of forceful diaphragmatic contractions during the fatigue protocol. In conclusion, induction of diaphragmatic fatigue with this experimental protocol produced a marked decrease in diaphragmatic contractility that persisted for at least 24 h.
Surges of muscle sympathetic nerve activity during obstructive apnea are linked to hypoxemia
Authors: Leuenberger U. , Jacob E. , Sweer L. , Waravdekar N. , Zwillich C. , Sinoway L.
Published: December 2017

Obstructive sleep apnea (OSA) is associated with oscillations of arterial blood pressure (BP) that occur in phase with irregularities of respiration. To explore the role of the sympathetic nervous system in these responses, we studied muscle sympathetic nerve activity (MSNA; peroneal microneurography), an index of vasoconstrictor nerve traffic, and BP during awake regular breathing and during spontaneous apneas in patients with OSA. To determine the role of the arterial chemoreflex, we also examined the effects of 100% O2 (hyperoxia) on MSNA and BP. In awake regularly breathing patients with OSA (n = 12), resting MSNA was markedly higher than in an age-matched control population (n = 15) [41 +/- 23 (SD) vs. 24 +/- 17 bursts/min; P < 0.05] and was unchanged during hyperoxia (n = 9). Apneas during sleep (n = 8) were associated with surges in MSNA followed by transient rises in BP when breathing resumed. In contrast to room air apneas, hyperoxic apneas of similar duration were associated with attenuated MSNA responses (+82 +/- 84% vs. +5 +/- 25% compared with awake baseline; P < 0.05; n = 6), even though O2 did not affect sleep stage and the occurrence of arousal. Thus the BP oscillations that occur with apnea during sleep may in part be mediated by intermittent surges of sympathetic activity resulting in vasoconstriction. Because the MSNA responses to obstructive apnea are blunted during O2 administration, they appear to be linked to intermittent arterial hypoxemia and stimulation of arterial chemoreceptors.
Subpleural pulmonary microvascular pressures in the dog lung
Authors: Haworth S. T. , Rickaby D. A. , Linehan J. H. , Dawson C. A.
Published: December 2017

The reported values for the pressure difference between lobar artery and subpleural arteriole and between subpleural venule and lobar vein as a fraction of the total arterial-to-venous pressure drop across the dog lung have varied considerably. We carried out the present study to provide an additional set of measurements and to determine whether it is likely that differences in venous pressure or transpulmonary pressure between studies might make a substantial contribution to variations between studies. We measured the lobar arterial pressure (Pa) to subpleural arteriole (22–60 microns diam) pressure (Pma) to subpleural venule (30–80 microns diam) pressure (Pmv) to lobar venous pressure (Pv) distribution over a range of alveolar pressures (PA; 2.5–13.1 mmHg) and venous pressures (0–24.2 mmHg) in isolated dog lung lobes using the micropuncture servo-null technique. On average, near functional residual capacity (PA = 3 mmHg) and venous pressure equal to PA, (Pa-Pma)/(Pma-Pmv)/(Pmv-Pv) was 37:30:33%. Under zone 3 conditions, there was a small positive correlation between the fractional Pa-to-Pma pressure difference and PA and Pv, but dependence of the Pmv-to-Pv fraction on PA and Pv was not consistent. The overall effects of PA and Pv on the fractional pressure drops were not sufficient to account for differences between previous studies. Under zone 2 conditions as the venous pressure was varied, the changes in Pmv were nearly equal to the changes in Pv, whereas Pma was relatively insensitive to Pv. Thus, the zone 2 results were consistent with a capillary location for the flow-limiting segment under zone 2 conditions.
Override of spontaneous respiratory pattern generator reduces cardiovascular parasympathetic influence
Authors: Patwardhan A. R. , Vallurupalli S. , Evans J. M. , Bruce E. N. , Knapp C. F.
Published: December 2017

We investigated the effects of voluntary control of breathing on autonomic function in cardiovascular regulation. Variability in heart rate was compared between 5 min of spontaneous and controlled breathing. During controlled breathing, for 5 min, subjects voluntarily reproduced their own spontaneous breathing pattern (both rate and volume on a breath-by-breath basis). With the use of this experimental design, we could unmask the effects of voluntary override of the spontaneous respiratory pattern generator on autonomic function in cardiovascular regulation without the confounding effects of altered respiratory pattern. Results from 10 subjects showed that during voluntary control of breathing, mean values of heart rate and blood pressure increased, whereas fractal and spectral powers in heart rate in the respiratory frequency region decreased. End-tidal PCO2 was similar during spontaneous and controlled breathing. These results indicate that the act of voluntary control of breathing decreases the influence of the vagal component, which is the principal parasympathetic influence in cardiovascular regulation.
Resistive training increases fat-free mass and maintains RMR despite weight loss in postmenopausal women
Authors: Ryan A. S. , Pratley R. E. , Elahi D. , Goldberg A. P.
Published: December 2017

Percent body fat increases with age and is often accompanied by a loss in muscle mass, strength, and energy expenditure. The effects of 16 wk of resistive training (RT) alone or with weight loss (RTWL) on strength (isokinetic dynamometer), body composition (dual-energy X-ray absorptiometry), resting metabolic rate (RMR) (indirect calorimetry), and sympathetic nervous system activity (catecholamines) were examined in 15 postmenopausal women (50–69 yr). RT resulted in significant improvements in upper and lower body strength in both groups (P < 0.01). The nonobese women in the RT group (n = 8) did not change their body weight or fat mass with training. In the obese RTWL group (n = 7), body weight, fat mass, and percent body fat were significantly decreased (P < 0.001). Fat-free mass and RMR significantly increased with training in both groups combined (P < 0.05). There were no significant changes in resting arterialized plasma norepinephrine or epinephrine levels in either group with training. RT increases strength with and without weight loss. Furthermore, RT and RTWL increase fat-free mass and RMR and decrease percent fat in postmenopausal women. Thus, RT may be a valuable component of an integrated weight management program in postmenopausal women.
Times of change
Authors: Johnson L. R.
Published: December 2017

January 1, 1996 will see several changes in policy for the publications of the American Physiological Society.
Airway edema potentiates airway reactivity
Authors: Brown R. H. , Zerhouni E. A. , Mitzner W.
Published: December 2017

Thickening of the airway wall has been hypothesized to be one of the mechanisms contributing to airway hyperresponsiveness in asthma. If such thickening of the wall is internal to the airway smooth muscle or otherwise causes a decrease in baseline airway caliber, it should also cause exaggerated airway responsiveness. In the present study, we used high-resolution computed tomography to directly measure the changes in the caliber and wall thickness of conducting airways after aerosol histamine challenge before and after normal saline volume loading. On separate days, five anesthetized dogs received either a baseline aerosol challenge of 3 mg/ml of histamine for five breaths or the same aerosol challenge immediately after a 100 ml/kg bolus of normal saline infused over a 10-min period. Baseline aerosol histamine challenge decreased airway area to 71 +/- 2% (SE) of the control value (P < 0.05). Intravenous administration of 100 ml/kg of normal saline increased wall area by decreasing airway luminal area to 78 +/- 3% of the control value (P < 0.01), with no change in outer airway area. Aerosol histamine challenge superimposed on this engorgement with normal saline challenge further decreased airway luminal area to 54 +/- 3% of the control value (P < 0.01). Quantitative modeling indicated that the edema in the airway wall was mostly outside the smooth muscle and that the smooth muscle shortening with histamine was similar with and without edema. We conclude that a moderate degree of acute airway wall thickening can lead to a potentiated constrictor response to histamine.