bluuebunny/crossref_metadata_2025 huggingface dataset:
Interdependent regional lung emptying during forced expiration: a transistor model
Authors: Solway J. , Fredberg J. J. , Ingram R. H. , Pedersen O. F. , Drazen J. M.
Published: December 2017

We recognized similarities between isovolume pressure-flow curves of the lung and emitter-collector voltage-current characteristics of bipolar transistors, and used this analogy to model expiratory flow limitation in a two-generation branching network with parallel nonhomogeneity. In this model, each of two bronchi empty parenchymal compliances through a common trachea, and each branch includes resistances upstream and downstream of a flow-limiting site. Properties of each airway are specified independently, allowing simulation of differences between the tracheal and bronchial generations and between the parallel bronchial paths. Simulations of four types of parallel asymmetry were performed: unilateral peripheral bronchoconstriction; unilateral central bronchoconstriction; asymmetric redistribution of parenchymal compliance; and unilateral alteration of the bronchial area-transmural pressure characteristic. Our results indicate that multiple axial choke points can exist simultaneously in a symmetric lung when large airway opening-pleural pressure gradients exist; despite severe nonhomogeneity of regional lung emptying, flow interdependence among parallel branches tends to maintain a near normal configuration of the overall maximal expiratory flow-volume (MEFV) curve throughout a large fraction of the vital capacity; and sudden changes of slope of the MEFV curve (“knees” or “bumps”) may reflect choking in one branch in a nonuniform lung, but need not be obvious even when severe heterogeneity of lung emptying exists.
Electrical and mechanical changes in immobilized human muscle
Authors: Duchateau J. , Hainaut K.
Published: December 2017

After forearm fracture, the human thumb was unilaterally immobilized in eight subjects for 6 wk in a standard plaster cast. Changes of contraction properties were studied in the adductor pollicis muscle. The contralateral muscle remained unrestrained and served as control. After immobilization, the maximal voluntary contraction was reduced by 55% (P less than 0.05), and the electrically evoked maximal tetanic contraction (Po) was reduced by 33% (P less than 0.05). The decrease of Po was associated with increased maximal rate of tension development (10%) and decreased maximal rate of tension relaxation (22%). The twitch times to peak and to half relaxation were increased by 16 and 14%, respectively, but the twitch tension (Pt) was not significantly changed and the Pt/Po ratio was increased by 43% after immobilization. The muscle surface action potential presented an increase of its duration (19%) and a decrease of the amplitude and the total area (15 and 26%, respectively). The comparison of the electrical and mechanical alterations recorded during voluntary contractions, and in contractions evoked by electrical stimulation of the motor nerve, suggests that immobilization not only modifies the peripheral processes associated with contraction but also changes central and/or neural command of the contraction. At peripheral sites, it is proposed that the intracellular processes of contraction play the major role in the contractile impairment recorded during immobilization.
Effect of hypoxia-induced periodic breathing on upper airway obstruction during sleep
Authors: Warner G. , Skatrud J. B. , Dempsey J. A.
Published: December 2017

We studied the effect of hypoxia-induced unstable and periodic breathing on the incidence of obstructed breaths in nine subjects who varied widely in their increase in total pulmonary resistance (RL) during non-rapid-eye-movement (NREM) sleep. During normoxic NREM sleep, all subjects showed hypoventilation, augmented diaphragmatic electromyogram (EMGdi), and increased RL. This response varied: two subjects doubled their mean RL (range 6–9 cmH2O X l–1 X s); four moderate snorers increased RL four- to eightfold (RL = 16–48 cmH2O X l–1 X s); three heavy snorers showed high RL (31–89 cmH2O X l–1 X s) plus cyclical obstructive hypopnea as their predominant breathing pattern. In seven of nine subjects, hypoxia and coincident hypocapnia initially caused an irregular cyclical breathing pattern with obstructed breaths (RL greater than 50 cmH2O X l–1 X s). The incidence of obstructed breaths induced by unstable breathing was closely correlated with the level of RL experienced in the control condition of normoxic sleep (r = 0.91). The obstructed breaths had relatively high O2 saturation (90–96%) and markedly reduced EMGdi activity and peak flow rate (less than 0.2 l/s) compared with breaths immediately after the obstructed breaths, which showed lower O2 saturation (81–93%) and markedly augmented EMGdi and flow rates. After 3–6 cycles of obstructive hypopnea, periodic breathing occurred in most subjects. During periodic breathing in six of seven subjects, the incidence of obstructed or high-resistance breaths was decreased or eliminated since each central apneic period was followed by breath clusters characterized by very high EMGdi, very low RL, and high flow rates. The remaining subject showed a high incidence of obstructed breaths during all phases of normoxic and hypoxic sleep. These data show that hypoxia-induced instability in breathing pattern can cause obstructed breaths during sleep coincident with reduced motor output to inspiratory muscles. However, this obstruction is only manifested in subjects susceptible to upper airway atonicity and narrowing (such as snorers) and can be prevented in most cases if respiratory drive is permitted to reach sufficiently high levels (as during central apnea).
Breathing pattern during exercise in young black and Caucasian subjects
Authors: Cerny F. J.
Published: December 2017

Lung volumes in sex-, age-, height-, and weight-matched Black subjects are 10–15% lower than those in Caucasians. To determine whether this decreased lung volume affected the ventilatory adaptation to exercise, minute ventilation (VE), its components, frequency (f) and tidal volume (VT), and breathing pattern were observed during incremental cycle-ergometer exercise. Eighteen Caucasian (age 8–30 yr) and 14 Black (age 8–25 yr) subjects were studied. Vital capacity (VC) was lower (P less than 0.001) in the Black subjects [90.6 +/- 8.6 (SD) vs. 112.9 +/- 9.9% predicted], whereas functional residual capacity/total lung capacity was higher (P less than 0.05). VE, mixed expired O2 and CO2, VT, f, and inspiratory (TI), expiratory (TE), and total respiratory cycle (TT) duration were measured during the last 30 s of each 2-min load. Statistical comparisons with increasing power output were made at rest and from 0.6 to 2.4 W/kg in 0.3-W/kg increments. VE was higher in Blacks at all work loads and reached significance (P less than 0.05) at 0.6 and 1.5 W/kg. VE/VO2 was also higher throughout exercise, reaching significance (P less than 0.01) at 1.2, 1.5, and 1.8 W/kg. The Black subjects attained any given level of VE with a higher f (P less than 0.001) and lower VT. TI and TE were shortened proportionately so that TI/TT was not different. Differences in lung volume and the ventilatory response to exercise in these Black and Caucasian subjects suggest differences in the respiratory pressure-volume relationships or that the Black subjects may breathe higher on their pressure-volume curve.
Platelet aggregation increases cholinergic neurotransmission in canine airway
Authors: Tamaoki J. , Sekizawa K. , Osborne M. L. , Ueki I. F. , Graf P. D. , Nadel J. A.
Published: December 2017

To determine whether thromboxane A2 released from aggregating platelets increases the contractile response of airway smooth muscle to cholinergic nerve stimulation and, if so, what the mechanism of action is, we studied in vitro bronchial segments from dogs under isometric conditions. The contractile responses to electrical field stimulation at 30 s and 1 min after the addition of autologous platelets were increased by 11.1 +/- 3.2 (SD) and 20.7 +/- 5.4%, respectively, and were accompanied by the release of thromboxane A2. These effects were inhibited either by pretreatment of platelets with indomethacin or by addition of the thromboxane A2 receptor antagonist SQ 29548. Likewise, the thromboxane A2 mimetic U 46619, in subthreshold doses (i.e., insufficient to increase base-line tension), increased electrical field stimulation-induced contraction by 18.7 +/- 4.8%. The increase was greater in the presence of a concentration of physostigmine that did not cause spontaneous contraction and was blocked by SQ 29548 but not by hexamethonium or by phentolamine. Methacholine-induced contractions were unaffected by U 46619. These results indicate that aggregating platelets, by releasing thromboxane A2, increase the airway contractile response to neural stimulation probably by the accelerated release of acetylcholine.
Effect of hemolysis on reflection coefficient determined by endogenous blood indicators
Authors: Maron M. B. , Pilati C. F. , Maender K. C.
Published: December 2017

The osmotic reflection coefficient (sigma) can be estimated from the increases in hematocrit and plasma protein concentration that result from fluid filtration occurring in an isolated perfused organ. We determined what effect perfusion pump-induced hemolysis has on the value of sigma determined by this technique in both the isolated canine left lower lung lobe (LLL) and forelimb by comparing estimates of sigma obtained before and after correction for hemolysis. Hemolysis was corrected by using the slopes of the relationships between hematocrit and plasma hemoglobin concentration and between the plasma protein and hemoglobin concentrations to correct hematocrit and protein concentration to a state of zero hemolysis. Uncorrected estimates of sigma in the LLL were 1.19 +/- 0.14 (SE) at a venous pressure (Pv) of 12 Torr (n = 7) and 0.90 +/- 0.02 at a Pv of 19 Torr (n = 6). Both sets of LLL's yielded sigma values of 0.77 +/- 0.03 after hemolysis correction. In the forelimb (n = 5), uncorrected and corrected estimates of sigma of 0.99 +/- 0.03 and 0.85 +/- 0.01, respectively, were obtained. The latter values were similar to sigma's (0.88 +/- 0.01) determined by lymph analysis in five additional forelimbs. We conclude that hemolysis results in overestimates of sigma. After hemolysis correction, this technique yields similar results to those obtained from lymph analysis for the forelimb and from published values for the LLL.
Contractile properties of expiratory abdominal muscles: effect of elastase-induced emphysema
Authors: Arnold J. S. , Thomas A. J. , Kelsen S. G.
Published: December 2017

The present study examined the intrinsic contractile properties and endurance of the transverse abdominis and external oblique abdominal expiratory muscles in adult hamsters and compared their performance with the diaphragm. Experiments were performed in vitro on isolated bundles of muscle stimulated electrically. In control animals peak twitch tension was similar in the two muscles. In contrast, the twitch contraction time and one-half relaxation time of the transverse abdominis were significantly greater than that of the external oblique. The isometric tension generated over a range of stimulus frequencies (i.e., the force-frequency relationship) was a greater percent of the maximum value in response to subtetanizing frequencies (10–40 Hz) in the transverse abdominis than in the external oblique. For both abdominal muscles, however, the tension generated over this range of stimulus frequencies was less than that of the diaphragm. The endurance of the transverse abdominis during repeated contractions was significantly greater than that of the external oblique but similar to the diaphragm. The effect of chronic hyperinflation produced by elastase-induced emphysema on the contractile function of the two muscles was assessed in a second group of adult hamsters. In emphysematous animals peak twitch tension, contraction time, and one-half relaxation time of the twitch and force-frequency curves of muscles from emphysematous animals were similar to values obtained in control animals for both the external oblique and transverse abdominis. However, the endurance of both the transverse abdominis and external oblique muscles was greater in emphysematous than control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Carnitine metabolism during exercise in patients with peripheral vascular disease
Authors: Hiatt W. R. , Nawaz D. , Brass E. P.
Published: December 2017

The distribution between carnitine and the acyl derivatives of carnitine reflects changes in the metabolic state of a variety of tissues. Patients with peripheral vascular disease (PVD) develop skeletal muscle ischemia with exertion. This impairment in oxidative metabolism during exercise may result in the generation of acylcarnitines. To test this hypothesis, 11 patients with PVD and 7 age-matched control subjects were evaluated with graded treadmill exercise. Subjects with PVD walked to maximal claudication pain at a peak O2 consumption (VO2) of 19.9 +/- 1.3 ml X kg-1 X min-1 (mean +/- SE). Control subjects were taken to a near-maximal work load at a VO2 of 31.3 +/- 1.0 ml X kg-1 X min-1. In patients with PVD, the plasma concentration of total acid-soluble, long-chain acylcarnitine and total carnitine was increased at peak exercise compared with resting values. Four minutes postexercise, the plasma short-chain acylcarnitine concentration was also increased. In control subjects taken to the higher work load, only the long-chain acylcarnitine concentration was increased at peak exercise. In patients with PVD, plasma short-chain acylcarnitine concentration at rest was negatively correlated with subsequent maximal walking time (r = -0.51, P less than 0.05). In conclusion, acylcarnitines increased in patients with PVD who walked to maximal claudication pain, whereas control subjects did not show equivalent changes even when taken to a higher work load. The relationship between short-chain acylcarnitine concentration at rest and subsequent exercise performance suggests that repeated episodes of ischemia may cause chronic accumulation of short-chain acylcarnitine in plasma in proportion to the severity of disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac, respiratory, and renal responses to stimulation of the external cuneate nucleus
Authors: Dean C. , Kostreva D. R.
Published: December 2017

The cardiac, respiratory, and renal responses of electrical stimulation and microinjection of excitatory amino acids into the external cuneate nucleus were investigated in 57 cats anesthetized with pentobarbital sodium, paralyzed, and artificially ventilated. Trains of rectangular cathodal pulses of 40–100 microA at 50 Hz and 0.1 ms duration were delivered through monopolar glass microelectrodes with a tip diameter of 10–20 micron, filled with indium-Woods metal alloy. Electrical stimulation at 232 histologically identified sites within the external cuneate nucleus could evoke changes in arterial blood pressure, heart rate, and efferent renal sympathetic nerve activity. In a further set of experiments, a change in respiration was observed at 74 identified sites. An increase or decrease in all parameters measured could be elicited at different stimulus sites within the external cuneate nucleus. Repositioning of the electrode (0.2–0.4 mm) in depth or laterally could result in a different response with stimulation. Microinjections of D,L-homocysteic acid or glutamate could mimic the evoked changes in blood pressure, heart rate, efferent renal sympathetic nerve activity, and respiration. This suggests that the external cuneate nucleus contains cell bodies that may modulate components of various cardiac, respiratory and renal reflexes. It is proposed that the external cuneate nucleus may be involved in the integration of somato-autonomic reflex responses.
Airway caliber and the work of breathing in humans
Authors: Jennings S. J. , Warren J. B. , Pride N. B.
Published: December 2017

Mechanical work rate of breathing was measured in five normal subjects during voluntary eucapnic hyperventilation at rates of approximately 10, 20, 40, 60, and 80 l/min before and after inhalation of 1 mg of ipratropium bromide, an anticholinergic agent. Chest wall recoil pressure was measured over a range of lung volumes in each subject and was used as the reference pressure in the calculation of work rate. There was little change in elastic or resistive work rate at rest when vagal tone was reduced by ipratropium. The mean work at 40, 60, and 80 l/min was 8.9, 17.2, and 34.0 cmH2O.l–1.s before and 5.6, 12.4 and 25.8 cmH2O.l–1.s after ipratropium. This suggests that vagal tone significantly influences the work of breathing at high ventilatory rates, such as occur during strenuous exercise.
Respiratory changes in thoracic muscle length during bronchoconstriction
Authors: van Lunteren E. , Haxhiu M. A. , Deal E. C. , Arnold J. S. , Cherniack N. S.
Published: December 2017

The purpose of the present study was to assess the effects of bronchoconstriction on respiratory changes in length of the costal diaphragm and the parasternal intercostal muscles. Ten dogs were anesthetized with pentobarbital sodium and tracheostomized. Respiratory changes in muscle length were measured using sonomicrometry, and electromyograms were recorded with bipolar fine-wire electrodes. Administration of histamine aerosols increased pulmonary resistance from 6.4 to 14.5 cmH2O X l–1 X s, caused reductions in inspiratory and expiratory times, and decreased tidal volume. The peak and rate of rise of respiratory muscle electromyogram (EMG) activity increased significantly after histamine administration. Despite these increases, bronchoconstriction reduced diaphragm inspiratory shortening in 9 of 10 dogs and reduced intercostal muscle inspiratory shortening in 7 of 10 animals. The decreases in respiratory muscle tidal shortening were less than the reductions in tidal volume. The mean velocity of diaphragm and intercostal muscle inspiratory shortening increased after histamine administration but to a smaller extent than the rate of rise of EMG activity. This resulted in significant reductions in the ratio of respiratory muscle velocity of shortening to the rate of rise of EMG activity after bronchoconstriction for both the costal diaphragm and the parasternal intercostal muscles. Bronchoconstriction changed muscle end-expiratory length in most animals, but for the group of animals this was statistically significant only for the diaphragm. These results suggest that impairments of diaphragm and parasternal intercostal inspiratory shortening occur after bronchoconstriction; the mechanisms involved include an increased load, a shortening of inspiratory time, and for the diaphragm possibly a reduction in resting length.
Interactive effects of CO2 and upper airway negative pressure on breathing pattern
Authors: van Lunteren E.
Published: December 2017

The interactive effects of upper airway negative pressure and hypercapnia on the pattern of breathing were assessed in pentobarbital-anesthetized cats. At any given level of pressure in the upper airway, hypercapnia increased respiratory rate, reduced inspiratory time, and augmented tidal volume, inspiratory airflow, and the peak and rate of rise of diaphragm electrical activity. Conversely, at any given level of CO2, upper airway negative pressure decreased respiratory rate, prolonged inspiratory time, and depressed inspiratory airflow and diaphragm electromyogram (EMG) rate of rise. Application of negative pressure to the upper airway shifted the relationship between tidal volume and inspiratory time upward and rightward. The relationship between inspiratory and expiratory times, however, was linearly correlated over a wide range of chemical drives and levels of upper airway pressure. These results suggest that in the anesthetized cat upper airway negative pressure afferent inputs 1) interact in an additive fashion with hypercapnia to alter the pattern of breathing, 2) interact multiplicatively with CO2 to influence mean inspiratory airflow and diaphragm EMG rate of rise, 3) depress the generation of central inspiratory activity, 4) increase the time-dependent volume threshold for inspiratory termination, and 5) affect the ratio between inspiratory and expiratory times in a similar manner as alterations in PCO2.
Effects of carbon dioxide on mental performance
Authors: Sayers J. A. , Smith R. E. , Holland R. L. , Keatinge W. R.
Published: December 2017

Although elevated levels of inspired CO2 have been recorded in work situations, little is known about effects of concentrations greater than 6% on mental performance. We have measured the effects of inhaling 0, 4.5, 5.5, 6.5, or 7.5% CO2 for 20 min on normal young adults unhabituated to CO2. Performance of reasoning tasks, such as AB logic problems, was significantly slowed at the higher levels of CO2, with a threshold at end-tidal PCO2 close to 51 Torr. Accuracy of reasoning and short-term memory were not significantly affected. More prolonged studies with inhalation of 6.5% CO2 showed that after the first 10 min ventilation tended to increase, end-tidal PCO2 to fall, and slowing of reasoning to recover, but substantial decrement in performance continued for 80 min, by which time performance virtually stabilized. On return to air breathing, preexposure performance was resumed within 10 min. Also caused by 6.5% CO2 was a significant rise in subjectively assessed irritability and discomfort, with no significant change in alertness or in either registration or recall of long-term memory.
Combined effects of hypertension and chronic running program on rat heart
Authors: Schaible T. , Malhotra A. , Ciambrone G. , Buttrick P. , Scheuer J.
Published: December 2017

Previous studies in hearts of female rats have demonstrated that ventricular hypertrophy due to systolic overload, when combined with hypertrophy induced by a chronic swimming program, results in increased cardiac performance and enhanced contractile protein activity compared with the effects of hypertension alone. To explore how a chronic running program affects the function of hypertensive hearts, renal hypertension was created in female rats, and the animals were subjected to a program of chronic treadmill running. Running alone caused enhanced cardiac function, an increase in myosin adenosinetriphosphatase (ATPase) activity, and an increase in the percent of the V1 myosin isoenzyme. Hypertension alone caused cardiac hypertrophy with a depression in myosin ATPase activity and a decrease in the percent of the V1 isoenzyme. Running improved cardiac function in hearts of normotensive rats but had no effect in hearts of hypertensive rats. Despite the diminished myosin ATPase activity in hearts of hypertensive runners and the decrease in percent of the V1 isoenzyme, cardiac function was well maintained. The results demonstrate that a chronic running program in hypertensive rats, in contrast to a chronic swimming program, had virtually no effect on cardiac performance or contractile proteins. The dissociation between myocardial performance and the contractile proteins implicates other biochemical mechanisms in the adaptations observed.
Low-frequency respiratory mechanical impedance in the rat
Authors: Hantos Z. , Daroczy B. , Suki B. , Nagy S.
Published: December 2017

modified forced oscillatory technique was used to determine the respiratory mechanical impedances in anesthetized, paralyzed rats between 0.25 and 10 Hz. From the total respiratory (Zrs) and pulmonary impedance (ZL), measured with pseudorandom oscillations applied at the airway opening before and after thoracotomy, respectively, the chest wall impedance (ZW) was calculated as ZW = Zrs - ZL. The pulmonary (RL) and chest wall resistances were both markedly frequency dependent: between 0.25 and 2 Hz they contributed equally to the total resistance falling from 81.4 +/- 18.3 (SD) at 0.25 Hz to 27.1 +/- 1.7 kPa.l–1 X s at 2 Hz. The pulmonary compliance (CL) decreased mildly, from 2.78 +/- 0.44 at 0.25 Hz to 2.36 +/- 0.39 ml/kPa at 2 Hz, and then increased at higher frequencies, whereas the chest wall compliance declined monotonously from 4.19 +/- 0.88 at 0.25 Hz to 1.93 +/- 0.14 ml/kPa at 10 Hz. Although the frequency dependence of ZW can be interpreted on the basis of parallel inhomogeneities alone, the sharp fall in RL together with the relatively constant CL suggests that at low frequencies significant losses are imposed by the non-Newtonian resistive properties of the lung tissue.
Almitrine bismesylate and the central and peripheral ventilatory response to CO2
Authors: Olievier C. N. , Berkenbosch A. , Degoede J. , Kruyt E. W.
Published: December 2017

Effects of almitrine bismesylate on the peripheral and central chemoreflex to a CO2 challenge during normoxia were studied in nine alpha-chloralose-urethan anesthetized cats. With the dynamic end-tidal CO2 forcing technique the ventilatory response after a square-wave change in end-tidal PCO2 (PETCO2) was partitioned into a central and a peripheral part using a two-compartment model. With almitrine administered intravenously (0.6 mg/kg followed by a maintenance dose of 0.4 mg.kg-1 X h-1) the CO2 sensitivity of the peripheral chemoreflex increased on the average from 0.315 to 0.564 l.min-1 X kPa-1 (P less than 0.001, 6 cats, 73 runs), whereas the CO2 sensitivity of the central chemoreflex remained the same (P = 0.87). The extrapolated PETCO2 at zero ventilation (apneic threshold) of the (total) steady-state response curve decreased on the average from 3.50 to 2.36 kPa (P less than 0.001). With the artificial brain stem perfusion technique it was confirmed that almitrine did not affect ventilation by administering it to the blood perfusing the brain stem. We conclude that almitrine bismesylate during normoxia enhances the CO2 sensitivity of the peripheral chemoreflex loop and decreases the apneic threshold due to an action located outside the brain stem.
Fiber type specific glycogen utilization in rat diaphragm during treadmill exercise
Authors: Green H. J. , Ball-Burnett M. E. , Morrissey M. A. , Spalding M. J. , Hughson R. L. , Fraser I. G.
Published: December 2017

To examine the significance of endogenous stores of glycogen in specific fiber types (I, IIa, IIb) of the costal region of the diaphragm, adult male Wistar rats performed continuous running (25 m/min, 8 degrees grade) exercise for either 30 min or until fatigue. At 30 min of exercise, glycogen loss, as measured microphotometrically using the periodic acid-Schiff technique averaged between 73 and 80% (P less than 0.05) in the different fiber types. When exercise was performed to exhaustion, representing an additional 94 min, no further reduction in glycogen was observed in any fiber type. Biochemical determinations of glycogen from the diaphragm confirmed the extensive reduction in glycogen concentration with exercise. Large reductions (P less than 0.05) in glycogen were also noted in the soleus, plantaris, and vastus lateralis red. Although significant depletion (P less than 0.05) occurred in the vastus lateralis white, it was not as pronounced as in these other muscles. Repletion to preexercise glycogen concentration was complete by 4 h of recovery in all muscles except the vastus lateralis white. It is concluded that endogenous glycogen is a significant substrate in all muscles sampled regardless of fiber composition. In the case of the costal region of the diaphragm, the increased work of breathing resulting from heavy exercise leads to the recruitment of all fiber types, and each fiber type depends on glycogen as a substrate at least early in the exercise.
Perceived exertion and gas exchange after calcium and beta-blockade in atrial fibrillation
Authors: Myers J. , Atwood J. E. , Sullivan M. , Forbes S. , Friis R. , Pewen W. , Froelicher V.
Published: December 2017

Nine male patients (mean age 65 yr) with chronic atrial fibrillation underwent maximal exercise testing during placebo, beta-adrenergic (celiprolol, 600 mg), or calcium (diltiazem, 30 or 60 mg four times daily) channel blockade. The results were analyzed to determine which factors most closely related to ratings of perceived exertion (RPE) during exercise. Heart rate (HR), blood pressure (BP), oxygen uptake (VO2), minute ventilation (VE), and carbon dioxide production (VCO2) were evaluated at rest, 3.0 mph/0% grade, the gas exchange anaerobic threshold (ATge), 80% of placebo maximal O2 uptake, and maximal exercise. Both beta-adrenergic and calcium channel blockade significantly reduced heart rate and systolic blood pressure relative to placebo; these effects were more profound during beta-adrenergic blockade and as exercise progressed. Correlation coefficients and estimates of slope were derived for changes in RPE during exercise vs. changes in HR, VO2, VE, and VCO2 during the three treatments (r = 0.76 to 0.92, P less than 0.001). Although RPE was significantly correlated with HR during placebo and diltiazem therapy (r = 0.45, P less than 0.01), this was not the case during beta-adrenergic blockade (r = 0.31, NS). Slope of the regression lines between RPE and VO2, VE, and VCO2 did not differ between the three treatments. Slope of the regression lines between RPE and HR differed only during calcium channel blockade. Because the presence of atrial fibrillation and beta-adrenergic blockade altered the associations between RPE, VO2, and HR, these results suggest that VE is more closely related to RPE than the other parameters.
Neuromuscular and mechanical responses to inspiratory resistive loading during sleep
Authors: Hudgel D. W. , Mulholland M. , Hendricks C.
Published: December 2017

The purposes of this study were 1) to characterize the immediate inspiratory muscle and ventilation responses to inspiratory resistive loading during sleep in humans and 2) to determine whether upper airway caliber was compromised in the presence of a resistive load. Ventilation variables, chest wall, and upper airway inspiratory muscle electromyograms (EMG), and upper airway resistance were measured for two breaths immediately preceding and immediately following six applications of an inspiratory resistive load of 15 cmH2O.l–1 X s during wakefulness and stage 2 sleep. During wakefulness, chest wall inspiratory peak EMG activity increased 40 +/- 15% (SE), and inspiratory time increased 20 +/- 5%. Therefore, the rate of rise of chest wall EMG increased 14 +/- 10.9% (NS). Upper airway inspiratory muscle activity changed in an inconsistent fashion with application of the load. Tidal volume decreased 16 +/- 6%, and upper airway resistance increased 141 +/- 23% above pre-load levels. During sleep, there was no significant chest wall or upper airway inspiratory muscle or timing responses to loading. Tidal volume decreased 40 +/- 7% and upper airway resistance increased 188 +/- 52%, changes greater than those observed during wakefulness. We conclude that 1) the immediate inspiratory muscle and timing responses observed during inspiratory resistive loading in wakefulness were absent during sleep, 2) there was inadequate activation of upper airway inspiratory muscle activity to compensate for the increased upper airway inspiratory subatmospheric pressure present during loading, and 3) the alteration in upper airway mechanics during resistive loading was greater during sleep than wakefulness.
Effect of airway wall flexibility on clearance by simulated cough
Authors: Soland V. , Brock G. , King M.
Published: December 2017

In our previous study, we investigated the relationship between mucus rheology, depth of mucus layer, and clearance by simulated cough. The purpose of the present study was to examine the effect of airway wall flexibility on the clearance of mucuslike gels. Transient airflows similar to cough were generated by both positive and negative pressure, the latter to mimic the dynamic compression that occurs during real cough. As in the previous study, the trachea was modeled as a trough of rectangular cross section with only the bottom lined with the mucus simulant. Clearance was followed by observing the displacement of marker particles. Since cough clearance is intimately related to wave formation in the mucus blanket, we hypothesized that clearance might be impeded if the wave formation occurred simultaneously in the wall and its lining layer. Thus, in one set of experiments the bottom rigid surface of the model trachea was replaced with a frame over which a flexible membrane could be drawn, whereas in the other set the rigid top was replaced by the frame. We also examined the effect of negative-pressure cough in excised canine tracheae, comparing the case where the tracheal membrane was free to deform vs. the case where it was secured. For the rigid-walled model, clearance by positive or negative pressure, with matched flow pattern, was the same. With the mucus simulant lining the flexible bottom surface, clearance increased with increasing membrane flexibility for negative-pressure cough and decreased for positive-pressure cough.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrolyte composition changes of chronically K-depleted rats after K loading
Authors: Sadre M. , Sheng H. P. , Fiorotto M. , Nichols B. L.
Published: December 2017

The responses of whole body, skeletal muscle, and plasma to oral K loading were studied in K-depleted male rats. Potassium depletion was induced by feeding the rats a K-deficient diet for 4 wk and injecting deoxycorticosterone acetate during the first week. After 4 wk, the rats were growth retarded and hypokalemic (1.9 mmol/l plasma) and had low whole-body and muscle K content, 188 +/- 27 and 276 +/- 19 mmol/kg fat-free dried tissue (FFDT), respectively, compared with 296 +/- 10 and 454 +/- 13 mmol/kg FFDT for the control group. Sodium and water retention also occurred in the K-deficient group. After K depletion, the rats were divided into four groups and received either 0, 1, 2, or 3 intragastric doses of 10 mmol KCl/kg at 8-h intervals. The rats were killed 8 h after the last dose. Control rats were treated similarly. K-depleted and control rats responded differently to K loading. In the normal rats, plasma K remained at 5.0 +/- 0.5 mmol/l, muscle K increased to 502 +/- 24 mmol/kg, and muscle K/N ratio increased from 3.0 to 3.4 mmol/g. In the K-depleted rats, plasma K increased to 7.2 +/- 0.7 mmol/l, muscle K increased to 453 +/- 50 mmol/kg, and muscle K/N ratio increased from 1.8 to 3.1 mmol/g. These data indicate that the capacity of the muscles to accumulate K was impaired after severe K depletion and caused elevated plasma K levels when repletion was complete.
Decline in peripheral chemoreceptor excitatory stimulation during acute hypoxia in the lamb
Authors: Carroll J. L. , Bureau M. A.
Published: December 2017

Chemoreceptor function was studied in eight 2- to 3-day-old unanesthetized lambs to sequentially assess hypoxic chemoreflex strength during an 18-min exposure to hypoxia [inspired O2 fraction (FIO2) = 0.08]. The immediate ventilatory (VE) drop in response to five breaths of pure O2 was measured at 3, 7, and 15 min during hypoxia. Each lamb was studied again at 10–11 days of age. At 2–3 days of age VE increased, with the onset of hypoxia, from 658 +/- 133 (SD) ml.min-1 X kg-1 to a peak of 1,124 +/- 177 ml.min-1 X kg-1. A dampening of the VE response then occurred, with a mean decline in VE of 319 ml.min-1 X kg-1 over the 18-min hypoxia period. Each pure O2 test (Dejours test) resulted in an abrupt fall in VE (delta VEDejours). This VE drop was 937 +/- 163, 868 +/- 244, and 707 +/- 120 ml.min-1 X kg-1 at 3, 7, and 15 min of hypoxia, respectively. Comparing the three O2 tests, delta VEDejours was significantly decreased by 15 min, indicating a loss of about one-fourth of the O2 chemoreflex drive during hypoxia. Testing at 10–11 days of age revealed a smaller VE decline during hypoxia. O2 tests at the beginning and end of the hypoxic period were not significantly different, indicating a smaller loss of hypoxic chemoreflex drive in the more mature animals.(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo functional antagonism between isoproterenol and bronchoconstrictants in the dog
Authors: Jenne J. W. , Shaughnessy T. K. , Druz W. S. , Manfredi C. J. , Vestal R. E.
Published: December 2017

The functional antagonism between isoproterenol and methacholine, histamine and serotonin, as described in vitro in respiratory smooth muscle was explored in vivo in a canine model. Infusions of isoproterenol were administered during brief peaks of bronchospasm produced by aerosolized methacholine and histamine, or during sustained bronchospasm produced by infused serotonin. In eight mongrel dogs anesthetized with pentobarbital sodium, the mean protection by infused isoproterenol against methacholine challenge decreased from 60.6 to 29.1% as the mean lung resistance (RL) was increased from 78 to 232% over base line by a fourfold increase in methacholine (P less than 0.002). In six dogs, the mean protection by isoproterenol against histamine decreased from 55.5 to 26.9% as the opposing RL increased from 80 to 182% over base line with a fourfold increase in histamine (P less than 0.02). However, with serotonin infusions there was only a small 18% mean decrease in protection (P = 0.05), associated with a correspondingly small 37% mean increase in dose of serotonin despite a 269% mean increase in resistance (P = 0.02). In all cases, the loss of protection correlated more closely with the dose of constrictant than the resistance increase over base line. These findings demonstrate in vivo functional antagonism between isoproterenol and the dose of bronchoconstrictant but not necessarily resistance increase per se.
Effects of blood pressure on force production in cat and human muscle
Authors: Hobbs S. F. , McCloskey D. I.
Published: December 2017

In anesthetized cats reducing local arterial pressure from 125 to 75 Torr decreased blood flow (53 +/- 5%) and force production (57 +/- 7%) in soleus and medial gastrocnemius. Force was produced in these muscles by aerobic, slowly fatiguing fibers. Similar reductions in arterial pressure did not affect force production in caudofemoralis, which contains mainly fast-fatiguing fibers. In human subjects the electromyogram produced by the ankle extensors during rhythmic constant-force contractions increased as the contracting muscles were raised above the heart during legs-up tilt. This suggests that force production of active muscle fibers at a given level of activation fell with muscle perfusion pressure, thus requiring augmentation of muscle activity to sustain the standard contractions. Because aerobic fibers contributed to these contractions, it appears that force production of human muscle fibers is sensitive to small changes in perfusion pressure and, presumably, blood flow. The critical dependence of developed muscular force on blood pressure is of importance to motor control and may also play a significant role in cardiovascular control during exercise.
Does rib cage-abdominal paradox signify respiratory muscle fatigue?
Authors: Tobin M. J. , Perez W. , Guenther S. M. , Lodato R. F. , Dantzker D. R.
Published: December 2017

Studies suggesting that abnormal motion of the rib cage (RC) and abdomen (Ab) may indicate respiratory muscle fatigue have not separated the influence of respiratory load from that of fatigue in its pathogenesis. We hypothesized that abnormalities on RC-Ab motion are primarily related to increased load rather than fatigue. We tested this hypothesis in subjects breathing against resistive loads while maintaining 30 and 60% of maximum mouth pressure (Pmmax). RC-Ab asynchrony and paradox and the degree of variation in compartmental contribution to tidal volume were measured by inductive plethysmography and quantitated by the Konno-Mead method of analysis. Comparing measurements of base line and 30 and 60% of Pmmax indicated that the degree of asynchrony, paradox, and variation in compartmental contribution were significantly related to the level of the load; significant abnormalities were observed at even 30% of Pmmax, a target pressure that can be sustained indefinitely. In another group of subjects, fatigue was induced by sustaining 60% of Pmmax to the limits of tolerance. Indexes of abnormal RC-Ab motion increased from base line during the 1st min of loaded breathing but displayed no progression from the beginning to the end of the fatigue run. Immediately on discontinuation of the load, the indexes returned to levels similar to base line despite persistence of the fatigue state. These results in healthy subjects breathing against severe resistances indicate that RC-Ab asynchrony and paradox and variation in compartmental contribution to tidal volume are predominantly due to increases in respiratory load rather than muscle fatigue.
Continuous monitoring of blood volume changes in humans
Authors: Hinghofer-Szalkay H. , Greenleaf J. E.
Published: December 2017

The mass density of antecubital venous blood was measured continuously for 80 min/session with 0.1 g/l precision at a flow rate of 1.5 ml/min in six male subjects. Each person participated in two different sessions with the same protocol. To induce transvascular fluid shifts, the subjects changed from sitting to standing and from standing to supine positions. There was transient blood density shifts immediately after postural changes, followed by an asymptotic approach to a new steady-state blood density level. Additional deviations from a simple time course were regularly observed. Blood density increased by 3.5 +/- 1.4 (SD) g/l when standing after sitting and decreased by 5.0 +/- 1.2 g/l while supine after standing. The corresponding half time of the blood density increase was 5.6 +/- 1.4 min (standing after sitting) and 6.9 +/- 3.1 min (supine after standing) of the blood density decrease. Erythrocyte density was calculated and did not change with body position. Whole-body blood density was calculated from plasma density, hematocrit, and erythrocyte density, assuming an F-cell ratio of 0.91. Volume shifts were computed from the density data; the subject's blood volume density decreased by 6.2 +/- 1.2% from sitting to standing and increased by 8.5 +/- 2.1% from standing to supine. Additional discrete plasma density and hematocrit measurements gave linear relations (P less than 0.001) between all possible combinations of blood density, plasma density, and hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)
Lowered pulmonary arterial pressure prevents edema after endotoxin in sheep
Authors: Allen S. J. , Drake R. E. , Katz J. , Gabel J. C. , Laine G. A.
Published: December 2017

Escherichia coli endotoxin causes increased capillary membrane permeability and increased pulmonary arterial pressure (PAP) in sheep. If the pulmonary hypertension extends to the level of the microvasculature, then the increased microvascular pressure may contribute to the pulmonary edema caused by endotoxin. We tested the hypothesis that reducing the pulmonary hypertension would reduce the amount of edema caused by endotoxin. Twelve sheep were chronically instrumented with catheters to measure PAP, left atrial pressure, and central venous pressure. The sheep were divided into two groups. One group (E) of six sheep received an intravenous infusion of 4 micrograms/kg of E. coli endotoxin. The second group (E + SNP) received the same dose of endotoxin as well as a continuous infusion of sodium nitroprusside (SNP) to reduce PAP. Three hours after the endotoxin infusions, the sheep were terminated and the extravascular fluid-to-blood-free dry weight ratios of the lungs were determined (EVF). The base-line PAP was 17.5 +/- 2.7 mmHg. A two-way analysis of variance demonstrated a significant difference (P less than 0.01) in PAP between the E and E + SNP groups. Although PAP in each group varied as a function of time, the difference between the two groups did not. The mean PAP for the E + SNP group (20.9 +/- 1.5 mmHg) was lower than the E group PAP of 27.3 +/- 2.1 mmHg after the endotoxin spike. Furthermore, the E + SNP group EVF (3.9 +/- 0.2) was significantly less than the EVF of the E group (4.7 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of the pericardium on right and left ventricular filling in the dog
Authors: Assanelli D. , Lew W. Y. , Shabetai R. , LeWinter M. M.
Published: December 2017

We compared the influence of the pericardium on left and right ventricular (LV, RV) filling by measuring LV and RV pressures and segment lengths (SL, LV free wall, and RV inflow and outflow tracts) in six open-chest, pentobarbital sodium-anesthetized dogs before and after pericardiectomy. End-diastolic pressure (EDP) was varied by partial caval occlusion and dextran infusion. At each site the ln EDP-SL relation was fitted by linear regression and characterized by its slope and 1-Torr EDP intercept. The slope and 1-Torr intercept of the LV ln EDP-SL relation changed variably after pericardiectomy, but in each dog a change occurred that shifted this relation downward. In contrast, the RV inflow tract slope invariably decreased significantly after pericardiectomy, whereas its intercept was unchanged in all but one dog. The RV outflow tract results were similar to the inflow tract but less consistent. By the use of the raw EDP-SL data points, we calculated that the absolute contribution of the pericardium to EDP (i.e., the effective pericardial surface pressure) was similar at the three sites. However, as EDP values increased the proportional contribution of the pericardium to right ventricular end-diastolic pressure (RVEDP) increased, whereas that to left ventricular end-diastolic pressure (LVEDP) remained relatively constant. As a result, at the higher EDP values tested, the pericardium was responsible for a larger proportion of RVEDP than LVEDP.(ABSTRACT TRUNCATED AT 250 WORDS)
Thermoregulation during prolonged exercise in heat: alterations with beta-adrenergic blockade
Authors: Freund B. J. , Joyner M. J. , Jilka S. M. , Kalis J. , Nittolo J. M. , Taylor J. A. , Peters H. , Feese G. , Wilmore J. H.
Published: December 2017

Thermoregulation and cardiovascular drift were studied under conditions of prolonged exercise in a warm environment (dry bulb temperature 31.7 +/- 0.3 degrees C, rh 44.7 +/- 4.7%) during beta-adrenergic blockade. Fourteen subjects performed 90-min rides on a cycle ergometer at a work rate equivalent to 40% of their control maximal O2 uptake under each of three treatments provided in a randomized double-blind manner: atenolol (100 mg/day), propranolol (160 mg/day), and a placebo. Exercise during the propranolol trial resulted in significantly higher forearm vascular resistance values and significantly lower forearm blood flows (FBF) compared with the placebo trial. However, the significantly lower FBF during propranolol did not significantly alter the rectal temperature (Tre) response to prolonged exercise. In addition, both beta-blockers produced lower FBF for any given Tre, suggesting that beta-adrenergic blockade affects FBF through nonthermal factors. The slight differences in Tre, despite the large differences in FBF between the various treatments, are apparently the result of an enhanced sweat loss and a lower mean skin temperature during exercise with beta-blockade. The uncoupling of FBF and sweat loss provides evidence of independent regulation. The reduction in FBF at any given Tre was concomitant to lower blood pressure values during beta-blockade and suggests that baroreflexes provide significant input to the control of skin blood flow when both pressure and temperature maintenance are simultaneously challenged.