bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiorespiratory reflexes from muscles during dynamic and static exercise in the dog
Authors: Tallarida G. , Baldoni F. , Peruzzi G. , Raimondi G. , Di Nardo P. , Massaro M. , Visigalli G. , Franconi G. , Sangiorgi M.
Published: December 2017

Cardiorespiratory reflex responses during the initial phase of dynamic and static contraction of hindlimb muscles were studied in anesthetized dogs. Muscle contractions were elicited by stimulating the femoral and gastrocnemius nerves at 3 and 100 Hz with the intensity of 2.0–2.5 times the motor threshold for a 20-s period. Rhythmic contractions caused a decrease in arterial pressure (Pa) and heart rate (HR) and increased pulmonary ventilation (VE) by increasing frequency (f) without significantly changing VT. Tetanic contractions provoked an increase in Pa and HR and a hyperpnea resulting from a rise in both f and VT. Similar responses were also obtained in anesthetized dogs with carotid sinuses denervated and cervical vagi cut. The abrupt increase in VE at the start of both types of exercise was not associated with immediate significant decreases in end-tidal CO2 values. These two patterns of cardiocirculatory and respiratory responses were closely similar to those reported in anesthetized rabbits in previous studies. Both patterns of responses were reflexes initiated by activation of muscle receptors verified by interrupting the afferents from the contracting muscles. It is concluded that, during dynamic and static work, two distinct muscular reflex mechanisms might exert their drives, related to the muscular metabolic rate, on the circulatory and respiratory function.
Endogenous prostaglandins modulate histamine-induced contraction in canine tracheal smooth muscle
Authors: Shore S. A. , Powell W. S. , Martin J. G.
Published: December 2017

We studied the role of endogenous prostaglandins in modulating the histamine response of canine tracheal smooth muscle (TSM) in vitro. Indomethacin (INDO) (10(-7) - 10(-5) M), a cyclooxygenase and prostaglandin synthesis inhibitor, significantly increased maximum histamine-induced tension (Tmax) and decreased the concentration of histamine required to produce 50% of Tmax (EC50). Acetylsalicylic acid (10(-5) -5 X 10(-4) M), another less potent cyclooxygenase inhibitor, also decreased EC50. Neither the lipoxygenase inhibitor nordihydroguaiaretic acid nor the leukotriene antagonist FPL 55712 had any effect on histamine-induced tension in INDO-pretreated TSM. INDO reduced the standard deviation of EC50 from 0.47 in control TSM (n = 51) to 0.26 in INDO-pretreated TSM (n = 31) (P less than 0.02). High-pressure liquid chromatography established prostacyclin (PGI2), through its degradation product 6-oxo-PGF1 alpha, as the predominant prostaglandin produced by canine TSM. Exogenous PGI2 caused a concentration-dependent relaxation of histamine-contracted TSM. In the tissue bath, spontaneous efflux of 6-oxo-PGF1 alpha from TSM, as measured by radioimmunoassay, averaged 4.7 ng . g muscle-1 . min-1 and increased to 10 ng/g muscle (n = 10, P less than 0.001) with administration of histamine. The isometric tension produced by histamine (10(-4) M) was inversely linearly correlated with the log concentration of endogenous 6-oxo-PGF1 alpha (r = 0.81, P less than 0.01). Our results are consistent with an important role for endogenous bronchodilating prostaglandins, probably prostacyclin, in determining both the histamine sensitivity of canine TSM in vitro and its variability among individual animals.
Inspiratory rhythm in airway smooth muscle tone
Authors: Mitchell R. A. , Herbert D. A. , Baker D. G.
Published: December 2017

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.
Increasing gracilis muscle interstitial potassium concentrations stimulate group III and IV afferents
Authors: Rybicki K. J. , Waldrop T. G. , Kaufman M. P.
Published: December 2017

Static muscular contraction reflexly increases arterial blood pressure and heart rate. One possible mechanism evoking this reflex is that potassium accumulates in the interstitial space of a working muscle to stimulate group III and IV afferents whose activation in turn evokes a pressor response. The responses of group III and IV muscle afferents to increases in interstitial potassium concentrations within the range evoked by static contraction are unknown. Thus we injected potassium chloride into the gracilis artery of anesthetized dogs while we measured both gracilis muscle interstitial potassium concentrations with potassium-selective electrodes and the impulse activity of afferents in the gracilis nerve. We found that increasing interstitial potassium concentrations to levels similar to those seen during static contraction stimulated 14 of 16 group III and 29 of 31 group IV afferents. The responses of the afferents to potassium were concentration dependent. The typical response to potassium consisted of a burst of impulses, an effect that returned to control firing rates within 26 s, even though interstitial potassium concentrations remained elevated for several minutes. Although our results suggest that potassium may play a role in initiating the reflex cardiovascular responses to static muscular contraction, the accumulation of this ion does not appear to be solely responsible for maintaining the pressor response for the duration of the contraction.
Diffusion limitation in normal humans during exercise at sea level and simulated altitude
Authors: Torre-Bueno J. R. , Wagner P. D. , Saltzman H. A. , Gale G. E. , Moon R. E.
Published: December 2017

The relative roles of ventilation-perfusion (VA/Q) inequality, alveolar-capillary diffusion resistance, postpulmonary shunt, and gas phase diffusion limitation in determining arterial PO2 (PaO2) were assessed in nine normal unacclimatized men at rest and during bicycle exercise at sea level and three simulated altitudes (5,000, 10,000, and 15,000 ft; barometric pressures = 632, 523, and 429 Torr). We measured mixed expired and arterial inert and respiratory gases, minute ventilation, and cardiac output. Using the multiple inert gas elimination technique, PaO2 and the arterial O2 concentration expected from VA/Q inequality alone were compared with actual values, lower measured PaO2 indicating alveolar-capillary diffusion disequilibrium for O2. At sea level, alveolar-arterial PO2 differences were approximately 10 Torr at rest, increasing to approximately 20 Torr at a metabolic consumption of O2 (VO2) of 3 l/min. There was no evidence for diffusion disequilibrium, similar results being obtained at 5,000 ft. At 10 and 15,000 ft, resting alveolar-arterial PO2 difference was less than at sea level with no diffusion disequilibrium. During exercise, alveolar-arterial PO2 difference increased considerably more than expected from VA/Q mismatch alone. For example, at VO2 of 2.5 l/min at 10,000 ft, total alveolar-arterial PO2 difference was 30 Torr and that due to VA/Q mismatch alone was 15 Torr. At 15,000 ft and VO2 of 1.5 l/min, these values were 25 and 10 Torr, respectively. Expected and actual PaO2 agreed during 100% O2 breathing at 15,000 ft, excluding postpulmonary shunt as a cause of the larger alveolar-arterial O2 difference than accountable by inert gas exchange.
Efficacy of high-frequency ventilation in presence of extensive ventilation-perfusion mismatch
Authors: Kaiser K. G. , Davies N. J. , Rodriguez-Roisin R. , Bencowitz H. Z. , Wagner P. D.
Published: December 2017

Ten anesthetized normal dogs were each given two methacholine inhalational challenges to produce large amounts of low ventilation-perfusion (VA/Q) regions but little shunt. After one challenge, high-frequency ventilation (HFV) was applied, whereas after the other conventional mechanical ventilation (MV) was used, the order being randomized. Levels of both ventilatory modes were selected prior to challenge so as to result in similar and normal mean airway pressures and arterial PCO2 levels during control conditions. Gas exchange was assessed by both respiratory and multiple inert-gas transfer. Comparing the effect of HFV and MV, no statistically significant differences were found for lung resistance, pulmonary hemodynamic indices, arterial and mixed venous PO2, expired-arterial PO2 differences, or inert-gas data expressed as retention-excretion differences. The only variables that were different were mean airway pressure (2 cm higher during HFV, P less than 0.04) and arterial PCO2 (10 Torr higher during HFV, P less than 0.002). These results suggest that in this canine model of lung disease characterized by large amounts of low VA/Q regions, HFV is no more effective in delivering fresh gas to such regions than is MV.
Influence of pulmonary embolism on absorption of inhaled iodide-125
Authors: Dawson C. A. , Skebba S. C. , Linehan J. H. , Bronikowski T. A.
Published: December 2017

To evaluate the influence of embolus size on the absorption of 125I- deposited on the bronchoalveolar surface, we exposed isolated perfused rabbit lungs to an aerosol containing 125I- for 5 min. We monitored the blood radioactivity for the subsequent 2 h. Several groups of lungs were studied, including those in which blood flow was varied and those in which enough glass beads ranging in size from 58 to 548 micron were injected into the pulmonary artery to approximately double the vascular resistance. The results indicated that under control conditions approximately 94% of the 125I- deposited on the intrapulmonary bronchoalveolar surface was able to reach the pulmonary circulation during the 2-h perfusion period, and the bronchoalveolar surface was sufficiently perfused so that absorption was limited by the rate of diffusion into the blood rather than the rate of blood flow. In the absence of embolization, the initial absorption rate was approximately 10.4%/min regardless of the total flow rate. The 58-micron beads reduced the rate to approximately 7.5%/min, whereas the beads greater than or equal to 194 micron in diameter reduced the rate to approximately 4.5%/min. Thus the effect of the embolization on the absorption rate was directly related to the bead diameter, even though the number of beads injected was adjusted to produce about the same increase in vascular resistance.
Single motor unit and fiber action potentials during fatigue
Authors: Sandercock T. G. , Faulkner J. A. , Albers J. W. , Abbrecht P. H.
Published: December 2017

Muscle fatigue is defined as a loss of tension development during constant stimulation. Although the relationship is not well documented, muscle fatigue has been inferred from electromyogram (EMG) signals. The purpose of this study was to determine the relationship between the amplitude and duration of single motor unit action potentials (MUAPs) and the loss of tension development (fatigue) in the medial gastrocnemius muscles of cats. Single motor units were fatigued by continuous stimulation at 10 or 80 Hz or with trains of 40-Hz stimuli. When motor units were stimulated at 10 Hz and with trains at 40 Hz (low frequency), tension declined and remained depressed during recovery. The changes in the MUAP correlated poorly with changes in tension. During and after stimulation at 80 Hz (high frequency), changes in the amplitude and duration of MUAPs correlated highly with changes in tension development. Since the EMG signal is dependent on a summation and cancellation of individual MUAPs, the EMG provides a reasonable estimate of high-frequency fatigue but an unreliable measure of low-frequency fatigue.
Sympathoadrenal system and activation of glycogenolysis during muscular activity
Authors: Cartier L. J. , Gollnick P. D.
Published: December 2017

Comparisons were made of the appearance of phosphorylase (PHOS) a and lactate (LA) during electrical stimulation of the gastrocnemius (GM) and soleus (SM) muscles of normal and sympathectomized (SYMPX) rats. Ten-second stimulation at 3 Hz increased PHOS a approximately fourfold in the GM of normal rats, whereafter it declined during stimulation until at 60 s it was similar to rest. The increase in PHOS a of GM from SYMPX rats after 10 s of stimulation was approximately 50% that of normal rats. Stimulation of the SM produced smaller and slower increases in PHOS a with the peak occurring after 60 s, which remained constant to 90 s. SYMPX did not alter this effect in the SM. LA production and creatine phosphate depletion in the GM were continuous throughout stimulation and uninfluenced by SYMPX. This was true for the SM with the exception of LA production being greater after SYMPX. [ATP] was unchanged by electrical stimulation. The rate and magnitude of the PHOS a appearance was a function of stimulation frequency. Reversion of PHOS to the b form after stimulation was rapid, with approximately 50% of the peak value being attained in 2.5 s, and at 5 s the values were those of rest. These data demonstrate that an intact sympathoadrenal system is not obligatory for the initiation of glycogenolysis in skeletal muscle.
Kinetics of O2 uptake and release by human erythrocytes studied by a stopped-flow technique
Authors: Yamaguchi K. , Nguyen-Phu D. , Scheid P. , Piiper J.
Published: December 2017

The kinetics of O2 uptake into and release from human erythrocytes was investigated at 37 degrees C by a stopped-flow technique. From the time course of O2 saturation (SO2) change a specific transfer conductance of erythrocytes for O2 (GO2) was calculated. The following results were obtained: 1) GO2 decreased in the course of O2 uptake, but initial GO2 was nearly independent of SO2 at which uptake started; 2) addition of albumin to the medium reduced GO2; 3) increasing dithionite concentration in the medium in O2-release experiments progressively enhanced GO2, which became virtually constant for nearly the entire course of release; and 4) O2 uptake and O2 release (without dithoite) in the same SO2 range yielded very similar GO2. These results suggested that O2 uptake and release were importantly limited by diffusion through the external medium and that in the SO2 range between 0.3 and 0.8, chemical reaction exerted little limiting effect. Since O2 release at the highest dithionite concentration (40 mmol/l) appeared to be virtually unlimited by external diffusion, GO2 measured under these conditions, averaging 8.7 ml X min-1 X Torr-1 X ml erythrocytes-1, was considered to mainly reflect intracellular diffusion limitation. The corresponding specific transfer conductance for O2 transfer in whole blood (hematocrit, 0.45) is 3.9 ml X min-1 X Torr-1 X ml blood-1.
Central and peripheral causes of hyperreflexia in humans breathing 5% trimix at 650 m
Authors: Parmentier J. L. , Harris D. J. , Bennett P. B.
Published: December 2017

To clarify the mechanism of increased stretch reflex responsiveness in deep divers (hyperbaric hyperreflexia), comparative studies of stretch (T) and Hoffmann (H) reflexes were done on three men breathing 5% N2–0.5 bar O2-balance He at pressures up to 650 m of seawater (msw) (Atlantis IV simulated dive, F.G. Hall Laboratory, Duke Medical Center). Electromyography revealed increases at depth of up to 160% in the T reflex recruitment ratio (T reflex/Mmax) compared with surface controls. The H reflex recruitment ratio (Hmax/Mmax) did not change significantly. It is concluded that hyperbaric hyperreflexia is mainly due to increased muscle spindle sensitivity, presumably arising as a central effect on gamma-motoneuron activity. However, a purely peripheral effect of pressure on the spindle end-organ itself is not ruled out. Increases of 100–200% in muscle twitch peak force are reported and provide evidence that pressure can act directly on peripheral physiology. Postreflex clonic potentials (rebounds) during voluntary plantar flexion were significantly increased both in amplitude and number, leading to sustained clonus in one subject. In this respect, 5% N2 was less effective than 10% N2 of Atlantis III in controlling underdamping of the reflex loop. Conversely, the twitch contraction rate and clonic frequency in this study were only half as slowed compared with results from the earlier dive.
Respiratory, cardiovascular, and metabolic adjustments to exercise in the Hereford calf
Authors: Kuhlmann W. D. , Hodgson D. S. , Fedde M. R.
Published: December 2017

Six Hereford steers were studied before, during, and after short exercise bouts on a motor-driven treadmill (3 degrees incline) at four speeds (1.0, 1.4, 1.8, and 2.2 m X s-1). Oxygen consumption (MO2) and carbon dioxide production (MCO2) were measured by collecting the expired gas. Arterial and mixed venous blood samples were obtained simultaneously from indwelling catheters in the aorta and pulmonary artery. A 10-fold increase was observed in MO2 and MCO2 at the highest work load. Minute ventilation increased proportionately less than MO2 and MCO2 with increasing work loads, but alveolar ventilation was found to increase in proportion to both MO2 and MCO2. The highest work load produced a threefold increase in cardiac output primarily as a result of increased heart rate. A 10-fold increase in lactate and a 63% increase in serum potassium concentration were observed at the highest work load. Plasma cortisol levels were highest at 10 min postexercise and reached levels of seven times the resting values following exercise at the highest speed. The responses to exercise in the calf are qualitatively similar to those observed in other species, but quantitative differences exist in some cardiovascular and metabolic responses which may limit this animal's ability to perform strenuous exercise.
Effects of early hypoxia on breathing pattern in rabbit pups before and after vagotomy
Authors: Trippenbach T. , Kelly G. , Affleck R.
Published: December 2017

We examined the influence of vagal pulmonary receptors exerted on the breathing pattern and inspiratory activities of phrenic nerve and intercostal electromyograms (EMG) during hypoxia in rabbit pups. Animals in their second week of life were anaesthetized with ketamine (50 mg/kg) and acepromazine (3 mg/kg) and tracheostomized. While they breathed spontaneously, we recorded tidal volume (VT), integrated phrenic activity (PHR), integrated external intercostal EMG (INT), and blood pressure (BP). To prevent secondary ventilatory depression, animals were exposed to 12% O2 (balanced with N2) for no longer than 5 min before and after vagotomy. All measurements were taken from 1 min following the onset of hypoxic exposure until the end of the run. During hypoxia, VT, PHR, and INT increased in intact rabbit pups. There was an almost immediate decrease in BP that was maintained during the total period of hypoxia exposure. Hypoxia resulted in inconsistent changes in inspiratory (TI) and expiratory (TE) time in intact animals. Following vagotomy, PHR, INT, VT, BP, and TE responses were the same as in intact animals. However, TI significantly decreased in all animals. In response to hypoxia with and without vagal feedback, INT increased less than PHR in most cases. Qualitatively similar effects of hypoxia were observed in an adult rabbit. The results reveal that the increase in VT and the shortening of TI in response to hypoxia do not depend on vagal feedback in rabbits during the early postnatal period. In fact TI shortening was significant only without vagal feedback.
Effect of ruminal CO2 on gas exchange and ventilation in the Hereford calf
Authors: Kuhlmann W. D. , Dolezal S. R. , Fedde M. R.
Published: December 2017

The contribution of ruminal CO2 to gas exchange measurements and ventilation was determined in four rumen-fistulated Hereford steers at rest and during exercise. The calves were exercised at 1.4 and 2.2m X s-1 under three treatments: 1)full rumen with fistula sealed, 2) full rumen with fistula open, and 3) empty rumen. Measurements also were made at rest while flushing the empty rumen with either 100% N2 or a mixture of 50% CO2–50% N2. O2 consumption, CO2 production (Mco2), and ventilation were measured by collecting the expired gas. Absorption across the ruminal epithelium during rest increased Mco2 by 3%, whereas absorption and eructation together increased Mco2 by 15%. The respiratory exchange ratio (R) was significantly different among the three treatments at rest, but no differences were observed in R among the treatments during exercise. No changes were observed in minute ventilation among the three conditions, but a decrease in respiratory frequency and an increase in tidal volume occurred when the rumen was empty. These changes in ventilatory pattern may have been due to a decrease in body temperature when the rumen was empty. When the empty rumen was flushed with 50% CO2, Mco2 was increased 21% over the value observed when flushing with 100% N2. CO2 of fermentation origin is added to the expired gas by both eructation and absorption and has a significant effect on R in the resting animal, but no effect on R during exercise.
Phrenic nerve conduction times and twitch pressures of the human diaphragm
Authors: McKenzie D. K. , Gandevia S. C.
Published: December 2017

A multilumen catheter was modified to allow simultaneous recording of transdiaphragmatic pressure (Pdi) and the electromyographic (EMG) activity of the diaphragm. The catheter was used in 20 healthy males to measure the conduction time of the phrenic nerves and the twitch pressure of each hemidiaphragm during single supramaximal shocks delivered to the phrenic nerve in the neck. Diaphragmatic EMG was also recorded with surface electrodes at various sites on the chest wall. The mean conduction time to the crural fibers was 6.82 +/- 0.64 ms on the right and 7.93 +/- 0.85 ms on the left, whereas that to the costal fibers adjacent to the midclavicular line was 7.68 +/- 0.56 ms on the right and 7.92 +/- 0.92 ms on the left. Significant correlations were found between the conduction time of each phrenic nerve and the height and the age of the subjects. Conduction times measured at different EMG recording sites varied by as much as 2 ms. This variability, and that of previously reported values for phrenic conduction time, may be largely accounted for by differences in the conduction distances that were measured to each site in three cadavers. The evoked change in Pdi had a mean rise time of 92 ms and an amplitude of approximately 10 cmH2O.
Airway hysteresis in normal subjects and individuals with chronic airflow obstruction
Authors: Fairshter R. D.
Published: December 2017

Specific conductance (sGaw) was measured without prior pharmacological induction of bronchoconstriction before and 5–10 s after a total lung capacity (TLC) volume history in normal subjects and in individuals with chronic airflow obstruction (CAO); increased sGaw after inspiration to TLC was considered evidence of airway hysteresis. Lung elastic recoil [Pst(L)] was also measured before and after inspiration to TLC. In the normal subjects 1) prebronchodilator sGaw increased significantly, whereas Pst(L) decreased significantly after inspiration to TLC; 2) modulators of cyclooxygenase activity had no significant effects on sGaw responses to deep inspiration; and 3) airway hysteresis diminished after inhalation of atropine or metaproterenol. In the CAO group 1) prebronchodilator sGaw and Pst(L) decreased significantly after inspiration to TLC, and 2) bronchoconstriction after deep inspiration diminished after inhalation of atropine or metaproterenol. This study demonstrates that normal airways exhibit hysteresis even without alteration of resting airway tone and that airway hysteresis is impaired in CAO.
Augmentation of parasympathetic contraction in tracheal and bronchial airways by PGF2 alpha in situ
Authors: Leff A. R. , Munoz N. M. , Tallet J. , Cavigelli M. , David A. C.
Published: December 2017

We studied the effect of exogenous prostaglandin F2 alpha (PGF2 alpha) on airway smooth muscle contraction caused by parasympathetic stimulation in 22 mongrel dogs in situ. Voltage (0–30 V, constant 20 Hz) and frequency-response (0–25 Hz, 25 V) curves were generated by stimulating the cut ends of both cervical vagus nerves. Airway response was measured isometrically as active tension (AT) in a segment of cervical trachea and as change in airway resistance (RL) and dynamic compliance (Cdyn) in bronchial airways. One hour after 5 mg/kg iv indomethacin, a cumulative frequency-response curve was generated in nine animals by electrical stimulation of the vagus nerves at 15-s intervals. Reproducibility was demonstrated by generating a second curve 7 min later. A third frequency-response curve was generated during active contraction of the airway caused by continuous intravenous infusion of 10 micrograms X kg-1 X min-1PPGF2 alpha. Additional frequency-response studies were generated 15 and 30 min after PGF2 alpha, when airway contractile response (delta RL = +2.8 +/- 0.65 cmH2O X 1(-1) X s; delta Cdyn = -0.0259 +/- 0.007 1/cmH2O) returned to base line. Substantial augmentation of AT, RL, and Cdyn responses was demonstrated in every animal studied (P less than 0.01 for all points greater than 8 Hz) 15 min after PGF2 alpha. At 30 min, response did not differ from initial base-line control. In four animals receiving sham infusion, all frequency-response curves were identical. We demonstrate that PGF2 alpha augments the response to vagus nerve stimulation in tracheal and bronchial airways. Augmentation does not depend on PGF2 alpha-induced active tone.
Effect of altered ambient temperature on breathing in ponies
Authors: Kaminski R. P. , Forster H. V. , Bisgard G. E. , Pan L. G. , Dorsey S. M.
Published: December 2017

The objective was to determine the effect of moderate changes in ambient temperature (TA) on breathing and body temperature in ponies chronically exposed to a TA of 21 degrees C in the summer and 5 degrees C in the winter. Normal (n = 6) and chronic carotid body-denervated (n = 6, 1–2 yr) ponies were studied during 1) winter months over 3–4 days at 5 (control TA) and 23 degrees C and 2) summer months over 2–4 days at 21 (control TA), 30, and 12 degrees C. Neither rectal nor arterial temperature changed with any alteration of TA (P greater than 0.10). Skin temperature (Tsk) always changed by 2–4 degrees C in the same direction as changes in TA (P less than 0.01), and Tsk was the only variable that differed between summer and winter control TA. While breathing room air 24–48 h after TA was altered, pulmonary ventilation (VE) and breathing frequency (f) were approximately 100 and 300%, respectively, above control with elevated TA and approximately 25–50% below control with reduced TA (P less than 0.01). Changes in f were closely related to changes in Tsk. Tidal volume (VT) changed inversely with changes in TA. Generally, while breathing room air, arterial PCO2 (Paco2) did not change from control during the first 48 h of altered TA. In studies when inspired CO2 was elevated VT increased by the same amount at all TA; f increased at low and control TA but decreased at elevated TA; and VE and Paco2 both increased relatively less at elevated TA, but the VE-Paco2 slope was independent of TA.
Inspiratory muscle forces and endurance in maximum resistive loading
Authors: Jones G. L. , Killian K. J. , Summers E. , Jones N. L.
Published: December 2017

The ability of the respiratory muscles to sustain ventilation against increasing inspiratory resistive loads was measured in 10 normal subjects. All subjects reached a maximum rating of perceived respiratory effort and at maximum resistance showed signs of respiratory failure (CO2 retention, O2 desaturation, and rib cage and abdominal paradox). The maximum resistance achieved varied widely (range 73–660 cmH2O X l-1 X s). The increase in O2 uptake (delta Vo2) associated with loading was linearly related to the integrated mouth pressure (IMP): delta Vo2 = 0.028 X IMP + 19 ml/min (r = 0.88, P less than 0.001). Maximum delta Vo2 was 142 ml/min +/- SD 68 ml/min. There were significant (P less than 0.05) relationships between the maximum voluntary inspiratory pressure against an occluded airway (MIP) and both maximum IMP (r = 0.80) and maximum delta Vo2 (r = 0.76). In five subjects, three imposed breathing patterns were used to examine the effect of different patterns of respiratory muscle force deployment. Increasing inspiratory duration (TI) from 1.5 to 3.0 and 6.0 s, at the same frequency of breathing (5.5 breaths/min) reduced peak inspiratory pressure and increased the maximum resistance tolerated (190, 269, and 366 cmH2O X l-1 X s, respectively) and maximum IMP (2043, 2473, and 2913 cmH2O X s X min-1, but the effect on maximum delta Vo2 was less consistent (166, 237, and 180 ml/min). The ventilatory endurance capacity and the maximum O2 uptake of the respiratory muscles are related to the strength of the inspiratory muscles, but are also modified through the pattern of force deployment.
Rib cage distortion during voluntary and involuntary breathing acts
Authors: McCool F. D. , Loring S. H. , Mead J.
Published: December 2017

We examined chest wall and rib cage configuration in seven normal subjects during a variety of breathing maneuvers. Magnetometers were used to measure lower rib cage anteroposterior, lower rib cage transverse, upper rib cage anteroposterior, and abdomen anteroposterior diameters. Changes of these diameters were recorded during voluntary maneuvers, rebreathing, reading, and “natural” breathing. Relative motion of the rib cage and abdomen was displayed with the rib cage represented by the product of its lower anteroposterior and transverse diameters. During spontaneous breathing the rib cage and chest wall are near their relaxation configuration. During chemically driven ventilation the chest wall and rib cage progressively depart from this configuration. Much greater distortions of the chest wall and rib cage occurred during some voluntary maneuvers. Additionally, esophageal pressure and gastric pressure were measured during voluntary distortion of the rib cage. Substantial changes in lower rib cage shape occurred during voluntary maneuvers when compared with spontaneous breaths at the same transmural pressure. We conclude that the unitary behavior of the rib cage in normal subjects requires muscle coordination.
Electrical properties of monolayers cultured from cells of human tracheal mucosa
Authors: Widdicombe J. H. , Coleman D. L. , Finkbeiner W. E. , Tuet I. K.
Published: December 2017

Dispersed isolated cells were obtained from human tracheal mucosa by digestion with collagenase. Up to 1.5 X 10(8) cells were obtained per trachea and showed up to 95% viability, as judged by trypan blue exclusion. When grown in culture, the cells formed monolayers after approximately 4 days. Electron microscopy of the monolayers revealed a polarized structure. An apical membrane, containing microvilli and a pronounced glycocalyx, was separated from a relatively unspecialized basolateral membrane by typical tight junctions. Monolayers grown on nucleopore filters showed resistances of 44–1,800 omega. cm2 and transepithelial potential differences of 0.1–7.6 mV. Short-circuit current (Isc) was increased by isoproterenol, prostaglandins E2 and F2 alpha, and bradykinin. The loop diuretic, bumetanide, reduced Isc when added to the basolateral (serosal) side but had no effect from the apical (mucosal) side of the monolayers. Furosemide and MK-196 also inhibited Isc. Mucosal amiloride inhibited Isc. Serosal amiloride or mucosal ouabain had no effect on Isc. Serosal ouabain brought Isc to zero after approximately 15 min.
Reflex tracheal contraction evoked in dogs by bronchodilator prostaglandins E2 and I2
Authors: Roberts A. M. , Schultz H. D. , Green J. F. , Armstrong D. J. , Kaufman M. P. , Coleridge H. M. , Coleridge J. C.
Published: December 2017

Bronchodilator prostaglandins E2 and I2 may cause airway irritation and bronchoconstriction in human subjects. These experiments were designed to test the hypothesis that this paradoxical bronchoconstriction is a vagal reflex triggered by stimulation of airway afferents. We recorded smooth muscle tension in an innervated upper tracheal segment in anesthetized dogs and injected prostaglandins into the general circulation or into a bronchial artery or administered them as aerosol to the lungs. Prostaglandins usually caused tracheal contraction, which survived vagal cooling to 5–7 degrees C but was abolished at 0 degrees C. Vagally mediated tracheal contraction was also evoked when prostacyclin was injected into the pulmonary circulation of dogs whose pulmonary and systemic circulations were independently pump perfused. Recordings of afferent vagal impulses indicated that bronchial arterial injection of prostaglandins stimulated bronchial C-fibers; aerosols of prostaglandin stimulated pulmonary and bronchial C-fibers and C-fibers in extrapulmonary airways. We postulate that in susceptible human subjects concentrations of these prostaglandins too low to have direct bronchodilator effects may cause reflex bronchoconstriction by stimulating afferent vagal C-fibers in the lower airways.
Decay of inspiratory muscle pressure during expiration in conscious humans
Authors: Shee C. D. , Ploy-Song-Sang Y. , Milic-Emili J.
Published: December 2017

In eight conscious spontaneously breathing adults we studied the decay of pressure developed by the inspiratory muscles during expiration (PmusI). PmusI was obtained according to the following equation: PmusI(t) = Ers X V(t) - Rrs X V(t), where V is volume and V is flow at any instant t during spontaneous expiration, and Ers and Rrs are, respectively, the passive elastance and resistance of the total respiratory system. Ers was determined with the relaxation method, and resistance with the interrupter method. All subjects showed marked braking of expiratory flow by PmusI. The mean time for PmusI to reduce to 50 and 0% amounted, respectively, to 23 and 79% of expiratory time. During expiration, 24–55% of the elastic energy stored during inspiration was used as resistive work and the remainder (45–76%) as negative work.
Peripheral chemoreceptors in respiratory oscillations
Authors: Lahiri S. , Hsiao C. , Zhang R. , Mokashi A. , Nishino T.
Published: December 2017

The hypothesis that instability of cardiorespiratory control may depend on the response and sensitivity of carotid body chemoreceptors to arterial blood gases was studied in anesthetized cats under three different experimental conditions. 1) Following administration of the peripheral dopamine receptor blocker [domperidone (0.6–0.8 mg X kg-1, iv)], carotid chemoreceptor activity and its sensitivity to CO2 during hypoxia increased, leading to cardiorespiratory oscillations at low arterial PO2 in four of eight cats. Inhalation of 100% O2 promptly decreased chemoreceptor activity and eliminated the oscillations. Inhalation of CO2 stimulated the chemoreceptor activity and ventilation but did not eliminate the oscillations. Bilateral section of carotid sinus nerves abolished the cardiorespiratory oscillations. The implication is that the dopaminergic system in the carotid body keeps chemoreceptor responses to blood gas stimuli suppressed and hence cardiorespiratory oscillations damped. 2) Hypotension and circulatory delay induced by the partial occlusion of venous return led to cardiorespiratory oscillations at low but not at high arterial PO2. 3) A few cats developed cardiorespiratory oscillations without any particular experimental intervention. These oscillations were independent of arterial PO2 and chemoreceptor activity. Thus it is reasonable to conclude that the peripheral chemoreflex can play a critical role in developing cardiorespiratory oscillations in certain instances.
Albumin attenuation of oleic acid edema in dog lung depleted of blood components
Authors: Hofman W. F. , Ehrhart I. C.
Published: December 2017

Circulating fatty acids are normally transported principally bound to serum albumin. We examined whether administering oleic acid (OA) in a concentrated albumin solution would attenuate its edemogenic potential in the isolated dog lung lobe perfused with a solution nearly depleted of blood cellular and protein components. The isolated ventilated lower left lobe (LLL) was perfused (7.3 +/- 0.6 ml X min-1 X g LLL-1) with a balanced salt solution containing 6% dextran and approximately 10% serum (vol/vol). Hourly weight gain, net LLL weight gain, and wet-to-dry weight ratio (W/D) were used as indices of extravascular lung fluid changes. Group I lobes (n = 5) were given saline, whereas both group II (n = 5) and III (n = 5) lobes were administered 1 microliter OA/kg body wt. The OA was incubated with 5 ml of albumin solution containing approximately 640 mg of bovine fatty acid-free albumin before infusion into group III lobes. Group I gained weight at rate of 10.8 +/- 0.5 g X h-1 X 100 g LLL-1 after saline, whereas group II exhibited a greater (P less than 0.005) rate of weight gain of 42 +/- 13 after OA. Group III weight gain of 8.4 +/- 0.5 g X h-1 X 100 g LLL-1 was not different (P greater than 0.05) from group I but was lower (P less than 0.005) than group II.
Respiratory muscle fatigue: a cause of ventilatory failure in septic shock
Authors: Hussain S. N. , Simkus G. , Roussos C.
Published: December 2017

The effect of endotoxic shock on the respiratory muscle performance was studied in spontaneously breathing dogs given Escherichia coli endotoxin (Difco Laboratories, 10 mg/kg). Diaphragmatic (Edi) and parasternal intercostal (Eic) electromyograms were recorded using fishhook electrodes. The recorded signals were then rectified and electrically integrated. Pleural, abdominal, and transdiaphragmatic (Pdi) pressures were recorded by a balloon-catheter system. After a short control period, the endotoxin was administered slowly intravenously (within 5 min). Death was secondary to respiratory arrest in all animals. All animals died within 150–270 min after the onset of endotoxic shock. Within 45–80 min of the endotoxin administration, mean blood pressure and cardiac output dropped to 42.1 +/- 4.1 and 40.1 +/- 6.0% (mean +/- SE) of control values, respectively, with little change afterward. Mean inspiratory flow rate and Pdi increased from control values of 0.27 +/- 0.03 l X s-1 and 5.75 +/- 0.7 cmH2O to mean values of 0.44 +/- 0.3 l X s-1 and 8.70 +/- 1.05 cmH2O and then decreased to 0.17 +/- 0.03 l X s-1 and 3.90 +/- 0.30 cmH2O before the death of the animals. There were no major changes in the mechanics of the respiratory system. Edi and Eic increased progressively to mean values of 360 +/- 21 and 263 +/- 22% of control, respectively, before the death of the animals. None of the dogs were hypoxic. Arterial PCO2 decreased from a control value of 42.9 +/- 1.7 Torr to a mean value of 29.9 +/- 2.8 Torr and then increased to 51 +/- 4.3 Torr before the death of the animals.
Effects of almitrine on hypoglossal and phrenic electroneurograms
Authors: Weese-Mayer D. E. , Brouillette R. T. , Klemka L. , Hunt C. E.
Published: December 2017

Almitrine increases breathing by stimulating peripheral chemoreceptors. Previous studies suggest clinical usefulness in the adult with chronic obstructive pulmonary disease, but little data are available to decide whether almitrine would be helpful in diseases involving pharyngeal airway obstruction, such as apnea of prematurity or obstructive sleep apnea. We investigated the effect of intravenous almitrine on hypoglossal (HG), an upper airway nerve, and phrenic (PHR) neural activity in eight alpha-chloralose-urethan anesthetized, paralyzed, vagotomized, and artificially ventilated cats. Recordings were made of raw and integrated HG and PHR electroneurograms (ENGs), alveolar PCO2, arterial PO2, arterial blood pressure, and rectal temperature. A dose-response study of cumulative almitrine doses ranging from 0.1 to 4.0 mg/kg was performed in three cats. The interactive effects of almitrine and hypoxic stimulation were investigated in four cats. The interactive effects of almitrine and hypercapnic stimulation were investigated in five cats. The interactive effects of almitrine and ventilatory timing were investigated in six cats. We found that 1) almitrine doses as low as 0.1 mg/kg iv increased both HG and PHR ENG activity, with a maximum effect at approximately 1.0 mg/kg; 2) almitrine markedly increased HG and PHR ENG activity at all arterial PO2 values from 35–175 Torr; 3) almitrine increased HG and PHR ENG activity at all arterial PCO2 values from 30–70 Torr; and 4) almitrine increased the ratio of tidal volume to inspiratory time and decreased the inspiratory muscle duty cycle at normoxia and eucapnia.
Effect of the larynx on oscillatory flow in the central airways: a model study
Authors: Menon A. S. , Weber M. E. , Chang H. K.
Published: December 2017

Measurements were made of the effect of the larynx on the oscillatory flow profiles in a 3:1 scale model of the human central airways. A fixed glottic aperture corresponding to the shape and size at midinspiration was used. Oscillatory airflows at peak Reynolds numbers, similar to those obtained during spontaneous breathing and panting, were studied. The flow distribution to the five lobar bronchi was maintained by distally placed linear resistors. A hot-wire anemometer probe was used to measure the local velocity along two perpendicular diameters at six stations distributed through the model. Near the proximal end of the trachea, the flat velocity profiles at the beginning of the flow cycle peaked at maximum flow because of the jet created by the glottic aperture. This peaked structure was conserved during the latter half of the inspiratory cycle. Close to the carina, the jet had almost dissipated and the entry conditions into the main bronchi corresponded to those in the absence of the laryngeal model. The effect of the glottic aperture on the mean velocity was not felt beyond the carina, and the characteristic skewed profiles seen in oscillatory flows, in the absence of the larynx, were present in the main and lobar bronchi.
Comparison of chemoreflex gains obtained with two different methods in cats
Authors: DeGoede J. , Berkenbosch A. , Ward D. S. , Bellville J. W. , Olievier C. N.
Published: December 2017

This study investigates the correspondence between results of the ventilatory response to CO2 obtained using the technique of dynamic end-tidal CO2 forcing (DEF) and results obtained using the technique of artificial brain stem perfusion (ABP). The DEF technique separates the dynamic ventilatory response into a slow and fast component with gains g1 and g2 as well as the extrapolated CO2 tension at zero ventilation (Bk). The ABP technique results in steady-state central (Sc) and peripheral (Sp) chemoreflex gains and extrapolated CO2 tension at zero ventilation (B). Experiments were performed on 14 alpha-chloralose-urethan anesthetized cats. A wide range of relative peripheral chemosensitivities was obtained by subjecting eight cats to normoxic and three cats to hypoxic CO2 challenges and three cats to both conditions. Statistical analysis of the experimental data showed that the vectors (g1, g2, Bk) and (Sc, Sp, B) for each cat did not differ significantly (P = 0.56). This was also the case for the vectors [g2/(g1 + g2), Bk] and [Sp/(Sc + Sp), B] (P = 0.21). We conclude that in the DEF experiments the slow ventilatory response to isoxic changes in end-tidal CO2 can be equated with the central chemoreflex loop and the faster ventilatory response to the peripheral chemoreflex loop. The agreement between the two techniques is good.
Neural and humoral factors in control of tracheal caliber
Authors: Mitchell G. S. , Vidruk E. H.
Published: December 2017

To assess the contributions of neural (vagal) and humoral (blood borne) mechanisms in the tracheal constriction that occurs when pump ventilation is transiently withheld, experiments were conducted on decerebrate dogs. The dogs were paralyzed and thoracotomized, and each lung was independently ventilated. Pressure changes within an isolated tracheal segment (Ps) were monitored as an index of tracheal caliber. In series I, pump ventilation was withheld 20 s at the prevailing end-expiratory pressure (3–5 cmH2O) from both lungs or either lung alone when 1) both lungs were intact; or 2) the left lung was vascularly isolated (VIL) by occluding the pulmonary artery and the right gas exchange lung (GEL) was vagally denervated. In series II, steady-state pressure changes in the VIL were made with constant GEL ventilation. With both lungs intact, 20-s apnea elicited a 17.3 +/- 2.6 cmH2O increase in Ps; the left and right lungs contributed equally to this response. Following vagotomy and pulmonary arterial occlusion, a 7.8 +/- 2.6 cmH2O increase in Ps was elicited from two lungs; the VIL response was 60 +/- 11% and the GEL 41 +/- 15%. Onset and one-half response times were faster from the VIL than GEL. Prolonged maneuvers elicited progressively larger responses from the GEL, but the VIL response plateaued within 30 s and then adapted towards the control level. In series II, steady-state increases or decreases in VIL pressure elicited small decreases or increases in Ps, respectively, which showed nearly complete adaptation within several minutes.
Serial determination of lung volume in small animals by nitrogen washout
Authors: Standaert T. A. , LaFramboise W. A. , Tuck R. E. , Woodrum D. E.
Published: December 2017

This report describes the design of an apparatus and the procedures used to serially measure the total lung capacity and the functional residual capacity of small animals utilizing the N2-washout technique. The calibration data indicate that the technique is accurate to within 1 ml and has a variance of less than 5%. The in vivo lung volume measurements of rats were validated by comparing them with values obtained with a water-displacement technique; the means were within 0.3 ml. Examples of the precision and changes in lung volume of animals during studies are included to demonstrate the reliability and usefulness of the technique.