bluuebunny/crossref_metadata_2025 huggingface dataset:
Central neural respiratory response to carotid sinus nerve stimulation in newborns
Authors: Lawson E. E. , Long W. A.
Published: December 2017

During exposure to hypoxia newborns hypoventilate following a brief period of hyperventilation. Failure of integration of the afferent signals from peripheral O2 chemoreceptors due to immaturity of the central respiratory centers could explain this paradoxical respiratory response. To test this hypothesis we have utilized anesthetized, paralyzed, mechanically ventilated newborn piglets and lambs (less than 11 days) and old piglets (19–35 days). The vagus nerves were cut in each animal. Respiratory activity was quantified by integration of phrenic neural activity. A carotid sinus nerve (CSN) was isolated and electrically stimulated for periods of 1–6 min. In all three groups of animals respiratory activity was continuously elevated throughout the period of CSN stimulation. After CSN stimulation respiratory activity immediately declined about 25% from the stimulated value. Thereafter respiratory activity declined in an exponential fashion toward the initial control level of respiratory activity. The time constant of this latter decay was 84.2 s in the young piglets, 83.2 s in the old piglets, and 63.0 s in the lambs. These results indicate that the respiratory centers of newborn piglets and lambs can maintain integration of continuous afferent CSN activity. Further, the respiratory afterdischarge that follows CSN stimulus cessation is similar to that of adults. These studies indicate that, during periods of O2 sufficiency, the central respiratory centers of newborns respond in a qualitatively similar manner to CSN stimulation as do adult cats.
Vagal control of respiratory pattern during hyperpnea in domestic fowl
Authors: Gleeson M. , Brackenbury J. H.
Published: December 2017

Minute volume, tidal volume, and respiratory frequency were measured during hyperpnea induced by exercise, increased body temperature, and CO2 inhalation. Ventilatory characteristics were compared before and after the vagus nerve had been blocked. In normal birds exercise produced increases in both tidal volume and respiratory frequency; hyperthermia produced a typical thermal polypnea consisting of greatly increased respiratory frequency and reduced tidal volume; CO2 inhalation produced increases in tidal volume and respiratory frequency when the birds were euthermic but a slowing of respiratory rate when the birds were hyperthermic. After vagal block these pronounced differences in the pattern of ventilatory response to the various respiratory stimuli were abolished. Instead there was a uniform ventilatory response to all three stimuli consisting mainly of increases in tidal volume combined with small increases in respiratory frequency. It is concluded that in the normal animal control of the varied pattern of ventilatory response to different respiratory stimuli is dependent on vagal fiber activity.
Effect on breathing of acute pressure rise in pulmonary artery and right ventricle
Authors: Lloyd T. C.
Published: December 2017

We tested the hypothesis that breathing would be regulated in response to right ventricular and pulmonary arterial pressure changes when secondary events are controlled. Dogs were anesthetized, thoracotomies were performed, and cardiopulmonary bypass perfusion was established. Lungs were inflated to sustained pressures. The left diaphragmatic lobe was retrogradely cannulated and all other lobar arteries were ligated, forming a pulmonary arterial sac that drained to the oxygenator from the cannula and filled from systemic venous return by the beating right ventricle. Right atrial pressure was adjusted to produce sac flows of approximately 400 ml/min. We recorded systemic and pulmonary arterial pressures, sac flow, and the integrated diaphragm electromyogram (DEMG). Resistive loads were imposed on sac outflow by adjusting a clamp. Loaded mean pulmonary arterial pressures ranged from 27 to 70 Torr. Loading increased respiratory frequency without affecting peak DEMG amplitude. Responses did not occur after vagotomy. Effects were quantitatively modest: pressurization to approximately 50 Torr increased frequency approximately 3.4 breaths/min (22%). The magnitude of change was insufficient to explain in intact dogs the ventilatory responses that have been attributed to this reflexogenic unit.
Blood lactate and ammonium ion accumulation during graded exercise in humans
Authors: Buono M. J. , Clancy T. R. , Cook J. R.
Published: December 2017

The purpose of this study was to determine the pattern of blood lactate and ammonium ion (NH+4) accumulation during graded exercise in humans. Six adult volunteers performed a maximum O2 uptake (VO2 max) test on a bicycle ergometer. Blood samples were collected each minute of the test. Both blood lactate (r = 0.92) and NH4+ (r = 0.70) increased exponentially in relation to increased work. However, closer examination of individual curves revealed that both metabolites remained near resting levels during mild exercise (less than 40% VO2 max) and then demonstrated abrupt upward break points at increased work loads (greater than 50% VO2 max). There was a significant linear relationship (r = 0.96) between the work load at which the lactate break point (LBP) and NH4+ break point (ABP) occurred in each subject. In addition, there was a significant linear relationship (r = 0.82) between the blood concentrations of NH4+ and lactate during exercise. The results suggest a connection between NH4+ production and glycolytic energy metabolism during exercise. Several possible explanations are offered; however, further work at the cellular level is needed before the exact relationship between NH4+ and lactate can be determined.
Pulmonary arterial and venous pressures measured with small catheters in dogs
Authors: Michel R. P. , Hakim T. S. , Chang H. K.
Published: December 2017

To further subdivide the pressure drops across the arterial, middle, and venous segments obtained from the occlusion technique, we compared the pressures at the distal end of the arterial segment (Pa') and the proximal end of the venous segment (Pv') measured with this technique, with the pressures measured with 1.2-mm catheters in a small artery (Psa) and a small vein (Psv) of left lower lobes of dogs perfused in situ. The arterial (Pa) and venous (Pv) pressures were monitored and blood flow kept constant. Under control conditions the mean Pa, Psa, Pa', Pv', Psv, and Pv were 18.1, 13.0, 11.3, 9.2, 8.4, and 0.7 mmHg, respectively, suggesting that 29 and 44% of the total pulmonary vascular resistance (PVR) were in arteries and veins with diameters larger than at least 1.2 mm. Serotonin and histamine increased the pressure drops in arteries and veins, respectively, both larger and smaller than 1.2 mm. The small catheter pressures increased with flow rate. Microvascular pressures calculated from occlusion and small catheter measurements were higher than those calculated from the formula assuming 40% of PVR on the venous side. Our data suggest that a substantial proportion of resistance in the lung may lie in larger arteries and veins, the fraction of resistance in vessels under 1.2 mm increases with vasoconstrictors, the arterial and venous segments include muscular vessels under 1.2 mm, and calculation of microvascular pressures assuming 40% of the resistance in the veins may be misleading, especially when vasomotor tone is increased.
An efferent pathway mediating reflex tracheal dilation in awake dogs
Authors: Bowes G. , Shakin E. J. , Phillipson E. A. , Zamel N.
Published: December 2017

Lung inflation is known to produce reflex relaxation of tracheal smooth muscle (TSM) and dilation of the upper airway, but the specific efferent pathway involved has not been established. Therefore we examined TSM tone in four trained awake dogs by measuring pressure changes in the water-filled cuff of an endotracheal tube that was inserted into the lower cervical trachea through a permanent tracheostomy. Under control conditions, sustained lung inflation with 1 liter of air produced apnea (Hering-Breuer inflation reflex) and a decrease in cuff pressure (Pcuff) of 37.4 +/- 12.0 (mean +/- SD) cmH2O. beta-Adrenergic blockade with propranolol had no effect on either the apneic or TSM responses to lung inflation. Efferent parasympathetic blockade with atropine sulfate (1.2–2.4 mg) abolished TSM tone, which was then restored to control levels by a continuous intravenous infusion of serotonin (14–28 micrograms X kg-1 X min-1). Under these conditions, lung inflation still induced reflex apnea but no longer relaxed TSM tone (mean decrease in Pcuff, 2.7 +/- 1.4 cmH2O, P less than 0.001). The findings indicate that reflex tracheal dilation in response to lung inflation is mediated by an efferent cholinergic (parasympathetic) pathway.
Combined effects of ozone exposure and ambient heat on exercising females
Authors: Gibbons S. I. , Adams W. C.
Published: December 2017

Ten aerobically trained young adult females exercised continuously at 66% of maximum O2 uptake for 1 h while exposed orally to filtered air and 0.15 and 0.30 parts per million (ppm) ozone (O3) in both moderate (24 degrees C) and hot (35 degrees C) ambient conditions. Exposure to 0.30 ppm O3 induced significant impairment in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and other pulmonary function variables. Exercise respiratory frequency (fR) increased, whereas tidal volume and alveolar volume (VA) decreased with 0.30 ppm O3 exposure. Significant interactions of O3 and ambient heat were obtained for fR and VA, whereas FVC and FEV1.0 displayed a trend toward an O3-temperature interaction. Although expired ventilation increased, the interactions could not be ascribed to a greater O3 effective dose in the 35 degrees C exposures. However, subjective discomfort increased with both O3 and heat exposure such that three subjects ceased exercise prematurely when O3 and ambient heat were combined. We conclude that accentuation of subjective limitations and certain physiological alterations by ambient heat coinciding with photochemical oxidant episodes is likely to result in more severe impairment of exercise performance, although the mechanisms remain unclear.
Coronary transport reserve in normal dogs
Authors: Laughlin M. H.
Published: December 2017

This study was designed to determine an acceptable method for producing maximal coronary vasodilation for quantifying coronary blood flow reserve and coronary capillary transport reserve. The anterior descending branch of the left coronary artery was cannulated and pump-perfused while aortic, central venous, and coronary perfusion pressures, heart rate, electrocardiogram, blood gases, and coronary blood flow (CBF) were continuously monitored. All parameters were measured at four to six points along the coronary pressure-flow autoregulation curve. Myocardial extraction and permeability-surface area products (PS) of 51Cr-ethylenediaminetetraacetic acid were determined with the single-injection indicator-diffusion method in intact working hearts of anesthetized dogs. Maximal vasodilations were produced with 2-min coronary occlusions and with intracoronary infusions of adenosine (ADO), dipyridamole, ADO + dipyridamole, papaverine, and ADO + alpha 1-receptor blockade. ADO was chosen to quantify coronary transport reserve because it produced maximal CBF's and PS's that were reproducible within and among animals and produced minimal effects on the cardiovascular system. Under base-line conditions, there was no relationship between PS and perfusion pressure. Base-line PS averaged 20 +/- 2 ml X min-1 X 100 g-1. Maximal vasodilation with constant CBF had no significant effect on PS. During maximal vasodilation, CBF and PS increased linearly with increasing perfusion pressure, and PS increased linearly with increasing plasma flow. Constant pressure maximal vasodilation with ADO caused PS to increase to 36 +/- 4 ml X min-1 X 100 g-1, and CBF was increased 380%.
Pulmonary C-fibers evoke both apnea and tachypnea of pulmonary chemoreflex
Authors: Green J. F. , Schmidt N. D. , Schultz H. D. , Roberts A. M. , Coleridge H. M. , Coleridge J. C.
Published: December 2017

Pulmonary C-fibers initiate the prompt apnea evoked by pulmonary arterial injections of capsaicin, but their role in the subsequent rapid shallow breathing of the pulmonary chemoreflex is disputed. To determine whether this reflex tachypnea is triggered by pulmonary C-fibers rather than by afferents further downstream, we separately perfused the pulmonary and systemic circulation in anesthetized dogs. When the lungs were rhythmically inflated, injection of capsaicin (0.5–20.0 micrograms X kg-1) into the isolated pulmonary circulation evoked an immediate cessation of phrenic nerve firing (“apnea”) and when phrenic bursts resumed, a reduction in their amplitude. Phrenic burst frequency was usually entrained to the ventilator cycle and did not increase. By contrast, when entrainment of phrenic bursts was avoided by statically inflating the lungs at a transpulmonary pressure of 3 cmH2O, the injection of capsaicin evoked apnea, followed by a prolonged increase in phrenic burst frequency and a decrease in amplitude (“rapid shallow breathing”). The infusion of capsaicin (10–20 micrograms X kg-1 X min-1) also evoked rapid shallow breathing, but without apnea. Our results are consistent with the hypothesis that in spontaneously breathing animals, stimulation of pulmonary C-fibers evokes rapid shallow breathing.
Diaphragm function and respiratory response after upper abdominal surgery in dogs
Authors: Road J. D. , Burgess K. R. , Whitelaw W. A. , Ford G. T.
Published: December 2017

Decreased diaphragm activity has been demonstrated after cholecystectomy in humans (Am. Rev. Respir. Dis. 127: 431–436, 1983). To investigate the mechanism(s) of postoperative diaphragm dysfunction we have established a dog model. Three groups of mongrel dogs were studied under general anesthesia: six dogs received no surgery (control); nine dogs underwent upper abdominal surgery (cholecystectomy); and six dogs underwent lower abdominal surgery (pseudoappendectomy). Diaphragm function was assessed by changes in transdiaphragmatic pressure swings, the ratio of changes in gastric to esophageal pressure swings, and the ratio of changes in abdominal to rib cage diameters during quiet tidal breathing. In the upper abdominal surgery group there were significant postoperative decreases in all parameters of diaphragm function and an increase in minute ventilation and respiratory frequency. However, there were no significant postoperative changes in the parameters of diaphragm function in the control or lower abdominal surgery groups. These studies establish that general anesthesia is not responsible for the reduced diaphragm activity seen postoperatively and that diaphragm function is not affected by lower abdominal surgery in dogs.
Lung clearance of inhaled 99mTc-DTPA in the dog
Authors: Oberdorster G. , Utell M. J. , Weber D. A. , Ivanovich M. , Hyde R. W. , Morrow P. E.
Published: December 2017

We studied the reproducibility of measuring an index of permeability of respiratory epithelium in dogs using aerosolized 99mTc-DTPA (diethylenetriaminepentaacetate). The method uses a gamma camera to measure the rate of clearance of soluble radioactive aerosol deposited in the lung. A solution of 99mTc-DTPA in normal saline was aerosolized by an ultrasonic nebulizer. Eleven anesthetized dogs breathing spontaneously inhaled the resulting droplets for 2 min. Mass median aerodynamic diameter of the droplets was 4.4 micron with a geometric standard deviation of 2.1. Clearance from the lung was monitored by quantitative gamma camera imaging for up to 2 h. For a 60-min observation period, the biological half-life for clearance of 99mTc-DTPA from both lungs was 66 +/- 11 (SD) min. Apical regions cleared significantly slower than basal regions, probably because of a larger portion of bronchial tissue in the apical region of the dog's lung. The best reproducibility of absorption of 99mTc-DTPA in the dog was obtained from basal regions and peripheral zones of the lung within 30 min after inhalation of the radioaerosol.
Upper airway walls impedance measured with head plethysmograph
Authors: Peslin R. , Duvivier C. , Jardin P.
Published: December 2017

Respiratory input impedance (Zrs) measured by forced oscillations needs to be corrected for the motion of extrathoracic airway walls. Two methods of obtaining the impedance of this shunt pathway [upper airway impedance (Zuaw)] were compared in six normal subjects. In the first, flow was measured at the airway opening during Valsalva maneuvers, as described by Michaelson et al. (10). In the second, motions of upper airway walls were directly assessed during respiratory impedance measurements by use of a head plethysmograph. Larger upper airway impedance values were found during Valsalva maneuvers, corresponding to a larger upper airway resistance (Ruaw) (at 20 Hz, Ruaw = 9.1 +/- 4.7 compared with 7.0 +/- 2.1 cmH2O X 1–1 X s with the second method) and inertance (Iuaw) (Iuaw = 0.053 +/- 0.036 vs. 0.025 +/- 0.008 cmH2O X 1–1 X s2, P less than 0.05) and a lower upper airway compliance (Cuaw) (Cuaw = 0.78 +/- 0.33 vs. 1.15 +/- 0.15 ml X cmH2O–1, P less than 0.05). Active contraction of facial muscles during Valsalva maneuvers may be responsible for this finding. As a consequence, respiratory impedance values are undercorrected when using the Valsalva method, leading in normal subjects to an overestimation of respiratory compliance by 30% and an underestimation of inertance by 16% (P less than 0.05) and promoting positive frequency dependence of respiratory resistance. Substantial errors may be avoided by using a head plethysmograph, which permits measuring Zrs and Zuaw simultaneously.
Gross and subgross anatomy of bronchial circulation in sheep
Authors: Charan N. B. , Turk G. M. , Dhand R.
Published: December 2017

The anatomy of the bronchial artery in sheep has recently been described. However, the course of the bronchial veins has not been well established. It has been suggested that the bronchial veins are the major site of fluid leakage following histamine infusion, and it has been postulated that the bronchial circulation may play a role in fluid reabsorption. We studied the anatomy of the bronchial circulation in 18 sheep with emphasis on bronchial venous drainage and bronchopulmonary communications. Following anesthesia animals were heparinized and exsanguinated. Evans blue dye was infused into the bronchial artery in six sheep and the gross and subgross anatomy of the bronchial circulation studied. In six other sheep the bronchial artery, pulmonary artery, and tracheobronchial tree were filled with Batson's solution of varying colors. The subgross anatomy was studied under a dissecting microscope, and samples were taken for scanning electron microscopy. In six separate sheep we studied the anatomy of the proximal vein by infusing dye directly into the vein and found that the extrapulmonary bronchial blood drained into the left azygos vein via a single vessel. Intrapulmonary bronchi are surrounded by a dense bronchial microvascular plexus which drains into the pulmonary vessels at the precapillary level.
Leukocyte kinetics in the human lung: role of exercise and catecholamines
Authors: Muir A. L. , Cruz M. , Martin B. A. , Thommasen H. , Belzberg A. , Hogg J. C.
Published: December 2017

In six normal supine subjects epinephrine infusion produced a greater leukocytosis with smaller changes in heart rate and blood pressure than did norepinephrine or isoproterenol. Upright exercise in those subjects produced a greater leukocytosis than supine exercise at the same work load. To determine the lung's participation in these events, indium-labeled neutrophils (PMN) were given to four of the subjects. We found that 20–25% were retained in the first pass through the lung when compared with technetium-labeled erythrocytes. The number of labeled PMN in the lung gradually decreased and the number in the spleen and the liver increased. Exercise and catecholamine infusion caused an acceleration in the release of labeled cells from the lung, an increase in both labeled and unlabeled cells in the peripheral blood, and an increase in the number of labeled cells in the liver and spleen. This suggests that increased perfusion of low-flow areas in the lung may contribute to the increased leukocytosis seen in association with both exercise and catecholamine infusion.
Actions of lipoxygenase metabolites in isolated rat lungs
Authors: Voelkel N. F. , Stenmark K. R. , Reeves J. T. , Mathias M. M. , Murphy R. C.
Published: December 2017

Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. We examined the production and action of lipoxygenase metabolites in isolated lungs, where we controlled the perfusing fluid used. Arachidonate injected into isolated rat lungs perfused with cell- and protein-free physiological salt solution caused a transient pressor response. Following indomethacin, arachidonate caused a delayed slow pressure rise followed by edema. The lung effluent contracted the guinea pig ileum. High-pressure liquid chromatography (HPLC) analysis of the perfusate demonstrated the presence of leukotrienes (LTC4 and LTD4). Diethylcarbamazine, a leukotriene synthesis inhibitor, prevented the slow pressure rise and edema seen after indomethacin plus arachidonate. In lungs perfused with cell- and protein-free physiological salt solution, LTC4, but not LTD4, caused a transient pressure rise followed by a sustained pressure rise. The sustained rise was abolished by a leukotriene-receptor blocker (FPL 55712) but not by indomethacin. In blood-perfused lungs, LTC4 caused only the transient pressure rise that was not blocked by FPL 55712. In lungs perfused with physiological salt solution containing albumin, LTC4 had no effect. We concluded that 1) perfused nonsensitized rat lungs produced LTC4 and LTD4; 2) LTC4 may be a major pulmonary vasoconstrictor; and 3) albumin binding limits the pressor effect of LTC4.
Heat exchange during upper- and lower-body exercise
Authors: Sawka M. N. , Gonzalez R. R. , Drolet L. L. , Pandolf K. B.
Published: December 2017

This study examined evaporative and dry heat exchange during upper- and lower-body exercise. Four male subjects performed arm-crank or cycle exercise at the same O2 uptake level (approximately 1.6 l/min) in an environment facilitating dry heat exchange [radiative and convective (R + C)] [ambient temperature (Ta) = 18 degrees C, dew-point temperature (Tdp) = 14 degrees C] and an environment facilitating evaporative heat loss (Esk) (Ta = 35 degrees C, Tdp = 14 degrees C). (R + C) was determined from the torso with a net radiometer and from the limbs with heat flow discs, whereas Esk was determined from the torso and limbs by ventilated dew-point sensors. In both environments neither esophageal temperature nor mean skin temperature were different between exercise types (P greater than 0.05). Torso (R + C) was significantly (P less than 0.05) greater during arm-crank than during cycle exercise in both environments. Torso Esk, as well as arm (R + C), and arm Esk were not different (P greater than 0.05) between exercise types in each environment. Leg (R + C) was greater (P less than 0.05) during cycle than during arm-crank exercise in the 18 degrees C environment, whereas leg Esk was greater (P less than 0.05) during cycle than during arm-crank exercise in the 35 degrees C environment. These data indicate that to compensate for greater torso sensible heat loss during upper body exercise lower body exercise elicits additional (R + C) or Esk from the legs. The avenue for this compensatory sensible and insensible heat loss depends upon the differential heat transfer coefficients which influence tissue conductivity and mass transfer.
Late phase bronchial obstruction following nonimmunologic mast cell degranulation
Authors: Russi E. W. , Perruchoud A. P. , Yerger L. D. , Stevenson J. S. , Tabak J. , Marchette B. , Abraham W. M.
Published: December 2017

Immunologic degranulation of airway mast cells after antigen inhalation produces early and late airway obstructions in allergic sheep. In this study we determined whether nonimmunologic degranulation of airway mast cells by inhalation of compound 48/80 had similar effects. In five sheep, pulmonary flow resistance (RL), thoracic gas volume (Vtg), and arterial O2 tension (Pao2) were determined prior to and at predetermined times after inhalation of 48/80 aerosol. Immediately after challenge mean specific lung resistance (sRL = RL X Vtg) increased by 259% and mean Pao2 decreased by 29%. All values returned to normal by 3 h. By 5-h postchallenge sRL again increased significantly; this second increase in sRL (92% above base line) was maximal at 7 h and was accompanied by a 17% drop in Pao2. In these same sheep inhalation of Ascaris suum antigen produced comparable early changes in sRL, but the onset of the late response was somewhat delayed and more pronounced. In a second group of sheep (n = 5), pretreatment with the mast cell stabilizer cromolyn sodium prevented both early and late responses by compound 48/80. Pretreatment with the histamine H1-antagonist chlorpheniramine had no significant effect on either response, whereas pretreatment with FPL 55712, an antagonist of slow-reacting substance of anaphylaxis (SRS-A), slightly but not significantly attenuated the early response and completely prevented the late response. We conclude that, like immunologic stimuli, nonimmunologic mast cell degranulation produces early and late bronchial obstructions in allergic sheep; that these responses are mediator dependent; and that while histamine and SRS-A contribute to the early response, it is the early appearance of SRS-A which is an important prerequisite for the late response.
Mechanical properties of pleural membrane
Authors: Stamenovic D.
Published: December 2017

The pleural membrane is modeled as a planar collection of interconnected randomly oriented line elements. By assuming that the line elements follow the strain field of a continuum, a strain-energy function is formulated. From the strain-energy function, an explicit stress-strain equation for large deformations is derived. In the linear approximation of the stress-strain equation the shear modulus and the area modulus of the membrane are respectively found to be 2.4 and 2.8 times the tension at the reference state. The stress-strain equation for large deformations is used to predict the displacement field around a circular hole in pleura. Good agreement is found between these predictions and measurements made on ablated pleura from dog lungs. From these theoretical and experimental results the conclusion is drawn that the pleura has a significant role in carrying shear forces and maintaining the lung's shape.
Responses of in vitro rat diaphragm to changes in acid-base environment
Authors: Fitzgerald R. S. , Hauer M. C. , Bierkamper G. G. , Raff H.
Published: December 2017

In vitro rat diaphragms initially demonstrated a decrease in the force of the twitch contraction (FC) in response to field electrode stimulation when exposed to an unbuffered increase in PCO2 (UIPCO2). These diaphragms tended to regain their initial FC upon addition of a beta-agonist even while the increased PCO2 perdured. The effect of the agonist could be reversed by propranolol. Four hemidiaphragms were bathed in a medium containing curare and exposed to UIPCO2. Their tension values were compared to the opposite sides bathed without curare and exposed to UIPCO2 of the same intensity and duration. There was no statistically significant difference in the response. Subsequently 10 rat diaphragms were each systematically challenged by UIPCO2, buffered increases in PCO2 (BIPCO2), unbuffered decreases in bicarbonate (UDHCO3), and buffered decreases in bicarbonate (BDHCO3) first without and then with isoproterenol (10(-6) M). Without isoproterenol all four challenges after 15-min exposure produced a decrease in FC, the least by BIPCO2; the largest, by UDHCO3. Upon addition of isoproterenol, FC actually increased during BIPCO2; the decreases in FC in response to UIPCO2 and UDHCO3 were abolished; the FC in response to BDHCO3 was still decreased, but less severely. The effect of the isoproterenol was not due to its following the four challenges without isoproterenol. The different magnitudes in the FC response and the presumed lack of uniform change in intracellular pH during the four challenges suggest the possibility that different components in the sarcolemma, or in the excitation-contraction coupling mechanisms responsible for the genesis of the FC are affected by the four challenges, but the nerve or neuromuscular junction may also be affected.
Early recovery from hypoxic pulmonary hypertension: a structural and functional study
Authors: Fried R. , Reid L. M.
Published: December 2017

This study follows the recovery during 1 mo in ambient air from the hemodynamic and structural changes found in Sprague-Dawley rats after 2 wk of hypobaric hypoxia. In the time studied there is some degree of recovery for all features analyzed. The only features that completely return to normal are hematocrit level, new muscle in arteries at alveolar wall level, medial thickness of intra-acinar arteries, and density of filled arteries. For some features much of the recovery is early or rapid; for other features the recovery is late or slow. The rapid changes, occurring within two days of removal from hypoxia, include a fall in pulmonary arterial pressure (36.6 +/- 1.5 to 30.1 +/- 1.1 mmHg), a drop in hematocrit (61.1 +/- 1.3 to 53.0 +/- 1.0%), and the disappearance of new muscle, as judged by light microscopy from many arteries at alveolar wall (39.5 +/- 4.9 to 17.7 +/- 4.0%) and alveolar duct (85.9 +/- 2.5 to 68.2 +/- 3.4%) levels. The slow recovery includes the decrease in right ventricular and arterial medial hypertrophy, disappearance of muscle from respiratory bronchiolar arteries, reduction in lung volume, and increased density of filled arteries. These slow changes are probably the response to a fall in pulmonary arterial pressure.
Respiratory changes in parasternal intercostal length
Authors: Decramer M. , De Troyer A.
Published: December 2017

In an attempt to understand the role of the parasternal intercostals in respiration, we measured the changes in length of these muscles during a variety of static and dynamic respiratory maneuvers. Studies were performed on 39 intercostal spaces from 10 anesthetized dogs, and changes in parasternal intercostal length were assessed with pairs of piezoelectric crystals (sonomicrometry). During static maneuvers (passive inflation-deflation, isovolume maneuvers, changes in body position), the parasternal intercostals shortened whenever the rib cage inflated, and they lengthened whenever the rib cage contracted. The changes in parasternal intercostal length, however, were much smaller than the changes in diaphragmatic length, averaging 9.2% of the resting length during inflation from residual volume to total lung capacity and 1.3% during tilting from supine to upright. During quiet breathing the parasternal intercostals always shortened during inspiration and lengthened during expiration. In the intact animals the inspiratory parasternal shortening was close to that seen for the same increase in lung volume during passive inflation and averaged 3.5%. After bilateral phrenicotomy, however, the parasternal intercostal shortening during inspiration markedly increased, whereas tidal volume diminished. These results indicate that 1) the parasternal intercostals in the dog are real agonists (as opposed to fixators) and actively contribute to expand the rib cage and the lung during quiet inspiration, 2) the relationship between lung volume and parasternal length is not unique but depends on the relative contribution of the various inspiratory muscles to tidal volume, and 3) the physiological range of operating length of the parasternal intercostals is considerably smaller than that of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute cardiorespiratory responses of hypertensive rats to swimming and treadmill exercise
Authors: Sturek M. L. , Bedford T. G. , Tipton C. M. , Newcomer L.
Published: December 2017

The acute cardiorespiratory responses of spontaneously hypertensive rats (SHR) to swimming and running exercise was investigated because SHR populations are hyperresponsive to external stimuli, of the paucity of existing data, and of the uncertainty on the role of exercise stimuli for training adaptations to occur. Male rats were assigned to one of five groups (n = 5–6/group) and designated as controls (C), inexperienced or naive free swimmers (NFS), experienced free swimmers (FS), experienced weighted swimmers (WS) (attached weights equal to 2% of their body weight) or experienced runners (R) who ran at an intensity of 75% of their VO2max. After 75 min in the water, all groups were acidotic and hypercapnic with the WS experiencing the greatest changes. Heart rate (HR) was increased in all swimmers during the initial 10 min, but declined thereafter, and after 75 min, the HR of WS (348 +/- 1 beats/min) was significantly lower than the C group (416 +/- 22 beats/min). At the same time interval, mean arterial blood pressure (MAP) was decreased in all swimming groups to values lower than the C animals. In addition, an exaggerated diving reflex was frequently noted when the rats were submerged. When the magnitudes of the changes were evaluated in the swimming animals they were directly associated with their submergence times, i.e., during 65–75 min of the swim, NFS, FS, and WS were submerged for 43, 46, and 66% of their total swim time, respectively. In sharp contrast to the swimmers, the runners exhibited increases in HR and MAP with their blood gas measurements being indicative of hyperventilation. We concluded that swimming as an exercise mode for hypertensive rats is best served to study the combined effects of excitement, prolonged submergence, and the consequences of the diving reflex.
Effects of CO2 and bronchoconstriction on costal and crural diaphragm electromyograms
Authors: van Lunteren E. , Haxhiu M. A. , Deal E. C. , Perkins D. , Cherniack N. S.
Published: December 2017

To determine if neural control of the crural diaphragm is similar to that of the costal diaphragm, electrical activity was recorded from these two parts of the diaphragm in 10 anesthetized dogs during resting O2 breathing and during progressive hyperoxic hypercapnia. Within a breath, the onset of crural diaphragm inspiratory activity started significantly earlier than that of the costal diaphragm under both resting and CO2 stimulated conditions, although the relative delay in costal diaphragm activity was smaller during hypercapnia than during resting O2 breathing. Following hyperventilation to apnea, both parts of the diaphragm resumed activity on the same breath. During CO2 rebreathing, the maximal increase in crural diaphragm peak electrical activity was significantly greater than that of the costal diaphragm. We also examined the effects of histamine-induced bronchoconstriction on diaphragm activity. Following administration of histamine aerosol there was a transient of irregular breathing during which in three animals costal diaphragm activity became nearly quiet, although there was continued activity of the crural diaphragm. Once breathing became more regular, there was a significantly greater stimulation of crural diaphragm than costal diaphragm activity; this difference persisted for 15 min after histamine inhalation. These results support the concept that electrical activity can be distributed nonuniformly to the costal and crural diaphragm and demonstrate that the crural diaphragm has a greater gain with hypercapnia and bronchoconstriction than does the costal diaphragm.
Right and left ventricular pressure-volume response to respiratory maneuvers
Authors: Santamore W. P. , Heckman J. L. , Bove A. A.
Published: December 2017

With respiration, right ventricular end-diastolic volume fluctuates. We examined the importance of these right ventricular volume changes on left ventricular function. In six mongrel dogs, right and left ventricular volumes and pressures and esophageal pressure were simultaneously measured during normal respiration, Valsalva maneuver, and Mueller maneuver. The right and left ventricular volumes were calculated from cineradiographic positions of endocardial radiopaque markers. Increases in right ventricular volume were associated with changes in the left ventricular (LV) pressure-volume relationship. With normal respiration, right ventricular end-diastolic volume increased 2.3 +/- 0.7 ml during inspiration, LV transmural diastolic pressure was unchanged, and LV diastolic volume decreased slightly. This effect was accentuated by the Mueller maneuver; right ventricular end-diastolic volume increased 10.4 +/- 2.3 ml (P less than 0.05), while left ventricular end-diastolic pressure increased 3.6 mmHg (P less than 0.05) without a significant change in left ventricular end-diastolic volume. Conversely, with a Valsalva maneuver, right ventricular volume decreased 6.5 +/- 1.2 ml (P less than 0.05), and left ventricular end-diastolic pressure decreased 2.2 +/- 0.5 mmHg (P less than 0.05) despite an unchanged left ventricular end-diastolic volume. These changes in the left ventricular pressure-volume relationship, secondary to changes in right ventricular volumes, are probably due to ventricular interdependence. Ventricular interdependence may also be an additional factor for the decrease in left ventricular stroke volume during inspiration.
Sleep-waking pattern and body temperature in hypoxia at selected ambient temperatures
Authors: Hale B. , Megirian D. , Pollard M. J.
Published: December 2017

We studied the effect of mild hypoxia (15% O2) and low ambient temperature (Ta = 15 degrees C) on the rat's sleep-waking pattern (SWP) and maximum-minimum core temperature (max-min Tb). Mild hypoxia at neutral Ta (29 degrees C) disrupted the SWP in the same way as low Ta during normoxia: both affected the pattern of frequency of state changes (P less than 0.01), not the pattern of epoch durations. Mild hypoxia and low Ta together caused a degree of disruption of the SWP which was the sum of each alone, i.e., additive. Although both mild hypoxia and low Ta significantly depressed max-min Tb, low Ta exerted a greater effect than mild hypoxia. Together they further depressed max-min Tb in an additive way. We conclude that mild hypoxia disrupts the rat's SWP independent of central thermoregulatory mechanisms at neutral Ta, that the effects of mild hypoxia and low Ta on the SWP are additive at the stimulus levels used, and that Ta, not inspired O2, determines Tb.
Insulin acts on the fibroblast to inhibit glucocorticoid stimulation of lung maturation
Authors: Carlson K. S. , Smith B. T. , Post M.
Published: December 2017

The effects of insulin and cortisol on saturated phosphatidylcholine synthesis are examined in fetal type II cell cultures and in mixed cell cultures containing type II cells and fibroblasts. In 19-day fetal rat lung type II cell cultures, 100 nM cortisol and 2 nM insulin have no significant effect. Fibroblast-pneumonocyte factor results in enhanced saturated phosphatidylcholine synthesis by fetal type II cells. The significant stimulatory effect of cortisol in mixed-cell cultures is abolished in the presence of insulin or of monoclonal antibodies to fibroblast-pneumonocyte factor. Incubation of type II cells with conditioned media from fibroblasts exposed to cortisol results in increased saturated phosphatidylcholine synthesis. This process is not stimulated when type II cells are incubated with conditioned media from fibroblasts exposed to insulin and cortisol (or to insulin alone). These observations demonstrate that insulin inhibits cortisol induction of lung maturation and suggest that this antagonism results from an inhibitory effect of insulin on the elaboration of fibroblast-pneumonocyte factor by fetal lung fibroblasts.
Effect of hyperosmolality on control of blood flow and sweating
Authors: Fortney S. M. , Wenger C. B. , Bove J. R. , Nadel E. R.
Published: December 2017

To study the effect of hyperosmolality on thermoregulatory responses, five men [average maximal O2 consumption (VO2 max) = 48 ml X kg-1 X min-1] cycled at 65-75% VO2max for up to 30 min in a 30 degrees C, 40% relative humidity environment under three conditions. First, control tests (C) were performed where preexercise plasma volume (PV) and osmolality (Osm) averaged 3,800 ml and 282 mosmol X kg-1, respectively. Second, exercise tests (D) were performed following dehydration induced by fluid restriction and mild exercise (30% VO2max) in hot (40 degrees C) ambient conditions. Each subject then rested in cool surroundings 1 h before performing the exercise test. Preexercise PV and Osm averaged 3,606 ml and 293 mosmol X kg-1, respectively. Third, exercise tests (I) were performed following dehydration, but during the 1-h rest interval, 3% saline was infused so that PV was restored to 3,826 ml and Osm averaged 294 mosmol X kg-1 prior to exercise. During D, esophageal temperatures (Tes) were significantly higher than C, an avg 0.56 degrees C after 20 min exercise due to a 0.22 degrees C increase in Tes threshold for vasodilation, a 39% reduction in slope of the forearm blood flow (BF)-Tes relationship, a 32% average reduction in maximal exercise BF, and a 0.22 degrees C increase in Tes sweating threshold. During I, responses were similar to D, except the BF-Tes slope and the maximum BF were not significantly different from C. Thus hyperosmolality modifies thermoregulation by elevating thresholds for both vasodilation and sweating even without decreases in PV.
Hypoxic insomnia: effects of carbon monoxide and acclimatization
Authors: Pappenheimer J. R.
Published: December 2017

Hypoxia causes severe disruption of both rapid-eye-movement (REM) and non-REM (NREM) sleep. Experiments were performed on rats to determine if hypoxic insomnia is mediated by peripheral chemoreceptors and if normal sleep is restored during acclimatization to low O2. Novel methods were devised to measure distribution of amplitudes of cortical slow waves during NREM sleep and to detect REM sleep from the ratio of amplitudes of theta-to delta-frequency bands in the hippocampal electroencephalogram (EEG). Acute exposure of rats to 10.5% O2 (5,030 m altitude equivalent) during daylight hours virtually abolished REM sleep and shifted the distribution of amplitudes of slow-wave sleep EEG toward awake values. Similar disruption of sleep occurred during inhalation of 0.05% CO with steady-state carboxyhemoglobin of approximately 35%. Respiratory rate and alveolar ventilation were greatly increased by 10.5% O2 but were unaffected by CO. Therefore, hypoxic disruption of sleep was not mediated by peripheral chemoreceptors regulating breathing. Partial recovery of sleep occurred after 1-2 wk of hypoxia, but both REM and NREM were still subnormal after 1 mo. Decreased intensity of NREM sleep during hypoxia, measured by amplitude of cortical slow waves, may explain the disparity between subjective complaints of insomnia at altitude and evaluations of sleep by direct observation or by conventional EEG. Loss of appetite, loss of weight, irritability, and other symptoms of altitude sickness may be related to hypoxic insomnia.
Reflex depression of cardiovascular function during lung inflation
Authors: Ashton J. H. , Cassidy S. S.
Published: December 2017

These experiments were intended 1) to determine the cardiovascular reflex response initiated by lung inflation and 2) to determine the autonomic neural mechanisms that mediate the reflex responses. To test only the reflex effects of lung inflation and eliminate the associated mechanical effects thereof, we isolated the left airway and left pulmonary artery of dogs and performed static inflations of the left lung. Left lung inflation (LLI) to 30 cmH2O caused left ventricular systolic pressure, heart rate, and hindlimb vascular resistance to fall 20, 31, and 15%, respectively. When the hearts were paced to eliminate Bowditch effects, LLI caused left ventricular contractility, which was measured as dP/dt at 30 mmHg developed pressure and as the maximal rate of shortening of the contractile element, to fall 23 and 20%, respectively, and cardiac output (stroke volume) to fall 31%. Transection of the left cervical vagus nerve, interrupting most afferent and some efferent pathways from the left lung, virtually eliminated subsequent cardiovascular responses to LLI. Hindlimb vasodilation was mediated by alpha-adrenergic activity, and the fall in left ventricular contractile state was caused by a reduction in beta-adrenergic activity. The reflex bradycardia was mediated by increased cholinergic and decreased beta-adrenergic activity. These data establish that reflex mechanisms exist whereby expansion of the lung can reflexly modulate heart rate, ventricular contractility, systemic vasomotor tone, cardiac output, and stroke volume independent of the direct mechanical influence of lung expansion on these circulatory phenomena.
Regional lung strain in dogs during deflation from total lung capacity
Authors: Rodarte J. R. , Hubmayr R. D. , Stamenovic D. , Walters B. J.
Published: December 2017

Regional lung distortion during deflation from total lung capacity to functional residual capacity (FRC) in intact supine and prone anesthetized dogs was determined from the displacement of multiple metallic markers embedded in the lung parenchyma. Distortion was expressed as strain (epsilon), which is related to fractional length changes. In the supine position, transverse strain (epsilon yy) was larger than vertical strain (epsilon xx) and cephalocaudal strain (epsilon zz) in the upper lobe. The FRC of the lower lobe was smaller than FRC of the upper lobe and all strains were larger, but epsilon zz increased most and became equal to epsilon yy. In the prone position, epsilon yy was largest in all upper lobes and in three of four lower lobes. Strains and volumes of the upper and lower lobes were similar. The upper and lower lobes rotated slightly around different axes, indicating that interpleural fissures allow additional degrees of freedom for the lungs to conform to the thoracic cavity. In the prone position, there were no consistent gradients of strain or volume. These results indicate that, in determining the regional distribution of FRC in the recumbent dog, in addition to the effect of gravity on the lung, there are important interactions between lung and thoracic cavity shapes.
Collateral ventilation during high-frequency oscillation in dogs
Authors: Armengol J. , Jones R. L. , King E. G.
Published: December 2017

Mechanics of collateral channels during high-frequency oscillatory ventilation (HFOV) were assessed in eight anesthetized dogs, using a modification of Hilpert's technique. Base-line functional residual capacity was measured with a body plethysmograph, with inspiratory efforts induced by phrenic nerve stimulation. The resistance (Rcoll) and time constant (Tcoll) of collateral channels at five lung volumes were measured during HFOV and positive end-expiratory pressure (PEEP). Rcoll and Tcoll were significantly higher during HFOV (P less than 0.001); the differences did not correlate with resting lung volumes. The calculated static compliance of the wedged segment was similar during HFOV and PEEP (P greater than 0.005). Mean pressures measured in small airways during HFOV corresponded to the midline between the inflation and deflation limbs of the static pressure-volume curves, indicating similar pressure-volume characteristics of the respiratory system during HFOV and static conditions. We conclude that HFOV increases resistance to gas flow through collateral channels but that this pathway may still be important in gas exchange.