bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of chest wall on volume and strain patterns in canine lungs
Authors: Krell W. S. , Rodarte J. R.
Published: December 2017

Lobar functional residual capacity-to-total lung capacity ratios (FRC/TLC) and strains in five supine anesthetized dogs were determined from volumes and side lengths of tetrahedra formed by multiple intraparenchymal markers whose positions were determined roentgenographically. Strain is related to fractional changes in length of elements in a Cartesian coordinate system and was used to describe parenchymal distortion. Volumes and strain patterns were compared in three states: intact dogs, after transection of forelimb structures to relieve traction on the chest wall, and in dogs' excised lungs. Removing traction (NT) decreased the plethysmographically determined FRC and the upper-to-lower lobe ratio (UL/LL) for FRC/TLC. The ratio in the NT state was more like the ratio in the excised lungs (UL/LL approximately equal to 1) than in the intact dog (UL/LL greater than 1). Strain patterns were similar between the intact and the NT states, indicating no lobar shape change at FRC between these two states. Strain in the excised lungs differed greatly from strains in the intact and NT states. We conclude that forelimb traction alters volume distribution between lobes and that lung-chest wall interactions are important in determining volume and strain patterns.
Hemodynamic effects of epinephrine: concentration-effect study in humans
Authors: Stratton J. R. , Pfeifer M. A. , Ritchie J. L. , Halter J. B.
Published: December 2017

The hemodynamic effects of three different infusion rates of epinephrine (25, 50, or 100 ng X kg-1 X min-1 for 14 min) were examined in 10 normal human subjects. Ejection fraction and changes in cardiac volumes were assessed by radionuclide ventriculography. Plasma epinephrine was increased to levels that spanned the normal physiological range (178 +/- 15, 259 +/- 24, and 484 +/- 69 pg/ml, respectively). Epinephrine infusions resulted in dose-dependent increases in heart rate (8 +/- 3, 12 +/- 2, and 17 +/- 1 beats/min, mean +/- SE) and systolic pressure (8 +/- 1, 18 +/- 2, and 30 +/- 6 mmHg). Although epinephrine infusions had minimal effects on end-diastolic volume, there were significant increases in stroke volume (+26 +/- 2, 31 +/- 4, and 40 +/- 4%), ejection fraction (+0.10 +/- 0.01, 0.14 +/- 0.02 and 0.16 +/- 0.03 ejection fraction units), and cardiac output (+41 +/- 4, 58 +/- 5, and 74 +/- 1%). These increases in left ventricular performance were associated with a decreased systemic vascular resistance (-31 +/- 3, -42 +/- 2, and -48 +/- 8%). Supine bicycle exercise resulted in similar plasma epinephrine levels (417 +/- 109 pg/ml) and similar changes in stroke volume, ejection fraction, and systemic vascular resistance but greater increases in heart rate and systolic blood pressure. Since infusion-associated hemodynamic changes occurred at plasma epinephrine levels commonly achieved during many types of physical and emotional stress, epinephrine release may have an important role in regulating systemic vascular resistance, stroke volume, and ejection fraction responses to stress in man.
Effect of breath-hold time on DLCO(SB) in patients with airway obstruction
Authors: Graham B. L. , Mink J. T. , Cotton D. J.
Published: December 2017

The single-breath diffusing capacity of the lung for CO [DLCO(SB)] is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin. Although incomplete mixing of inspired gas with alveolar gas could theoretically influence overall diffusion, conventional calculations of DLCO(SB) spuriously overestimate DLCO(SB) during short breath-holding periods when incomplete mixing of gas within the lung might have the greatest effect. Using the three-equation method to calculate DLCO(SB) which analytically accounts for changes in breath-hold time, we found that DLCO(SB) did not change with breath-hold time in control subjects but increased with increasing breath-hold time in both patients with asthma and patients with emphysema. The increase in DLCO(SB) with increasing breath-hold time correlated with the phase III slope of the single-breath N2 washout curve. We suggest that in patients with ventilation maldistribution, DLCO(SB) may be decreased for the shorter breath-hold maneuvers because overall diffusion is limited by the reduced transport of CO from the inspired gas through the alveolar gas prior to alveolar-capillary gas exchange.
Action of abdominal muscles on rib cage in humans
Authors: Mier A. , Brophy C. , Estenne M. , Moxham J. , Green M. , De Troyer A.
Published: December 2017

To assess the actions of the rectus abdominis and external oblique muscles on the rib cage in humans, these two muscles were stimulated with surface electrodes in four normal supine subjects at functional residual capacity. Changes in anteroposterior and transverse rib cage diameters and changes in xiphipubic distance were measured with pairs of magnetometers. Stimulation of rectus abdominis produced a marked decrease in the xiphipubic distance and in the anteroposterior diameter, thus making the rib cage more elliptic. In contrast, stimulation of the external oblique caused a decrease in the transverse diameter, making the rib cage more cylindrical. When both muscles were stimulated simultaneously, the resultant rib cage distortion depended on the relative voltage at which each muscle was stimulated. Electromyogram recordings showed that there was no cross contamination or activity of the diaphragm during the muscle stimulations. Transdiaphragmatic pressure increased with the voltage of stimulation, suggesting passive lengthening of the diaphragm. X-ray studies were performed in two subjects and confirmed the main magnetometer findings. These studies thus confirm that the rib cage in humans is more easily distortable than conventionally thought. The abdominal muscles can distort it in either direction depending on which muscles are contracting.
Effect of endotoxemia on hypoxic pulmonary vasoconstriction in unanesthetized sheep
Authors: Hutchison A. A. , Ogletree M. L. , Snapper J. R. , Brigham K. L.
Published: December 2017

This study examined the effect of acute endotoxemia on hypoxic pulmonary vasoconstriction (HPV) in awake sheep. Thirteen sheep were chronically instrumented with Silastic catheters in the pulmonary artery, left atrium, jugular vein, and carotid artery; with a Swan-Ganz catheter in the main pulmonary artery; with a chronic lung lymph fistula; and with a tracheostomy. Base-line HPV was determined by measuring the change in pulmonary vascular resistance (PVR) while sheep breathed 12% O2 for 7 min. Concentrations of immunoreactive 6-keto-PGF1 alpha and thromboxane B2 (TXB2) were measured in lung lymph during the hypoxic challenge. Escherichia coli endotoxin (0.2–0.5 micrograms/kg) was infused intravenously. Four hours after endotoxemia, HPV was measured. In five sheep, meclofenamate was infused at 4.5 h after endotoxemia and HPV measured again. During the base-line hypoxic challenge, PVR increased by 36 +/- 9% (mean +/- SE). There was no significant change in lung lymph 6-keto-PGF1 alpha or TXB2 levels with hypoxia. Twelve of the 13 sheep showed a decrease in HPV 4 h after endotoxemia; the mean change in PVR with hypoxia was -8 +/- 5%, which was significantly (P less than 0.05) reduced compared with base-line HPV. The infusion of meclofenamate at 4.5 h after endotoxin did not restore HPV.
Motor responses to positive-pressure breathing in the developing opossum
Authors: Farber J. P.
Published: December 2017

The suckling opossum exhibits an expiration-phased discharge in abdominal muscles during positive-pressure breathing (PPB); the response becomes apparent, however, only after the 3rd-5th wk of postnatal life. The purpose of this study was to determine whether the early lack of activation represented a deficiency of segmental outflow to abdominal muscles or whether comparable effects were observed in cranial outflows to muscles of the upper airways due to immaturity of afferent and/or supraspinal pathways. Anesthetized suckling opossums between 15 and 50 days of age were exposed to PPB; electromyogram (EMG) responses in diaphragm and abdominal muscles were measured, along with EMG of larynx dilator muscles and/or upper airway resistance. In animals older than approximately 30 days of age, the onset of PPB was associated with a prolonged expiration-phased EMG activation of larynx dilator muscles and/or decreased upper airway resistance, along with expiratory recruitment of the abdominal muscle EMG. These effects persisted as long as the load was maintained. Younger animals showed only those responses related to the upper airway; in fact, activation of upper airway muscles during PPB could be associated with suppression of the abdominal motor outflow. After unilateral vagotomy, abdominal and upper airway motor responses to PPB were reduced. The balance between PPB-induced excitatory and inhibitory or disfacilitory influences from the supraspinal level on abdominal motoneurons and/or spinal processing of information from higher centers may shift toward net excitation as the opossum matures.
Pulmonary vasodilator responses to vasoactive intestinal peptide in the cat
Authors: Nandiwada P. A. , Kadowitz P. J. , Said S. I. , Mojarad M. , Hyman A. L.
Published: December 2017

We investigated the effects of vasoactive intestinal peptide (VIP) in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow when pulmonary vascular tone was at base-line levels and when vascular resistance was elevated. Under base-line conditions, VIP caused small but significant reductions in lobar arterial pressure without affecting left atrial pressure. Decreases in lobar arterial pressure in response to VIP were greater and were dose related when lobar vascular resistance was increased by intralobar infusion of U 46619, a stable prostaglandin endoperoxide analogue. Acetylcholine and isoproterenol also caused significant decreases in lobar arterial pressure under base-line conditions, and responses to these agents were enhanced when lobar vascular tone was elevated. Moreover, when doses of these agents are expressed in nanomoles, acetylcholine and isoproterenol were more potent than VIP in decreasing lobar arterial pressure. Responses to VIP were longer in duration with a slower onset than were responses to acetylcholine or isoproterenol. Pulmonary vasodilator responses to VIP were unchanged by indomethacin, atropine, or propranolol. The present data demonstrate that VIP has vasodilator activity in the pulmonary vascular bed and that responses are dependent on the existing level of vasoconstrictor tone. These studies indicate that this peptide is less potent than acetylcholine or isoproterenol in dilating the feline pulmonary vascular bed and that responses to VIP are not dependent on a muscarinic or beta-adrenergic mechanism or release of a dilator prostaglandin.
O2 exchange between blood and brain tissues studied with 18O2 indicator-dilution technique
Authors: Grieb P. , Forster R. E. , Strome D. , Goodwin C. W. , Pape P. C.
Published: December 2017

A technique has been developed to record 18O2 dilution curves of an organ in vivo by use of 51Cr-labeled erythrocytes as a reference tracer. The technique employs anaerobic sampling of venous outflow following an intraarterial injection of tracer-laden blood and off-line determination of [18O2] and [51Cr] profiles in the venous outflow. O2 and reference indicator-dilution curves of cerebral circulation were recorded in eight experiments with six halothane-anesthetized dogs. Autologous blood labeled with the tracers was injected into a carotid artery, and brain venous outflow was sampled from the sagittal sinus. The total net extraction of O2 tracer was equal to the extraction of elemental O2. Instantaneous extraction of 18O2 along the outflow curve fell linearly with time, from an initial value of 0.6–0.7 to very small or even negative values toward the end of a pulse. This indicates that O2 undergoes a flow-limited distribution. In all experiments, the mean transit time of unmetabolized 18O2 was longer than the mean transit time of the Cr tracer. An index of the tissue O2 dilution space, hence the mean tissue PO2, is calculated from this data with the use of a modified central volume principle. This estimate of mean tissue PO2 increases as a linear function of sagittal sinus PO2 with a slope of 0.97. The method may provide an index of the critical PO2 of venous blood, the PO2 below which O2 diffusion from blood to tissue may limit its rate of metabolic uptake.
Model of gas transport during high-frequency ventilation
Authors: Permutt S. , Mitzner W. , Weinmann G.
Published: December 2017

We analyze gas exchange during high-frequency ventilation (HFV) by a stochastic model that divides the dead space into N compartments in series where each compartment has a volume equal to tidal volume (V). We then divide each of these compartments into alpha subcompartments in series, where each subcompartment receives a well-mixed concentration from one compartment and passes a well-mixed concentration to another in the direction of flow. The number of subcompartments is chosen on the basis that 1/alpha = (sigma t/-t)2, where -t is mean transit time across a compartment of volume, and sigma t is standard deviation of transit times. If (sigma t/-t)D applies to the transit times of the entire dead space, the magnitude of gas exchange is proportional to (sigma t/-t)D, frequency, and V raised to some power greater than unity in the range where V is close to VD. When V is very small in relation to VD, gas exchange is proportional to (sigma t/-t)2D, frequency, and V raised to a power equal to either one or two depending on whether the flow is turbulent or streamline, respectively. (sigma t/-t)D can be determined by the relation between the concentration of alveolar gas at the air outlet and volume expired as in a Fowler measurement of the volume of the dead space.
Effect of normoxemic and hypoxemic exercise on renin and aldosterone
Authors: Shigeoka J. W. , Colice G. L. , Ramirez G.
Published: December 2017

Five subjects (group 1) performed progressive treadmill exercise on 2 separate days, once while breathing room air (normoxemic) and the other time while breathing gas with a fractional inspired O2 of 17% (hypoxemic). Five other subjects (group 2) performed two progressive treadmill exercise tests on each of 2 separate days in a crossover design. On 1 day normoxemic exercise was first, followed by hypoxemic exercise, and on the other day the pattern was reversed. Plasma renin activity (PRA) increased to a similar extent with hypoxemic exercise as with normoxemic exercise. Plasma aldosterone concentrations (PAC) rose to a significantly higher level during normoxemic exercise than with hypoxemic exercise. Comparing changes in PRA to PAC with progressive exercise revealed dissociation of PAC from PRA during hypoxemic exercise. The PAC response remained depressed when normoxemic exercise followed hypoxemic exercise. These results indicate that hypoxemia interferes with PRA-mediated aldosterone secretions. The mechanism of this inhibition is unclear.
Effects of elevated and exercise-reduced muscle glycogen levels on insulin sensitivity
Authors: Ivy J. L. , Frishberg B. A. , Farrell S. W. , Miller W. J. , Sherman W. M.
Published: December 2017

The effects of an exercise-induced muscle glycogen reduction and an elevated muscle glycogen concentration on glucose tolerance and the insulin response to an oral glucose tolerance test (GTT) were examined. GTTs were administered to seven male subjects after 3 days on a mixed diet (C), after exhaustive exercise and 1 day on a high-fat protein diet (L-FP), after exhaustive exercise and 1 day on a mixed diet (L-M), and after exhaustive exercise and 3 days on a high-carbohydrate diet (H-CHO). The L-M treatment resulted in a significant reduction in muscle glycogen (C, 79.6 +/- 4.2 mmol/kg wet wt vs. L-M, 53.9 +/- 1.2 mmol/kg wet wt) and a 31.7% reduction in the insulin-glucose (IG) index, a measure of insulin sensitivity in vivo. Muscle glycogen was also significantly reduced by the L-FP treatment (49.1 +/- 2.4 mmol/kg wet wt), but there was no change in the IG index. Preventing a decrease in the IG index during the L-FP treatment may have been a result of elevated free fatty acids (67%) and ketones (552%) prior to the GTT. Muscle glycogen was significantly increased by the H-CHO treatment (124.8 +/- 11.1 mmol/kg wet wt); however, the IG index was not different from that of the C treatment. The results suggest that an exercise-induced reduction in muscle glycogen can improve insulin sensitivity in vivo but that this effect is diet dependent.
Submaximal exercise responses of tetraplegics and paraplegics
Authors: Coutts K. D. , Rhodes E. C. , McKenzie D. C.
Published: December 2017

This study describes responses of 21 wheelchair users to a continuous, increasing work rate test to exhaustion on a wheelchair ergometer. Heart rate, ventilation, O2 uptake, respiratory exchange ratio, ventilation equivalent for O2, and O2 pulse were determined for each minute. Subjects were divided into tetraplegic (n = 8), high-lesion paraplegic (n = 6), and low-lesion paraplegic (n = 7) groups. Linear regression analyses, with O2 uptake as the independent variable, were used to determine the strength of relationships within each group and differences between groups in slopes and intercepts of regression equations. All variables were significantly (P less than 0.05) related to O2 uptake (r = 0.42–0.94). The only significant difference between the high- and low-lesion paraplegic groups was for heart rate intercept, as the heart rate for the low-lesion group tended to be lower at any given O2 uptake. Tetraplegics had a higher intercept and/or slope for ventilation equivalent, ventilation, and respiratory exchange ratio and lower intercepts for heart rate and O2 pulse. These differences in responses to a progressive exercise task are logically related to the differences in maximal O2 uptake, functional muscle mass, and vasomotor and cardiac control of the groups.
Respiratory resistance in dogs by the single-breath and the forced oscillation methods
Authors: Harf A. , Decramer M. , Zin W. , Milic-Emili J. , Chang H. K.
Published: December 2017

Total respiratory resistance (Rrs) was measured in six anesthetized dogs with two different methods: the single-breath (SB) method, which provides the time constant of the system during a relaxed expiration and the forced oscillation (FO) method, which uses a pseudorandom noise signal applied at the airway opening. The comparison was made in three conditions: before muscle paralysis (A), after muscle paralysis (B), and after tracheal banding (C). In conditions A and B the two computed resistances correlated very well with each other (r = 0.98). No systematic difference between Rrs values obtained with the two methods was found. In condition C the respiratory resistance was clearly nonlinear from the flow-volume curves during SB and could be described with Rohrer's equation: Rrs = K1 X V + K2 X V2, where K1 and K2 are Kohrer's constant and V is flow. Rrs measured with FO was not frequency dependent during tracheal banding (C) and was virtually equivalent to K1. Since the FO method uses low flows as the input of the respiratory system and K1 could be ascribed to laminar flow, the numerical matching appears reasonable and tends to reinforce the validity of both methods of measurement. We conclude that, for the normal respiratory system, FO and SB methods are approximately equivalent. In the presence of a markedly alinear central airway resistance with normal lungs, the SB method appears to provide a more adequate description of the flow-resistive properties of the system.
Increased gravitational stress does not alter maximum expiratory flow
Authors: Pyszczynski D. , Mink S. N. , Anthonisen N. R.
Published: December 2017

We measured maximum expiratory flow-volume (MEFV) curves in six seated subjects during normal (+1 Gz) and increased (+2 and +3 Gz) gravitational stress. Full MEFV curves, initiated at total lung capacity, were recorded, as were partial MEFV curves, initiated at approximately 60% of the vital capacity. Data were acquired in all subjects breathing air at +1 and +2 Gz; results were available for three subjects breathing 80% He-20% O2 at +1 and +2 Gz, and in two subjects, results were obtained at +3 Gz. Changes in gravitational stress were not associated with changes of either full or partial MEFV curves. The known increase in differences of regional lung volume and recoil caused by increased gravitational stress did not influence maximum expiratory flow. Though increased gravitational stress probably changed regional emptying sequences little during full MEFV maneuvers, substantial changes of emptying sequence were expected during partial maneuvers. It is possible that such changes in emptying sequence occurred but were not associated with changes in maximum flow because the latter was determined by choking in central airways common to all regions.
Promethazine or DPPD pretreatment attenuates oleic acid-induced injury in isolated canine lungs
Authors: Townsley M. I. , Taylor G. E. , Korthuis R. J. , Taylor A. E.
Published: December 2017

Oleic acid causes pulmonary edema by increasing capillary endothelial permeability, although the mechanism of this action is uncertain. We tested the hypothesis that the damage is an oxidant injury initiated by oleic acid, using isolated blood-perfused canine lung lobes. The lobes were dilated with papaverine and perfused in zone III with a constant airway pressure of 3 cmH2O. Changes in isogravimetric capillary pressure (Pc,i) and capillary filtration coefficient (Kf,C) were used as indices of alterations in microvascular permeability in lungs treated with silicone fluid (n = 3), oleic acid (n = 11), oleic acid after pretreatment with the antioxidants promethazine HCl (n = 11) or N,N′-diphenyl-p-phenylenediamine (DPPD; n = 4), or oleic acid following pretreatment with methylprednisolone (n = 4). Kf,C averaged 0.21 +/- 0.02 ml X min-1 X cmH2O–1 X 100 g-1 in control and increased to 0.55 +/- 0.05 and 0.47 +/- 0.05 when measured 20 and 180 min after the administration of oleic acid. When oleic acid was infused into lungs pretreated with promethazine, Kf,C increased to only 0.38 +/- 0.05 ml X min-1 X cmH2O–1 X 100 g-1 after 20 min and had returned to control levels by 180 min. Pretreatment with DPPD, but not methylprednisolone, similarly attenuated the increase in Kf,C following oleic acid. Silicone fluid had no effect on Kf,C. That oleic acid increases vascular permeability was also evidenced by a fall (P less than 0.05) in Pc,i from control when measured at 180 min in every group.
Measurement of bronchial arterial blood flow and bronchovascular resistance in sheep
Authors: Charan N. B. , Turk G. M. , Ripley R.
Published: December 2017

We studied the bronchial arterial blood flow (Qbr) and bronchial vascular resistance (BVR) in sheep prepared with carotid-bronchial artery shunt. Nine adult sheep were anesthetized, and through a left thoracotomy a heparinized Teflon-tipped Silastic catheter was introduced into the bronchial artery. The other end of the catheter was brought out through the chest wall and through a neck incision was introduced into the carotid artery. A reservoir filled with warm heparinized blood was connected to this shunt. The height of blood column in the reservoir was kept constant at 150 cm by adding more blood. Qbr was measured, after interrupting the carotid-bronchial artery flow, by the changes in the reservoir volume. The bronchial arterial back pressure (Pbr) was measured through the shunt when both carotid-bronchial artery and reservoir Qbr had been temporarily interrupted. The mean Qbr was 34.1 +/- 2.9 (SE) ml/min, Pbr = 17.5 +/- 3.3 cmH2O, BVR = 3.9 +/- 0.5 cmH2O X ml-1 X min, mean pulmonary arterial pressure = 21.5 +/- 3.6 cmH2O, and pulmonary capillary wedge pressure (Ppcw) = 14.3 +/- 3.7 cmH2O. We further studied the effect of increased left atrial pressure on these parameters by inflating a balloon in the left atrium. The left atrial balloon inflation increased Ppcw to 25.3 +/- 3.1 cmH2O, Qbr decreased to 21.8 +/- 2.4 ml/min (P less than 0.05), and BVR increased to 5.5 +/- 1.0 cmH2O.ml-1.min (P less than 0.05).
Endurance training in humans: aerobic capacity and structure of skeletal muscle
Authors: Hoppeler H. , Howald H. , Conley K. , Lindstedt S. L. , Claassen H. , Vock P. , Weibel E. R.
Published: December 2017

The adaptation of muscle structure, power output, and mass-specific rate of maximal O2 consumption (VO2max/Mb) with endurance training on bicycle ergometers was studied for five male and five female subjects. Biopsies of vastus lateralis muscle and VO2max determinations were made at the start and end of 6 wk of training. The power output maintained on the ergometer daily for 30 min was adjusted to achieve a heart rate exceeding 85% of the maximum for two-thirds of the training session. It is proposed that the observed preferential proliferation of subsarcolemmal vs. interfibrillar mitochondria and the increase in intracellular lipid deposits are two possible mechanisms by which muscle cells adapt to an increased use of fat as a fuel. The relative increase of VO2max/Mb (14%) with training was found to be smaller by more than twofold than the relative increase in maximal maintained power (33%) and the relative change in the volume density of total mitochondria (+40%). However, the calculated VO2 required at an efficiency of 0.25 to produce the observed mass-specific increase in maximal maintained power matched the actual increase in VO2max/Mb (8.0 and 6.5 ml O2 X min-1 X kg-1, respectively). These results indicate that despite disparate relative changes the absolute change in aerobic capacity at the local level (maintained power) can account for the increase in aerobic capacity observed at the general level (VO2max).
Total respiratory input and transfer impedances in humans
Authors: Peslin R. , Duvivier C. , Gallina C.
Published: December 2017

Total respiratory input (Zrs,in) and transfer (Zrs,tr) impedances were obtained from 4 to 30 Hz in 10 healthy males by simultaneously measuring mouth and chest flow while applying pseudo-random pressure variations at the mouth. Compared with Zrs,in, the real part of Zrs,tr was larger up to 10 Hz but exhibited a much stronger negative frequency dependence. The imaginary part was larger at all frequencies, with a resonant frequency (fn) at 6.0 +/- 0.8 Hz compared with 8.2 +/- 2.9 Hz for Zrs,in. The two impedances were analyzed with a model featuring airway resistance and inertance, alveolar gas compressibility, and tissue resistance, inertance, and compliance. A good fit was generally obtained but, in most cases, with a different partitioning of resistance between airway and tissue for Zrs,in and Zrs,tr. The data were also used to compute separately airway and tissue (Zt) impedances. In most subjects Zt could not be properly fitted with a simple resistance-inertance-compliance unit and was consistent with a slow (fn = 7.4 +/- 2.3 Hz) overdamped compartment in parallel with a fast (fn = 37.1 +/- 5.6 Hz) underdamped one.
Distortion of submerged dog lung lobes
Authors: Olson L. E. , Wilson T. A. , Rodarte J. R.
Published: December 2017

The conically shaped caudal lobes of dog lungs were submerged, tip downward in saline, and the lateral surfaces of the lobes were thereby exposed to a hydrostatic gradient in transpulmonary pressure. The force that was required to balance the buoyancy was applied through a clip attached to the tip of the lobe. The locations of metal markers implanted in the parenchyma and attached to the surface were tracked, and regional volume and the horizontal and vertical components of strain were obtained as functions of vertical position. An engineering analysis of the deformation is qualitatively consistent with the data, but the predicted strains are larger than the observed strains. From the experimental and analytical results, we conclude that, for this deformation, the regional volume-local transpulmonary pressure curve closely follows the pressure-volume curve because negative horizontal strains nearly balance the positive vertical strain caused by the buoyancy force.
Passage of uncharged dextrans from blood to lung lymph in awake sheep
Authors: Lanken P. N. , Hansen-Flaschen J. H. , Sampson P. M. , Pietra G. G. , Haselton F. R. , Fishman A. P.
Published: December 2017

To examine how molecular size alone influences the passage of macromolecules from the pulmonary microcirculation into lymph collected from the caudal mediastinal lymph node of the sheep, we infused polydisperse uncharged [3H]dextrans intravenously at a constant rate over a period of 7.5 h in nine awake sheep with lung lymph fistulas. Lymph and plasma were collected during hours 5.5–7.5 of the infusions, and the [3H]dextrans were separated by molecular sieve chromatography into fractions that ranged from 1.6 to 8.4 nm in effective molecular (Stokes-Einstein) radius. Lymph-to-plasma (L/P) ratios for [3H]dextrans were near 1.0 at 1.6-nm radius, decreased with increasing molecular size, and approached zero at radii above 5.0 nm. We confirmed that these L/P ratios represented steady-state values by extending the duration of the infusion to approximately 30 h in two of the nine sheep and finding that the L/P ratios remained unchanged. These results were consistent with molecular sieving through a homoporous membrane with cylindrical pores of 5.0-nm radius. We also found that the L/P ratio for albumin [0.76 +/- 0.13 (SE)] in five of the same sheep was much higher than that for the [3H]dextran fraction of the same effective molecular radius [0.11 +/- 0.02 (SE)]. These results suggest that the movement of macromolecules from the pulmonary microcirculation into pulmonary lymph collected from the caudal mediastinal node of the sheep is influenced by both molecular size and molecular charge and that, compared with uncharged dextrans, the steady-state passage of anionic endogenous proteins from plasma to lymph is enhanced.
Selenium deficiency potentiates paraquat-induced lipid peroxidation in isolated perfused rat lung
Authors: Glass M. , Sutherland M. W. , Forman H. J. , Fisher A. B.
Published: December 2017

Glutathione peroxidase (GSHPx), a seleno-enzyme, reduces lipid hydroperoxides while producing oxidized glutathione (GSSG), which can efflux from cells. To study the role of GSHPx in antioxidant defense, isolated lungs from selenium-deficient rats were perfused for 2 h with or without 1 mM paraquat. Perfusate GSSG was measured as an index of GSHPx activity, and malondialdehyde (MDA) as an index of lipid peroxidation. Selenium deficiency decreased lung GSHPx activity 75–80%. During perfusion control lungs showed GSSG efflux of 8.5 +/- 4.5 nmol/h and with paraquat 49.1 +/- 12.1 nmol/h. Selenium-deficient lungs with or without paraquat showed GSSG efflux of 16.4 +/- 5.3 and 13.7 +/- 8.9 nmol/h, respectively. MDA efflux occurred only in paraquat-perfused selenium-deficient lungs (7.8 +/- 2.7 nmol/h). Lung homogenates from this group had lower GSH + GSSG than the other three groups. These results indicate an inverse correlation between GSSG efflux and MDA accumulation from paraquat-perfused lungs and suggest that increased turnover of the GSHPx reaction protects paraquat-perfused lungs from lipid peroxidation.
Biochemical and physiological changes in overloaded rat fast- and slow-twitch ankle extensors
Authors: Roy R. R. , Baldwin K. M. , Martin T. P. , Chimarusti S. P. , Edgerton V. R.
Published: December 2017

The rat soleus (SOL) or medial gastrocnemius (MG) were chronically overloaded by removing their major synergists bilaterally. After 12–14 wks the overloaded SOL (OS) and overloaded MG (OMG) muscles had approximately 50% greater cross-sectional areas (CSA) than the controls. Maximum twitch (Pt) and tetanic (Po) tensions were approximately 46% larger in the OS compared with the normal SOL. The OMG produced 10 and 37% higher Pt and Po, respectively. Specific tension (Po/CSA) was not altered in either group (P greater than 0.05). Contraction times and half-relaxation times were unchanged. Myofibrillar and myosin ATPase specific activities indicated a shift toward that resembling a slower muscle in both the OS and the red portion but not the white portion of the OMG. Generally, markers of glycogen metabolism were reduced (P less than 0.05) in the same muscle areas that showed reduced ATPase activity. These biochemical results were consistent with the apparent histochemical conversion of fibers from fast-twitch, glycolytic----fast-twitch, oxidative-glycolytic----slow-twitch, oxidative types in these muscle areas. These results suggest that overloading either a fast- or slow-twitch plantarflexor results in an increase in muscle mass and maximum tension and in metabolic shifts that generally resemble those observed in a slower muscle. Further, the degree of adaptation appears to be related to the initial fiber type composition of the muscle and/or of the muscle region.
Beta-adrenergic mediators increase pulmonary retention of instilled phospholipids
Authors: Fisher A. B. , Dodia C. , Chander A.
Published: December 2017

Retention of radiolabeled phospholipid vesicles instilled into the alveolar space was studied with the isolated perfused rat lung and quantitated by measuring the percent of instilled radioactivity remaining in lung after five lavages. With synthetic [14C]dipalmitoyl phosphatidylcholine (PC):egg PC: phosphatidylglycerol:cholesterol (10:5:2:3) vesicles, there was a rapid (within 5 min) base-line retention of 10.3 +/- 0.25% (n = 11) followed by a slower phase of linear retention over the next 4 h. Retention at 2 h with perfused lungs was 18.6 +/- 0.60% (n = 9) and was similar to values obtained with lungs in vivo. Net retention (total minus base line) was stimulated 93% by isoproterenol, 173% by 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP), and 39% by 8-bromoguanosine 3′,5′-cyclic monophosphate; propranolol blocked the effect of isoproterenol. The retention of natural (biosynthesized) surfactant [14C]PC was stimulated 92% by 8-Br-cAMP. The results suggest that the retention of exogenous phospholipid by the isolated perfused lung represents phospholipid uptake and that this process is under beta-adrenergic control. Secretion and uptake may be physiologically linked to regulate the concentration of surfactant on the alveolar surface.
Obesity alters regional ventilation in lateral decubitus position
Authors: Hurewitz A. N. , Susskind H. , Harold W. H.
Published: December 2017

Alterations of regional ventilation were determined as a function of body position in five morbidly obese subjects using 81mKr to assess ventilation (V) and 127Xe at equilibrium to determine lung volume (V). With subjects in seated and supine positions, the left lung contributed an average of 43% of the total V/V. When the apical-basal gradient within each lung was examined in subjects in the seated position, V/V was greatest in the dependent (basal) regions in half of the subjects, whereas the others showed greater V/V near the upper lung regions. All obese subjects preferentially ventilated the nondependent lung in both the left and right lateral decubitus positions. In a control group of three nonobese subjects, V/V was found to be equally distributed between left and right lungs in both the seated and supine positions. In contrast with the results in the obese group, V/V was slightly greater in the dependent lung in both lateral decubitus positions. Although the combination of 127Xe images and He-dilution measurement of functional residual capacity in the lateral decubitus positions indicated a reduction in the volume of the dependent lung of the obese when compared with values in the seated position, other factors affecting the mechanical function of either the diaphragm or the intercostal muscles could also have produced these positional alterations of ventilation.
Role of hilar nerve afferents in hyperpnea of exercise
Authors: Flynn C. , Forster H. V. , Pan L. G. , Bisgard G. E.
Published: December 2017

The objective of this study was to determine the role of hilar nerve (lung vagal) afferents in the hyperpnea of exercise. Ten ponies were studied before and 2–4 wk and 3–12 mo after sectioning only the hilar branches of the vagus nerves (HND). After HND, lung volume feedback to the medullary centers was attenuated as indicated in the anesthetized state by 1) attenuation or absence of the Hering-Breuer inflation reflex (P less than 0.01) and 2) attenuation of the lengthened inspiratory time (TI) when the airway was occluded at end expiration (P less than 0.01). Moreover, after HND in the awake state, there was an increase in the ratio of TI to total cycle time (P less than 0.01). These changes verify a compromise in lung innervation comparable to cervical vagotomy. Resting arterial PCO2, PO2, and pH were not altered following HND (P greater than 0.10). Moreover, at three levels of mild and moderate treadmill exercise, no difference in either the temporal pattern or the absolute levels of arterial blood gases and arterial pH was found between pre- and post-HND studies (P greater than 0.10). In addition, minute ventilation (VE) at rest and during exercise was not altered by HND (P greater than 0.10). However, 2–4 wk after HND the increase in breathing frequency (f) during exercise was less, whereas the increase in tidal volume during exercise was greater than pre-HND (P less than 0.05). The reduced f was due to an increase in TI with no change in expiratory time. We conclude that lung afferents via the hilar nerves influence the pattern of breathing at rest and during exercise in ponies.
Use of aerosols to measure in vivo volume-dependent changes in lung air space dimensions
Authors: Bennett W. D. , Mitzner W.
Published: December 2017

Using measurements of aerosol recovery following a 5-s breath hold [NRC(5)] as indices of lung air space dimensions, we evaluated the in vivo changes in these dimensions associated with changes in lung volume (VL). In anesthetized dogs, single breaths of a 1.2-micron monodisperse aerosol were introduced into the respirator's cycle at a number of isovolume points on the inflation and deflation limb of the pressure-volume curve for the dog's lungs. At isovolume, NRC(5) measured off the inflation limb was slightly larger than NRC(5) measured off the deflation limb, implying a larger mean air space dimension for the air space configuration on the inflation vs. the deflation limb. Since a constant aerosol tidal volume (VT) was used for all VL in all dogs, the proportion of the lung filled with aerosol, VT/VL = Pn (where Pn is defined as an index of aerosol penetration into the lung periphery), varied along with VL. In all dogs, we found that, for NRC(5) measurements with Pn less than 0.33, NRC(5) steadily increased with increasing VL, which implies an increasing mean air space dimension as VL increases. However, when we account for the effect that changes in Pn with increasing VL have on NRC(5), we conclude that the observed increase in NRC(5) with VL is primarily due to decreases in Pn and not increases in the mean air space dimension as VL increases.
Responses of bulbospinal and laryngeal respiratory neurons to hypercapnia and hypoxia
Authors: St John W. M. , Bianchi A. L.
Published: December 2017

The purpose was to evaluate activities of medullary respiratory neurons during equivalent changes in phrenic discharge resulting from hypercapnia and hypoxia. Decerebrate, cerebellectomized, paralyzed, and ventilated cats were used. Vagi were sectioned at left midcervical and right intrathoracic levels caudal to the origin of right recurrent laryngeal nerve. Activities of phrenic nerve and single respiratory neurons were monitored. Neurons exhibiting antidromic action potentials following stimulations of the spinal cord and recurrent laryngeal nerve were designated, respectively, bulbospinal or laryngeal. The remaining neurons were not antidromically activated. Hypercapnia caused significant augmentations of discharge frequencies for all neuronal groups. Many of these neurons had no change or declines of activity in hypoxia. We conclude that central chemoreceptor afferent influences are ubiquitous, but excitatory influences from carotid chemoreceptors are more limited in distribution among medullary respiratory neurons. Hypoxia will increase activities of neurons that receive sufficient excitatory peripheral chemoreceptor afferents to overcome direct depression by brain stem hypoxia. The possibility that responses of respiratory muscles to hypoxia are programmed within the medulla is discussed.
Effect of increased bronchial venous pressure on lung lymph flow
Authors: Charan N. B. , Turk G. M. , Hey D. H.
Published: December 2017

We postulated that if the bronchial circulation affects lung fluid balance, increases in bronchial venous pressures may influence lung lymph flow. This hypothesis was tested in eight anesthetized sheep prepared with acute lung lymph fistulas. After control data, we increased bronchial venous pressure by infusing saline directly into the bronchial vein at a controlled infusion pressure of 20–25 cmH2O. Evans blue dye (2.5 mg/ml) was added into the saline as a marker for assessing leakage that might occur from either the catheter or the ruptured bronchial veins. Lymph flow was measured every 15 min. Lymph as well as plasma samples were collected every 30 min for measurement of protein. In five sheep we also measured Evans blue dye content both in lymph and plasma to further characterize the role of bronchial circulation in lung fluid balance. The control lymph flow was 1.9 +/- 0.2 ml/15 min, and lymph-to-plasma protein ratio was 0.65 +/- 0.3 (mean +/- SE). With infusion of saline into the bronchial vein, the mean lung lymph flow and lymph-to-plasma protein ratio did not change significantly. There was a progressive increase in dye content both in lymph and plasma. The mean Evans blue dye content in lymph was 0.087, 0.16, and 0.26 microgram/ml, whereas in plasma it was 0.43, 1.15, and 1.45 microgram/ml in samples obtained at 30, 60, and 90 min, respectively. The dye content was significantly higher in the plasma compared with the lymph in all three samples (less than 0.05). Pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac output did not change significantly throughout the experiment.
Respiratory effects of brief baroreceptor stimuli in the anesthetized dog
Authors: Dove E. L. , Katona P. G.
Published: December 2017

To quantify the immediate isocapnic respiratory response to baroreceptor stimulation, pressure in the isolated externally perfused carotid sinuses (CS) of 24 vagotomized alpha-chloralose-anesthetized dogs was increased selectively during either inspiration or expiration as a step (from time of onset to end of respiratory phase) or a pulse (500 ms). The rise time (150 ms), base-line pressure (80 mmHg), and stimulus magnitude (40 mmHg) were similar for the two stimuli. The time of stimulus onset (delay), expressed as a percent of control time of inspiration (TI) or expiration (TE), was varied. TI, TE, and tidal volume (VT) were expressed as percent changes from control. Stimuli delivered early in inspiration lengthened TI [23.5 +/- 6.4% (SE) for step and 11.7 +/- 6.3% for pulse stimuli at 5% delay] more effectively than late stimuli. VT was essentially unaltered. In contrast, step stimuli delivered during expiration caused a lengthening of TE (32.7 +/- 6.3% at 5% delay) that did not depend on the delay (up to 75%). Very late (85%) pulse stimuli lengthened TE (15.2 +/- 5.7%) more effectively than early stimuli. For both stimuli, the expiratory VT was unaltered. When the responses are compared before and after separation of the blood supply of the carotid bodies from the CS region and when they are compared before and after inhibition of reflex systemic hypotension by ganglionic blockade, the observed responses were shown to be due solely to CS baroreceptor stimulation and not to alterations in carotid body blood flow or reflex changes in systemic cardiovascular variables.
Role of beta-adrenergic mechanisms during exercise in poorly controlled diabetes
Authors: Wasserman D. H. , Lickley H. L. , Vranic M.
Published: December 2017

To examine the beta-adrenergic effects of the catecholamines in poorly controlled diabetes, we have studied insulin-deprived alloxan-diabetic (A-D) dogs during 90 min of moderate exercise (100 m/min, 10–12 degrees) alone (C) or with propranolol (5 micrograms . kg-1 . min-1) (P) or combined P and somatostatin infusion (0.5 microgram . kg-1 . min-1) (P + St). In P, in contrast to C, immunoreactive glucagon (IRG) rose only after 50 min of exercise. However, hepatic glucose production (Ra) rose normally. In P + St, IRG fell 50% below basal, and the Ra response to exercise was abolished. Interestingly, in P and P + St, glucose metabolic clearance rate (MCR) rose by 400% above the inadequate MCR response to exercise in C, despite 30% lower insulin levels. Compared with C, free fatty acids (FFA) and lactate were sharply reduced during P and P + St. Plasma glucose (G) did not change in C, but due to elevated glucose uptake, G fell over 120 mg/dl in P, and due to diminished Ra, G fell 170 mg/dl in P + St. Norepinephrine was similar in all groups. Epinephrine and cortisol were higher in P + St by 90 min of exercise, perhaps as a result of hypoglycemia. In summary, during exercise in poorly controlled A-D dogs, beta-blockade does not appear to affect Ra; beta-blockade leads to diminished mobilization of extrahepatic substrate as evidenced by reduced FFA and lactate levels; beta-blockade increases MCR to levels seen in normal dogs during exercise alone.
Effect of 71 ATA He-O2 on organ blood flow in the rat
Authors: Aanderud L. , Onarheim J. , Tyssebotn I.
Published: December 2017

Cardiac output and organ blood flow to major organs were investigated in awake rats at 1 atmosphere absolute (ATA) air and at 71 ATA He-O2. Radioactively labeled microspheres [15 +/- 1 (SD) micron] were injected into the left ventricle during constant-rate arterial blood sampling at 1 ATA air and subsequently at 71 ATA He-O2. Intra-arterial blood pressure was continuously recorded. The partial pressure of O2 was kept between 0.4 and 0.6 ATA. The results indicate that the mean blood pressure, heart rate, cardiac output, and organ blood flow are essentially unaltered in the rat at 71 ATA except for increased blood flow to the liver (122%, P less than 0.05), whereas the blood flow to the adrenals, the diaphragm, and the leg muscle fell (P less than 0.05).
Interspike interval dependency from arterial chemoreceptors
Authors: Donnelly D. F. , Nolan W. F. , Smith E. J. , Dutton R. E.
Published: December 2017

The carotid body impulse generator has been previously characterized as a Poisson-type random process. We examined the validity of this characterization by analyzing sinus nerve spike trains for interspike interval dependency. Fifteen single chemoreceptive afferents were recorded in vivo under hypoxic-hypercapnic conditions, and approximately 1,000 consecutive interspike intervals for each fiber were timed and analyzed for serial dependence. The same set of intervals placed in shuffled order served as a control series without serial dependence. The original spike interval trains showed significantly negative first-order serial correlation coefficients and less variability in joint interval distributions than did the shuffled interval trains. These results suggest that the chemoreceptor afferent train is not random and may reflect a negative feedback system operating within the carotid body that limits variation about a mean frequency.