bluuebunny/crossref_metadata_2025 huggingface dataset:
Rib cage and abdominal expiratory muscle responses to CO2 and esophageal distension
Authors: van Lunteren E. , Haxhiu M. A. , Cherniack N. S. , Arnold J. S.
Published: December 2017

The present study compared the responses of rib cage and abdominal expiratory muscles to chemical and mechanical stimuli. In pentobarbital-anesthetized spontaneously breathing dogs, electromyograms (EMG) were recorded from the triangularis sterni (TS) and transverse abdominis (TA) muscles using bipolar intramuscular wire electrodes. During resting oxygen breathing, both muscles were electrically active during expiration. Progressive hyperoxic hypercapnia significantly augmented the expiratory activity of both the TA and the TS. However, the mean percent increases in electrical activity in response to CO2 were substantially greater for the TA than for the TS at all PCO2 levels greater than 50 Torr (P less than 0.01). Occlusion of the airway at end inspiration significantly delayed the onset of TS EMG (from 0.35 +/- 0.07 to 3.35 +/- 0.67 sec; P less than 0.002) and decreased TS EMG rate of rise (P less than 0.002), but did not significantly alter these parameters for the TA. Esophageal distension increased TS EMG in all dogs (by mean of 220 +/- 64%; P less than 0.01), but in contrast decreased TA EMG in all dogs (by a mean of 63 +/- 12%; P less than 0.001). The response to esophageal distention occurred in a graded manner and appeared to be mediated predominantly via vagal afferents. We concluded that expiratory muscles of the rib cage and abdomen manifest substantial differences in their electrical responses to chemoreceptor, pulmonary stretch receptor, and esophageal mechanoreceptor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunoglobulin E anaphylaxis in rabbits: mechanisms of pulmonary resistance and compliance changes
Authors: Habib M. P. , Dunn A. M. , Sobonya R. E. , Baumgartener C. C. , Newell J. D. , Halonen M.
Published: December 2017

Factors causing changes in pulmonary resistance and dynamic compliance with immunoglobulin (Ig) E anaphylaxis in spontaneously breathing rabbits were assessed in ventilated rabbits using tantalum bronchography and wet-to-dry wt ratios. Ventilated rabbits demonstrated changes in resistance and compliance similar to spontaneously breathing rabbits. Chlorpheniramine pretreatment prevented increases in resistance but not decreases in compliance. Anaphylaxis constricted small (less than 1 mm) airways 20.9 ± 16.0% (mean ±- SD) and intermediate (between 1 and 3 mm) airways 21.8 ± 19.8%. Chlorpheniramine (10 mg/kg) prevented small airway changes and attenuated those in intermediate airways. Chlorpheniramine prevented histamine-induced constriction of small (23.6 ± 15.7%) and intermediate (17.6 ±- 15.0%) airways. Lung wet-to-dry wt ratios were unchanged. Changes in resistance and compliance during rabbit IgE anaphylaxis are not due to changes in tidal volume or frequency. Histamine, via H1 receptors, is the principal mediator of pulmonary resistance increases but not dynamic compliance reductions. Chlorpheniramine-sensitive increases in resistance are caused by constrictions of intermediate and small airways, whereas the chlorpheniramine-resistant decrease in compliance is not caused directly by constriction of the smallest measurable airways (0.25 mm) or changes in lung water.
Mechanism of action of physical antipyresis in the rat
Authors: Banet M.
Published: December 2017

To study the mechanism of action of physical antipyresis, core temperature was measured in two groups of rats in which heat loss was increased by cold exposure and by cooling an inferior cava heat exchanger, respectively, both before and after infection with Salmonella enteritidis. Cold exposure did not influence core temperature. On the other hand, cooling the heat exchanger caused a fall in core temperature of approximately 0.7 degree C, to 37 degrees C in normothermia and to 38.5 degrees C 24 h after the infection. These lower core temperatures were then regulated against any further increase in heat loss until the thermoregulatory metabolic capacity of the animals was exhausted and a hypothermia developed. It is concluded that in infectious fever the threshold temperature of shivering increases as much as core temperature. Furthermore it is suggested that physical antipyresis, such as sponging with tepid water, induces a moderate but regulated fall in temperature to about the threshold of shivering and that its efficacy may increase with ambient temperature.
Failure of neuromuscular propagation during human maximal voluntary contraction
Authors: Bellemare F. , Garzaniti N.
Published: December 2017

The mechanism for fatigue of the adductor pollicis was studied in normal subjects during maximal voluntary contractions (MVC) sustained for 90-100 s, by comparing the force and electrical response of this muscle to voluntary motor drive with that obtainable with artificial stimulation of the ulnar nerve. The adequacy of nerve stimulation was checked by recording simultaneously the electrical response of a nonfatiguing muscle, the abductor of the small finger. The decrease in force and in the natural electrical activity with fatigue was accompanied by a parallel decrease in the amplitude of synchronous muscle action potentials (M waves) evoked by artificial stimulation of the ulnar nerve at different frequencies. The decline in M-wave amplitude in the adductor pollicis was not due to a submaximal nerve stimulation, since the amplitudes recorded simultaneously from the nonfatiguing abductor digiti minimi remained unchanged. The force and the electrical responses from the adductor pollicis recovered in parallel with a half time of approximately 1 min. These results suggest that the loss of force of the adductor pollicis with fatigue and its subsequent recovery are largely determined by the extent of neuromuscular propagation failure. The slow recovery of the M-wave amplitude during repetitive stimulation suggests that it may be related to some aspect of muscle metabolism.
Equivalent pore estimate for the alveolar-airway barrier in isolated dog lung
Authors: Conhaim R. L. , Eaton A. , Staub N. C. , Heath T. D.
Published: December 2017

In high-pressure pulmonary edema, lung interstitial and air space edema liquids have equal protein concentrations (Am. J. Physiol. 231: 1466, 1976). This suggests that the alveolar-airway barrier separating the air and interstitial spaces is relatively unrestrictive, even without apparent epithelial injury. To estimate the equivalent pore population of the alveolar-airway barrier we inflated each of 18 isolated dog lung lobes for 1 h with a solution of colored tracer of uniform radius. Tracer radii ranged from 1.3 to 405 nm. After freezing the lobes in liquid N2, we measured interstitial tracer concentrations in frozen perivascular cuffs or in samples thawed after dissection from frozen cuffs. Relative to the concentrations instilled, interstitial concentrations ranged from 0.34 for the smallest particles (1.3 and 3.5 nm radius) to zero for particles with radii of 405 nm. From the results we designed a pore model of the alveolar-airway barrier to reproduce the concentrations we measured. No single-pore model could be obtained, although a three-pore model fit the data well. The model results predict that pores with radii of 1, 40, and 400 nm would account for 68, 30, and 2% of total liquid flux, respectively. The majority of liquid flux (68%) would occur through passageways smaller than the smallest tracer we used (1.3 nm radius). We believe the alveolar-airway barrier consists not only of tight intercellular junctions that allow passage of only water and electrolytes but also of a smaller number of large leaks that allow passage of particles up to nearly 400 nm in radius.
Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep
Authors: Miyamoto K. , Schultz E. , Heath T. , Mitchell M. D. , Albertine K. H. , Staub N. C.
Published: December 2017

We studied the effects of liposomes on the pulmonary circulation of sheep and found a close correlation between liposome retention in the lung and the intravascular macrophages. A test dose of liposomes (5.5 mumol of total lipids) injected intravenously transiently increased pulmonary arterial pressure from 24± 2 to 55 ± 16 (SD) cmH2O. The pulmonary arterial pressure responses were dose dependent and reproducible. The rise in pulmonary arterial pressure was blocked completely by indomethacin and 75% by a thromboxane synthase inhibitor. Systemic arterial thromboxane B2 concentration increased from a base-line level of less than 50 pg/ml to 250 ± 130 pg/ml at the peak of the pressor response. Larger doses of liposomes (220 mumol of total lipids) infused intravenously over 1 h increased pulmonary arterial pressure maximally within the first 15 min. Lymph flow increased and lymph protein concentration decreased, suggesting venoconstriction. Over half (62.4 ± 15.7%) of 111In-labeled liposomes remained in the lung after 2 h. Fluorescence and transmission electron microscopy showed that greater than 90% of the liposomes were associated with mononuclear cells in the lumen of the alveolar wall microvessels. We conclude that liposomes affect pulmonary arterial pressure transiently by a mechanism involving the arachidonate cascade, principally thromboxane. Our observations suggest that a population of pulmonary intravascular macrophages is likely to be the source of the thromboxane and the pulmonary hemodynamic and lymph dynamic changes that occur in a dose-dependent fashion, although interactions between liposomes, leukocytes, or endothelial cells, in addition to the macrophages, have not been completely ruled out. We believe this is the first demonstration that pulmonary intravascular macrophages may be the source of the arachidonate metabolites rather than endothelial cells, neutrophils, or perivascular interstitial cells.
Diaphragmatic O2 and lactate extraction during submaximal and maximal exertion in ponies
Authors: Manohar M. , Goetz T. E. , Holste L. C. , Nganwa D.
Published: December 2017

Diaphragmatic O2 and lactate extraction were studied in 10 healthy ponies at rest and during treadmill exercise. The phrenic vein was aseptically catheterized via a lateral thoracotomy 8-35 days before the study. Arterial and phrenic venous blood samples were obtained simultaneously at rest and at 30-s intervals during 4 min of exertion. Three levels of exertion were studied (moderate, 10 mi/h; heavy, 15 mi/h; maximal, 20 mi/h), and a rest period of at least 90 min was allowed between them. Each pony was studied twice at least 2-3 days apart. At rest the diaphragmatic venous PO2, O2 saturation, arteriovenous O2 content difference, and O2 extraction were 43.2 ± 2.0 Torr, 76.1 ± 3.2%, 3.14 ± 0.43 ml/dl, and 23.60 ± 3.61%, respectively. Significant decrease in phrenic venous PO2 and O2 saturation occurred within 30 s of exercise. Phrenic venous PO2 decreased to 20.3 ± 1.0, 18.9 ± 1.1, and 15.4 ± 0.9 Torr at 120 s of moderate, heavy, and maximal exercise, respectively. Corresponding values of phrenic venous O2 saturation were 33.6 ± 2.2, 25.8 ± 2.1, and 17.9 ± 0.5%, respectively. Diaphragmatic arteriovenous O2 content difference expanded to 13.11 ± 0.49, 15.00 ± 0.60, and 16.90 ± 0.60 ml/dl at 120 s of moderate, heavy, and maximal exercise, respectively, as O2 extraction rose to 65.93 ± 1.98, 73.90 ± 1.99, and 80.95 ± 0.47%, respectively. During heavy and maximal exercise, the diaphragmatic venous lactate concentration remained similar to the arterial concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of mechanical load on tidal volume during high-frequency jet ventilation
Authors: Berdine G. G. , Strollo P. J.
Published: December 2017

High-frequency jet ventilation (HFJV) was studied in twelve deeply anesthetized, paralyzed dogs. Entrained volume and total expired volume were directly measured by integration of flow. Jet volume was computed from these measurements. Seven dogs were ventilated with a driving pressure of 10 psi at rates of 2 and 5 Hz for each of three mechanical loads: control, thoracoabdominal wrap, and histamine infusion. Both load conditions reduced total expired volume and entrained volume but had no effect on jet volume. Wrap reduced entrainment more at 2 Hz while the effect of histamine infusion was frequency independent. Control arterial blood gases demonstrated that PO2 was higher and PCO2 was lower during 2 Hz ventilation than during 5 Hz ventilation despite equivalent minute volumes. Five additional dogs were studied using control and wrap loads and an additional ventilator setting of 15 psi at 5 Hz. This group demonstrated that wrap reduces entrainment more at lower frequencies for ventilatory settings providing equivalent gas exchange. We conclude that increasing mechanical load reduces entrainment during HFJV and that this reduction is frequency dependent for restrictive loads.
Abnormal control of ventilation in high-altitude pulmonary edema
Authors: Hackett P. H. , Roach R. C. , Schoene R. B. , Harrison G. L. , Mills W. J.
Published: December 2017

We wished to determine the role of hypoxic chemosensitivity in high-altitude pulmonary edema (HAPE) by studying persons when ill and upon recovery. We studied seven males with HAPE and seventeen controls at 4,400 m on Mt. McKinley. We measured ventilatory responses to both O2 breathing and progressive poikilocapnic hypoxia. Hypoxic ventilatory response (HVR) was described by the slope relating minute ventilation to percent arterial O2 saturation (delta VE/delta SaO2%). HAPE subjects were quite hypoxemic (SaO2% 59 ± 6 vs. 85 ± 1, P less than 0.01) and showed a high-frequency, low-tidal-volume pattern of breathing. O2 decreased ventilation in controls (-20%, P less than 0.01) but not in HAPE subjects. The HAPE group had low HVR values (0.15 ± 0.07 vs. 0.54 ± 0.08, P less than 0.01), although six controls had values in the same range. The three HAPE subjects with the lowest HVR values were the most hypoxemic and had a paradoxical increase in ventilation when breathing O2. We conclude that a low HVR plays a permissive rather than causative role in the pathogenesis of HAPE and that the combination of extreme hypoxemia and low HVR may result in hypoxic depression of ventilation.
A continuous noncontact method for measuring in situ vascular diameter with a video camera
Authors: Bell L. B. , Hopp F. A. , Seagard J. L. , Van Brederode H. F. , Kampine J. P.
Published: December 2017

A new, continuous, on-line, video diameter-measuring technique, utilizing a video camera mounted on the sidearm of a stereo microscope, is described. Vessel diameter is derived from changes in the video output signal of the camera or a video recorder when the vessel of interest is displayed horizontally on a monitor and well contrasted with its background. A comparator threshold is set on the filtered video output signal and generates an output pulse that is used to gate horizontal video sync pulses to a digital counter-timer. The number of pulses counted for each video field (no. of horizontal video lines) is proportional to the vessel diameter. The video-derived diameter is calibrated using known standards and correlates well with sonomicrometer-derived diameters of the carotid artery and jugular vein during increasing pressure ramps (r greater than 0.999). The diameter update rate is 60 Hz, and the resolution of the system is one horizontal video line, independent of the vessel size. With suitable magnification and contrast both arteries and veins as small as 200 micron have been measured using this system.
Hypoxia does not increase CSF or plasma beta-endorphin activity
Authors: Freedman A. , Scardella A. T. , Edelman N. H. , Santiago T. V.
Published: December 2017

The ability of moderate (30-50 Torr arterial PO2) and severe (less than 30 Torr arterial PO2) hypoxia to generate endogenous opioids that modulate ventilation was studied in unanesthetized goats. Ventilation and its components, arterial blood gas tensions and pH, and plasma and cerebrospinal fluid (CSF) beta-endorphin activity were measured before and after 4 h of sustained moderate or severe hypoxia. Ventilation, as expected, increased with hypoxia. There were no significant changes in either plasma or CSF beta-endorphin activity after sustained hypoxia. To rule out elaboration of endogenous opioids other than beta-endorphin after hypoxia, naloxone or saline was administered to five of the seven goats exposed to 4 h of severe hypoxia, and their ventilatory responses were compared for 30 additional min of hypoxic breathing. No significant differences in ventilation occurred in the two treatment groups during this time period. We conclude that, unlike increases in airway resistance, moderate and severe hypoxia do not cause the elaboration of endogenous opioids that modify respiratory output in unanesthetized adult goats. The apparent ability of hypoxia to cause elaboration of endogenous opioids in the neonate may represent a maturational phenomenon.
Linear relationship between VO2max and VO2max decrement during exposure to acute hypoxia
Authors: Lawler J. , Powers S. K. , Thompson D.
Published: December 2017

The purpose of these experiments is to test the hypothesis that exercise-induced hypoxemia at sea level in highly trained athletes might be exacerbated during acute hypoxia and therefore result in correspondingly larger decrements in maximal O2 uptake (VO2max) compared with less trained individuals. Thirteen healthy male volunteers were divided into two groups according to their level of fitness: 1) trained endurance athletes (T) (n = 7), with a VO2max range of 56-75 ml.kg-1.min-1 and 2) untrained individuals (UT) (n = 6), with a VO2max range of 33-49 ml.kg-1.min-1. Subjects performed two incremental cycle ergometry tests to determine VO2max under hypoxic conditions [14% O2-86% N2, barometric pressure (PB) = 760 Torr] and normoxic conditions (21% O2-79% N2, PB = 760 Torr). Tests were single blind, randomly administered, and separated by at least 72 h. Mean percent oxyhemoglobin saturation (%SaO2) during maximal exercise under hypoxic conditions was significantly (P less than 0.05) lower in the T group (77%) compared with the UT group (86%). Furthermore, the T group exhibited larger decrements (P less than 0.05) in VO2max (normoxic-hypoxic) compared with the UT group. Finally, a significant linear correlation (r = 0.94) existed between normoxic VO2max (ml.kg-1.min-1) and delta VO2max (normoxic-hypoxic). These data suggest that highly T endurance athletes suffer more severe gas exchange impairments during acute exposure to hypoxia than UT individuals, and this may explain a portion of the observed variance in delta VO2max among individuals during acute altitude or hypoxia exposure.
Noninvasive measurement of regional interstitial lung volume in sheep
Authors: Gorin A. B.
Published: December 2017

The noninvasive external radioflux detection method (ERD) measures net transvascular flux of tracer protein into and out of the lung extravascular compartment (EV) and time to zero flux between compartments. With this information we can now estimate regional interstitial volume in the field of the external probe (VIs). Dividing the mass of EV tracer by VIs, we obtain interstitial concentration ([Is]). Directly sampling plasma concentration of the tracer, we can construct plasma-interstitium equilibration curves that are analogous to plasma-lymph equilibration curves without invasive surgery. We completed 46 ERD studies in 21 sheep with chronic lung lymph fistulas. Sheep were studied under baseline conditions (n = 30) and after elevating left atrial pressure by mitral obstruction (n = 7), or intravascular volume infusion (n = 8), and increasing lung vascular permeability (n = 1). In each study we compared the slope of the regression through plasma-lymph concentration of tracer protein over time ([P]-[L], measured directly) with that through values of plasma-interstitial concentration ([P]-[Is], assessed noninvasively), an index of vascular permeability. For this correlation, r = 0.94, and the regression line approximates identity. Mean [Is] appears to approximate [L] in sheep.
Bronchoalveolar cell activation after inhalation of a bronchoconstricting agent
Authors: Cooper J. A. , Merrill W. W. , Rankin J. A. , Sibille Y. , Buck M. G.
Published: December 2017

Airway inflammation is thought to be an important determinant of bronchoconstriction and bronchial hyperreactivity. We have recently demonstrated that bronchoconstriction induced by an aqueous extract of cotton bracts (CBE) is associated with bronchoalveolar complement activation, release of polymorphonuclear neutrophil (PMN) chemoattractants by pulmonary cells, and increased numbers of bronchoalveolar lavage PMN's. In the present study we performed bronchoalveolar lavage (BAL) on subjects after CBE or control (saline) challenge and examined whether BAL cells were activated in vitro to produce other inflammatory agonists. After CBE administration, cultured BAL cells released increased amounts of the reactive O2 species, superoxide (O2-.), and the cyclooxygenase products prostaglandin E2 and thromboxane B2. Although none of these in vitro parameters of BAL cell activation appeared to correlate with the degree of bronchoconstriction induced by CBE, BAL fluid levels of thromboxane B2 were also increased after CBE administration and in vivo amounts of this eicasanoid did correlate with the degree of bronchoconstriction induced by CBE (r = 0.50, P less than 0.04). Finally, although cell culture supernatants were highly chemotactic for PMN's, concentrations of leukotriene B4 were not increased, suggesting other chemotaxins were released by BAL cells in this setting. We conclude that CBE administration activates bronchoalveolar cells to release reactive O2 species and cyclooxygenase products that may be important in the bronchoconstricting response to CBE.
Graded cutaneous vascular responses to dynamic leg exercise
Authors: Taylor W. F. , Johnson J. M. , Kosiba W. A. , Kwan C. M.
Published: December 2017

The cutaneous vascular conductance-esophageal temperature (CVC-Tes) relationship was examined at five work loads (75–200 W) in each of four men to find whether there is a role for exercise intensity in the control of skin blood flow (SkBF). Several factors contributed to our evaluation of the CVC-Tes relationship during work. Laser-Doppler velocimetry (LDF) provided a continuous measure of SkBF that is not influenced by underlying muscle blood flow. Local warming to 39 degrees C at the site of measurement of SkBF provided a consistent skin temperature and facilitated observation of changes in LDF. Mean arterial pressure was measured noninvasively once per minute to calculate CVC. Supine exercise minimized baroreceptor-induced cutaneous vasoconstriction. Our major finding was that the internal temperature at which CVC began to rise during exercise (CVC threshold) was graded with work load beyond 125 W (P less than 0.05). In that range the CVC threshold increased by 0.16 degrees C for every increment of 25 W. The CVC threshold was never reached at the highest work load in three of the four subjects. There was no consistent effect of work load on the slope of the CVC-Tes relationship or on the internal temperature at which sweating began during exercise (sweat rate threshold). We conclude that the level of work beyond 125 W affects the CVC-Tes relationship in a graded fashion, principally through shifts in threshold.
Role of circulating platelets and granulocytes in PAF-induced pulmonary dysfunction in awake sheep
Authors: Christman B. W. , Lefferts P. L. , King G. A. , Snapper J. R.
Published: December 2017

The effects of a single intravascular bolus injection of platelet-activating factor (PAF) on pulmonary hemodynamics, lung mechanics, and lung fluid and solute exchange were studied in 13 chronically instrumented unanesthetized sheep. Since PAF has profound effects on both platelets and granulocytes, we investigated the effects of platelet and granulocyte depletion on the sheep's response to exogenous PAF. Sheep received PAF when granulocyte and platelets counts were normal and after platelet depletion with rabbit antisheep platelet antibodies (n = 5) or granulocyte depletion with hydroxyurea (n = 5). Sheep served as their own controls, and the order of experimentation was varied. Bolus injections of PAF had reproducible effects on pulmonary hemodynamics (pulmonary arterial pressure increased acutely to 85 +/- 3.7 cmH2O) and lung mechanics (dynamic compliance of the lungs decreased to 24.5 +/- 3.8% of base line and resistance to airflow across the lungs increased greater than 10-fold) and caused marked increases in lung lymph concentrations of thromboxane B2 and 6-ketoprostaglandin F1 alpha. The single bolus injection of PAF also caused marked prolonged elevations in lung lymph flow and increases in the lymph-to-plasma protein concentration ratio for 3 h after PAF. PAF had profound effects despite platelet and granulocyte depletion. Platelet depletion slightly attenuated the pulmonary hypertension observed after PAF injection. Platelet depletion also attenuated the increases in thromboxane B2 concentrations in lung lymph, and lung mechanics normalized more rapidly in platelet-depleted sheep. There were no statistically significant effects of granulocyte depletion to less than 200 granulocytes/mm3 on any of the measured variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Autonomic mediation of the pressor responses to isometric exercise in humans
Authors: Seals D. R. , Chase P. B. , Taylor J. A.
Published: December 2017

The purpose of this study was to determine the respective contributions of tachycardia and increases in sympathetic nerve activity (SNA) in mediating the pressor responses to fatiguing vs. nonfatiguing levels of isometric handgrip exercise (IHE) in humans. We performed direct (microneurographic) measurements of muscle SNA from the right peroneal nerve in the leg and recorded arterial pressure (AP) and heart rate (HR) in eight healthy subjects before (control), during, and after 2.5 min of IHE at 15, 25, or 35% of maximal voluntary contraction (MVC). At 15% MVC, AP increased during the initial 1.5 min of IHE (7 mmHg, P less than 0.05) and remained at this level; at 25 and 35% MVC, AP increased throughout IHE (22 and 34 mmHg vs. control, respectively, P less than 0.05). HR increased during the initial 1.5 min of IHE at all three levels (5, 12, and 19 beats/min, respectively, P less than 0.05) but did not increase further over the last minute. At 15% MVC, muscle SNA did not increase above control; during 25 and 35% MVC, muscle SNA did not increase during the 1st min of IHE but increased progressively thereafter (109 and 205% vs. control, respectively, P less than 0.05). The magnitudes of the average increases in AP and muscle SNA over the last minute of IHE were directly related (r = 0.99, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Correlation of left phrenic arterial flow with regional diaphragmatic blood flow
Authors: Nichols D. G. , Scharf S. M. , Traystman R. J. , Robotham J. L.
Published: December 2017

Previous work has assumed that left phrenic arterial blood flow (Qpa) reflects diaphragmatic blood flow. We have tested this assumption in four anesthetized mechanically ventilated dogs by measuring Qpa with a Doppler flow probe and regional diaphragmatic blood flow with radiolabeled microspheres. Flows were examined during control 1 (diaphragm at rest), pacing (phrenic pacing: rate 20/min, duty cycle 0.33), control 2, hypotension (rest with mean arterial pressure reduced by 45% of the control 1 value), and hypotension and pacing. As a percent of the control 1 value, Qpa was 511 +/- 107% during pacing, 139 +/- 12% during control 2, 40 +/- 13% during hypotension, and finally 347 +/- 31% during hypotension and pacing. Similarly, percent left hemidiaphragmatic blood flow (Qlh) was 362 +/- 91% during pacing, 91 +/- 10% during control 2, 14 +/- 2% during hypotension, and finally 213 +/- 50% during hypotension and pacing. The changes in flow to the left costal and crural diaphragm were similar to those recorded for Qlh. We conclude that Qpa correlates with total and regional diaphragmatic blood flow (r = 0.77–0.81, P less than 0.001) under conditions of supramaximal phrenic nerve stimulation in which the metabolic demands of the region perfused by the phrenic artery are presumed to be similar to the metabolic demands of the rest of the diaphragm.
Ventilatory and diaphragmatic EMG changes during negative-pressure ventilation in healthy subjects
Authors: Rodenstein D. O. , Cuttitta G. , Stanescu D. C.
Published: December 2017

To evaluate the response of normal subjects to assisted ventilation, we studied 6 naive healthy subjects before and during negative-pressure ventilation (NPV) with "low" (-10 cmH2O) and "high" (-30 cmH2O) pressures in an Emerson tank respirator. Ventilation was measured with an inductive plethysmograph (Respitrace), and diaphragmatic electromyogram (DEMG) was studied with a bipolar esophageal electrode. During NPV a 1:1 phase lock was observed between subjects and iron lung frequency in all subjects. Tidal volume increased in most subjects, more with high than with low pressures (P less than 0.05), whereas DEMG increased, decreased, or showed no change. Postinspiratory inspiratory diaphragmatic activity (PIIA) significantly increased during high-pressure NPV and was accompanied by an increase in tonic DEMG in one-half of the subjects. Voluntary relaxation resulted in a decrease in DEMG and PIIA. We suggest that cortical activity can explain persistency of active breathing during negative-pressure ventilation.
Role of beta 2-adrenergic receptors on coronary resistance during exercise
Authors: DiCarlo S. E. , Blair R. W. , Bishop V. S. , Stone H. L.
Published: December 2017

The effects of regional alpha- and specific beta 2-adrenergic receptor blockade on measurements of late diastolic coronary resistance (LDCR) and mean coronary blood flow velocity (CBFV) during exercise were examined in 14 conscious adult mongrel dogs. Specific beta 2-adrenergic receptor blockade (ICI 118.551) significantly decreased CBFV and increased LDCR by blockade of beta 2-vasodilator tone independent of alpha-adrenergic receptor-mediated tone and independent of altering myocardial metabolism. alpha-Adrenergic receptor blockade (phentolamine, 1 mg) significantly increased CBFV and decreased LDCR by blocking sympathetically mediated vasoconstrictor tone. There was no significant difference in the magnitude of response between alpha- and beta 2-adrenergic receptor blockade. These results demonstrate that alpha- and beta 2-adrenergic receptors have a significant and evidently equal influence on CBFV and LDCR during exercise. Four weeks of daily exercise and left stellate ganglionectomy (LSGx) prevented phentolamine-induced vasodilation but not ICI 118.551-induced vasoconstriction. This suggests that daily exercise and LSGx significantly decreased the alpha-adrenergic receptor-mediated vasoconstrictor tone on the coronary circulation, resulting in an apparently greater role for the coronary vascular beta 2-adrenergic receptor on the control of CBFV and LDCR during exercise.
Effects of glucose infusion in exercising rats
Authors: Winder W. W. , Arogyasami J. , Yang H. T. , Thompson K. G. , Nelson L. A. , Kelly K. P. , Han D. H.
Published: December 2017

To determine whether feedforward control of liver glycogenolysis during exercise is subject to negative feedback by elevated blood glucose, glucose was infused into exercising rats at a rate that elevated blood glucose greater than 10 mM. Liver glycogen content decreased 22.4 mg/g in saline-infused rats compared with 13.6 mg/g in glucose-infused rats during the first 40 min of treadmill running (21 m/min, 15% grade). Liver adenosine 3',5'-cyclic monophosphate (cAMP) concentration was significantly lower in the glucose-infused rats during the exercise bout. The concentration of hepatic fructose 2,6-bisphosphate remained elevated throughout the exercise bout in glucose-infused rats but decreased markedly in saline-infused rats. Plasma insulin concentration was higher and plasma glucagon concentration lower in glucose-infused rats than in saline-infused rats during exercise. Early in exercise, liver glycogenolysis proceeds in the glucose-infused rats despite the fact that glucose and insulin concentrations are markedly elevated and liver cAMP is unchanged from resting values. These observations suggest the existence of a cAMP-independent feedforward system for activation of liver glycogenolysis that can override classical negative feedback mechanisms during exercise.
Comparison of afferent and efferent lung lymph in the sheep
Authors: McClure D. E. , Weidner W. J.
Published: December 2017

Efferent lymph collected from the caudal mediastinal lymph node (CMN) in the sheep lung lymph fistula model has been reported to represent free pulmonary interstitial fluid. Studies that utilize this model assume that nodal transit does not alter the composition of lymph. We collected afferent lymph from the tracheobronchial node (TBN) while simultaneously collecting CMN efferent lymph in acutely prepared sheep. We compared afferent and efferent lymph protein concentrations (CA and CE) and changes in flow rates (QLA and QLE) during base line and periods of elevated left atrial pressure (Pla). As a result of elevated Pla, QLA and QLE increased and the afferent lymph-to-plasma protein concentration ratio (CA/Cp) and the efferent lymph-to-plasma protein concentration ratio (CE/Cp) fell. The CA/Cp was significantly lower than the CE/Cp during base line (0.67 vs. 0.80) and periods of elevated Pla (0.41 vs. 0.61). Although we cannot exclude regional permeability differences, the difference between CA/Cp and CE/Cp is most likely due to the concentration of lymph within the CMN. Our data suggest nodal modification of CA is correlated with the afferent lymph-to-plasma colloid osmotic pressure ratio (pi A/pi p) and further suggest that nodal alteration of lymph during elevated Pla is due to the influence of decreased pi A/pi p at the blood-to-lymph barrier. We conclude that afferent lymph is a more accurate representation of lung free interstitial fluid because collection of pulmonary afferent lymph obviates the complications introduced by the CMN. Studies utilizing efferent lymph may have overestimated lung microvascular permeability in the acute sheep preparation.
Muscle atrophy and hypoplasia with aging: impact of training and food restriction
Authors: Daw C. K. , Starnes J. W. , White T. P.
Published: December 2017

The purpose of this work is to study the influence of aging, training, and food restriction on skeletal muscle mass and fiber number. Male Fischer 344 rats (n = 49) at 3 mo postpartum were assigned to three groups: 1) sedentary control (confined to cage), 2) exercise trained (18 m/min, 8 degrees grade, 20 min/day, 5 days/wk), or 3) food restricted (alternate days of free access and no access to food). At 12 and 27 mo postpartum the soleus and extensor digitorum longus (EDL) muscles were excised, weighed, and fiber number was quantified after HNO3 digestion. At 27 mo the masses of soleus and EDL muscles of sedentary control rats were 83 and 70%, respectively, of 12-mo values (138 +/- 5 and 151 +/- 4 mg). At 27 mo, soleus muscle mass of trained rats was 113% of sedentary control values, whereas EDL muscle mass was unaffected by training. At 27 mo, food restriction had no effect on the mass of both muscles compared with 27-mo sedentary control values. Fiber number was not affected by training or food restriction in both muscles. Fiber number for soleus and EDL muscles of combined groups declined with age by 5.6 and 4.2%, respectively. With aging, the small loss of muscle fibers can account at most for approximately 25% of the observed skeletal muscle atrophy.
Airway reactivity to methacholine in nonatopic asymptomatic adults
Authors: Casale T. B. , Rhodes B. J. , Donnelly A. L. , Weiler J. M.
Published: December 2017

We studied 50 nonsmoking volunteers, ages 18–35 yr, with no past or present history or physical examination findings of asthma, rhinitis, allergic disease, or recent respiratory infections, to evaluate the usefulness of the methacholine bronchoprovocation challenge (MBPC) as a screening test for asthma. All were skin-test-negative to 29 aeroallergens and had base-line pulmonary function values greater than 80% predicted. Fourteen (28%) subjects had a drop in forced expiratory volume in 1 s (FEV1) of 20% or greater at a provocative dose (PD20FEV1) less than or equal to 225 breath units. Moreover, when these subjects were compared with 21 asymptomatic allergic asthmatics, there was significant overlap between the two groups in concentration of methacholine causing this decline in FEV1. A positive MBPC at methacholine concentrations less than or equal to 5 mg/ml was not diagnostic of asthma, and a negative MBPC at methacholine concentrations greater than or equal to 10 mg/ml did not rule out asthma. These data strongly suggest that MBPC should not be used as the sole factor for the diagnosis of clinically significant asthma. A positive MBPC is one indication of the presence of airway hyperresponsiveness and thus is only one of many factors that must be considered in the diagnosis of asthma.
Effects of endotoxemia on the sheep lung microvascular membrane: a two-pore theory
Authors: Bradley J. D. , Roselli R. J. , Parker R. E. , Harris T. R.
Published: December 2017

We analyzed the effects of Escherichia coli endotoxin infusion on pulmonary microvessels in sheep by using a two-pore mathematical model of the microvascular barrier. Five sheep were prepared with lung lymph fistulas and instrumented to measure pulmonary arterial and left atrial pressures. Multiple indicator-dilution curves (with 125I-labeled albumin, 51Cr-labeled erythrocytes, [14C]urea, and 3H2O) were measured at base line and during phases 1 and 2 of the endotoxin response. Alterations in the membrane integrity in response to endotoxin infusion were quantified by using a two-pore theory of the microvascular barrier that incorporated lymph, protein, pressure, and multiple indicator measurements. The modeling results showed a slight change in the size of the pores during phase 1 but a 56% decrease in the number of small pores and a twofold increase in the number of large pores with respect to base-line values. During phase 2 the large pore size increased by 40%, and the total number of pores returned to base-line values. The analysis showed that endotoxin effects on fluid and protein exchange in the lung cannot be explained by hemodynamic and surface area changes alone. An apparent increase in lung microvascular permeability occurs during phases 1 and 2 of the endotoxin reaction, with a substantial decrease in perfused microvascular surface area during phase 1.
Exercise-induced muscle damage, repair, and adaptation in humans
Authors: Clarkson P. M. , Tremblay I.
Published: December 2017

This study examined exercise-induced muscle damage, repair, and rapid adaptation. Eight college-age women performed three eccentric exercises of the forearm flexors. One arm performed 70 maximal contractions (70-MAX condition), and the other arm performed 24 maximal contractions (24-MAX) followed 2 wk later by 70 maximal contractions (70-MAX2). Criterion measures of serum creatine kinase, muscle soreness and pain, isometric strength, and muscle shortening were assessed before, immediately after, and for 5 days after each exercise. Significant changes in all criterion measures were found after the 70-MAX exercise with a slow recovery that was not complete by day 5 after exercise. The 24-MAX condition showed only small changes in the criterion measures. Changes in the criterion measures after the 70-MAX2 exercise were significantly smaller than those after the 70-MAX exercise. Results from this study, with regard to the ability of the muscle to adapt to exercise-induced damage, suggest that an adaptation takes place such that the muscle is more resistant to damage and any damage that does occur is repaired at a faster rate. It is also clear that a relatively small insult will produce this adaptation.
Pulmonary effects of acute prenatal asphyxia in ventilated premature lambs
Authors: Berry D. , Jobe A. , Ikegami M. , Seidner S. , Pettenazzo A. , Elkady T.
Published: December 2017

The effect of profound repetitive prenatal asphyxial insults on the cardiopulmonary function of premature ventilated lambs was studied. Twenty-nine fetal lambs (approximately 138 days gestational age) were exteriorized. In 16 of these lambs, the umbilical cord was occluded for 4 min then released for 10 min. This asphyxial episode was repeated until the arterial pH was approximately 7.00, and the mean arterial blood pressure was less than 40 mmHg and falling. The 13 control lambs were simply exteriorized with the umbilical circulation intact. The lambs were then ventilated for 3-4 h. There were no differences between the control vs. asphyxiated lambs in pulmonary compliances (0.57 and 0.58 ml.cmH2O-1.kg-1) wet-to-dry weight ratios (8.18 and 7.55), cardiac outputs (177.8 and 141.8 ml.kg-1.min-1), surfactant-saturated phosphatidylcholine pool sizes, or atrial and/or ductal shunts. Asphyxia did not interfere with the redirection of blood away from atelectatic lung segments created by bronchial obstruction with balloon catheters. Also, although the bidirectional flux of protein into and out of the airways of these preterm lambs was large relative to term lambs, there was no effect of asphyxia on this protein leak. In this animal model, prenatal asphyxia did not impact negatively on the severity of the respiratory failure.
Adenosine transport by the lung
Authors: Das D. K. , Steinberg H.
Published: December 2017

Adenosine, a nucleoside and potent vasodilator, has been found to be taken up by the lung and converted by deamination into inosine and hypoxanthine. In a single circulation through an isolated rat lung, 69.3 +/- 3.3% of infused [14C]adenosine (10 microM) was removed from the circulation. Uptake of [14C]adenosine remained unchanged when deamination of adenosine was inhibited by 8-azaguanine or coformycin. In a single passage of adenosine through the pulmonary artery, very little of the deaminated products appeared in the pulmonary circulation, but when adenosine was recirculated through the pulmonary circulation inosine and hypoxanthine appeared in the venous effluent. These adenosine metabolites were also taken up by the lung. A major portion of the circulating adenosine was transported into the lung, where it was used to synthesize adenine nucleotides. Inhibition of adenosine kinase by iodotubercidin resulted in reduced formation of ATP and ADP. Uptake of adenosine by the lung was saturable on a concentration gradient and was a passive process because it was not affected by the absence of glucose or the presence of ouabain. Km and Vmax for adenosine transport were 0.227 mM and 4.6 mumol.min-1.g lung-1, respectively. Adenosine transport was inhibited by adenosine analogues, and the inhibitions were found to be competitive in nature. These results suggest that a specific and rate-limiting transport system exists in the lung for adenosine.
Shift in body fluid compartments after dehydration in humans
Authors: Nose H. , Mack G. W. , Shi X. R. , Nadel E. R.
Published: December 2017

To investigate the influence of [Na+] in sweat on the distribution of body water during dehydration, we studied 10 volunteer subjects who exercised (40% of maximal aerobic power) in the heat [36 degrees C, less than 30% relative humidity (rh)] for 90-110 min to produce a dehydration of 2.3% body wt (delta TW). After dehydration, the subjects rested for 1 h in a thermoneutral environment (28 degrees C, less than 30% rh), after which time the changes in the body fluid compartments were assessed. We measured plasma volume, plasma osmolality, and [Na+], [K+], and [Cl-] in plasma, together with sweat and urine volumes and their ionic concentrations before and after dehydration. The change in the extracellular fluid space (delta ECF) was estimated from chloride distribution and the change in the intracellular fluid space (delta ICF) was calculated by subtracting delta ECF from delta TW. The decrease in the ICF space was correlated with the increase in plasma osmolality (r = -0.74, P less than 0.02). The increase in plasma osmolality was a function of the loss of free water (delta FW), estimated from the equation delta FW = delta TW - (loss of osmotically active substance in sweat and urine)/(control plasma osmolality) (r = -0.79, P less than 0.01). Free water loss, which is analogous to "free water clearance" in renal function, showed a strongly inverse correlation with [Na+] in sweat (r = -0.97, P less than 0.001). Fluid movement out of the ICF space attenuated the decrease in the ECF space.(ABSTRACT TRUNCATED AT 250 WORDS)
Indirect estimate of perimicrovascular pressure rise in edema in isolated zone 1 lung
Authors: Tanita T. , Onizuka M. , Staub N. C.
Published: December 2017

To determine how liquid accumulation affects extra-alveolar perimicrovascular interstitial pressure, we measured filtration rate under zone 1 conditions (25 cmH2O alveolar pressure, 20 or 10 cmH2O vascular pressure) in isolated dog lung lobes in which all vessels were filled with autologous plasma. In the base-line condition, starting with normal extra-alveolar water content, filtration rate decreased by about one-half over 1 h as edema liquid slowly accumulated. We repeated each experiment after inducing edema (up to 100% lung weight gain). The absolute values and time course of filtration in the edema condition did not differ from base-line, i.e., the edema did not affect the time course of filtration. To compute the maximal initial and maximal change in extra-alveolar perimicrovascular pressure that occurred over each 1-h filtration study, we first assumed that the reflection coefficient is 0 in the Starling equation, then calculated perimicrovascular pressure and filtration coefficient from two equations with two unknowns. The mean filtration coefficient in 10 lobes is 0.063 g/(min X cmH2O X 100 g wet wt), and the initial perimicrovascular pressure is 3.9 cmH2O, rising by 4-7 cmH2O at 1 h. Finally we tested low protein perfusates and found the filtration rate was higher. We calculated an overall reflection coefficient = 0.44, a decrease in the initial perimicrovascular pressure to 1.9 cmH2O and a slightly lower increase after 1 h of edema formation, 2.2-6.6 cmH2O.
Influences of superior laryngeal afferent stimulation on expiratory activity in cats
Authors: Bongianni F. , Corda M. , Fontana G. , Pantaleo T.
Published: December 2017

The effects of superior laryngeal nerve (SLN) stimulation on the activity of the expiratory muscles and medullary expiration-related (ER) neurons were investigated in 24 pentobarbital-anesthetized cats. In some experiments the animals were also paralyzed and artificially ventilated. Sustained tetanic stimulation of SLN consistently caused an apneic response associated with the appearance of tonic CO2-dependent activity in the expiratory muscles and in ER neurons located in the caudal ventral respiratory group (VRG) and the Botzinger complex. Single shocks or brief tetani at the same stimulation intensities failed to evoke excitatory responses in the expiratory muscles and in the vast majority of ER neurons tested. At higher stimulation strengths, single shocks or short tetani elicited excitatory responses in the expiratory muscles (20- to 35-ms latency) and in the majority of ER neurons of the caudal VRG (7.5- to 15.5-ms latency). These responses were obtained only during the expiratory phase and proved to be CO2 independent. On the contrary, only inhibitory responses were evoked in the activity of Botzinger complex neurons. The observed tonic expiratory activity most likely represents a disinhibition phenomenon due to the suppression of inspiratory activity; activation of expiratory muscles at higher stimulation intensities appears to be a polysynaptic reflex mediated by ER neurons of the caudal VRG but not by Botzinger complex neurons.