bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated model for the interaction of muscle relaxants with their antagonists
Authors: Unadkat J. D. , Sheiner L. B. , Hennis P. J. , Cronnelly R. , Miller R. D. , Sharma M.
Published: December 2017

An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions. Edrophonium arterial concentrations and twitch tension of the anterior tibialis muscle were measured. Both the integrated and the naive model were fit to the twitch tension data using a model with a hypothetical “effect” compartment. The integrated model consistently fit the twitch tension data better than the naive model; the sum of squared deviations was lower by 46, 45, 87, and 69%, respectively, with the integrated model than with the naive model. Also, in contrast to the naive model, the integrated model is capable of describing the interaction of the anticholinesterase agent and the neuromuscular blocking agent when the concentration of either varies with time.
Nonthermoregulatory control of human skin blood flow
Authors: Johnson J. M.
Published: December 2017

Although it is well accepted that skin blood flow (SkBF) in humans is controlled by thermoregulatory reflexes, the conclusion that the cutaneous circulation is also controlled by reflexes of nonthermoregulatory origin is not universally held. This review considers the extent to which the cutaneous circulation participates in baroreceptor-mediated reflexes and in the reflexes associated with exercise. Exercise is explored in some detail, because it elicits both thermoregulatory and nonthermoregulatory reflexes. The overall conclusion reached is that thermoregulatory control of SkBF is subject to modification by or competition from several other sources. The fundamental pattern for control of SkBF is described by the threshold and slope of the SkBF-internal temperature relationship. Reflex effects of skin temperature act to shift the threshold of this relationship such that lower levels of skin temperature are associated with higher threshold internal temperatures at which cutaneous vasodilation begins. Similarly, baroreceptor reflexes, reflexes associated with exercise, and effects of some cardiovascular disease also operate against this background. Although modification of the SkBF-internal temperature slope is occasionally seen, the most consistent effect of these nonthermoregulatory factors is to elevate the threshold internal temperature for cutaneous vasodilation. The consequence of this modification of thermoregulatory control of SkBF is that temperature regulation will often suffer when increases in SkBF are delayed or limited. Blood flow to other regions, possibly including active skeletal muscle, may also be compromised when thermoregulatory demands for SkBF are high.
Effects of subanesthetic doses of inert gases on behavioral thermoregulation in mice
Authors: Pertwee R. G. , Marshall N. R. , Macdonald A. G.
Published: December 2017

Mice exposed to subanesthetic partial pressures of N2O (0.25 to 0.75 atm) or N2 (5.7 or 11.33 atm) and allowed to choose between a warm and a cool environment showed a marked preference for the cooler environment. This behavior was associated with the onset of hypothermia, with deep body temperature falling by up to about 3 degrees C, usually to a new, steady level. Both the length of time spent in the cooler environment and the degree of the hypothermia produced increased with the partial pressure of N2O or N2 used. The effects of N2O on behavioral thermoregulation and body temperature were reversible. There was a correlation between anesthetic potency and the ability of both gases to alter thermoregulation, suggesting that the effect of these agents on thermoregulation was caused by the same molecular interactions as those which underlie anesthesia. Since both gases elicited changes in behavioral thermoregulation promoting rather than opposing the onset of hypothermia, it is concluded that they may have acted to lower the level at which deep body temperature was being regulated.
Longevity of cold-exposed rats: a reevaluation of the "rate-of-living theory"
Authors: Holloszy J. O. , Smith E. K.
Published: December 2017

It has been postulated that increased energy expenditure results in shortened survival. To test this “rate-of-living theory” we examined the effect of raising energy expenditure by means of cold exposure on the longevity of rats. Male 6-mo-old SPF Long-Evans rats were gradually accustomed to immersion in cool water (23 degrees C). After 3 mo they were standing in the cool water for 4 h/day, 5 days/wk. They were maintained on this program until age 32 mo. The cold exposure resulted in a 44% increase in food intake (P less than 0.001). Despite their greater food intake, the cold-exposed rats' body weights were significantly lower than those of control animals from age 11 to 32 mo. The average age at death of the cold-exposed rats was 968 +/- 141 days compared with 923 +/- 159 days for the controls. The cold exposure appeared to protect against neoplasia, particularly sarcomas; only 24% of the necropsied cold-exposed rats had malignancies compared with 57% for the controls. The results of this study provide no support for the concept that increased energy expenditure decreases longevity.
Increased epinephrine response and inaccurate glucoregulation in exercising athletes
Authors: Kjaer M. , Farrell P. A. , Christensen N. J. , Galbo H.
Published: December 2017

Epinephrine responses to insulin-induced hypoglycemia have indicated that athletes have a higher adrenal medullary secretory capacity than untrained subjects. This view was tested by an exercise protocol aiming at identical stimulation of the adrenal medulla in the two groups. Eight athletes (T) and eight controls (C) ran 7 min at 60% maximal O2 consumption (VO2max), 3 min at 100% VO2max, and 2 min at 110% VO2max. Plasma epinephrine both at rest and at identical relative work loads [110% VO2max: 8.73 +/- 1.51 (T) vs. 3.60 +/- 1.09 mmol X l-1 (C)] was higher [P less than 0.05) in T than in C. Norepinephrine, as well as heart rate, increased identically in the two groups, indicating identical sympathetic nervous activity. Lactate and glycerol were higher in T than in C after running. Glucose production peaked immediately after exercise and was higher in T than in C. Glucose disappearance increased less than glucose production and was identical in T and C. Accordingly plasma glucose increased, more in T than in C (P less than 0.01). In T glucose levels approached the renal threshold greater than 20 min postexercise. Glucose clearance increased less in T than in C during exercise and decreased postexercise to or below (T, P less than 0.05) basal levels, despite increased insulin levels. Long-term endurance training increases responsiveness of the adrenal medulla to exercise, indicating increased secretory capacity. During maximal exercise this may contribute to higher glucose production, lower clearance, more inaccurate glucoregulation, and higher lypolysis in T compared with C.
Effect of rib cage and abdominal restriction on total respiratory resistance and reactance
Authors: van Noord J. A. , Demedts M. , Clement J. , Cauberghs M. , Van de Woestijne K. P.
Published: December 2017

In 14 healthy male subjects we studied the effects of rib cage and abdominal strapping on lung volumes, airway resistance (Raw), and total respiratory resistance (Rrs) and reactance (Xrs). Rib cage, as well as abdominal, strapping caused a significant decrease in vital capacity (respectively, -36 and -34%), total lung capacity (TLC) (-31 and -27%), functional residual capacity (FRC) (-28 and -28%), and expiratory reserve volume (-40 and -48%) and an increase in specific airway conductance (+24 and +30%) and in maximal expiratory flow at 50% of control TLC (+47 and +42%). The decrease of residual volume (RV) was significant (-12%) with rib cage strapping only. Abdominal strapping resulted in a minor overall increase in Rrs, whereas rib cage strapping produced a more marked increase at low frequencies; thus a frequency dependence of Rrs was induced. A similar pattern, but with lower absolute values, of Rrs was obtained by thoracic strapping when the subject was breathing at control FRC. Xrs was decreased, especially at low frequencies, with abdominal strapping and even more with thoracic strapping; thus the resonant frequency of the respiratory system was shifted toward higher frequencies. Partitioning Rrs and Xrs into resistance and reactance of lungs and chest wall demonstrated that the different effects of chest wall and abdominal strapping on Rrs and Xrs reflect changes mainly of chest wall mechanics.
Distortion of calculated whole-body hematocrit during lower-body immersion in water
Authors: Knight D. R. , Santoro T. , Bondi K. R.
Published: December 2017

We found a difference between the venous hematocrits of immersed and nonimmersed arms during immersion of the lower body in cold water but not during a comparable exposure to warm water. Fourteen healthy men were exposed to three different experimental conditions: arm immersion, body immersion, and control. The men always sat upright while both upper extremities hung vertically at their sides. During arm immersion, one forearm was completely immersed for 30 min in either cold water (28 degrees C, n = 7) or warm water (38 degrees C, n = 7). This cold-warm water protocol was repeated on separate days for exposure to the remaining conditions of body immersion (immersion of 1 forearm and all tissues below the xiphoid process) and control (no immersion). Blood samples were simultaneously drawn from cannulated veins in both antecubital fossae. Hematocrit difference (Hct diff) was measured by subtracting the nonimmersed forearm's hematocrit (Hct dry) from the immersed forearm's hematocrit (Hct wet). Hct diff was approximately zero when the men were exposed to the control condition and body immersion in warm water. In the remaining conditions, Hct wet dropped below Hct dry (P less than 0.01, 3-way analysis of variance). The decrements of Hct diff showed there were differences between venous hematocrits in immersed and nonimmersed regions of the body, indicating that changes of the whole-body hematocrit cannot be calculated from a large-vessel hematocrit soon after immersing the lower body in cold water.
Airflow characteristics in a baboon nasal passage cast
Authors: Patra A. L. , Gooya A. , Morgan K. T.
Published: December 2017

Airflow patterns in the nasal passages influence the distribution of air-pollutant-induced lesions in the airway mucosa. Little is known about airflow characteristics of the complex nasopharyngeal airway of humans and experimental animals. Airflow characteristics in the nasopharyngeal airways of an adult male baboon (13.9 kg body wt) were investigated with thermistor probes and the findings compared with flow visualization, using a cinephotographic technique. A clear, acrylic, hollow cast of a baboon nose was made, and thermistor probes were inserted to record air velocity in the cast lumen using a wind tunnel to propel air through the cast. An identical cast was studied by passing water through the cast, with pulses of dye to reveal flow, and cinephotography was used for determination of flow velocities and flow patterns. Flow rates adjusted on the basis of a Reynolds conversion showed good correlations between the two methods, whereas cinephotography revealed areas of turbulence and vortex-like flow not detected by thermistor probes. These results suggest that water flow may provide useful information in complex airways where airflow cannot be determined by other methods.
Platelet-activating factor increases lung vascular permeability to protein
Authors: Burhop K. E. , Garcia J. G. , Selig W. M. , Lo S. K. , van der Zee H. , Kaplan J. E. , Malik A. B.
Published: December 2017

We studied the effects of platelet-activating factor (PAF) on pulmonary hemodynamics and microvascular permeability in unanesthetized sheep prepared with lung-lymph fistulas. Since cyclooxygenase metabolites have been implicated in mediating these responses, we also examined the role of the cyclooxygenase pathway. PAF infusion (4 micrograms X kg-1 X h-1 for 3 h) produced a rapid, transient rise in pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), plasma thromboxane B2 concentration (TxB2), and pulmonary lymph flow (Qlym). The lymph-to-plasma protein concentration ratio (L/P) did not change from base line. Pretreatment with the cyclooxygenase inhibitor, sodium meclofenamate, prevented the generation of TxB2 and the hemodynamic changes but did not prevent the increase in Qlym. The estimated protein reflection coefficient decreased from a control value of 0.66 +/- 0.04 to 0.43 +/- 0.06 after PAF infusion. We also studied the effects of PAF on endothelial permeability in vitro by measuring the flux of 125I-albumin across cultured bovine pulmonary artery endothelial cells (EC) grown to confluency on a gelatinized micropore filter and mounted within a modified Boyden chemotaxis chamber. PAF (10(-8) to 10(-4) M) had no direct effect on EC albumin permeability, suggesting that the increase in permeability in sheep was not the direct lytic effect of PAF. In conclusion, PAF produces pulmonary vasoconstriction mediated by cyclooxygenase metabolites. PAF also increases pulmonary vascular permeability to protein that is independent of cyclooxygenase products and is not the result of a direct effect of PAF on the endothelium.
O2 metabolites and neutrophil elastase synergistically cause edematous injury in isolated rat lungs
Authors: Baird B. R. , Cheronis J. C. , Sandhaus R. A. , Berger E. M. , White C. W. , Repine J. E.
Published: December 2017

Addition of glucose oxidase (GO) increased H2O2 concentrations and decreased antielastolytic activities of beta-D-glucose containing perfusates of isolated rat lungs. Pretreatment with GO also caused acute edematous injury (increased lung weight gains, increased recovery of Ficoll in lung lavages, and increased pulmonary arterial pressures) in isolated lungs perfused with purified human neutrophil elastase (NE). Acute edematous injury in isolated lungs pretreated with GO and then NE exceeded levels found in lungs following addition of GO or NE alone or NE before GO. Simultaneous addition of catalase (an H2O2 scavenger) or methoxy-succinyl-L-alanyl-L-alanyl-prolyl-L-valine-chloromethyl ketone (an NE inhibitor, but not aminotriazole-inactivated catalase, N-tosyl-L-phenyl-alanine chloromethyl ketone (a chymotrypsin inhibitor) or N-alpha-p-tosyl-L-lysine chloromethyl ketone (a trypsin inhibitor), prevented acute edematous injury in isolated lungs perfused with both GO and NE. This observation indicated that injury was dependent on both H2O2 and NE, especially since the relative inactivating specificities of the inhibitors for H2O2 or NE, respectively, were confirmed under similar conditions in vitro. The synergistic nature of the interaction between H2O2 and NE-mediated injury was further clarified when GO- and NE-induced lung injury was prevented by addition of an oxidant-resistant NE inhibitor (Eglin-C), but not an oxidant-sensitive NE inhibitor (human alpha 1-protease inhibitor, alpha 1PI). Moreover, treatment with H2O2 also decreased the ability of alpha 1PI but not Eglin-C to decrease NE activity in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Anatomy of diaphragmatic circulation
Authors: Comtois A. , Gorczyca W. , Grassino A.
Published: December 2017

The diaphragmatic circulation was studied in 48 mongrel dogs weighing 10–35 kg by injecting acrylic coloring into the arteries and veins of the diaphragm. The phrenic arteries and internal mammary arteries were found to anastomose head to head, forming an internal arterial circle around the medial leaflet of the diaphragm tendon. This arterial circle emitted vascular branches that traveled between muscle fibers toward the periphery of the diaphragm. These branches anastomosed with vessels of the intercostal arteries to form costophrenic arcades all along the fibers of the crural and costal diaphragms. The intercostal arteries were anastomosed to one another by small vessels within the muscular diaphragm, thus forming an arterial ring around the insertions of the diaphragm on the ribs. The venous drainage has an anatomic distribution similar to that observed on the arterial side, but with the additional presence of valves that could play a role in directing blood flow.
Effect of granulocyte depletion in a ventilated surfactant-depleted lung
Authors: Kawano T. , Mori S. , Cybulsky M. , Burger R. , Ballin A. , Cutz E. , Bryan A. C.
Published: December 2017

In a previous paper Cutz, Bryan et al. showed that in rabbits after repetitive lung lavage high-frequency oscillatory ventilation maintained excellent gas exchange and did not cause hyaline membrane formation (J. Appl. Physiol. 55: 131–138, 1983). In contrast, conventional mechanical ventilation had poor gas exchange and extensive hyaline membrane formation and we attributed these differences to mechanical barotrauma. However, we completely overlooked the large number of granulocytes in the damaged lung. To investigate this using the same model we have used mechanical ventilation on two groups of rabbits, one with normal granulocytes, the other depleted of granulocytes by pretreatment with nitrogen mustard. The nondepleted rabbits had poor gas exchange, a substantial protein leak into the lung and extensive hyaline membranes. The depleted animals had good gas exchange, a very small protein leak and no hyaline membranes. Repletion of granulocytes from donor rabbits lead to poor gas exchange and hyaline membrane formation. It is concluded that lung lavage causes prompt margination of granulocytes which become activated by the ongoing epithelial barotrauma of conventional ventilation.
Validation of esophageal balloon technique at different lung volumes and postures
Authors: Baydur A. , Cha E. J. , Sassoon C. S.
Published: December 2017

The esophageal balloon technique for measuring pleural surface pressure (Ppl) has recently been shown to be valid in recumbent positions. Questions remain regarding its validity at lung volumes higher and lower than normally observed in upright and horizontal postures, respectively. We therefore evaluated it further in 10 normal subjects, seated and supine, by measuring the ratio of esophageal to mouth pressure changes (delta Pes/delta Pm) during Mueller, Valsalva, and occlusion test maneuvers at FRC, 20, 40, 60, and 80% VC with the balloon placed 5, 10, and 15 cm above the cardia. In general, delta Pes/delta Pm was highest at the 5-cm level, during Mueller maneuvers and occlusion tests, regardless of posture or lung volume (mean range 1.00–1.08). At 10 and 15 cm, there was a progressive increase in delta Pes/delta Pm with volume (from 0.85 to 1.14). During Valsalva maneuvers, delta Pes/delta Pm also tended to increase with volume while supine (range 0.91–1.04), but was not volume-dependent while seated. Qualitatively, observed delta Pes/delta Pm fit predicted corresponding values (based on lung and upper airway compliances). Quantitatively there were discrepancies probably due to lack of measurement of esophageal elastance and to inhomogeneities in delta Ppl. At every lung volume in both postures, there was at least one esophageal site where delta Pes/delta Pm was within 10% of unity.
Breathing pattern in hypoxic exposures of varying duration
Authors: Bender P. R. , Weil J. V. , Reeves J. T. , Moore L. G.
Published: December 2017

The relative contributions of breathing frequency and tidal volume to the increase in ventilation during acute or prolonged exposure to hypoxia is uncertain. We examined the changes in breathing pattern during hypoxic exposures lasting minutes, hours, and days using data from previous studies. Increased tidal volume accounted for the increased ventilation during 7–10 and 30 min of isocapnic and poikilocapnic (no CO2 added) hypoxic exposures as well as during 7 h of poikilocapnic hypobaric hypoxia (4,800 m). Tidal volume was also a greater overall contributor than frequency to increased ventilation in sea-level residents during 3 days of isocapnic hypobaric hypoxia (4,100–4,600 m) and in Denver (1,600 m) residents during 5 days on Pikes Peak (4,300 m). In sea-level residents during 3 days of poikilocapnic hypobaric hypoxia (3,600–4,300 m) and during 7–8 days on Pikes Peak, increased frequency accounted for the rise in ventilation. Tidal volume thus contributed more than frequency to increasing ventilation during brief hypoxia, whereas the contribution of frequency was increased in prolonged hypoxia involving a 4,300-m altitude ascent and hypocapnia.
Partitioning of pulmonary resistance during constriction in the dog: effects of volume history
Authors: Ludwig M. S. , Dreshaj I. , Solway J. , Munoz A. , Ingram R. H.
Published: December 2017

We assessed the relative changes in airways and lung tissue with bronchoconstriction, and the changes in each during and following a deep inhalation (DI). We partitioned pulmonary resistance (RL) into airway (Raw) and tissue (Vtis) components using alveolar capsules in 10 anesthetized, paralyzed, and open-chested dogs ventilated sinusoidally with 350-ml breaths at 1 Hz. We made measurements before and during bronchoconstriction induced by vagal stimulation or inhalation of histamine or prostaglandin F2 alpha (PGF2 alpha), each of which decreased dynamic compliance by approximately 40%. With histamine and PGF2 alpha the rise in RL was predominantly due to Vtis. With vagal stimulation there was a relatively greater increase in Raw than Vtis. At higher lung volumes, Vtis increases offset falls in Raw, producing higher RL at these volumes before and during constriction with PGF2 alpha and histamine. During constriction with vagal stimulation, the fall in Raw with inflation overrode the rise in Vtis, resulting in a lower RL at the higher compared with the lower lung volume. The changes seen after a DI in the control and constricted states were due to alterations in tissue properties, both viscous and elastic. However, the relative hysteresis of the airways and parenchyma were equal, since Raw, our index of airway size, was unchanged after a DI.
Role of carotid chemoreceptors and pulmonary vagal afferents during helium-oxygen breathing in ponies
Authors: Pan L. G. , Forster H. V. , Bisgard G. E. , Lowry T. F. , Murphy C. L.
Published: December 2017

Our purpose was to assess compensatory breathing responses to airway resistance unloading in ponies. We hypothesized that the carotid bodies and hilar nerve afferents, respectively, sense chemical and mechanical changes caused by unloading, hence carotid body-denervated (CBD) and hilar nerve-denervated ponies (HND) might demonstrate greater ventilatory responses when decreasing resistance. At rest and during treadmill exercise, resistance was transiently reduced approximately 40% in five normal, seven CBD, and five HND ponies by breathing gas of 79% He-21% O2 (He-O2). In all groups at rest, He-O2 breathing did not consistently change ventilation (VE), breathing frequency (f), tidal volume (VT), or arterial PCO2 (PaCO2) from room air-breathing levels. During treadmill exercise at 1.8 mph-5% grade in normal and HND ponies, He-O2 breathing did not change PaCO2 but at moderate (6 mph-5% grade), and heavy (8 mph-8% grade) work loads, absolute PaCO2 tended to decrease by 1 min of resistance unloading. delta PaCO2 calculated as room air minus He-O2 breathing levels at 1 min demonstrated significant changes in PaCO2 during exercise resistance unloading (P less than 0.05). No difference between normal and HND ponies was found in exercise delta PaCO2 responses (P greater than 0.10); however, in CBD ponies, the delta PaCO2 during unloading was greater at any given work load (P less than 0.05), suggesting finer regulation of PaCO2 in ponies with intact carotid bodies. During heavy exercise VE and f increased during He-O2 breathing in all three groups of ponies (P less than 0.05), although there were no significant differences between groups (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The heat-acclimated pigeon: an ideal physiological model for a desert bird
Authors: Marder J. , Gavrieli-Levin I.
Published: December 2017

Acclimation of rock pigeon (Columba livia) to high ambient temperature (Ta) 50 degrees C from the time of hatching resulted in a well-developed cutaneous evaporative cooling mechanism (CECM), which became the dominant mechanism for heat dissipation. After the age of 15 days and in adults, acclimated pigeons exposed to 48–60 degrees C Ta could regulate normal body temperature (Tb) without employing either panting or gular fluttering. Respiration rate varied between 36 +/- 12 (SD) and 35 +/- 14 breaths/min at moderate and at extreme high Ta's, respectively. During thermal stress (42, 45, and 47 degrees C) imposed in a metabolic chamber, nonpanting pigeons' heat balance was achieved by adjusting low-level heat production (46.2 +/- 6.8 W/m2) and by use of an efficient CECM that dissipated 145% of the metabolic heat. Tb was regulated between 40.7 +/- 0.5 and 41.8 +/- 0.4 degrees C over a wide range of Ta's (20–56 degrees C). The respiratory evaporative cooling mechanism (RECM) was effective since hatching. The CECM developed approximately 24 h later during the ontogeny of the altricial nestling pigeon. This trait, which exists in many bird species and may be a recent development, possibly evolved as an adaptation to hot environments. In the present study we have brought evidence for a multitrait physiological adaptation that takes preeminence in adjusting the processes involved in maintaining heat balance. This integrative complex creates a powerful, efficient tool for contending with the most extreme thermal conditions.
Exercise-induced glycogen utilization by the respiratory muscles
Authors: Ianuzzo C. D. , Spalding M. J. , Williams H.
Published: December 2017

Some controversy exists in the literature as to whether or not diaphragmatic glycogen is utilized during exercise. In this study male Sprague-Dawley rats were used to determine whether prolonged treadmill exercise would result in a significant reduction of glycogen concentration in the respiratory muscles. Untrained rats were run to exhaustion at a speed of 24 m/min, up a 10% grade. Run time averaged 48:30 min. After exercise a significant reduction in glycogen was observed in the diaphragm (43% of control), intercostals (43%), heart (39%), and plantaris (76%). In the diaphragm a significant reduction was shown in both types I and II fibers using the periodic acid-Schiff (PAS) stain for glycogen. These findings show that muscles with vastly different aerobic capacities utilize endogenous glycogen during moderately intense submaximal endurance exercise and that the costal diaphragm muscle is not an exception as has recently been suggested.
Sepsis in sheep reduces pulmonary microvascular sieving capacity
Authors: Smith L. , Andreasson S. , Thoren-Tolling K. , Rippe B. , Risberg B.
Published: December 2017

The changes in pulmonary microvascular permeability in sheep, after infusion of live Escherichia coli, were studied using estimations of the osmotic reflection coefficients (sigma) for total protein, albumin, immunoglobins (Ig) G and M and based on these estimations equivalent pore dimensions were calculated. A chronic lung lymph fistula was prepared in seven sheep. After a base-line period, left atrial pressure (Pla) was increased. E. coli (10(9) X kg body wt) were given after attaining filtration independent L/P values. The sigma's for the normal lung were calculated to 0.73 for total protein and to 0.65, 0.76, and 0.91 for albumin, IgG, and IgM, respectively. The equivalent pore radii were determined to 50 and 175 A with 35% of the filtration accounted for by the large pores. After bacterial infusion, the sigma's for total protein, albumin, IgG, and IgM decreased significantly from preseptic values to 0.58, 0.50, 0.64, and 0.83, respectively. After sepsis the small pores were 50 A and the large pores 200 A with 49% of total volume flow at maximum lymph flows occurring through the large pores. Assuming a constant small-pore population the large-pore number increased 32% after bacterial infusion. These results indicate that pulmonary microvascular permeability may have increased due to the sepsis.
Epinephrine, glucose, and lactate infusion in exercising adrenodemedullated rats
Authors: Winder W. W. , Yang H. T. , Jaussi A. W. , Hopkins C. R.
Published: December 2017

The purpose of this study was to determine the metabolic function of the marked increase in plasma epinephrine which occurs in fasted rats during treadmill exercise. Fasted adrenodemedullated (ADM) and sham-operated (SHAM) rats were run on a rodent treadmill (21 m/min, 15% grade) for 30 min or until exhaustion. ADM rats were infused with saline, epinephrine, glucose, or lactate during the exercise bouts. ADM saline-infused rats showed markedly reduced endurance, hypoglycemia, elevated plasma insulin, reduced blood lactate, and reduced muscle glycogenolysis compared with exercising SHAM's. Epinephrine infusion corrected all deficiencies. Glucose infusion restored endurance run times and blood glucose to normal without correcting the deficiencies in blood lactate and muscle glycogenolysis. Infusion of lactate partially corrected the hypoglycemia at 30 min of exercise, but endurance was not restored to normal and rats were hypoglycemic at exhaustion. We conclude that in the fasted exercising rat, actions of epinephrine in addition to provision of gluconeogenic substrate are essential for preventing hypoglycemia and allowing the rat to run for long periods of time.
Effect of substance P on cardiovascular and respiratory function in subjects
Authors: Fuller R. W. , Maxwell D. L. , Dixon C. M. , McGregor G. P. , Barnes V. F. , Bloom S. R. , Barnes P. J.
Published: December 2017

The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2–3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.
Effects of lung volume and alveolar surface tension on pulmonary vascular resistance
Authors: Sun R. Y. , Nieman G. F. , Hakim T. S. , Chang H. K.
Published: December 2017

Utilizing the arterial and venous occlusion technique, the effects of lung inflation and deflation on the resistance of alveolar and extraalveolar vessels were measured in the dog in an isolated left lower lobe preparation. The lobe was inflated and deflated slowly (45 s) at constant speed. Two volumes at equal alveolar pressure (Palv = 9.9 +/- 0.6 mmHg) and two pressures (13.8 +/- 0.8 mmHg, inflation; 4.8 +/- 0.5 mmHg, deflation) at equal volumes during inflation and deflation were studied. The total vascular pressure drop was divided into three segments: arterial (delta Pa), middle (delta Pm), and venous (delta Pv). During inflation and deflation the changes in pulmonary arterial pressure were primarily due to changes in the resistance of the alveolar vessels. At equal Palv (9.9 mmHg), delta Pm was 10.3 +/- 1.2 mmHg during deflation compared with 6.8 +/- 1.1 mmHg during inflation. At equal lung volume, delta Pm was 10.2 +/- 1.5 mmHg during inflation (Palv = 13.8 mmHg) and 5.0 +/- 0.7 mmHg during deflation (Palv = 4.8 mmHg). These measurements suggest that the alveolar pressure was transmitted more effectively to the alveolar vessels during deflation due to a lower alveolar surface tension. It was estimated that at midlung volume, the perimicrovascular pressure was 3.5–3.8 mmHg greater during deflation than during inflation.
Respiratory load-compensating mechanisms in muscular dystrophy
Authors: Axen K. , Bishop M. , Haas F.
Published: December 2017

First-breath ventilatory responses to graded elastic and resistive loads were obtained from 15 people with Duchenne muscular dystrophy (DMD), 5 people with facioscapulohumeral MD (FSH), 3 people with Becker MD, and 3 people with limb-girdle MD. For each load tidal volumes from different individuals ranged from relatively small to comparatively large values, indicating a correspondingly wide range of end-inspiratory efforts; strong tidal volume defenders generally employed longer inspirations and higher mean inspiratory airflows than did weak tidal volume defenders; and individual frequency responses were mediated by changes in inspiratory and/or expiratory timing. Thus the loaded breathing responses of people with MD are qualitatively the same as those of quadriplegic and able-bodied people. Quantitatively, however, the DMD group generated considerably larger tidal volumes than did the FSH group during both elastic and resistive loading. These larger tidal volumes were achieved by both longer inspirations (a neurally mediated phenomenon) and higher mean inspiratory airflows (a mechanically and/or neurally mediated phenomenon). These findings, which could not be attributed to differences in respiratory motor function, suggest that there are differences between the respiratory sensory and/or central functions in the Duchenne and facioscapulohumeral types of MD.
Effect of thoracoabdominal breathing patterns on inspiratory effort sensation
Authors: Fitting J. W. , Chartrand D. A. , Bradley T. D. , Killian K. J. , Grassino A.
Published: December 2017

The respiratory sensations evoked by added inspiratory loads are currently thought to be largely mediated by the activity of the inspiratory muscles. Because of the differences in proprioceptors and in afferent and efferent innervations among the inspiratory muscles, we hypothesized that the sensation evoked by a given load would be different when the motor command is directed mainly to rib cage muscles or mainly to the diaphragm. To test this hypothesis, we studied six normal subjects breathing against several inspiratory resistances while emphasizing the use of rib cage muscles, or the diaphragm, or a combination of both. At the end of 10 loaded breaths the subjects rated the perceived magnitude of inspiratory effort on a Borg scale. A linear and unique relationship (r = 0.96 +/- 0.02; P less than 0.001) was found between the sensation and esophageal pressure (Pes) in the three thoracoabdominal breathing patterns. We conclude that the level of Pes, whether generated mainly by the rib cage muscles or the diaphragm, is the main variable related to the sensation of inspiratory effort under external inspiratory loads.
Training effects on regional blood flow response to maximal exercise in foxhounds
Authors: Musch T. I. , Haidet G. C. , Ordway G. A. , Longhurst J. C. , Mitchell J. H.
Published: December 2017

The effect of training on the regional blood flow response to maximal exercise was investigated in the foxhound. Training consisted of 8–12 wk of treadmill running at 80% of maximal heart rate 1 h/day for 5 days/wk and resulted in a 31% increase in maximal O2 consumption, a 28% increase in maximal cardiac output, and a 23% decrease in systemic vascular resistance during maximal exercise. Blood flow to the heart, diaphragm, brain, skin, and 9 of 10 muscles investigated was similar during maximal exercise pre- and posttraining; however, blood flow to the gastrocnemius muscle was greater posttraining than it was pretraining. Blood flow to the stomach, small intestine, and pancreas decreased during maximal exercise pre- and posttraining; however, blood flow to the large intestine, spleen, liver, adrenal glands, and kidneys decreased during maximal exercise only posttraining. In addition, a larger decrease in blood flow to the stomach during maximal exercise was found posttraining compared with pretraining. These results demonstrate that blood flow to skeletal muscle, the kidneys, and the splanchnic region of the foxhound during maximal exercise can be significantly altered by dynamic exercise training.
Reproducibility of the multiple inert gas elimination technique
Authors: Wagner P. D. , Hedenstierna G. , Bylin G. , Lagerstrand L.
Published: December 2017

Although measurement errors in the multiple inert gas elimination technique have a coefficient of variation of approximately 3%, small biological fluctuations in ventilation, blood flow, or other variables must contribute additional variance to this method of assessing ventilation-perfusion (VA/Q) mismatch. To determine overall variance of computed indices of VA/Q mismatch, an analysis of variance was carried out using a total of 400 duplicate pairs of inert gas samples obtained from canine (N = 118) and human (N = 282) studies in the past 2 years. In both sets VA/Q mismatch ranged from minimal (2nd moment of ventilation and blood flow distributions, log SDV and log SDQ, respectively approximately equal to 0.3 each) to severe (log SDV and log SDQ approximately equal to 2.0). Differences between duplicate log SD values were computed and found to be a constant fraction of the mean log SD of each duplicate pair, averaging 13% for both canine and human ventilation and blood flow data. The resultant coefficient of variation for a single measurement of log SD about its mean averaged 8.6% for all data combined. This analysis demonstrates excellent reproducibility of these dispersion indices over a wide range of conditions, and if the mean of duplicate values is used, thus reducing variability by square root 2 to 6.1%, log SD can be estimated with an approximately 95% confidence limit of +/- 12%.
Entrainment of respiratory frequency to exercise rhythm during hypoxia
Authors: Paterson D. J. , Wood G. A. , Marshall R. N. , Morton A. R. , Harrison A. B.
Published: December 2017

Breathing frequency (f) is often reported as having an integer-multiple relationship to limb movement (entrainment) during rhythmic exercise. To investigate the strength of this coupling while running under hypoxic conditions, two male Caucasians and four male Nepalese porters were tested in the Annapurna region of the Himalayas at altitudes of 915, 2,135, 3,200, 4,420, and 5,030 m. In an additional study in a laboratory at sea level, three male and four female subjects inspired various O2-N2 mixtures [fraction of inspired O2 (FIO2) = 20.93, 17.39, 14.40, 11.81%] that were administered in a single-blind randomized fashion during a treadmill run (40% FIO2 maximum O2 consumption). Breathing and gait signals were stored on FM tape and later processed on a PDP 11/73 computer. The subharmonic relationships between these signals were determined from Fourier analysis (power spectrum), and the coincidence of coupling occurrence was statistically modeled. Entrainment decreased linearly during increasing hypoxia (P less than 0.01). Moreover, a significant linear increase in f occurred during hypoxia (P less than 0.05), whereas stride frequency and metabolic rate remained constant, suggesting that hypoxic-induced increases in f decreased the degree of entrainment.
Consumption of platelets in decompression sickness of rabbits
Authors: Tanoue K. , Mano Y. , Kuroiwa K. , Suzuki H. , Shibayama M. , Yamazaki H.
Published: December 2017

Platelet behavior was studied in rabbit decompression sickness which was brought about by the exposure to 6 ATA for 40 min (bottom time) followed by rapid decompression. Platelet counts significantly decreased after the decompression. Kinetic studies with 111In-oxine-labeled platelets revealed shortened survivals of circulating platelets, and audioradiograms indicated the accumulation of radioactivity in the lungs after the decompression. Although there was no change in the mode volume of platelets after the decompression, the transient appearance of circulating smaller or fragmented platelets suggested a random overdestruction of platelets. Whole and releasable adenine nucleotide contents of platelets were decreased significantly after the decompression. There were no significant changes in cytoplasmic adenine nucleotide contents. Therefore, in decompression sickness, the circulating platelets behaved similarly to those in acquired storage pool disease. Platelet thrombi were found in the pulmonary arteries, compatible with the accumulation of 111In-oxine-labeled platelets. These findings suggest that circulating air bubbles interact with platelets, causing the platelet release reaction, and these activated platelets participate in the formation of thrombi in experimental decompression sickness.
Reduction in metabolic heat production during exposure to radio-frequency radiation in the rat
Authors: Gordon C. J.
Published: December 2017

The purpose of this study was to assess the ability of the rat to reduce metabolic rate when exposed to deep-penetrating radio-frequency (RF) radiation. Male Sprague-Dawley rats were maintained at an ambient temperature (Ta) of 10 degrees C and exposed to 600-MHz radiation while metabolic rate (MR) was measured by indirect calorimetry. RF radiation exposures were made in a waveguide-type system that permitted the continuous control of specific absorption rate (SAR). SAR's of 2–5 W/kg led to significant reductions in MR when averaged from 30 to 60 min after the initiation of RF radiation exposure. The total decrease in MR during RF radiation exposure accounted for approximately 37% of the total RF heat load. Exposure of another group of rats to the same SAR's at a Ta of 10 degrees C resulted in a significant elevation in colonic temperature. Thus, despite the decrease in MR, heat gain still exceeded heat loss during RF radiation exposure, with a resultant elevation in deep body temperature. In conclusion, in a cold environment the rat exposed to RF radiation decreases its MR. However, the response time and efficiency of the response is not adequate to prevent an increase in body temperature.
Airway responses to methacholine in asymptomatic nonatopic cigarette smokers
Authors: Casale T. B. , Rhodes B. J. , Donnelly A. L. , Weiler J. M.
Published: December 2017

We prospectively performed methacholine bronchoprovocation challenges on 46 young smokers to examine the effects of cigarette smoking on airway responsiveness. The subjects, ages 18–35 yr, had no past or present history or physical examination findings of asthma or other lung diseases, rhinitis, allergic diseases, or respiratory infections; were skin test negative to 29 common aeroallergens; and had base-line pulmonary function values greater than 80% predicted. Sixteen of 46 (35%) subjects had a 20% or greater drop in forced expiratory volume in 1 s at a provocative methacholine concentration less than or equal to 25 mg/ml. The degree of methacholine responsiveness was not dependent upon base-line pulmonary function values or the amount of cigarettes consumed, and there was no association between the amount of cigarettes consumed and base-line pulmonary function values. These data suggest that many young asymptomatic nonatopic smokers have increased airway responsiveness to inhaled methacholine without clinically significant hyperreactive airway disease.
Development of rat muscle during short- and long-term hindlimb suspension
Authors: Elder G. C. , McComas A. J.
Published: December 2017

Histochemical and contractile properties of developing rat soleus (Sol) and plantaris (P) muscles were studied after hindlimb suspension to determine the effects of reduced activity levels on muscle development. Suspension (S) began at age 18 days and lasted for 14, 28, and 206 days, and results were compared with age-matched controls. Body weights were normal until 14 days and Sol growth was inhibited more than P, weighing 38 and 47% of controls at 46 and 224 days compared with 68 and 59% in P. The Sol did not develop into a slow-twitch (ST) muscle as evidenced by faster times to peak tension and half-relaxation times, faster times to develop 50% of maximum tetanic tension (Po) and a mean of 33% fewer ST fibers. Twitch tension and Po were lower in S-Sol and S-P, but force/cross-sectional area was unchanged. Fiber areas were smaller, but no structural changes characteristic of disuse atrophy were found. Fiber type populations were unchanged in P, and contractile properties were only minimally affected, demonstrating the greater importance of activity for ST muscles during development.
Carotid body chemosensory function in prolonged normobaric hyperoxia in the cat
Authors: Lahiri S. , Mulligan E. , Andronikou S. , Shirahata M. , Mokashi A.
Published: December 2017

The effects of normobaric hyperoxia on carotid body chemosensory function in the cat were studied. The hypothesis was that carotid body chemosensory function would be affected by chronic exposure to 100% O2 at sea level. It was based on the assumptions that carotid body tissue is exposed to high PO2 because of its high blood flow and that its O2 chemosensing mechanism is sensitive to O2 radical-induced reactions. Twelve cats were exposed to 100% O2 for 60–67 h, and 10 control cats were maintained in room air at sea level. They were anesthetized with pentobarbital sodium (Nembutal), and chemosensory afferents from a cut carotid sinus nerve were isolated and identified. The responses of single or a few clearly identifiable chemoreceptor afferents to isocapnic hypoxia and hypercapnia during hyperoxia and to the bolus injections of cyanide, nicotine, and dopamine were studied. We found that chronic hyperoxia severely blunted or eliminated the O2-sensitive response of the carotid chemoreceptors while augmenting the hypercapnic response. The response to cyanide but not to nicotine and dopamine were attenuated. Thus the hypoxic and hypercapnic responses that normally interact were separable. The lack of the cyanide response was consistent with the lack of the hypoxic response, suggesting a possible shared mechanism of carotid chemoreceptor response. Qualitatively normal responses to dopamine and nicotine indicated that the respective receptors were relatively intact after chronic exposure to hyperoxia and that the sensory nerves themselves were not affected by the prolonged O2 exposure.
Effect of lung volume on breath holding
Authors: Whitelaw W. A. , McBride B. , Ford G. T.
Published: December 2017

The mechanism by which large lung volume lessens the discomfort of breath holding and prolongs breath-hold time was studied by analyzing the pressure waves made by diaphragm contractions during breath holds at various lung volumes. Subjects rebreathed a mixture of 8% CO2–92% O2 and commenced breath holding after reaching an alveolar plateau. At all volumes, regular rhythmic contractions of inspiratory muscles, followed by means of gastric and pleural pressures, increased in amplitude and frequency until the breakpoint. Expiratory muscle activity was more prominent in some subjects than others, and increased through each breath hold. Increasing lung volume caused a delay in onset and a decrease in frequency of contractions with no consistent change in duty cycle and a decline in magnitude of esophageal pressure swings that could be accounted for by force-length and geometric properties. The effect of lung volume on the timing of contractions most resembled that of a chest wall reflex and is consistent with the hypothesis that the contractions are a major source of dyspnea in breath holding.