bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid body control of bronchial circulation in sheep
Authors: Alsberge M. , Magno M. , Lipschutz M.
Published: December 2017

The bronchial vascular response to chemoreceptor stimulation was studied in sheep anesthetized with alpha-chloralose, paralyzed with pancuronium, and artificially ventilated with room air. Blood flow through the common bronchial artery was measured with an electromagnetic flow-meter. Pressures were measured in the left atrium and aorta using appropriately placed catheters connected to pressure transducers. The carotid body was vascularly isolated and perfused at aortic pressure with blood of varied PO2 and PCO2. The viability of our preparation was assessed by the occurrence of a bradycardia in response to carotid body stimulation, and only data from animals demonstrating a bradycardia were analyzed. During hypoxic perfusion of the carotid body, heart rate decreased 6% (P less than 0.05). Bronchial blood flow increased by 46% and bronchial vascular resistance decreased by 23%, both of which were significant changes (P less than 0.05). During control experiments in which the carotid body was perfused with normoxic blood, there were no significant (P greater than 0.05) changes in any of the parameters. These data suggest that carotid body stimulation results in a reflex bronchial vasodilation.
Erythrocyte transit and neutrophil concentration in the dog lung
Authors: Hogg J. C. , McLean T. , Martin B. A. , Wiggs B.
Published: December 2017

We subdivided regional erythrocyte (RBC) transit time into the fraction spent in the large (greater than 50 microns), small (20-50 microns), and capillary (less than 20 microns) vessels of canine lungs. Using a combination of physiological and morphological techniques, the number of RBC and granulocytes in each vessel size was obtained by dividing the aggregate volume of the cell by the calculated volume of a single cell. The data show that the average transit time was 0.60 s in large vessels, 0.10 s in small vessels, and 1.37 s in capillary vessels and was longer (P less than 0.05) in the upper lung regions for small vessels and capillaries. RBCs pass through approximately 60 capillary segments at an average velocity of approximately 550 micron/s. Pulmonary hematocrit averaged 0.95 of the systemic hematocrit and was lower in capillaries than small vessels. PMN's were concentrated approximately 10-fold in the small vessels and 100-fold in the capillaries compared with peripheral blood. The multisegmented nature of the capillary bed allows this concentration because RBCs find pathways to stream around the slower moving PMNs.
Release of epithelium-derived relaxing factor after ozone inhalation in dogs
Authors: Jones G. L. , Lane C. G. , Daniel E. E. , O'Byrne P. M.
Published: December 2017

Airway epithelium has been reported to release epithelium-derived relaxing factor (EpDRF), which inhibits contraction of airway smooth muscle. This study tested the hypothesis that airway hyperresponsiveness after inhalation of ozone in dogs results from an inability to produce EpDRF. Two groups of five dogs each were studied; one group inhaled ozone, the other dry room air. Ozone-treated dogs developed airway hyperresponsiveness, whereas the control group did not. The acetylcholine provocative concentration decreased from 4.17 (%SE 1.35) to 0.56 mg/ml (%SE 1.24) (P = 0.0006) in the ozone-treated dogs and was 18.76 (%SE 2.04) and 29.77 mg/ml (%SE 2.07) in the air-treated dogs (P = 0.47). In vitro the presence of airway epithelium reduced the constrictor responses to acetylcholine, histamine, serotonin, and KCl in trachealis strips from the control dogs. This effect of epithelium was still present in trachealis strips from dogs with airway hyperresponsiveness. These results demonstrate that EpDRF is released from canine tracheal epithelium, that this function is not impaired in dogs with airway hyperresponsiveness after inhaled ozone, and that loss of EpDRF is not responsible for the development of airway hyperresponsiveness after inhaled ozone in dogs.
Human platelets attenuate oxidant injury in isolated rabbit lungs
Authors: Heffner J. E. , Katz S. A. , Halushka P. V. , Cook J. A.
Published: December 2017

Because platelets contain active antioxidant systems, the capacity of platelets to attenuate oxidant lung injury was investigated. Purine and xanthine oxidase were infused into isolated perfused rabbit lungs (IPL) to generate H2O2, thereby causing increased membrane permeability edema. The coinfusion of washed human platelets (1.20 +/- 0.07 x 10(10) cells) attenuated the degree of edema formation as measured by lung weight gain and lung lavage albumin concentration. Electron microscopy of lung preparations demonstrated platelet adherence to capillary endothelial luminal surfaces of oxidant-injured lungs, but there was no evidence of vascular plugging with platelet macroaggregates. The platelet glutathione redox cycle or platelet catalase were inhibited before infusion of platelets into the IPL with purine and xanthine oxidase. Inhibition of the glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-chloro-2,4-dinitrobenzene, or buthionine sulfoximine prevented platelet attenuation of lung injury. Inactivation of platelet catalase with 3-amino-1,2,4-triazole, however, did not significantly reduce the platelet-induced lung protection. We conclude that the platelet glutathione redox cycle plays a major role in reducing enzymatically generated toxic O2 metabolites and attenuating lung injury.
Measurement of alveolar gas volume by ambient pressure changes in isolated lungs
Authors: Martin R. R. , Peslin R. , Duvivier C. , Gallina C.
Published: December 2017

Alveolar gas volume (AGV) may be measured in humans (Peslin et al., J. Appl. Physiol. 62: 359-363, 1987) by applying very slow sinusoidal variations of ambient pressure (delta Pam) around the body and studying the relationship between delta Pam and the resulting gas displacement at the mouth (delta Vaw): AGVapc = (PB.delta Vaw)/(delta Pam.cos phi), where AGVapc is AGV measured by ambient pressure changes, PB is barometric minus alveolar water vapor pressure, and phi is the phase angle between Pam and Vaw. The applicability of this method to excised lungs at various transpulmonary pressures was assessed in six rabbit lungs and three dog lobes by reference to AGV measurements by He dilution (AGVdil) and by a volumetric method (AGVvol). Except in one instance, AGVapc did not change significantly when the frequency of delta Pam was varied from 0.02 to 0.2 Hz. AGVapc was highly correlated (P less than 0.001) to both AGVdil and AGVvol. It did not differ significantly from AGVdil (81.4 +/- 50.6 vs. 80.2 +/- 44.2 ml) and was only marginally higher than AGVvol (64.6 +/- 26.9 vs. 62.4 +/- 24.4 ml, P less than 0.05). We conclude that the method usually provides accurate results in excised lung preparations. Its main advantages are that it does not require manipulating the lung or changing its volume and that the measurement takes less than 1 min.
Effect of papaverine on pulmonary vascular permeability to proteins
Authors: Maron M. B. , Pilati C. F.
Published: December 2017

Previous studies have suggested that papaverine, a drug commonly used in studies of transvascular fluid and solute exchange to eliminate confounding effects of changes in vascular tone, may itself increase vascular permeability. In this study, we determined the ability of papaverine to alter pulmonary vascular protein permeability by measuring the osmotic reflection coefficient (sigma) for total proteins in a canine isolated perfused left lower lung lobe (LLL) preparation. The reflection coefficient, determined by the hematocrit-protein double-indicator technique, for control LLL's was 0.83 +/- 0.04 (SE) (n = 7). In separate groups of LLL's, blood papaverine HCl concentrations of 10(-5), 10(-4), and 10(-3) M resulted in sigma's of 0.84 +/- 0.02 (n = 6), 0.73 +/- 0.04 (n = 7), and 0.53 +/- 0.04 (n = 6), respectively. When two LLL's from the 10(-4) M group with sigma's of 0.56 and 0.57 were excluded from the analysis, the average sigma for this group was 0.79 +/- 0.02. We conclude that papaverine increases protein permeability at a concentration of 10(-3) M but does so in only some lobes at 10(-4) M. These results suggest that caution be taken when using high concentrations of papaverine in fluid balance studies.
Absence of neural modulation of hypoxic pulmonary vasoconstriction in conscious dogs
Authors: Lodato R. F. , Michael J. R. , Murray P. A.
Published: December 2017

Our objectives were 1) to quantify the magnitude of the hypoxic pulmonary vasoconstrictor (HPV) response in conscious dogs by utilizing pulmonary vascular pressure-cardiac index (P/Q) plots and 2) to assess the extent to which the autonomic nervous system (ANS) modulates the HPV response. Multipoint P/Q plots were constructed in conscious dogs during normoxia and during bilateral alveolar hypoxia by stepwise constriction of the thoracic inferior vena cava to reduce Q. With the ANS intact, the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) increased (P less than 0.01) approximately twofold during hypoxia over a broad range of Q. The absolute magnitude of the HPV response was related (P less than 0.01) to the level of Q. We hypothesized that if ANS activation reduces the magnitude of HPV in intact dogs, then we would expect the magnitude of HPV to be increased both after combined sympathetic alpha-(phentolamine) and beta-(propranolol) adrenergic block and after total autonomic ganglionic block (hexamethonium). A marked HPV response (P less than 0.01) was observed after both combined sympathetic block and ganglionic block over a broad range of Q during alveolar hypoxia. The magnitude of the HPV response with the ANS intact, however, was not significantly different from the magnitude of HPV after combined sympathetic block (P = 0.45) or after ganglionic block (P = 0.64) at any level of Q. Thus, during bilateral alveolar hypoxia, the ANS does not appear to attenuate the HPV response of intact conscious dogs.
Sodium-dependent lysine flux across bullfrog alveolar epithelium
Authors: Kim K. J. , Crandall E. D.
Published: December 2017

Amino acid transport across the alveolar epithelial barrier was studied by measuring radiolabeled lysine fluxes across bullfrog lungs in an Ussing chamber. In the absence of a transmural electrical gradient, L-[14C]lysine was instilled into the upstream reservoir and the rate of appearance of the radiolabel in the downstream reservoir was determined. Two lungs from the same animal were used simultaneously to determine tracer fluxes both into and out of the alveolar bath. Results showed that the radiolabel flux measured in the alveolar to the pleural direction was greater than that measured in the opposite direction in the presence of sodium in the bathing fluids. The net flux of L-[14C]lysine was saturable with [Na+], with an apparent transport coefficient (Kt) of 28 mM for Na+. Hill analysis of [14C]lysine flux vs. [Na+] indicated a coupling ratio of 1:1 between sodium and radiolabeled L-lysine. Total L-lysine flux as a function of [L-lysine] was also saturable, with Kt of 7.3 mM for L-lysine. Ouabain significantly decreased absorptive (alveolar-to-pleural) radiolabel flux, while slightly increasing the flux observed in the opposite direction. L-leucine completely inhibited absorptive net flux of L-[14C]lysine. alpha-Methylaminoisobutyric acid (MeAIB), on the other hand, only slightly reduced net flux of L-[14C]lysine from the control value. The presence of a net absorptive, Na+-dependent amino acid flux across the alveolar epithelial barrier indicates that the tissue is capable of removing amino acids and sodium from the alveolar fluid by a coupled cotransport mechanism, which may be important for both protein metabolism and fluid balance by alveolar epithelium.
In vitro tracheal mechanics by nuclear magnetic resonance imaging
Authors: Lambert R. K. , Pack R. J. , Xia Y. , Eccles C. D. , Callaghan P. T.
Published: December 2017

Images of rabbit tracheal cross sections were obtained at a series of transmural pressures ranging from 22 to -95 cmH2O by use of a nuclear magnetic resonance imaging microscope. The excised, washed tracheas were immersed in a solution of phosphate-buffered saline made up in deuterium oxide (D2O, pH 7.3). The images are maps of proton density in the image slice (2.5 mm thick). All but one series of images showed a collapse process in which the trachealis muscle invaginated asymmetrically, i.e., the muscle appeared to favor one side of the cartilage ring system more than the other. The connecting tissue between the cartilage rings appeared to be more compliant than the rings themselves, thus suggesting that the tracheal lumen became corrugated at negative pressures. In the plane of a cartilage ring, the lumen appeared to remain patent at pressures as low as -95 cmH2O. However, between rings, where the tracheal wall was more compliant, the lumen appeared to be totally occluded at -53 cmH2O. Lumen areas in both the plane of the cartilage rings and in a plane between rings were measured from each series of printed images for six tracheas. These measurements, when normalized, averaged, and plotted against transmural pressure gave asymptotic logarithmic compliances (n1 in the model of Lambert et al., J. Appl. Physiol. 52: 44-56, 1982) of 1.2 +/- 0.4 and 20 +/- 7 for the interring and ring regions, respectively. These values are greater than the critical value of 0.5 (J. Appl. Physiol. 62: 2426-2435, 1987) and are thus consistent with wave speed flow limitation being possible anywhere in the trachea during forced expiration.
Muscle glycogen storage after different amounts of carbohydrate ingestion
Authors: Ivy J. L. , Lee M. C. , Brozinick J. T. , Reed M. J.
Published: December 2017

The purpose of this study was to determine whether the rate of muscle glycogen storage could be enhanced during the initial 4-h period postexercise by substantially increasing the amount of the carbohydrate consumed. Eight subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. Immediately and 2 h after exercise they consumed either 0 (P), 1.5 (L), or 3.0 g glucose/kg body wt (H) from a 50% glucose polymer solution. Blood samples were drawn from an antecubital vein before exercise, during exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately, 2 h, and 4 h after exercise. Blood glucose and insulin declined significantly during exercise in each of the three treatments. They remained below the preexercise concentrations during recovery in the P treatment but increased significantly above the preexercise concentrations during the L and H treatments. By the end of the 4 h-recovery period, blood glucose and insulin were still significantly above the preexercise concentrations in both treatments. Muscle glycogen storage was significantly increased above the basal rate (P, 0.5 mumol.g wet wt-1.h-1) after ingestion of either glucose polymer supplement. The rates of muscle glycogen storage, however, were not different between the L and H treatments during the first 2 h (L, 5.2 +/- 0.9 vs. H, 5.8 +/- 0.7 mumol.g wet wt-1.h-1) or the second 2 h of recovery (L, 4.0 +/- 0.9 vs. H, 4.5 +/- 0.6 mumol.g wet wt-1. h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of tidal volume and frequency on the temporal fall in lung compliance
Authors: Huang Y. C. , Weinmann G. G. , Mitzner W.
Published: December 2017

In this study we have investigated how changes in respiratory frequency and tidal volume in anesthetized dogs affect the fall in dynamic compliance (Cdyn) that occurs with time after a hyperinflation. Results showed that increasing frequency [at controlled arterial (PaCO2)] PCO2 from 16 to 32 breaths/min had no effect on either the rate of fall or the magnitude of the fall up to 1 h after the hyperinflation. However, increasing the tidal volume from 300 to 750 ml abolished the fall in Cdyn from 10 to 50 min after the hyperinflation; the fall within the first 10 min remained unchanged. We also examined the effect of a simulated "hyperinflation" on the compliance of strips of parenchymal tissue in vitro. This result indicated that in the absence of surface forces, parenchymal tissue demonstrates a fall in compliance, which is complete within 10 min. Overall our findings are consistent with the hypothesis that the fall in Cdyn after hyperinflation is a two-phase process. The initial rapid fall in Cdyn (i.e., within 10 min) may simply represent a passive recovery process from the hyperinflation stress on the parenchymal tissue. The slower fall occurring after 10 min likely results from progressive increases in surface tension, and this increase can apparently be blocked by increases in tidal volume.
Muscle glycogen utilization during shivering thermogenesis in humans
Authors: Martineau L. , Jacobs I.
Published: December 2017

The purpose of the present study was to clarify the importance of skeletal muscle glycogen as a fuel for shivering thermogenesis in humans during cold-water immersion. Fourteen seminude subjects were immersed to the shoulders in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Biopsies from the vastus lateralis muscle and venous blood samples were obtained before and immediately after the immersion. Metabolic rate increased during the immersion to 3.5 +/- 0.3 (SE) times resting values, whereas Tre decreased by 0.9 degrees C to approximately 35.8 degrees C at the end of the immersion. Intramuscular glycogen concentration in the vastus lateralis decreased from 410 +/- 15 to 332 +/- 18 mmol glucose/kg dry muscle, with each subject showing a decrease (P less than 0.001). Plasma volume decreased (P less than 0.001) markedly during the immersion (-24 +/- 1%). After correcting for this decrease, blood lactate and plasma glycerol levels increased by 60 (P less than 0.05) and 38% (P less than 0.01), respectively, whereas plasma glucose levels were reduced by 20% after the immersion (P less than 0.001). The mean expiratory exchange ratio showed a biphasic pattern, increasing initially during the first 30 min of the immersion from 0.80 +/- 0.06 to 0.85 +/- 0.05 (P less than 0.01) and decreasing thereafter toward basal values. The results demonstrate clearly that intramuscular glycogen reserves are used as a metabolic substrate to fuel intensive thermogenic shivering activity of human skeletal muscle.
Role of lungs and inactive muscle in acid-base control after maximal exercise
Authors: Kowalchuk J. M. , Heigenhauser G. J. , Lindinger M. I. , Obminski G. , Sutton J. R. , Jones N. L.
Published: December 2017

The pulmonary responses and changes in plasma acid-base status occurring across the inactive forearm muscle were examined after 30 s of intense exercise in six male subjects exercising on an isokinetic cycle ergometer. Arterial and deep forearm venous blood were sampled at rest and during 10 min after exercise; ventilation and pulmonary gas exchange variables were measured breath by breath during exercise and recovery. Immediately after exercise, ventilation and CO2 output increased to 124 +/- 17 1/min and 3.24 +/- 0.195 l/min, respectively. The subsequent decrease in CO2 output was slower than the decrease in O2 intake (half time of 105 +/- 15 and 47 +/- 4 s, respectively); the respiratory exchange ratio was greater than 1.0 throughout the 10 min of recovery. Arterial plasma concentrations of Na+, K+, and Ca2+ increased transiently after exercise. Arterial lactate ion concentration ([La-]) increased to 14-15 meq/l within 1.5 min and remained at this level for the rest of the study. Throughout recovery there was a positive arteriovenous [La-] difference of 4-5 meq/l, associated with an increase in the arteriovenous strong ion difference ([SID]) and by a large increase in the venous Pco2 and [HCO3-]. These findings were interpreted as indicating uptake of La- by the inactive muscle, leading to a fall in the muscle [SID] and increase in plasma [SID], associated with an increase in muscle PCO2. The venoarterial CO2 content difference was 38% greater than could be accounted for by metabolism of La- alone, suggesting liberation of CO2 stored in muscle, possibly as carbamate.(ABSTRACT TRUNCATED AT 250 WORDS)
Thoracic influence on upper airway patency
Authors: Van de Graaff W. B.
Published: December 2017

Patency of the upper airway (UA) is usually considered to be maintained by the activity of muscles in the head and neck. These include cervical muscles that provide caudal traction on the UA. The thorax also applies caudal traction to the UA. To observe whether this thoracic traction can also improve UA patency, we measured resistance of the UA (RUA) during breathing in the presence and absence of UA muscle activity. Fifteen anesthetized dogs breathed through tracheostomy tubes. RUA was calculated from the pressure drop of a constant flow through the isolated UA. RUA decreased 31 +/- 5% (SEM) during inspiration. After hyperventilating seven of these dogs to apnea, we maximally stimulated the phrenic nerves to produce paced diaphragmatic breathing. Despite absence of UA muscle activity, RUA fell 51 +/- 11% during inspiration. Graded changes were produced by reduced stimulation. In six other dogs we denervated all UA muscles. RUA still fell 25 +/- 7% with inspiration in these spontaneously breathing animals. When all caudal ventrolateral cervical structures mechanically linking the thorax to the UA were severed, RUA increased and respiratory fluctuations ceased. These findings indicate that tonic and phasic forces generated by the thorax can improve UA patency. Inspiratory increases in UA patency cannot be attributed solely to activity of UA muscles.
Immature tendon adaptation to strenuous exercise
Authors: Curwin S. L. , Vailas A. C. , Wood J.
Published: December 2017

White Leghorn roosters (3 wk old) were randomly assigned to runner or control groups. Runners were subjected to a progressive treadmill running program for 8 wk, 5 days/wk at 70-80% maximal O2 consumption (VO2 max). After 8 wk, runners showed a significant elevation in gastrocnemius fumarase activity (51%) and a 21% increase in VO2max compared with controls. The exercise program induced a significant increase in tendon collagen deposition (46%) without any changes in DNA, proteoglycan, and collagen concentrations or tendon dry weight. Also, tendon collagen from runners contained fewer (50%) pyridinoline cross-links. These results suggest that high-intensity exercise causes greater matrix-collagen turnover in growing chickens, resulting in reduced maturation of tendon collagen.
Bioelectric properties and ion transport across excised canine fetal and neonatal airways
Authors: Cotton C. U. , Boucher R. C. , Gatzy J. T.
Published: December 2017

Knowledge of liquid secretion by fetal lung stems from studies of sheep. We extended these studies to dogs and examined the persistence of the fetal pattern of airway epithelial permeability and ion transport in the neonatal animal. Plasma and lung liquid from fetal dogs were analyzed for Na+, K+, Cl-, and HCO3-. Only the Cl- concentration of fetal lung liquid (129 meq/l) was significantly different from that of fetal plasma (111 meq/l). Segments of trachea from fetal and neonatal (less than 1, 7-10, and 21-46 days after birth) dogs were excised and mounted in flux chambers. The transepithelial potential difference (PD) of all tissues was oriented lumen negative (9.8-14.8 mV). Under short-circuit conditions, unidirectional Na+ flows were symmetrical. Cl- was secreted, and the secretion was equivalent to short-circuit current (Isc). Cl- secretion persisted under open-circuit conditions. Lobar bronchi from 21- to 46-day neonates absorbed Na+ (1.9 mueq.cm-2.h-1), but unidirectional flows of Cl- were symmetrical. Amiloride (10(-4) M) reduced Isc of neonatal bronchi by 47% but did not affect fetal bronchi. Isoproterenol increased Isc of both fetal (33%) and neonatal (40%) bronchi. These responses suggest that fetal bronchi do not absorb Na+ but can be stimulated to secrete Cl-. We conclude that Cl- secretion by epithelium of large airways may contribute to fetal lung liquid production, but it is unlikely that the tracheal epithelium is involved in fluid absorption at birth. Whereas fetal bronchi appear to secrete Cl-, neonatal bronchi absorb Na+.(ABSTRACT TRUNCATED AT 250 WORDS)
Paths of ion transport across canine fetal tracheal epithelium
Authors: Cotton C. U. , Boucher R. C. , Gatzy J. T.
Published: December 2017

Fluid secretion by the fetal sheep lung is thought to be driven by secretion of Cl- by the pulmonary epithelium. We previously demonstrated Cl- secretion by tracheal epithelium excised from fetal dogs and sheep. In this study we characterized the ion transport pathways across fetal canine tracheal epithelium. The transport of Na+ and Cl- across trachea excised from fetal dogs was evaluated from transepithelial electrical properties and isotope fluxes. Under basal conditions the tissues were characterized by a lumen-negative potential difference (PD) of 11 mV and conductance of 5.2 mS/cm2. The short-circuit current (Isc) was 43 microA/cm2 (1.6 mueq.cm-2.h-1). Basal Na+ flows were symmetrical, but net Na+ absorption (1.1 mueq.cm-2.h-1) could be induced by exposure of the luminal surface to amphotericin B (10(-6) M). Bilateral replacement of Na+ reduced Isc by 85%. Replacement of submucosal Na+ or exposure to submucosal furosemide (10(-4) M) reduced net Cl- secretion by 60-70%. Luminal exposure to indomethacin (10(-6) M) induced a 50% decrease in Isc, whereas isoproterenol (10(-6) M) increased Isc by 120%. The properties of the Cl- secretory pathway across fetal dog trachea are consistent with the model proposed for Cl- secretion across adult dog trachea and other Cl- -secreting tissues (e.g., bullfrog cornea and shark rectal gland). The absence of basal Na+ absorption by fetal dog trachea probably reflects limited apical membrane Na+ permeability.
Neuromuscular and hormonal adaptations in athletes to strength training in two years
Authors: Hakkinen K. , Pakarinen A. , Alen M. , Kauhanen H. , Komi P. V.
Published: December 2017

Neuromuscular and hormonal adaptations to prolonged strength training were investigated in nine elite weight lifters. The average increases occurred over the 2-yr follow-up period in the maximal neural activation (integrated electromyogram, IEMG; 4.2%, P = NS), maximal isometric leg-extension force (4.9%, P = NS), averaged concentric power index (4.1%, P = NS), total weight-lifting result (2.8%, P less than 0.05), and total mean fiber area (5.9%, P = NS) of the vastus lateralis muscle, respectively. The training period resulted in increases in the concentrations of serum testosterone from 19.8 +/- 5.3 to 25.1 +/- 5.2 nmol/l (P less than 0.05), luteinizing hormone (LH) from 8.6 +/- 0.8 to 9.1 +/- 0.8 U/l (P less than 0.05), follicle-stimulating hormone (FSH) from 4.2 +/- 2.0 to 5.3 +/- 2.3 U/l (P less than 0.01), and testosterone-to-serum sex hormone-binding globulin (SHBG) ratio (P less than 0.05). The annual mean value of the second follow-up year for the serum testosterone-to-SHBG ratio correlated significantly (r = 0.84, P less than 0.01) with the individual changes during the 2nd yr in the averaged concentric power. The present results suggest that prolonged intensive strength training in elite athletes may influence the pituitary and possibly hypothalamic levels, leading to increased serum levels of testosterone. This may create more optimal conditions to utilize more intensive training leading to increased strength development.
Hyperammoniemia during prolonged exercise: an effect of glycogen depletion?
Authors: Broberg S. , Sahlin K.
Published: December 2017

Eight healthy men exercised to exhaustion on a cycle ergometer at a work load of 176 +/- 9 (SE) W corresponding to 67% (range 63-69%) of their maximal O2 uptake (exercise I). Exercise of the same work load was repeated after 75 min of recovery (exercise II). Exercise duration (range) was 65 (50-90) and 21 (14-30) min for exercise I and II, respectively. Femoral venous blood samples were obtained before and during exercise and analyzed for NH3 and lactate. Plasma NH3 was 12 +/- 2 and 19 +/- 6 mumol/l before exercise I and II, respectively and increased during exercise to exhaustion to peak values of 195 +/- 29 (exercise I) and 250 +/- 30 (exercise II) mumol/l, respectively. Plasma NH3 increased faster during exercise II compared with exercise I and at the end of exercise II was threefold higher than the value for the corresponding time of exercise I (P less than 0.001). Blood lactate increased during exercise I and after 20 min of exercise was 3.7 +/- 0.4 mmol/l and remained unchanged until exhaustion. During exercise II blood lactate increased less than during exercise I. It is concluded that long-term exercise to exhaustion results in large increases in plasma NH3 despite relatively low levels of blood lactate. It is suggested that the faster increase in plasma NH3 during exercise II (vs. exercise I) reflects an increased formation in the working muscle that may be caused by low glycogen levels and impairment of the ATP resynthesis.
Oxygen uptake kinetics during exercise in diabetic neuropathy
Authors: Kremser C. B. , Levitt N. S. , Borow K. M. , Jaspan J. B. , Lindbloom C. , Polonsky K. S. , Leff A. R.
Published: December 2017

To assess the effect of autonomic and sensorineural dysfunction on O2 uptake kinetics, we studied the exercise response of seven diabetic humans having peripheral sensory and cardiac autonomic neuropathy, eight diabetics without neuropathy, and eight normal subjects. Maximal O2 uptake (VO2max), ventilatory anaerobic threshold, and O2 uptake kinetics were assessed. Metabolic control was optimized 12 h prior to and during testing by intravenous insulin infusion. Patients with diabetic neuropathy had a reduced VO2max [83 +/- 6% predicted vs. 104 +/- 6% (nonneuropathic diabetics) and 107 +/- 5% (normals); P less than 0.05]. However, there was no difference in ventilatory anaerobic threshold [14.8 +/- 0.9 (neuropathic diabetics) vs. 18.0 +/- 1.0 (nonneuropathic diabetics) and 16.7 +/- 1.5 ml O2.kg-1.min-1 (normals); P greater than 0.25]. The phase I increment in O2 uptake (VO2) and estimated cardiac output and the time constant of VO2 during constant-load exercise at 40% VO2max also were similar in all groups. We propose that the instantaneous increase in VO2 and cardiac output at exercise onset in diabetes with impaired neurogenic reflexes is caused primarily by mechanical and metabolic events in exercising muscle that cause venous compression and vasodilation.
Coexistence of twitch potentiation and tetanic force decline in rat hindlimb muscle
Authors: Rankin L. L. , Enoka R. M. , Volz K. A. , Stuart D. G.
Published: December 2017

An experimental protocol designed to assess fatigability in motor units has been applied to two hindlimb muscles of anesthetized adult rats to study the effects of whole-muscle fatigue on the isometric twitch. Both soleus and extensor digitorum longus exhibited a linear relationship between fatigability (i.e., force decline after a 360-s fatigue test) and the magnitude of the twitch force following the fatigue test. Twitch force after the fatigue test was potentiated (i.e., greater than the value before the fatigue test) in many muscles, despite the development of considerable fatigue. This coexistence of fatigue and twitch potentiation was observed in 7% (5/70) of soleus and 48% (31/64) of extensor digitorum longus muscles. The coexistence was exhibited only by the least fatigable muscles of the fast-contracting extensor digitorum longus. The extensor digitorum longus muscles that did not exhibit twitch potentiation probably experienced a higher proportion of muscle-fiber inactivation, such as due to failure of neuromuscular propagation, that was induced by the fatigue regimen.
Cardiovascular failure and apnea in shock
Authors: Nava S. , Bellemare F.
Published: December 2017

A model of shock was developed in anesthetized dogs by limiting venous return with a balloon inflated in the right atrium. The change in ventilation (VE) in response to a sustained decrease in arterial pressure (Pa) to 50–60 Torr was studied by recording transdiaphragmatic pressure (Pdi) and diaphragm (Edi) and parasternal intercostal (Eic) electrical activity. Four dogs died of cardiac arrest after 20–60 min. In 11 dogs, VE, after an initial increase, decreased progressively until apnea occurred after 103 +/- 24 min, after 60% reductions in breathing frequency, Pdi, and Eic and a 30% fall in Edi. No decrease in diaphragm contractility was found in response to artificial phrenic nerve stimulation. The cardiocirculatory function deteriorated during shock until it became irreversible at apneic time. No recovery from apnea occurred without a recovery of Pa. We conclude that the fall in VE and ensuing apnea in this model resulted from a decrease in central respiratory neural output associated with a progressive deterioration of the cardiocirculatory function.
Determinants of VO2max in rats after high-intensity sprint training
Authors: Hilty M. R. , Groth H. , Moore R. L. , Musch T. I.
Published: December 2017

The hemodynamic response to maximal exercise was determined in rats that were subjected to high-intensity sprint training (HIST) and rats that served as sedentary controls. Training consisted of five 1-min bouts of treadmill running at work loads (15% grade, 97 m/min) in excess of the animals' maximal O2 uptake (VO2max) interspersed with 90 s of rest. Training was performed 6 days/wk for 6 wk. After the training regimen, all rats were acutely instrumented with catheters in the right carotid artery and right ventricle. O2 uptakes, hemodynamic parameters, arterial and mixed venous O2 concentrations, blood gases, and acid-base status were determined at rest and during submaximal and maximal exercise. Results demonstrated that VO2max of HIST rats was significantly greater than that found for sedentary control rats. This increase in VO2max was due to an increase in maximal cardiac output (Qmax), since maximal arteriovenous O2 difference was similar between trained and sedentary rats. The increase in Qmax was due to an increase in maximal stroke volume (SVmax), because maximal heart rate in trained rats was similar to that in sedentary control rats. Citrate synthase and phosphofructokinase activities measured in the white gastrocnemius, plantaris, and soleus muscles of trained and sedentary rats were similar. These results suggest that the increase in VO2max produced with HIST in rats is strongly linked to an increase in central cardiac function as indicated by an increase in Qmax and SVmax.
Induction of alveolar epithelial injury by phospholipase A2
Authors: Niewoehner D. E. , Rice K. , Duane P. , Sinha A. A. , Gebhard R. , Wangensteen D.
Published: December 2017

Severe damage to the alveolar type I epithelial cell is a characteristic morphological feature of lung injury due to numerous cases. It is postulated that excess phospholipase A2 (PLA2) activity might be responsible for these changes, as one of the naturally occurring products of this enzyme, lysophosphatidylcholine (lysoPC) has been shown to cause selective injury to the type I pneumonocyte when it is instilled into the lower air spaces of the lung. To further investigate this potential mechanism of type I epithelial cell toxicity, we have measured the epithelial permeability-surface area product (PS) for [14C]sucrose as well as whole-lung lysoPC content at several times after instilling PLA2 (Naja naja venom) into either the air spaces or the perfusate of an isolated hamster lung preparation. As a molar percentage of total phospholipids, the normal hamster lung contains approximately 1.5% lysoPC, and this value is not affected by fluid filling of the air spaces or perfusion of the excised lung for periods up to 90 min. When 0.15 U/ml PLA2 is instilled into the air spaces, lung lysoPC content increases to approximately 2.5% and there are barely detectable increases in [14C]sucrose PS. With air space PLA2 concentrations of 0.30 U/ml, lysoPC content increases to between 4 and 5%, [14C]sucrose PS increases by greater than a factor of 10, and flooding of the alveolar spaces occur. Ultrastructural studies of similarly treated lungs show widespread but selective damage to the type I epithelial cells. These same biochemical and functional changes are not seen when the same concentrations of PLA2 are added to the lung perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)
Coupling of cardiac and locomotor rhythms
Authors: Kirby R. L. , Nugent S. T. , Marlow R. W. , MacLeod D. A. , Marble A. E.
Published: December 2017

The pressure within exercising skeletal muscle rises and falls rhythmically during normal human locomotion, the peak pressure reaching levels that intermittently impede blood flow to the exercising muscle. Speculating that a reciprocal relationship between the timing of peak intramuscular and pulsatile arterial pressures should optimize blood flow through muscle and minimize cardiac load, we tested the hypothesis that heart rate becomes entrained with walking and running cadence at some locomotion speeds, by means of electrocardiography and an accelerometer to provide signals reflecting heart rate and cadence, respectively. In 18 of 25 subjects, 1:1 coupling of heart and step rates was present at one or more speeds on a motorized treadmill, generally at moderate to high exercise intensities. To determine how exercise specific this phenomenon is, and to refute the competing hypothesis that coupling is due to vertical accelerations of the heart during locomotion, we had 12 other subjects cycle on an electronically braked bicycle ergometer. Coupling was found between heart rate and pedaling frequency in 10 of them. Cardiac-locomotor coupling appears to be a normal physiological phenomenon, and its identification provides a fresh perspective from which to study endurance.
Brain hypoxia preferentially stimulates genioglossal EMG responses to CO2
Authors: Hutt D. A. , Parisi R. A. , Santiago T. V. , Edelman N. H.
Published: December 2017

Although the dominant respiratory response to hypoxia is stimulation of breathing via the peripheral chemoreflex, brain hypoxia may inhibit respiration. We studied the effects of two levels of brain hypoxia without carotid body stimulation, produced by inhalation of CO, on ventilatory (VI) and genioglossal (EMGgg) and diaphragmatic (EMGdi) responses to CO2 rebreathing in awake, unanesthetized goats. Neither delta VI/delta PCO2 nor VI at a PCO2 of 60 Torr was significantly different between the three conditions studied (0%, 25%, and 50% carboxyhemoglobin, HbCO). There were also no significant changes in delta EMGdi/delta PCO2 or EMGdi at a PCO2 of 60 Torr during progressive brain hypoxia. In contrast, delta EMGgg/delta PCO2 and EMGgg at a PCO2 of 60 Torr were significantly increased at 50% HbCO compared with either normoxia or 25% HbCO (P less than 0.05). The PCO2 threshold at which inspiratory EMGgg appeared was also decreased at 50% HbCO (45.6 +/- 2.6 Torr) compared with normoxia (55.0 +/- 1.4 Torr, P less than 0.02) or 25% HbCO (53.4 +/- 1.6 Torr, P less than 0.02). We conclude that moderate brain hypoxia (50% HbCO) in awake, unanesthetized animals results in disproportionate augmentation of EMGgg relative to EMGdi during CO2 rebreathing. This finding is most likely due to hypoxic cortical depression with consequent withdrawal of tonic inhibition of hypoglossal inspiratory activity.
Effect of pentoxiphylline on oxygen transport during hypothermia
Authors: Hershenson M. B. , Schena J. A. , Lozano P. A. , Jacobson M. J. , Crone R. K.
Published: December 2017

At least two investigators have demonstrated a reduction in O2 extraction during induced hypothermia (Cain and Bradley, J. Appl. Physiol. 55: 1713–1717, 1983; Schumacker et al., J. Appl. Physiol. 63: 1246–1252, 1987). We hypothesized that administration of pentoxiphylline (PTX), a theobromine that lowers blood viscosity and has vasodilator effects, would increase O2 extraction during hypothermia. To test this hypothesis, we studied O2 transport in anesthetized, paralyzed, mechanically ventilated beagles exposed to hypoxic hypoxia during either 1) normothermia (38 degrees C), 2) hypothermia (30 degrees C), or 3) hypothermia + PTX (30 degrees C and PTX, 20 mg.kg-1.h-1). Measurements included arterial and mixed venous PO2, hemoglobin concentration and saturation, cardiac output, systemic vascular resistance (SVR), blood viscosity, and O2 consumption (VO2). Critical levels of O2 delivery (DO2, the product of arterial O2 content and cardiac output) were determined by a system of linear regression. Hypothermia significantly decreased base line cardiac output (-35%), DO2 (-37%), and VO2 (-45%), while increasing SVR and blood viscosity. Addition of PTX increased cardiac output (35%) and VO2 (14%), and returned SVR and blood viscosity to normothermic levels. Hypothermia alone failed to significantly reduce the critical level of DO2, but addition of PTX did [normothermia, 11.4 +/- 4.2 (SD) ml.kg-1.min-1; hypothermia, 9.3 +/- 3.6; hypothermia + PTX, 6.6 +/- 1.3; P less than 0.05, analysis of variance]. The O2 extraction ratio (VO2/DO2) at the critical level of DO2 was decreased during hypothermia alone (normothermia, 0.60 +/- 0.13; hypothermia, 0.42 +/- 0.16; hypothermia + PTX, 0.62 +/- 0.19; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Preferential axial flow during high-frequency oscillations: effects of gas density
Authors: Alleyne C. M. , Frantz I. D. , Fredberg J. J.
Published: December 2017

Allen et al. (J. Clin. Invest. 76: 620–629, 1985) reported that regional phasic lung distension during high-frequency oscillations (HFO) is substantially and systemically heterogeneous when both frequency (f) and tidal volume (VT) are large. They hypothesized that this phenomenon was attributable to central airway geometry and preferential axial flow induced therein by the momentum flux of the inspiratory gas stream. According to that hypothesis, the observed distribution of phasic lung distension would depend on the ratio VT/VD* (where VD* is an index of anatomic dead space), independent of gas density (rho), when f is scaled in proportion to lung resonant frequency, fo. To test this hypothesis, we used the methods of Allen et al. (ibid.) to study six excised dog lungs during HFO (f = 2–32 Hz; VT = 5–80 ml) using gases of different densities. Alveolar pressure excursions (PA) were measured as rho spanned a 12-fold range using He, air, and SF6. The apex-to-base and right-to-left ratios of PA were used as indexes of regional heterogeneity of phasic lung distension. For each gas at low f, distension of the lung base was favored slightly independent of VT, but at higher f distension of the lung apex was favored when VT was small, whereas distension of the lung base was favored when VT was large. In addition, we observed substantial right-to-left differences in apical lobes during oscillation at high f not seen before.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular responses in forearm and calf to contralateral static exercises
Authors: Duprez D. A. , Essandoh L. K. , Vanhoutte P. M. , Shepherd J. T.
Published: December 2017

Ten normal subjects performed a 90-s isometric exercise [20, 30, and 40% of maximal voluntary contraction (MVC) of the flexor muscle of the right index finger or quadriceps muscle of the right leg. Contralateral forearm and calf blood flows (strain gauge plethysmography) and arterial blood pressure (auscultation) were measured simultaneously. Each exercise caused a decrease in forearm vascular resistance and a progressive increase in calf resistance. These changes were greatest with the 40% MVC. With finger exercise at 20 and 40% MVC, the percentage decreases in forearm vascular resistance from control were 12.3 and 22.7%, respectively (P less than 0.01). Similar decreases (9.5 and 24.9%, respectively; P less than 0.01) were noted with exercise of the quadriceps muscle. By contrast, the corresponding increases in calf vascular resistance were greater (P less than 0.01) with quadriceps exercise (13.3 and 55.4%, respectively) than with finger exercise (6.0 and 36.0%). Arrest of the circulation to the exercising muscles just before the exercise ended caused an abrupt increase in forearm vascular resistance and a decrease in calf resistance. These studies provide further evidence of the heterogeneity of responses of forearm and calf resistance vessels to certain cardiovascular stimuli.
Effect of inhaled endotoxin on bronchial reactivity in asthmatic and normal subjects
Authors: Michel O. , Duchateau J. , Sergysels R.
Published: December 2017

Endotoxins are released from the membrane of Gram-negative bacteria present in the environment and in oral and nasal cavities. They are proinflammatory substances that could participate in bronchial obstruction and hyperreactivity in asthmatic patients. This hypothesis was tested by using bronchial challenge tests with inhaled lipopolysaccharides (LPS) from Escherichia coli 026:B6 (22.2-micrograms total dose) followed by a histamine nonspecific challenge test and compared with a placebo procedure, in which the diluent was substituted for the LPS solution. In doing so we showed that LPS induces a slight but significant (P less than 0.01) bronchial obstruction (measured as forced expiratory volume in 1 s) in asthmatics (n = 8) but not in normal subjects (n = 6). The histamine hyperresponsiveness, expressed as the dosage of histamine necessary to decrease the bronchial specific conductance by 50%, was increased 5 h after LPS inhalation in asthmatics (P less than 0.05) but not in normal subjects. This effect of LPS on bronchial obstruction and hyperresponsiveness was observed in extrinsic (n = 6) as well as in intrinsic (n = 2) asthma.
Hypercapnia and response of cerebral blood flow to hypoxia in newborn lambs
Authors: Massik J. , Jones M. D. , Miyabe M. , Tang Y. L. , Hudak M. L. , Koehler R. C. , Traystman R. J.
Published: December 2017

Individual effects of hypoxic hypoxia and hypercapnia on the cerebral circulation are well described, but data on their combined effects are conflicting. We measured the effect of hypoxic hypoxia on cerebral blood flow (CBF) and cerebral O2 consumption during normocapnia (arterial PCO2 = 33 +/- 2 Torr) and during hypercapnia (60 +/- 2 Torr) in seven pentobarbital-anesthetized lambs. Analysis of variance showed that neither the magnitude of the hypoxic CBF response nor cerebral O2 consumption was significantly related to the level of arterial PCO2. To determine whether hypoxic cerebral vasodilation during hypercapnia was restricted by reflex sympathetic stimulation we studied an additional six hypercapnic anesthetized lambs before and after bilateral removal of the superior cervical ganglion. Sympathectomy had no effect on base-line CBF during hypercapnia or on the CBF response to hypoxic hypoxia. We conclude that the effects of hypoxic hypoxia on CBF and cerebral O2 consumption are not significantly altered by moderate hypercapnia in the anesthetized lamb. Furthermore, we found no evidence that hypercapnia results in a reflex increase in sympathetic tone that interferes with the ability of cerebral vessels to dilate during hypoxic hypoxia.