bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorimetric device for measurement of transvascular fluid flux in blood-perfused organs
Authors: Oppenheimer L. , Richardson W. N. , Bilan D. , Hoppensack M.
Published: December 2017

The aim of this study was to develop a device capable of measuring transvascular fluid flux in blood-perfused organs. For any given blood flow through the organ (QT), transvascular flux (QF) can be considered as the fraction of QT exchange. Presumably, QF would change the background concentration of an impermeable tracer residing in the perfusate. Thus QF could be calculated from the relative changes in tracer concentration for any given QT. We have used Blue Dextran (1 g/l of blood) as the reference tracer. Because the minimum molecular weight of Blue Dextran is 2 X 10(6), we anticipated it to behave as an impermeable tracer in most organs. QF was simulated with continuous infusions of plasma, normal saline solution, and a 50% mixture of both. Changes in Blue Dextran concentration were continuously followed colorimetrically by changes in transmission of specific light at a wavelength of 632 nm. Because 632-nm light is affected by hematocrit and O2 saturation changes, two additional wavelengths were used: 815-nm, which is not affected by saturation or Blue Dextran concentration changes, was used to account for changes in hematocrit, and 887-nm specific light, which is not affected by Blue Dextran, served to correct for saturation changes. Red cells could not be used as the reference tracer because of the possibility of hematocrit changes independent of fluid flux (Fahraeus effect). The device so constructed proved capable of measuring rates of fluid infusion in the order of 0.1% of QT with a variability of 10% around the mean.
Adipocyte insulin resistance: effects of aging, obesity, exercise, and food restriction
Authors: Craig B. W. , Garthwaite S. M. , Holloszy J. O.
Published: December 2017

This study examined the effects of aging, exercise training, and food restriction on epididymal fat cell size and resistance to insulin in rats. The exercise group was given access to voluntary running wheels at age 6 mo. The rats were studied at ages 12 and 28 mo. Sedentary free-eating (SFE) rats were obese and their fat cells were extremely insulin resistant, showing minimal increases in glucose oxidation and 2-deoxy-D-glucose (2-DOG) uptake in response to high insulin concentrations. The runners' adipocytes were smaller and had a greater responsiveness to insulin (approximately 9-fold for 2-DOG uptake and approximately 30-fold for glucose oxidation) than those of the SFE rats. Sedentary rats that were food restricted to keep their body weights the same as those of the runners had fat cells that were intermediate both in size and insulin responsiveness relative to those of the SFE rats and runners. There was a close correlation between fat cell size and responsiveness to insulin of 2-DOG uptake and glucose oxidation independent of age. There were no significant differences in fat cell size, insulin sensitivity, or insulin responsiveness between the adult (12 mo) and old (28 mo) rats in the same treatment groups. We conclude that aging alone has little or no effect on the responsiveness to insulin of glucose metabolism in fat cells and that the insulin resistance of adipocytes from obese older rats is due to fat cell hypertrophy, not aging. Exercise is effective in protecting against development of fat cell hypertrophy and insulin resistance.
Reliability of parameter estimates from models applied to respiratory impedance data
Authors: Lutchen K. R. , Jackson A. C.
Published: December 2017

Many previous studies have fit lumped parameter models to respiratory input (Zin) and transfer (Ztr) impedance data. For frequency ranges higher than 4–32 Hz, a six-element model may be required in which an airway branch (with a resistance and inertance) is separated from a tissue branch (with a resistance, inertance, and compliance) by a shunt compliance. A sensitivity analysis is applied to predict the effects of frequency range on the accuracy of parameter estimates in this model obtained from Zin or Ztr data. Using a parameter set estimated from experimental data between 4 and 64 Hz in dogs, both Zin and Ztr were simulated from 4 to 200 Hz. Impedance sensitivity to each parameter was also calculated over this frequency range. The simulation predicted that for Zin a second resonance occurs near 80 Hz and that the impedance is considerably more sensitive to several of the parameters at frequencies surrounding this resonance than at any other frequencies. Also, unless data is obtained at very high frequencies (where the model is suspect), Zin data provides more accurate estimates than Ztr data. After adding random noise to the simulated Zin data, we attempted to extract the original parameters by using a nonlinear regression applied to three frequency ranges: 4–32, 4–64, and 4–110 Hz. Estimated parameters were substantially incorrect when using only 4- to 32-Hz or 4- to 64-Hz data, but nearly correct when fitting 4- to 110-Hz data. These results indicate that respiratory system parameters can be more accurately extracted from Zin than Ztr, and to make physiological inferences from parameter estimates based on Zin impedance data in dogs, the data must include frequencies surrounding the second resonance.
Sequential changes in lung metabolism, permeability, and edema after ANTU
Authors: Minty B. D. , Scudder C. M. , Grantham C. J. , Jones J. G. , Bakhle Y. S.
Published: December 2017

Lung injury and pulmonary edema were induced in rats after intraperitoneal injection of 10 mg/kg alpha-naphthylthiourea (ANTU). The time course of development of lung injury was assessed by the clearance of 99mTc-diethylenetriamine pentaacetate (99mTcDTPA) from the lung into the blood, the pharmacokinetics of tritiated prostaglandin E2 [( 3H]PGE2) in the isolated perfused lung, and by increase in the weight ratio (wet-to-dry) of lung. Two hours after ANTU administration, the clearance of 99mTcDTPA was significantly faster than in untreated animals and implied an increase in permeability of the alveolar-capillary barrier. This change preceded the increase in wet-to-dry weight ratio of lung, which was not significant until 5 h after ANTU administration. The pharmacokinetics of [3H]PGE2 were significantly altered after ANTU and these changes persisted beyond the time when both lung weight ratio and 99mTcDTPA clearance had recovered to normal values. We conclude that both 99mTcDTPA clearance and PGE2 pharmacokinetics change in ANTU-induced lung injury but with different time courses. In the progressive phase of lung injury due to ANTU, the early change in clearance of 99mTcDTPA suggests that an increased permeation of the alveolar capillary barrier by this small molecule precedes pulmonary edema due to an increased colloid permeability of the barrier. Abnormal metabolism in the pulmonary microvasculature persists when the permeability defect and edema have recovered.
Skeletal muscle glycogenolysis, glycolysis, and pH during electrical stimulation in men
Authors: Spriet L. L. , Soderlund K. , Bergstrom M. , Hultman E.
Published: December 2017

Glycogenolytic and glycolytic rates were estimated and muscle pH (pHm) was measured in electrically stimulated quadriceps femoris muscles of seven men. Leg blood flow was occluded and muscles were stimulated 64 times at 20 Hz, with contractions lasting 1.6 s and separated by pauses of 1.6 s. Muscle biopsies were obtained at rest and following 16, 32, 48, and 64 contractions. Glycolytic intermediates and several modulators of the glycolytic enzyme phosphofructokinase (PFK) were measured. Glycogenolytic and glycolytic rates were 1.68 and 1.26 mmol glucosyl units X kg dry muscle-1 X S-1 contraction time during the initial 16 contractions and pHm decreased from 7.00 +/- 0.01 to 6.70 +/- 0.03. During the subsequent 32 contractions both glycogenolytic and glycolytic rates were maintained at approximately 0.70 mmol X kg-1 X S-1 and pHm decreased to 6.45 +/- 0.04. In the final 16 contractions, both rates were very low and pHm was unchanged. Therefore, PFK remained active despite increasing acidity until pHm decreased to approximately 6.45. We conclude that increases in the concentrations of several positive modulators partially reverses pH-dependent ATP inhibition of PFK in vivo, permitting glycolytic activity to continue in the pHm range of 6.70–6.45.
Measurement in vitro of pulsatile arterial diameter using a helium-neon laser
Authors: Brant A. M. , Rodgers G. J. , Borovetz H. S.
Published: December 2017

A noncontacting in vitro measurement of pulsatile arterial diameter using a scanning optical micrometer is described. The major component of this system is a He-Ne laser whose beam scans the pulsating artery to be measured. The laser micrometer was integrated into a pulsatile perfusion apparatus that imposed various hemodynamic conditions on excised canine vessels. The laser system reliably tracked the pulsating arterial diameter at a particular longitudinal site as well as at various increments in the presence of an experimentally created stenosis. The He-Ne laser measured the radial motion of canine arteries and various vascular substitutes anastomosed in an end-to-end fashion. From these novel measurements, calculations were made of arterial compliance and bending stress, two biomechanical parameters that are implicated as potential causes of anastomotic intimal hyperplasia and graft failure. Although this device is inherently limited to in vitro use, it is a potentially useful instrument for vascular physiology and biophysics.
Positive effort dependence of maximal expiratory flow
Authors: Allen J. L. , Castile R. G. , Mead J.
Published: December 2017

The maximal expiratory-flow volume (MEFV) curve in normal subjects is thought to be relatively effort independent over most of the vital capacity (VC). We studied seven normal males and found positive effort dependence of maximal expiratory flow between 50 and 80% VC in five of them, as demonstrated by standard isovolume pressure-flow (IVPF) curves. We then attempted to distinguish the effects of chest wall conformational changes from possible mechanisms intrinsic to the lungs as an explanation for positive effort dependence. IVPF curves were repeated in four of the subjects who had demonstrated positive effort dependence. Transpulmonary pressure was varied by introducing varied resistances at the mouth but effort, as defined by pleural pressure, was maintained constant. By this method, chest wall conformation at a given volume would be expected to remain the same despite changing transpulmonary pressures. When these four subjects were retested in this way, no increases in flow with increasing transpulmonary pressure were found. In further studies, voluntarily altering the chest wall pattern of emptying (as defined by respiratory inductive plethysmography) did however alter maximal expiratory flows, with transpulmonary pressure maintained constant. We conclude that maximal expiratory flow can increase with effort over a larger portion of the vital capacity than is commonly recognized, and this effort dependence may be the result of changes in central airway mechanical properties that occur in relation to changes in chest wall shape during forced expiration.
Substance P-inducing massive postmortem bronchoconstriction in guinea pig lungs
Authors: Lai Y. L. , Cornett A. F.
Published: December 2017

To further examine the role that substance P plays in initiating the observed massive postmortem bronchoconstriction in guinea pig lungs and to explore the role of neural reflex in this airway spasm, six groups of animals were employed: control (n = 6), morphine (n = 6), substance P (n = 5), chronic capsaicin pretreatment + substance P (n = 5), tetrodotoxin (TTX) + acute capsaicin (n = 4), and chlorisondamine + acute capsaicin (n = 5). Pressure-volume curves were performed prior to and following the initiation of artificial pulmonary perfusion with 1% bovine serum albumin and 5% dextran in Tyrode's solution. A decrease in inflation volume (the lung volume between transpulmonary pressure of 0 and 30 cmH2O during inflation) was used as an index of bronchoconstriction. In control animals, inflation volume decreased to 20–30% of the base-line value at 15–30 min of perfusion, indicating massive bronchial constriction during this time period. Morphine (an agent inhibiting substance P release) significantly attenuated the spasm, whereas the presence of substance P in the perfusate markedly enhanced the constriction. Depletion of endogenous substance P by chronic capsaicin pretreatment did not affect exogenous substance P-induced spasm. Acute capsaicin-induced bronchoconstriction was significantly attenuated by TTX but was not affected by the ganglionic blocking agent, chlorisondamine. These data suggest that substance P initiates the massive postmortem bronchoconstriction in guinea pig lungs and that substance P is released by local stimulation of sensory nerve endings via axonal reflex.
Automated data collection and processing for a cycle ergometer
Authors: Harman E. , Knuttgen H. G. , Frykman P.
Published: December 2017

A system is described for collection and processing of data from a cycle ergometer. Cycle pedals, specially made to withstand the extremely high forces exerted during maximal power cycling, contain transducers to measure pedal angle relative to the crank and foot forces both perpendicular and parallel to the pedal surface. An additional transducer monitors crank position. Output signals are conditioned, amplified, digitized by a 12-bit analog-to-digital converter, fed into a computer at 100 Hz/channel, and mathematically smoothed to attenuate noise. For each sample interval, foot force components perpendicular and parallel to the crank arm are calculated. Power generated on each crank revolution is determined from transducer information. Computer graphics display pedaling parameters vs. crank angle in both rectangular and circular format. Data files containing variables descriptive of pedaling force curves are produced to enable computerized statistical analysis of cycling performance.
Segmental vascular resistances and compliances in dog lung
Authors: Rippe B. , Parker J. C. , Townsley M. I. , Mortillaro N. A. , Taylor A. E.
Published: December 2017

The segmental distribution of vascular resistances and compliances were evaluated in isolated blood perfused lung lobes using arterial, venous, and double-occlusion pressures and were compared with filtration midpoint capillary pressures (Pc,f). We separated total vascular resistance (RT) and compliance (CT) into large artery (Ra, Ca), large vein (Rv, Cv), and microvascular compartments (Rmc, Cmc) at base-line and increased vascular pressures and during infusions of histamine, serotonin, and norepinephrine. In control lobes, double-occlusion pressure (Pdo) closely approximated Pc,f at all vascular pressures. Pre- and postcapillary resistance were approximately equal when referenced to either Pc,f or Pdo. Although Rmc comprised 42% of RT and Cmc constituted 76% of CT, a twofold increase in base-line Pc,f caused RT to decrease to 67% and Rmc/RT to 29% of control values, whereas CT decreased to 87% and Cmc/CT decreased to 88% of control values over the same Pc,f range. Mean static CT was 2.25 +/- 0.09 ml X cmH2O–1. 100 g-1, whereas dynamic CT was 1.54 +/- 0.08 ml X cmH2O–1. 100 g-1, or only 68% of static vascular compliance. Drug infusions increased mean RT from 4.2- to 5.3-fold and significantly decreased both static and dynamic CT. Although all vascular segments were constricted, histamine affected primarily large veins, serotonin increased Ra greater than Rv, and norepinephrine constricted upstream and downstream vessels about equally. Increased Pc,f in the presence of these drugs decreased RT significantly in every case primarily through attenuation of the drug vasoconstrictor effect on Rmc and decreased CT primarily due to a decrease in Cmc, but increased Cmc/(Ca + Cv). Thus the microvascular compartment appears to be the major site of both fluid filtration and vascular compliance and contributes significantly to total vascular resistance. Drug infusions constricted large and small vessel compartments as defined here, but increased Pc,f attenuated microvascular vasoconstriction and to a lesser extent large vessel vasoconstriction resulting in a reduced microvascular resistance in both drug-treated and control lobes. This effect can be attributed to recruitment and/or distension of microvessels and distension of larger vessels.
Influence of exercise training on spatial R-wave amplitude in patients with coronary artery disease
Authors: Myers J. , Ahnve S. , Froelicher V. , Sullivan M. , Friis R.
Published: December 2017

To evaluate the influence of an exercise program on spatial and left precordial R-wave amplitude among patients with coronary artery disease, computerized electrocardiogram (ECG) data were acquired during maximal treadmill testing before and after 1 yr in 89 patients randomized to either exercise (n = 40) or control (n = 49) groups. Spatial and lateral R-wave amplitudes were derived from the orthogonal Frank (XYZ) lead system. The exercise group significantly increased maximal O2 consumption (0.17 l/min), whereas controls decreased significantly (0.12 l/min, P less than 0.01 between groups). No significant changes in electrocardiographic R-wave voltage measurements occurred within or between groups during the year. It is concluded that exercise training does not result in increases in R-wave voltage in patients with coronary artery disease.
Canine diaphragm muscle after 1 yr of continuous electrical stimulation: its potential as a myocardial substitute
Authors: Acker M. A. , Mannion J. D. , Brown W. E. , Salmons S. , Henriksson J. , Bitto T. , Gale D. R. , Hammond R. , Stephenson L. W.
Published: December 2017

Skeletal muscle has been rendered fatigue resistant by chronic stimulation and therefore has potential as an active substitute for damaged myocardium. It is therefore important to know whether stimulation produces any deleterious effects in the long term. Hemidiaphragm muscles of four dogs were examined after chronic stimulation for 1 yr at either 2 or 4 Hz. The stimulated hemidiaphragms appeared normal on gross inspection and were still contracting vigorously. By histochemical and immunohistochemical criteria, they had acquired a uniformly type I character, in contrast to the mixed fiber type composition of the unstimulated hemidiaphragms. This transformation was also reflected in their complement of myosin isozymes. There was some enzymatic evidence of an associated shift towards aerobic pathways of energy generation. Histological examination revealed no evidence of degenerative changes. Trends, observed in the shorter term (6–8 wk), toward a decrease in fiber area and an increase in connective tissue showed no further progression at 1 yr. Thus hemidiaphragm muscle stimulated at frequencies at or above the normal heart rate does not appear to undergo adverse long-term changes that would constrain its use in a myocardial assist role.
The American Physiological Society in its centenary year
Authors: Morgan H. E.
Published: December 2017

THE AMERICAN PHYSIOLOGICAL SOCIETY celebrates its Centennial this year. As pointed out by Dr. Fishman in his introduction, this is an appropriate time to take stock of recent changes and challenges facing our discipline and the response of the Society to them.
CVF-induced decomplementation: effect on lung transvascular protein flux after thrombin
Authors: Johnson A. , Lo S. K. , Blumenstock F. B. , Malik A. B.
Published: December 2017

We examined the effects of cobra venom factor (CVF) on the changes in pulmonary hemodynamics and transvascular fluid and protein exchange following thrombin-induced pulmonary microembolism. Studies were made in unanesthetized sheep prepared with lung lymph fistulas. The animals received tranexamic acid (100 mg) to suppress fibrinolysis and were then challenged with an intravenous infusion of alpha-thrombin (80 U/kg). Control-thrombin challenged sheep were compared with the CVF-treated sheep challenged with the same thrombin dosage. CVF treatment (187 U X kg-1 X day-1 for 4 days) decreased the total hemolytic complement activity by 45% of control. Thrombin infusion in control sheep increased the mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and lymph protein clearance (pulmonary lymph flow X lymph-to-plasma protein concentration ratio, Clym). Thrombin infusion in CVF-treated sheep produced smaller increments in Ppa, PVR, and Clym. Pulmonary lymph obtained from control-thrombin and CVF-thrombin sheep induced migration of granulocytes obtained from normal unchallenged sheep. The granulocytes obtained from CVF-treated sheep responded relatively less to the migratory and O-2-generating stimuli (i.e., zymosan-treated serum, pulmonary lymph from sheep after thrombin challenge, and plasma from sheep after CVF treatment) compared with normal granulocytes. The attenuation of the thrombin-induced increases in Ppa, PVR, and lung transvascular fluid and protein exchange by CVF treatment may be the result of impaired function of granulocytes.
Effect of exposing mice to 50 ATA helium pressure at different stages of pregnancy
Authors: Wardley-Smith B. , Dore C. , Monk S. , Cohen S. , Eusden S. , Hawley D. , Halsey M. J.
Published: December 2017

Pregnant T-O mice were exposed to 50 ATA He-O2 pressure for 4 days at different stages of gestation: 4–7, 6–9, and 9–12 days gestation. Controls were exposed to 1 atmosphere absolute (ATA) air. After the exposure period, pregnancy continued until 18 days gestation when the mice were killed and autopsied. Data were collected relating to the litters and placentas (Litter size, percent resorptions, placental weight, fetal-to-placental ratio) and fetuses (weight, crown-rump length, sex, skeletal abnormalities) and analyzed using analysis of variance. Results showed a small but significant increase in the percent resorptions in the pressure group and also a decrease in crown-rump length and placental weight. None of these changes were related to the stage of gestation in which the mice were exposed. No teratogenic effects of pressure were seen. We conclude that exposure to 50 ATA He-O2 during pregnancy in mice produces a small nonselective effect on fetal growth and development but does not affect any specific event taking place during these stages of embryogenesis.
Effects of norepinephrine and fluid administration on diaphragmatic O2 consumption in septic shock
Authors: Hussain S. N. , Rutledge F. , Graham R. , Magder S. , Roussos C.
Published: December 2017

The effects of norepinephrine infusion and fluid administration on diaphragmatic O2 consumption during endotoxic shock were assessed in spontaneously breathing anesthetized dogs. Blood flow was measured with the microsphere technique, and diaphragmatic venous blood was obtained via a catheter inserted into the left inferior phrenic vein. One group of dogs (n = 6) received 10 mg/kg Escherichia coli endotoxin intravenously (E group). In the second and third groups, blood pressure after endotoxin injection was restored by continuous infusion of norepinephrine tartrate (N group) or by infusion of normal saline and dextran infusion (F group). The animals were observed for 2 h after endotoxin injection. Cardiac output fell significantly in the E and N group, whereas it was restored in the F group. Minute ventilation and diaphragmatic pressure-time index rose twofold in the three groups of dogs. Diaphragmatic O2 consumption (VO2 di) increased substantially in the E group to a mean value of 3.46 ml X 100 g-1 X min-1, which was achieved by higher blood flow and by an increase in O2 extraction. In the N group, VO2 di was higher than control but was lower than that of the E group (mean value of 1.43 ml X 100 g-1 X min-1), which was achieved solely by increasing O2 extraction. In the F group, VO2 di was also lower than that of the E group (mean value of 1.51 ml X 100 g-1 X min-1), which was achieved by high diaphragmatic blood flow. Thus, at any given diaphragmatic task, the diaphragm consumed less O2 in the N and F group than in the E group.
Effect of beta-adrenergic blockade on thermoregulation during exercise
Authors: Pescatello L. S. , Mack G. W. , Leach C. N. , Nadel E. R.
Published: December 2017

To resolve conflicting reports concerning the effects of beta-blockade (BB) on thermoregulatory reflexes during exercise, we studied six fit men during 40 min of cycle ergometer exercise at 60% maximum O2 consumption at ambient temperatures of 22 and 32 degrees C. Two hours before exercise, each subject ingested a capsule containing either 80 mg of propranolol or placebo in single-blind fashion. Heart rate at 40 min of exercise was reduced (P less than 0.01) from 125 to 103 beats min at 22 degrees C and 137 to 104 beats min at 32 degrees C, demonstrating effective BB. After 40 min of exercise, esophageal temperature (Tes) was elevated with BB (P less than 0.05) from 37.66 +/- 0.04 to 38.14 +/- 0.03 and 38.13 +/- 0.04 to 38.41 +/- 0.04 degrees C at 22 and 32 degrees C, respectively. The elevated Tes resulted from a reduced core-to-skin heat flux at both temperatures, indicated by a reduction in the slope of the forearm blood flow (FBF)-Tes relationship, and a decrease in maximal FBF. Systolic blood pressure was decreased 20 mmHg with BB (P less than 0.01), whereas diastolic blood pressure was unchanged, reducing arterial pulse pressure (PP). Because PP was decreased and cardiac filling pressure was presumably not reduced (since cardiac stroke volume was elevated), we suggest that at least a part of the relative increase in peripheral vasomotor tone during BB was the consequence of reduced sinoaortic baroreceptor stimulation.
Effect of high-intensity exercise on the VE-VCO2 relationship
Authors: Caiozzo V. J. , Davis J. A. , Berriman D. J. , Vandagriff R. B. , Prietto C. A.
Published: December 2017

The intrinsic relationship between ventilation (VE) and carbon dioxide output (VCO2) is described by the modified alveolar ventilation equation VE = VCO2 k/PaCO2(1-VD/VT) where PaCO2 is the partial pressure of CO2 in the arterial blood and VD/VT is the dead space fraction of the tidal volume. Previous investigators have reported that high-intensity exercise uncouples VE from VCO2; however, they did not measure the PaCO2 and VD/VT components of the overall relationship. In an attempt to provide a more complete analysis of the effects of high-intensity exercise on the VE-VCO2 relationship, we undertook an investigation where five subjects volunteered to perform three steady-state tests (SS1, SS2, SS3) at 60 W. One week after SS1 each subject was required to perform repeated 1-min bouts of exercise corresponding to a work rate of approximately 140% of maximal oxygen uptake (VO2max). Two and 24 h later the subjects performed SS2 and SS3, respectively. This exercise intervention caused PaCO2 during SS2 and SS3 to be regulated (P less than 0.01) approximately 4 Torr below the control (SS1) value of 38.8 Torr. Additionally, significant alterations were noted for VCO2 with corresponding values of 1.15 (SS1), 1.10 (SS2), and 1.04 (SS3) l/min. No changes were noted in either VD/VT or VE. In summary, it seems reasonable to suggest that the disproportionate increase in VE with respect to VCO2 noted in earlier work does not reflect an uncoupling. Rather the slope of the VE-VCO2 relationship is increased in a predictable manner as described by the modified alveolar ventilation equation.
Three-dimensional reconstruction of alveoli in the rat lung for pressure-volume relationships
Authors: Mercer R. R. , Laco J. M. , Crapo J. D.
Published: December 2017

To determine alveolar pressure-volume relationships, alveolar three-dimensional reconstructions were prepared from lungs fixed by vascular perfusion at various points on the pressure-volume curve. Lungs from male Sprague-Dawley rats were fixed by perfusion through the pulmonary artery following a pressure-volume maneuver to the desired pressure point on either the inflation or deflation curve. Tissue samples from lungs were serially sectioned for determination of the volume fraction of alveoli and alveolar ducts and reconstruction of alveoli. Alveoli from lungs fixed at 5 cmH2O on the deflation curve (approximating functional residual volume) had a volume of 173 X 10(3) microns3, a surface area of 11,529 microns2, a mouth opening diameter of 72.7 microns, and a mean caliper diameter of 91.8 micron (SE). Alveolar shape changes during deflation from total lung capacity to residual volume was first (30 to 10 cmH2O) associated with little change in the diameter of the alveoli (102.7 +/- 2.4 to 100.3 +/- 3.3 microns). In the range overlapping normal breathing (10 to 0 cmH2O) there was a substantial decrease in diameter (100.3 +/- 3.3 to 43.3 +/- 2.3 microns). These measurements and others made on the relative changes in the dimensions of the alveolus suggest that the elastic network, particularly around the alveolar ducts, are predominant in determining lung behavior near the volume expansion limits of the lung while the elastic and surface tension properties of the alveoli are predominant in the volume range around functional residual capacity.
Evidence that hypoxic pulmonary vascular remodeling in rats is polyamine dependent
Authors: Atkinson J. E. , Olson J. W. , Altiere R. J. , Gillespie M. N.
Published: December 2017

This study tested the hypothesis that the polyamines, a family of low-molecular-weight organic cations with documented regulatory roles in cell growth and differentiation, are mediators of chronic hypoxia-induced pulmonary vascular remodeling. Relative to room air controls, chronically hypoxic animals (inspired O2 fraction = 0.1; 21 days) exhibited higher pulmonary arterial pressures (measured in room air), thicker medial layers in pulmonary arteries of 50–100 microns diam, increased hematocrits, and right ventricular hypertrophy. In addition, lung contents of the polyamines, putrescine, spermidine, and spermine were greater in hypoxic animals than in controls. alpha-Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, attenuated the hypoxia-induced elevations in lung putrescine and spermidine content and blunted the increases in pulmonary arterial pressure and medial thickness. Neither the increased hematocrit nor right ventricular hypertrophy associated with chronic hypoxia were abrogated by DFMO. In addition, DFMO failed to influence vasoconstrictor responses provoked by acute hypoxic ventilation in isolated, buffer-perfused rat lungs. These observations suggest that depression of polyamine biosynthesis with DFMO blunts the sustained increase in pulmonary arterial pressure by attenuating hypoxia-induced medial thickening.
Relationship between ozone exposure and pulmonary function changes
Authors: Hazucha M. J.
Published: December 2017

A detailed comparison of literature-reported averaged decrements in pulmonary function of normal subjects exposed to O3 has been undertaken. The data base was formed by including data published during the past 20 yr from studies that reported at least one of the pulmonary function variables (forced vital capacity, forced expiratory volume at 1 s, mean forced expiratory flow between 25 and 75% of forced vital capacity, and airway resistance) acquired at 2 h of exposures utilizing either original or modified Bates-Hazucha (intermittent exercise) protocol and that satisfied selection criteria. The final set of data (24 studies involving 299 subjects) was divided by ventilation rate (exercise loads) into four categories: light, moderate, high, and very high ventilation level. For each pulmonary function variable and ventilation level a quadratic function has been fitted to the data using regression procedures. The curve parameter estimates have been computed, tabulated, and statistically evaluated. The slope (quadratic coefficient) for each variable within a group and almost all variables between groups were significantly different from zero and from each other at P less than or equal to 0.0001.
Effect of regional alveolar hypoxia on permeability pulmonary edema formation in dogs
Authors: Cheney F. W. , Bishop M. J. , Chi E. Y. , Eisenstein B. L.
Published: December 2017

We studied the effects of regional alveolar hypoxia on permeability pulmonary edema formation. Anesthetized dogs had a bronchial divider placed so that the left lower lobe (LLL) could be ventilated with a hypoxic gas mixture (HGM) while the right lung was continuously ventilated with 100% O2. Bilateral permeability edema was induced with 0.05 ml/kg oleic acid and after 4 h of LLL ventilation with an HGM (n = 9) LLL gross weight was 161 +/- 13 (SE) g compared with 204 +/- 13 (SE) g (P less than 0.05) in the right lower lobe (RLL). Bloodless lobar water and dry weight were also significantly lower in the LLL as compared with the RLL of the study animals. In seven control animals in which the LLL fractional inspired concentration of O2 (FIO2) was 1.0 during permeability edema, there were no differences in gravimetric variables between LLL and RLL. In eight additional animals, pulmonary capillary pressure (Pc), measured by simultaneous occlusion of left pulmonary artery and vein, was not significantly different between LLL FIO2 of 1.0 and 0.05 either before or after pulmonary edema. We conclude that, in the presence of permeability pulmonary edema, regional alveolar hypoxia causes reduction in edema formation. The decreased edema formation during alveolar hypoxia is not due to a reduction in Pc.
Analysis of receptor reserves in canine tracheal smooth muscle
Authors: Gunst S. J. , Stropp J. Q. , Flavahan N. A.
Published: December 2017

The receptor reserves for acetylcholine, 5-hydroxytryptamine, and histamine in canine tracheal muscle were evaluated. Muscle strips were dissected free of epithelial and connective tissue and suspended for isometric tension recording in modified Krebs-Ringer solution. Dissociation constants for all three agonists were determined by analysis of their concentration-response curves under control conditions and after partial inactivation of receptors by phenoxybenzamine dihydrochloride. The values of KA for acetylcholine, 5-hydroxytryptamine, and histamine were 1.8 X 10(-5) M, 1.35 X 10(-6) M, and 5.0 X 10(-5) M, respectively. Dissociation constants were used to determine receptor occupancy-response relationships. Maximal responses to acetylcholine were obtained by activation of only 4.0 +/- 1.0% of receptors, indicating the presence of a very large receptor-reserve. In contrast, a maximal response to 5-hydroxytryptamine and histamine required activation of 78.0 +/- 11.0 and 87.7 +/- 1.6% of the receptors, respectively, indicating very modest receptor reserves. The differences in receptor-reserve characteristics for these agonists in airway muscle might contribute to the differential effects of inhibitory and facilitory influences on contractions elicited by them.
Wither or whither?
Authors: Fishman A. P.
Published: December 2017

On previous pages of the Centennial Update, attention was called to the celebration in Washington, DC, of the 100th birthday of the American Physiological Society.
Voluntary strength and muscle characteristics in untrained men and women and male bodybuilders
Authors: Sale D. G. , MacDougall J. D. , Alway S. E. , Sutton J. R.
Published: December 2017

Eight untrained women (F), 13 untrained men (M), and 11 male bodybuilders (BB) did maximal elbow flexions on an isokinetic dynamometer at velocities of 30, 120, 180, 240, and 300 degrees/s, from which impact torque (IT), peak torque (PT), and work (W) were measured. Biceps and total flexor cross-sectional area (CSA) were measured by computerized tomographic scanning. Muscle fiber area, fiber composition, and collagen volume density were determined from single needle biopsies of biceps brachii. Biceps fiber number was estimated as the ratio of biceps CSA (corrected for connective tissue) to mean fiber area. PT and W decreased at higher velocities in M and BB but not in F; consequently, the correlation between CSA and PT and W was lower at 300 degrees/s (r = 0.58, 0.60) than 30 degrees/s (r = 0.80, 0.79). The ratio of PT to flexor CSA was similar in all groups at 30 degrees/s, whereas F had greater ratios than M and BB at the remaining velocities. F had greater W/CSA ratios than M and BB at all velocities. IT increased at higher velocities in all groups; the increase was greater in F and M than in BB. In contrast to PT and W, the correlation between IT and CSA was greater at 300 degrees/s (r = 0.67) than 30 degrees/s (r = 0.58), and there were no differences among groups in the IT/CSA ratios. Flexor CSA correlated negatively with the ratio of IT, PT, and W to CSA. Muscle fiber composition failed to correlate with any measure of strength. M and BB had greater biceps area, fiber number, and fiber area than F.(ABSTRACT TRUNCATED AT 250 WORDS)
Dry air-induced constriction: effects of pharmacological intervention and temperature
Authors: Freed A. N. , Wang D. , Menkes H. A.
Published: December 2017

We studied airway wall temperature (Taw) during dry air challenge of the canine lung periphery. We measured collateral resistance (Rcs) before and after periods of elevated airflow using a wedged bronchoscope technique. As flow rate increased, Taw dropped and postchallenge Rcs rose. A significant negative correlation was found between Taw recorded during challenge and Rcs observed 5 min after challenge. Repetitive dry air challenge produced similar changes in Rcs and Taw. However, responses to warm moist air were significantly lower than consecutive responses to dry air. Taw was significantly lower during dry air challenge than during moist air challenge. Indomethacin (5 mg/kg) and atropine (1 mg/kg) reduced responses to dry airflow challenge. Indomethacin did not affect Taw during the challenge, whereas atropine reduced the fall in Taw. We conclude that temperature correlates negatively with peripheral lung tone 5 min after dry air challenge. This correlation holds under conditions where airflow is increased, air is humidified, or atropine is administered. The dissociation between Taw and physiological response after indomethacin likely reflects a decrease in mediators released during challenge.
Temperature alters bronchial blood flow response to pulmonary arterial obstruction
Authors: Agostoni P. G. , Deffebach M. E. , Kirk W. , Mendenhall J. M. , Albert R. K. , Butler J.
Published: December 2017

Lobar bronchial blood flow has been reported to increase and decrease acutely after pulmonary arterial obstruction (PAO). Because bronchial blood flow (Qbr) to the trachea and bronchi is influenced by inspired air temperature, we investigated whether temperature differences could explain these disparate results. In 10 open-chested dogs the left lower lobe (LLL) was isolated and perfused in situ with autologous blood at a controlled temperature with an independent vascular circuit. The abdomen and the chest of the dog were enclosed in a Plexiglas box in which air was fully humidified and temperature could be regulated. Qbr, determined by the reference flow technique using 16 micron microspheres, was measured before and 30 min after onset of PAO with the air in the box being either at 27 or 39 degrees C and with warmed LLL blood (37 degrees C) in the latter condition. Anastomotic bronchial blood flow [Qbr(s-p), determined as overflow from the closed LLL vascular circuit and measured in ml X min-1 X 100 g dry lung wt-1 X 100 Torr mean systemic pressure-1] was measured continuously at both temperatures. Both before and after PAO, Qbr and Qbr(s-p) were closely correlated: Qbr (ml/min) = 1.12 + 0.978Qbr(s-p); R = 0.912. This was true regardless of the presence or the absence of pulmonary flow, showing that the distribution of bronchial blood flow between the anastomotic and the nonanastomotic portion does not change acutely during PAO. When the air in the box was 27 degrees C, Qbr(s-p) was 19.5 +/- 5.2 (SE) and increased to 38.6 +/- 8.1 with PAO (P less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)
Supramaximal exercise after training-induced hypervolemia. II. Blood/muscle substrates and metabolites
Authors: Green H. J. , Thomson J. A. , Houston M. E.
Published: December 2017

Blood and muscle substrates and metabolites were investigated in six healthy males (ranging in age from 19 to 23 yr) during three consecutive days of supramaximal exercise training. Muscle biopsies from the vastus lateralis and arterialized blood samples from a hand vein were extracted before the exercise and at selected times during the intermittent (1 min work to 4 min rest) cycling. The results indicated that blood glucose concentration was significantly depressed (P less than 0.05) on both days 2 and 3 of the training, whereas plasma free fatty acids and blood glycerol, pyruvate, alanine, and lactate were unaffected. At the muscle level, glucose and lactate concentrations were depressed on days 2 and 3, whereas ATP and glycogen were reduced only on the final day of training. No training-induced alterations were noted for muscle glucose 6-phosphate or muscle ADP. These results indicate that the approximate 10–11% reduction in O2-carrying capacity accompanying the short-term training does not directly and negatively influence muscle energy metabolism during the exercise. Rather, the explanation for the altered muscle and blood constituents must be sought from other effects of the training such as impaired carbohydrate repletion.
Effects of continuous positive airway pressure on upper airway and respiratory muscle activity
Authors: Alex C. G. , Aronson R. M. , Onal E. , Lopata M.
Published: December 2017

To study the effects of continuous positive airway pressure (CPAP) on lung volume, and upper airway and respiratory muscle activity, we quantitated the CPAP-induced changes in diaphragmatic and genioglossal electromyograms, esophageal and transdiaphragmatic pressures (Pes and Pdi), and functional residual capacity (FRC) in six normal awake subjects in the supine position. CPAP resulted in increased FRC, increased peak and rate of rise of diaphragmatic activity (EMGdi and EMGdi/TI), decreased peak genioglossal activity (EMGge), decreased inspiratory time and inspiratory duty cycle (P less than 0.001 for all comparisons). Inspiratory changes in Pes and Pdi, as well as Pes/EMGdi and Pdi/EMGdi also decreased (P less than 0.001 for all comparisons), but mean inspiratory airflow for a given Pes increased (P less than 0.001) on CPAP. The increase in mean inspiratory airflow for a given Pes despite the decrease in upper airway muscle activity suggests that CPAP mechanically splints the upper airway. The changes in EMGge and EMGdi after CPAP application most likely reflect the effects of CPAP and the associated changes in respiratory system mechanics on the afferent input from receptors distributed throughout the intact respiratory system.
Fatigue from high- and low-frequency muscle stimulation: contractile and biochemical alterations
Authors: Metzger J. M. , Fitts R. H.
Published: December 2017

This study examined the effect of high- (75 Hz, 1 min) and low- (5 Hz, 1.5 min) frequency stimulation on contractile and biochemical properties of the diaphragm. Tension was reduced to 21 +/- 1 and 54 +/- 2% (SE) of the initial value after high- and low-frequency stimulation, respectively. After 0, 0.25, 1, and 2 min of recovery from high-frequency stimulation, 5 Hz elicited more force (expressed as % of initial tension) than 75-Hz stimulation. Time 0 recovery values were 21 +/- 1 and 78 +/- 6% of the initial force for 75- and 5-Hz stimulation, respectively. By 1 min of recovery, force elicited by 5-Hz stimulation had returned to the prefatigue value. In contrast, force production with 75-Hz stimulation did not full recover until 10–15 min. After fatigue produced by low-frequency stimulation, force production with 5-Hz stimulation was reduced to 54 +/- 2% of the initial tension, a value significantly lower than the 71 +/- 2% of initial force elicited by 75-Hz stimulation. Force production with 5-Hz stimulation increased rapidly in the first 15 s of recovery (54 +/- 2% at 0 and 70 +/- 2% at 15 s) and by 5 min was significantly greater than the force elicited by 75-Hz stimulation (100 +/- 3 vs. 93 +/- 1%). As before, force production at 75-Hz stimulation did not fully recover until 10–15 min. Both fatigue protocols produced a significant prolongation in isometric twitch contraction and one-half relaxation times. Creatine phosphate (CP) concentration was reduced and muscle lactate increased by both fatigue protocols.(ABSTRACT TRUNCATED AT 250 WORDS)
Regression of calculated variables in the presence of shared measurement error
Authors: Stratton H. H. , Feustel P. J. , Newell J. C.
Published: December 2017

To test hypotheses regarding relations between meaningful parameters, it is often necessary to calculate these parameters from other directly measured variables. For example, the relationship between O2 consumption and O2 delivery may be of interest, although these may be computed from measurements of cardiac output and blood O2 contents. If a measured variable is used in the calculation of two derived parameters, error in the measurement will couple the calculated parameters and introduce a bias, which can lead to incorrect conclusions. This paper presents a method of correcting for this bias in the linear regression coefficient and the Pearson correlation coefficient when calculations involve the nonlinear and linear combination of the measured variables. The general solution is obtained when the first two terms of a Taylor series expansion of the function can be used to represent the function, as in the case of multiplication. A significance test for the hypothesis that the regression coefficient is equal to zero is also presented. Physiological examples are provided demonstrating this technique, and the correction methods are also applied in simulations to verify the adequacy of the technique and to test for the magnitude of the coupling effect. In two previous studies of O2 consumption and delivery, the effect of coupled error is shown to be small when the range of O2 deliveries studied is large, and measurement errors are of reasonable size.
An isovolume method for analysis of density dependence of maximal expiratory flows
Authors: Rubinstein I. , Vanek A. W. , McClean P. A. , Boucher R. , Zamel N. , Slutsky A. S.
Published: December 2017

The usual method of measuring density dependence of maximum expiratory flows is superimposition at total lung capacity or residual volume of maximum expiratory flow volume (MEFV) curves obtained breathing air and a mixture of 80% He plus 20% O2 (HeO2). A major problem with this technique is the large variability in results, which has been thought to be due to errors in matching lung volumes on both gases. Accordingly, we obtained MEFV curves breathing air and HeO2 using a bag-in-the-box system so that the curves breathing the two gas mixtures could be directly superimposed without removing the mouthpiece (isovolume). Ten healthy, nonsmoking subjects performed MEFV curves on each gas mixture for six consecutive experiments. We compared the increase in flow at 50% of vital capacity (delta Vmax50) and volume of isoflow (Viso) by superimposing and matching the MEFV curves at total lung capacity, at residual volume, and using the isovolume method. The variability of each method was assessed by the mean intersubject and intrasubject coefficients of variation. In all subjects, the mean delta Vmax50 and Viso as well as their corresponding coefficients of variation were not significantly different among the three methods. We conclude that, in healthy nonsmoking young adults, the method chosen for superimposing and matching MEFV curves has no effect on the variability of delta Vmax50 and Viso.