bluuebunny/crossref_metadata_2025 huggingface dataset:
On-line measurement of nitric oxide generation in buffer-perfused rabbit lungs
Authors: Spriestersbach R. , Grimminger F. , Weissmann N. , Walmrath D. , Seeger W.
Published: December 2017

In buffer-perfused rabbit lungs, the mixed expired gas was continuously analyzed for nitric oxide (NO) by chemiluminescence detection, and recovery data in dependency of the alveolar O2 tension were established. A small aliquot of the lung effluent was continuously forwarded to a reaction vessel in which the NO decomposition products nitrite, peroxynitrite, and nitrate [summarized as NOx; acidic vanadium (III) chloride reagent] or nitrite (acidic sodium iodide reagent) were quantitatively reduced back to NO, which was then transferred to a second chemiluminescence detector. Under baseline conditions, the perfused lungs continuously released 2.2 +/- 0.21 nmol/min of NO (n = 10) into the gas space. NO was permanently liberated into the intravascular compartment at 7.0 +/- 0.3 nmol/min (n = 4). According to a very low buffer-gas partition coefficient of NO (estimated to be 0.0292 +/- 0.005 in separate equilibration experiments), NO aerated into the prelung perfusate largely escaped into the alveolar space within one lung passage, whereas only low percentages of inhaled NO were detected as NOx in the buffer medium. Immediate increase of lung NO generation in response to A-23187 challenge and inhibition by NG-monomethyl-L-arginine were demonstrated. In conclusion, in buffer-perfused lungs, total NO generation may be monitored by continuous analysis of NO exhalation and perfusate NOx accumulation.
Role of EDRF in the cardiopulmonary dysfunction produced by massive sympathetic activation
Authors: Pilati C. F. , Maron M. B. , Bosso F. J.
Published: December 2017

This study was undertaken to determine whether endothelium-derived relaxing factor (EDRF) modulates the pulmonary and systemic hemodynamic responses to massive sympathetic nervous system (SNS) activation and, in so doing, also modulates the degree of SNS-induced left ventricular (LV) dysfunction and the likelihood for pulmonary edema formation. The SNS of 13 anesthetized untreated rabbits and 14 anesthetized rabbits pretreated with the EDRF inhibitor, N omega-nitro-L-arginine (L-NNA, 20 mg/kg), was massively activated with an intracisternal injection of veratrine. Pulmonary and systemic arterial pressures increased to the same extent in both groups, but LV end-diastolic pressure was significantly lower in untreated rabbits. During this time, cardiac output decreased by 37% in L-NNA pretreated rabbits compared with 8% in untreated animals. Peak systemic and pulmonary vascular resistances increased significantly in L-NNA rabbits, whereas only systemic vascular resistance increased significantly in untreated rabbits. However, this increase in systemic vascular resistance was threefold less than that observed for L-NNA-treated animals. Although the degree of LV dysfunction was greater in the L-NNA rabbits, pulmonary edema developed less frequently in this group. We suggest that when EDRF release is inhibited during massive SNS activity, pulmonary vascular resistance increases markedly, which causes the right ventricle to fail. We further suggest that the reduced right ventricular output maintains pulmonary microvascular pressure below levels required for edema development.
Effects of oxygenation and hypercapnia on diaphragmatic function and central drive during respiratory failure
Authors: Ferguson G. T.
Published: December 2017

The effects of oxygenation and hypercapnia on diaphragmatic function and central drives were assessed during the development of respiratory failure in anesthetized unbound spontaneously breathing rabbits. Oxygenation significantly altered endurance times, whereas hypercapnia had no effect. Isolated high-frequency contractile fatigue of the diaphragm was found in hyperoxic animals; all other animals had no evidence of contractile fatigue. Oxygenation and hypercapnia did not significantly alter the response of breathing frequency or duty cycle to loading. In all animals, there was a falloff in the intensity of central drive before apnea, with intensity of central drive remaining submaximal throughout loading. Oxygenation significantly altered the time and/or load at which drive intensity fell off, although critical blood gas levels were not associated with the falloff in intensity. We conclude that oxygenation influences the development of respiratory failure during inspiratory loading but does not directly explain the alterations is central drive. On the other hand, hypercapnia has no direct effect on respiratory muscle function or central drives during loading to respiratory failure. When the effects of hypoxemia are obviated by hyperoxia, high-frequency contractile fatigue may occur.
Continuous measurement of ATP by 31P-NMR in term human dually perfused placenta in vitro: response to ischemia
Authors: Malek A. , Miller R. K. , Mattison D. R. , Ceckler T. , Panigel M. , di Sant'Agnese P. A. , Jessee L. N.
Published: December 2017

ATP was examined in dually perfused term human placentas by using 31P-nuclear magnetic resonance (NMR) spectroscopy. 31P-NMR spectra were acquired every 30 min starting approximately 30 min after establishing fetal and maternal perfusions, and maternal perfusate samples were obtained to monitor glucose utilization, lactate production, and human chorionic gonadotropin (hCG) and human placental lactogen (hPL) release. In continuous-perfusion experiments, placentas were perfused as long as 10 h. ATP increased and Pi fell after initiation of perfusion. Fetal volume loss was < 2 ml/h, and constant production of hCG, hPL, and lactate as well as constant utilization of glucose were observed. In additional experiments, ischemia was produced by halting maternal and fetal perfusion pumps after a 2-h control period. After 2, 3, or 4 h of ischemia, ATP decreased 46 +/- 17, 51 +/- 5, and 85% of control, respectively. When perfusion was reinitiated, ATP increased and was maintained for the duration of the experiment (an additional 2 h). Recovery of ATP after reperfusion was not paralleled by recovery in glucose utilization, lactate production, or hPL and hCG release. However, during the reperfusion period, fetal pressure was < 70 mmHg and fetal volume loss was < 2 ml/h. These investigations suggest that the dually perfused human placental lobule can maintain ATP for > or = 10 h. Although the perfused human placenta recovers ATP and maintains fetal perfusion volume after ischemia lasting up to 4 h, utilization of glucose, production of lactate, and production and release of hCG and hPL are impaired.
Maximal exercise performance in chronic hypoxia and acute normoxia in high-altitude natives
Authors: Favier R. , Spielvogel H. , Desplanches D. , Ferretti G. , Kayser B. , Hoppeler H.
Published: December 2017

Maximal O2 uptake (VO2max) was determined on a bicycle ergometer in chronic hypoxia (CH) and during acute exposure to normoxia (AN) in 50 healthy young men who were born and had lived at 3,600 m altitude (La Paz, Bolivia). VO2max was significantly improved (approximately 8%) by AN. However, the difference in VO2max measured in CH and AN (delta VO2max) was lower than that reported in sea-level natives (SN) who exercised in chronic normoxia and acute hypoxia. It is shown that high-altitude natives (HN) and SN have a similar VO2max in normoxia, but highlanders can attain a greater VO2max when O2 availability is reduced by altitude exposure. In addition, in HN, the higher the subject's VO2max in hypoxia, the smaller his delta VO2max. These results contrast with the data obtained in 14 lowlanders acclimatized to high altitude who showed that their delta VO2max was positively related to their VO2max in hypoxia, as previously reported in SN who exercised in acute hypoxia (A. J. Young, A. Cymerman, and R. L. Burse. Eur. J. Appl. Physiol. Occup. Physiol. 54: 12–15, 1985). Furthermore, arterial O2 saturation of HN behaved differently from acclimatized lowland natives, inasmuch as it fell less during exercise both in CH and AN. HN with high aerobic capacity display a lower exercise ventilation and a reduced arterial saturation, which could explain their inability to improve VO2max with normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Rat aortic vasoreactivity is altered by old age and hindlimb unloading
Authors: Delp M. D. , Brown M. , Laughlin M. H. , Hasser E. M.
Published: December 2017

Prolonged bed rest in young adults leads to a number of cardiovascular alterations, including orthostatic intolerance and decreased exercise capacity. Similar changes occur with advanced age. These modifications of cardiovascular function have been suggested to be causally related to changes in peripheral vascular reactivity. Using rat hindlimb unloading as an animal model of physical inactivity, this study was designed to determine whether prolonged decreases in weight-bearing activity induce changes in vascular reactivity that are similar to those occurring in senescent rats and whether the imposition of inactivity on old rats further modifies any age-related alterations in vasomotor responsiveness. Responses to vasoactive compounds were examined in vitro by using isolated abdominal aortic rings. Maximal isometric contractile force evoked by the vasoconstrictors KCl, norepinephrine (NE), and arginine vasopressin was lower in aortic segments from young hindlimb-unloaded (YHU), old control (OC), and old hindlimb-unloaded (OHU) rats compared with that from young control (YC) rats. Sensitivity [mean effective concentration (EC50)] to KCl was enhanced in segments from both old and unloaded animals compared with YC rats, but EC50 values for the other constrictors were not different among groups. Vasorelaxation responses induced by acetylcholine (10(-7) M NE preconstriction) were lower in vessel rings from OC (1 x 10(-7) to 3 x 10(-6) M), YHU (10(-7) to 10(-5) M), and OHU (10(-7) to 10(-5) M) rats than those from YC animals. In addition, vessel rings from OC, YHU, and OHU rats were less sensitive to sodium nitroprusside-induced relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of exercise on lipolytic sensitivity in endurance-trained athletes
Authors: Klein S. , Coyle E. F. , Wolfe R. R.
Published: December 2017

Studies performed in vitro suggest that an acute bout of exercise increases the lipolytic response to beta-adrenergic stimulation. We evaluated the effect of exercise on lipolytic sensitivity in vivo in five endurance-trained athletes. The rate of appearance (Ra) of glycerol in plasma, an index of whole body lipolysis, was determined during 60 min of epinephrine infusion (0.015 microgram.kg-1.min-1) on two occasions: 1) at basal resting conditions and 2) 90 min after completing 1 h of high-intensity (70% O2 uptake) cycle ergometer exercise. Total glycerol Ra during epinephrine infusion in the basal state (352 +/- 35 mumol.kg-1. 60 min-1) was not significantly different from the value obtained after high-intensity exercise (439 +/- 58 mumol.kg-1. 60 min-1). However, the increase in glycerol Ra above baseline during epinephrine infusion was lower after (30 +/- 16 mumol.kg-1. 60 min-1) than before (148 +/- 28 mumol.kg-1. 60 min-1) exercise because of the high postexercise baseline value (P < 0.05). Mean plasma free fatty acid (FFA) concentration was lower during exercise than during epinephrine infusion despite a greater rate of lipolysis during exercise. The slope of change in plasma FFA with respect to glycerol RA was lower during exercise (0.0171 +/- 0.006) than during epinephrine infusion (0.0835 +/- 0.018) (P < 0.05). We conclude that a single bout of intense exercise does not increase in vivo lipolytic sensitivity to beta-adrenergic stimulation in endurance-trained athletes. In addition, plasma FFA concentration represents the balance between plasma FFA inflow and tissue uptake and cannot be used as an index of lipolytic activity during certain physiological conditions, such as exercise.
Phorbol ester potentiation of canine pulmonary vasoreactivity to histamine
Authors: Barman S. A. , Ikeda S. R.
Published: December 2017

The effect of phorbol myristate acetate (PMA) on canine pulmonary vasoreactivity to histamine was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured by using vascular occlusion techniques. Histamine (10(-5) M) significantly increased postcapillary resistance by venoconstriction and significantly attenuated total vascular compliance by decreasing large-vessel compliance and middle-compartment compliance. Pretreatment with the phorbol ester PMA (10(-7) M) significantly potentiated the vasoactive response to histamine and elicited an edemagenic effect in the isolated dog lung through modulation of the histaminergic vasoconstrictor effect on precapillary resistance, postcapillary resistance, and pulmonary vascular compliance. Pretreatment with the protein kinase C inhibitors staurosporine (10(-7) M) and calphostin C (10(-6) M) and the dihydropyridine Ca2+ channel blocker nifedipine (10(-5) M) significantly attenuated the effect of PMA on histaminergic-mediated vasoconstriction. The results of this study indicate that phorbol esters may exert their effect on canine pulmonary vasoreactivity predominantly through activation of protein kinase C and influx of Ca2+ through voltage-dependent Ca2+ channels.
Monitoring urine oxygen tension during acute change in cardiac output in dogs
Authors: Kitashiro S. , Iwasaka T. , Sugiura T. , Takayama Y. , Tamura T. , Tamura K. , Inada M.
Published: December 2017

To evaluate whether renal blood flow (RBF) can be monitored during acute change in cardiac index, ureter urine oxygen tension (PuO2) and bladder urine oxygen tension (PbO2) were measured in six mongrel dogs. PuO2, cardiac index, and RBF increased after dobutamine infusion and decreased after propranolol infusion. PuO2 had an excellent correlation with RBF (r = 0.94) and a fair correlation with cardiac index (r = 0.50) and mean blood pressure (r = 0.56); RBF had a fair correlation with mean blood pressure (r = 0.52, P < 0.05) but was not related to cardiac index. With multiple-regression analysis, PuO2 was found to be the significant factor related to RBF. PbO2 had a good correlation with PuO2 (r = 0.94) at control levels. Furthermore, when two dogs were added to evaluate relationships among PbO2, PuO2, and RBF, PbO2 had an excellent correlation with PuO2 (r = 0.92) and RBF (r = 0.91). These data indicate that PuO2 is a more sensitive predictor of RBF than cardiac index and mean blood pressure and that PbO2 can be a noninvasive indicator reflecting RBF during acute circulatory change in dogs.
Pressure-flow relationships in in vitro model of compartment syndrome
Authors: Shrier I. , Magder S.
Published: December 2017

Compartment syndrome is a condition in which an increase in intramuscular pressure decreases blood flow to skeletal muscle. According to the Starling resistor (i.e., vascular waterfall) model of blood flow, the decrease in flow could occur through an increase in arterial resistance (Rart) or an increase in the critical closing pressure (Pcrit). To determine which explains the decrease in flow, we pump perfused a canine gastrocnemius muscle placed within an airtight box, controlled box pressures (Pbox) so that flow ranged from 100 to 50%, and measured Pcrit, Rart, arterial compliance, small venular pressure (measured by the double-occlusion technique), and venous pressure. An increase in Pbox limited flow mainly through an increase in Pcrit (75–85%), with only small changes in Rart (15–25%) and no change in arterial compliance. Increases in Pbox also produced a vascular waterfall in the venous circulation, but small venular transmural pressure always remained less than control levels. We conclude that increases in Pbox mostly limit blood flow through increases in Pcrit and that Rart plays a minor role. Transmural pressure across the small venules decreases with increases in intramuscular pressure, which contradicts the currently held belief that compartment syndrome is due to a cycle of swelling-ischemia-swelling.
Arterial, capillary, and venous transit times and dispersion measured in isolated rabbit lungs
Authors: Ayappa I. , Brown L. V. , Wang P. M. , Lai-Fook S. J.
Published: December 2017

Transit time and relative dispersion of the arterial, capillary, and venous segments of the pulmonary circulation were measured in isolated perfused rabbit lungs. Fluorescence videomicroscopy was used to record the passage of dye through the main pulmonary artery, subpleural microcirculation, and venous outflow. Dye dilution curves were obtained at the main pulmonary artery, subpleural arterioles and venules, and pulmonary vein. Measurements were made at 5-cmH2O airway pressure, at blood flows of approximately 80, 50, and 25 ml.min-1.kg-1, and at left atrial pressures of approximately 0 cmH2O (zone 2) and approximately 12 cmH2O (zone 3). The dye dilution curves were modeled as lagged normal density curves that were used to calculate transit time and relative dispersion between the pulmonary artery and arteriole (artery), arteriole and venule (capillary), venule and pulmonary vein (vein), and pulmonary artery and pulmonary vein (whole lung). In open-chest anesthetized dogs, the passage of dye was recorded from the subpleural arterioles and venules between the seventh and eighth ribs in the left lateral position. At comparable blood flows, capillary transit time was larger in the dog than in the rabbit lung [3.4 +/- 2.4 (SD) vs. 0.87 +/- 0.47 s]. In the rabbit lung, relative dispersion was greater in pulmonary capillaries (average values 0.83–1.6) and veins (0.91–1.6) than in arteries (0.39–0.50), which was similar to the whole lung dispersion (0.47–0.52). A similarly high dispersion (0.93) was measured in the dog's pulmonary capillaries. Thus high dispersion in pulmonary capillaries and veins cannot be detected by whole lung dispersion measurements.
Maximal rate of blood lactate accumulation during exercise at altitude in humans
Authors: Grassi B. , Ferretti G. , Kayser B. , Marzorati M. , Colombini A. , Marconi C. , Cerretelli P.
Published: December 2017

The lower peak lactate accumulation in blood ([La(b)]p) at altitude may be associated with a reduced maximal glycolytic flux. Based on certain assumptions, the latter can be indirectly evaluated in vivo, during short supramaximal exercises, by measuring the maximal rate of lactate accumulation in blood (delta [La(b)]max). delta [La(b)]max was determined on six white subjects at sea level (SL1), after approximately 1 wk (Alt1) and 4 wk (Alt2) of a 35-day sojourn at 5,050 m, and 1 wk after return to sea level (SL2). The subjects performed exercises of increasing duration (5, 15, 25, 35, 45 s or until exhaustion) on a bicycle ergometer at loads = 200% of the individual Wmax. The latter was previously determined in each condition as the greatest work rate that could be sustained for 2–4 min during an incremental exercise. Net [La(b)] accumulation (delta [La(b)]) was measured after each exercise bout. delta [La(b)] resulted to be linearly related to exercise duration. The slopes of the individual delta [La(b)] vs. exercise duration lines were taken as delta [La(b)]max. Exhaustion times were approximately 30–45 s in all conditions. [La(b)]p (in mM) during recovery after the exhaustive load was higher at SL1 (10.22 +/- 1.09; means +/- SD) than at Alt1 (5.08 +/- 0.82), Alt2 (8.13 +/- 2.67), and SL2 (8.18 +/- 1.43). delta [La(b)]max was lower at Alt1 (0.09 +/- 0.02) and at Alt2 (0.17 +/- 0.05) than at SL1 (0.25 +/- 0.05) and SL2 (0.23 +/- 0.06). Both [La(b)]p and delta [La(b)]max increased during acclimatization.
Climate-related corrections for improved estimation of energy expenditure from heart rate in children
Authors: Hebestreit H. , Bar-Or O. , McKinty C. , Riddell M. , Zehr P.
Published: December 2017

The purpose of this study was to determine the relationship between children's heart rate (HR) and climatic heat stress at several O2 uptake (Vo2) levels and to construct equations and nomograms for an improved estimation of energy expenditure (EE) from HR monitoring. On four occasions 12 boys and 8 girls (8–11 yr) cycled for 5 min each at 35, 55, and 75% of peak Vo2 (random order), with rest periods in between, in a climatic chamber. The randomly assigned conditions were 22 degrees C dry bulb temperature, 50% relative humidity (RH); 28 degrees C, 55% RH; 32 degrees C, 52% RH; or 35 degrees C, 58% RH. HR and Vo2 were determined during the final 2 min of rest and exercise bouts. HR measured at a dry bulb temperature (T) (HRmeas) was then related to a HR at 22 degrees C that would have been expected to occur at an identical Vo2 (HRcalc22) by using individual 22 degrees C HR-Vo2 regression lines. HRcalc22 could be estimated from HRmeas.[1.175032-(0.007956.T)], with a mean error of prediction for the entire group < 1.5 beats/min for each temperature. The following conclusions were drawn: 1) children's HR at a given Vo2 increases linearly with ambient temperature at 22–35 degrees C, 50–60% RH; and 2) HR can be corrected for the influence of climate in groups of children resting and exercising at the above conditions, thereby reducing the error of estimating EE from HR.
Lung tissue resistance and hysteretic moduli of lung parenchyma
Authors: Kimmel E. , Seri M. , Fredberg J. J.
Published: December 2017

Lung tissue resistance (Rti) represents a large and labile component of total pulmonary resistance, but the mechanism is unknown. One hypothesis that has received some support in the literature is that on exposure to contractile agonists airway smooth muscle shortens and then, by the agency of elastic interdependence, induces distortion in surrounding parenchyma. Parenchymal distortion induced in the vicinity of a constricted airway is a pure shear deformation, but currently there are no data available for shear hysteresivity. Guided by a microstructural model, we have assigned stiffness and hysteresivity to microstructural elements and then computed how those properties are expressed at the macroscale in bulk hysteresivities for both shear and volumetric expansion. Hysteresivity for volumetric expansion is shown to be a stiffness-weighted average of hysteresivities of all microstructural components. But as the hysteresivity of microstructural elements increases, that for shear deformation increases to some degree but eventually attains a plateau. Blunted hysteretic response in shear seems to be an intrinsic property of pressure-supported structures, like the lung, that require an inflating pressure to ensure mechanical stability. The analysis indicates that that part of Rti attributable to parenchymal distortion can be at most a small fraction of that attributable to volumetric expansion. These results are purely theoretical in nature, and this suggests that caution is necessary in their interpretation. However, the mechanical basis of the results is sufficiently general to conclude that the hypothesis that parenchymal distortion secondary to bronchoconstriction can account for Rti and its changes seems to be implausible.
Sites of leukocyte sequestration in the pulmonary microcirculation
Authors: Gebb S. A. , Graham J. A. , Hanger C. C. , Godbey P. S. , Capen R. L. , Doerschuk C. M. , Wagner W. W.
Published: December 2017

The location and mechanisms of leukocyte sequestration in the pulmonary circulation have been investigated by using high-magnification in vivo videomicroscopy to record the passage of unlabeled native leukocytes through canine pulmonary capillaries. Of 650 leukocytes traversing capillary networks, 46 +/- 6% (SE) of the leukocytes passed through without stopping, 42 +/- 9% stopped in segments between junctions, and 12 +/- 4% stopped in junctions. Leukocytes rolling along arteriolar walls were nearly spherical, as 94% had aspect ratios (major axis divided by minor axis) < or = 1.25. To pass through the capillary bed, the leukocytes deformed into elongated shapes. Many leukocytes remained elongated after entering the venules (53% had aspect ratios > or = 1.25). Venular rolling was blocked by fucoidin (blocking both L- and P-selectin) but not by anti-P-selectin antibodies alone, indicating that rolling leukocytes adhered to the venular endothelium by L-selectin. These observations demonstrate that leukocytes deform to transit the capillary bed, that they stop more frequently in segments than in junctions, and that rolling leukocytes in the venular marginated pool adhere via L-selectin.
Reactive hyperemia unmasks reduced compliance of cutaneous arteries in essential hypertension
Authors: Heron E. , Chemla D. , Megnien J. L. , Pourny J. C. , Levenson J. , Lecarpentier Y. , Simon A.
Published: December 2017

To evaluate changes in distal cutaneous arteries during hypertension, we used a noninvasive method to assess the compliance and vascular resistance of the hand radial arteries, mainly distributed to the skin, in 10 normotensive and 10 hypertensive (HT) men. Radial artery diameter and blood velocity were measured by means of pulsed Doppler concomitantly with measurements of finger arterial pressure by photoplethysmography. Hand radial vascular resistance was calculated as the ratio of mean arterial pressure to mean radial blood flow. A simple resistive-capacitive model of large and small arteries of the hand allowed us to evaluate arterial compliance from the exponential slope of finger diastolic pressure decay and vascular resistance. Measurements were made at baseline and during reactive hyperemia after 5 min of complete occlusion of the brachial artery with a pneumatic cuff. Except for pressure, there were no baseline differences between the groups. In normotensive and HT subjects, hyperemia increased radial artery diameter and blood velocity (P < 0.001) and compliance (P < 0.01 and P < 0.05, respectively) and decreased mean pressure (P < 0.01 and P < 0.001, respectively) and resistance (P < 0.001). During hyperemia, the only difference between the groups, except for pressure, was lower compliance in HT subjects (P < 0.01). Moreover, compliance during hyperemia negatively correlated with baseline mean pressure (P = 0.001). Thus hyperemia unmasked reduced compliance in the HT patients but did not show abnormal resistance, suggesting that the elastic properties of the hand skin radial arteries might be more sensitive than their resistive properties to high blood pressure.
Comparison of four methods of assessing airflow resistance before and after induced airway narrowing in normal subjects
Authors: Phagoo S. B. , Watson R. A. , Silverman M. , Pride N. B.
Published: December 2017

Four methods for assessing airflow resistance were compared in seven normal adults at baseline and after inducing airway narrowing with inhaled methacholine. Airway resistance (Raw) was measured during panting at 1–2 Hz within a body plethysmograph; total lung resistance was measured by using an esophageal balloon during quiet breathing (RLq) and with doubling of frequency while maintaining the original tidal volume; total respiratory resistance (Rrs) was measured at 6 Hz during forced oscillation applied at the airway opening, and interruption resistance (Rint) was measured at midtidal expiratory flow. Three methods of obtaining Rint after airflow interruption were compared [smooth curve fit of mouth pressure (Pm) back extrapolated to valve closure; two-point linear fit of Pm back extrapolated to 15 ms after closure; and Pm at 100 ms after valve closure]. We found similar basal median values (cmH2O.l-1.s) of Raw (1.3), RLq (1.4), RL of double resting frequency (1.9), Rrs (1.7), and smooth curve fit of Pm back extrapolated to valve closure (1.5); basal values of two-point linear fit of Pm back extrapolated to 15 ms after closure (2.4) and Pm at 100 ms after valve closure (4.4) were considerably larger. After induced airway narrowing, all methods of measuring resistance showed significant increases; these were largest with RLq (median %change of 265) and smallest with the three Rint methods (median %change of 62–72). Rint and Rrs methods had poorer sensitivity for detecting bronchoconstriction than lung resistance of Raw. Of the Rint methods, end interruption pressure was the most sensitive.
Measuring pulmonary microvessel diameters using video image analysis
Authors: Hanger C. C. , Hillier S. C. , Presson R. G. , Glenny R. W. , Wagner W. W.
Published: December 2017

To directly determine the pressure-diameter relationship of individual pulmonary microvessels, it is necessary to measure the width of the column of blood in the vessel because microvascular walls are invisible when using intravital microscopy. To identify the margins of the blood column accurately, we developed a method for computer enhancement and measurement of vessel images. After recording microvessels on videotape, consecutive frames from the videotape were digitized by a computer. Pixels that changed from frame to frame (moving erythrocytes) were turned white, and unchanging pixels were turned black. In this way an image of the erythrocyte column with distinct edges was produced. The width of this column was measured with a heuristic technique involving interactions between the computer and the user. The measurements were reproducible and accurate. This technique has been used to measure microvascular diameters over a range of well-defined microvascular pressures and construct precise pressure-diameter curves.
Chaotic mixing of alveolated duct flow in rhythmically expanding pulmonary acinus
Authors: Tsuda A. , Henry F. S. , Butler J. P.
Published: December 2017

We examined the effects of rhythmic expansion of alveolar walls on fluid mechanics in the pulmonary acinus. We generated a realistic geometric model of an alveolated duct that expanded and contracted in a geometrically similar fashion to simulate tidal breathing. Time-dependent volumetric flow was generated by adjusting the proximal and distal boundary conditions. The low Reynolds number velocity field was solved numerically over the physiological range. We found that for a given geometry, the ratio of the alveolar flow (QA) to the ductal flow (QD) played a major role in determining the flow pattern. For larger QA/QD (as in the distal region in the acinus), the flow in the alveolus was largely radial. For small QA/QD (as in the proximal region in the acinus), the flow in the alveolus was slowly rotating and the velocity field near the alveolar opening was complex with a stagnation saddle point typical of chaotic flow structures. Performing Lagrangian fluid particle tracking, we demonstrated that in such a flow structure the motion of fluid could be highly complex, irreversible, and unpredictable even though it was governed by simple deterministic equations. These are the characteristics of chaotic flow behavior. We conclude that because of the unique geometry of alveolated duct and its time-dependent motion associated with tidal breathing, chaotic flow and chaotic mixing can occur in the lung periphery. Based on these novel observations, we suggest a new approach for studying acinar fluid mechanics and aerosol kinetics.
Effect of T-kinin on microvascular permeability and its modulation by peptidases in rat airways
Authors: Yamawaki I. , Tamaoki J. , Takeda Y. , Chiyotani A. , Sakai N. , Kameyama S. , Konno K.
Published: December 2017

T-kinin (Ile-Ser-bradykinin), the product of T-kininogen, has been found in rat plasma during systemic inflammation, but the effect of this kinin on airway inflammatory response is unknown. We examined the effect of T-kinin on vascular permeability in airways of anesthetized rats in vivo by using photometric measurement of the extravasated Evans blue. Intravenous injection of T-kinin (0.1–10 mumol/kg) increased dye extravasation in a dose-dependent manner, with 134% for trachea and 117% for bronchi by 1 mumol/kg. Pretreatment with bradykinin B2-receptor antagonist Hoe-140 (100 nmol/kg), but not the B1-receptor antagonist des-Arg9-Leu8-bradykinin (5 mg/kg), abolished plasma extravasation evoked by T-kinin (1 mumol/kg). NK1 tachykinin-receptor antagonist CP-99994 (4 mg/kg) did not affect T-kinin-induced vascular leakage. Pretreatment with captopril (2.5 mg/kg), angiotensin-converting enzyme inhibitor, potentiated T-kinin (100 nmol/kg)-induced plasma extravasation, whereas phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, had no effect. We conclude that T-kinin produces airway vascular extravasation via stimulation of B2 receptors. The effect is modulated by endogenous angiotensin-converting enzyme and is not mediated via activation of sensory nerve.
Evidence that PGF2 alpha-induced contraction of isolated guinea pig bronchi is mediated in part by release of tachykinins
Authors: Fujii K. , Kohrogi H. , Iwagoe H. , Hamamoto J. , Hirata N. , Yamaguchi T. , Kawano O. , Ando M.
Published: December 2017

To investigate whether prostaglandin F2 alpha (PGF2 alpha) stimulates the release of tachykinins and whether the tachykinins play a role in the PGF2 alpha-induced bronchial contraction, we examined the contractile response to PGF2 alpha in the presence or absence of a neutral endopeptidase (NEP) inhibitor phosphoramidon in the guinea pig main bronchus in vitro. Because NEP effectively cleaves tachykinins, we hypothesized that the inhibition of NEP would enhance a PGF2 alpha-induced bronchial contraction if PGF2 alpha stimulates the release of tachykinins. Phosphoramidon significantly enhanced the concentration-response curve to PGF2 alpha. And it also significantly enhanced 10(-5) M PGF2 alpha-induced contraction. The enhancement was significantly attenuated in tissues where the tachykinins had been depleted by treatment with capsaicin. Furthermore, the enhancement of contraction was also significantly attenuated in the presence of tachykinin antagonist FK-224 (10(-5) M). Tetrodotoxin, a sodium-channel blocker that blocks nerve conduction, did not affect the enhancement. From these results we conclude that 1) PGF2 alpha causes the release of tachykinin-like substances, 2) these substances play a role in bronchial contraction in tissues where NEP activity is inhibited, and 3) nerve conduction is not necessary for the release of these substances in the guinea pig bronchus.
Comparative study of intra-airway gas transport by alternative modes of ventilation
Authors: Gavriely N. , Gaver D. P. , Solway J. , Grotberg J. B.
Published: December 2017

The effectiveness of three alternative modes of ventilation [high-frequency ventilation (HFV), constant-flow ventilation (CFV), and high-frequency external vibration ventilation (HFVV)] was compared. Local intra-airway gas transport was measured with catheters placed in the distal trachea and in bronchi located 5.5, 9, and 11 cm from the carina. A new bolus dispersion method was devised to measure the local effective diffusivities (Deff) induced by these modes of ventilation and by cardiogenic oscillations relative to molecular diffusivity (Dmol). Mixing induced by cardiogenic oscillations was 7 +/- 2- to 26 +/- 4-fold greater than by molecular diffusion alone. Intra-airway transport by CFV, applied at three flow rates (0.3, 1.0, and 3.0 l.min-1.kg-1), was most effective in the trachea but fell sharply in the more peripheral airways. Local transport by HFVV, at a frequency of 22 Hz and a vertical amplitude of 0.4 cm, was most effective in the periphery (Deff = 793 x Dmol), whereas the effectiveness of transport by HFV, applied with 10 and 20 ml at 22 Hz, was evenly distributed. Doubling the HFV oscillatory volume caused a 4.5 +/- 2.7-fold increase in Deff/Dmol. Combining HFVV with CFV at 0.3 l.min-1.kg-1 induced transport rates that were 187- to 2,034-fold greater than by molecular diffusion alone in the bronchi and a higher relative transport (due to convection) in the trachea. We conclude that the combination of HFVV with low-flow CFV provides a high rate of intra-airway transport with minimal mechanical perturbations to the pulmonary system.
Effect of skeletal muscle fiber type on the pressor response evoked by static contraction in rabbits
Authors: Wilson L. B. , Dyke C. K. , Parsons D. , Wall P. T. , Pawelczyk J. A. , Williams R. S. , Mitchell J. H.
Published: December 2017

The purpose of this study was to determine whether the reflex hemodynamic responses to static contraction of predominately glycolytic muscle are greater than the changes elicited by primarily oxidative muscle. Low-frequency electrical stimulation (continuous 21 days) of the tibial nerve of one hindlimb of adult rabbits converted the metabolic characteristics of the predominately glycolytic gastrocnemius to a muscle that was primarily oxidative. After 21 days of stimulation, the rabbits were decerebrated, and static contraction of the glycolytic muscle (unstimulated gastrocnemius) initially decreased heart rate (HR; -16 +/- 3 beats/min) and mean arterial pressure (MAP; -17 +/- 3 mmHg). Thereafter, MAP increased 13 +/- 3 mmHg above baseline. Static contraction of the oxidative muscle (stimulated gastrocnemius) produced similar decreases in HR and MAP (-12 +/- 4 beats/min and -12 +/- 3 mmHg, respectively). However, the subsequent increase in MAP (8 +/- 3 mmHg; above baseline) was less than that evoked by contraction of the glycolytic muscle. The responses evoked by stretch of each muscle and high-intensity electrical stimulation were the same, indicating that the afferents from the muscle were not destroyed by the chronic-stimulation technique. These results support the hypothesis that metabolic by-products play a role in the pressor response to static contraction of skeletal muscle. In addition, these data confirm that contraction of predominately oxidative muscle can evoke a reflex pressor response, albeit smaller than the change elicited from primarily glycolytic muscle.
Dispersion of aerosol boluses in the human lung: dependence on lung volume, bolus volume, and gender
Authors: Brown J. S. , Gerrity T. R. , Bennett W. D. , Kim C. S. , House D. E.
Published: December 2017

The dispersion of aerosol boluses in the human lungs has been studied in health and disease, usually as a means of investigating convective mixing. However, there are limited data on the roles of critical factors, such as the volume of inhaled boluses, lung inflation, and gender on dispersion. To examine these factors, we measured the difference in volume variance between exhaled and inhaled boluses (sigma 2V) of a 0.5-micron aerosol in 11 healthy male and 12 healthy female subjects as a function of tidal volume (VT = 1,000 and 1,500 ml in females and 1,000 and 2,000 ml in males), bolus penetration volume (Vi at 250-ml increments over each VT), and bolus volume (target VBol = 75, 150, and 300 ml). Analysis of variance showed marginally significant gender effects (P = 0.073) on sigma 2V, with sigma 2V greater in males than in females. There was also a significant effect of VBol on sigma 2V (P < 0.001). A Vi-dependent mean volume shift between inhaled and exhaled boluses (delta V) was observed at all Vi except 500 ml. The observation of gender and VBol effects and the existence of a nonzero delta V suggest that convective mixing mechanisms other than longitudinal dispersion alone occur in the healthy lung. The lack of VT dependence suggests a minimal role of lung inflation above functional residual capacity on dispersion. The dependence of sigma 2V on Vi2 up to 1,750 ml and minimal VBol effects demonstrates that convective mixing processes continue far into the gas exchange regions of the lung and support a significant role for axial streaming.
Automatic assessment of electromyogram quality
Authors: Sinderby C. , Lindstrom L. , Grassino A. E.
Published: December 2017

Power spectrum analysis of the diaphragm electromyogram (EMGdi) is time consuming, and no criteria have been developed to objectively quantify contamination of the signal. The present work describes a set of computer algorithms that automatically select EMGdi free of the electrocardiogram and numerically quantify the common artifacts that affect the EMGdi. The algorithms were tested 1) on human EMGdi (n = 5) obtained with esophageal electrodes positioned at the level of the gastroesophageal junction, 2) on EMGdi obtained in mongrel dogs (n = 5) with intramuscular electrodes in the costal diaphragm, and 3) on computer-simulated power spectra. For authentic and simulated power spectra, indexes were obtained by the algorithms and were able to quantify signal disturbances induced by noise, electrode motion, esophageal peristalsis (in humans), and non-QRS complex-related electrocardiogram activity. With the index inclusion thresholds set to levels that allowed for a high signal acceptance rate with relatively small artifact-induced fluctuations (10–15%) of the EMGdi center frequency, the computer algorithms were found to be as reliable as or more reliable than other methods, including careful visual selection of the time domain signals by experienced analysts. In conclusion, the frequency domain application of computer algorithms offers a reliable and reproducible means to objectively quantify the sources that contaminate the interference pattern EMG.
Assessing total body protein, mineral, and bone mineral content from total body water and body density
Authors: Siconolfi S. F. , Gretebeck R. J. , Wong W. W.
Published: December 2017

We hypothesized that investigators could assess bone mineral content (BMC), total body mineral (M), and protein (P) from body water (W) and density (DB) based on the theory of W. E. Siri (Advances in Biological and Medical Physics, 1956, p. 239–280 and Techniques for Measuring Body Composition, 1961, p. 223–224) for body composition analysis. Siri used one or more of the body components and the densities of the body, fat (F), W, M, and P to estimate one of the remaining fractional masses. We compared M, BMC, P. F, and fat-free mass (FFM) in 31 subjects (15 women and 16 men) computed from measurements of W and DB with [4-compartment (4C) model] and without [3-compartment (3C) model] BMC (from dual X-ray absorptiometry). 4C model P was calculated by difference (P = FFM - W - M). Mean difference (P > 0.05) ranged from 0.1 to 0.8%. Correlations [+/- standard error of estimate (%)] between 4C and 3C model values were significant (r = 0.907 +/- 8.8, 0.907 +/- 8.7, 0.969 +/- 6.6, 0.998 +/- 2.0, and 0.999 +/- 0.7% for M, BMC, P, F, and FFM, respectively). We concluded that investigators can assess M, BMC, and P from W and DB.
Perfusion through vessels open in zone 1 contributes to gas exchange in rabbit lungs in situ
Authors: Lamm W. J. , Obermiller T. , Hlastala M. P. , Albert R. K.
Published: December 2017

We previously found that up to 15% of the normal cardiac output can flow through lungs that are entirely in zone 1 and that the zone 1 pathway utilizes alveolar corner vessels. Because of the proximity of these vessels to alveoli, we hypothesized that lungs perfused under zone 1 conditions would exchange gas. We used the multiple inert gas elimination technique to assess the ventilation-perfusion (VA/Q) distribution under zones 1 and 2 in six rabbit lungs perfused with tris(hydroxymethyl)aminomethane-buffered Tyrode solution containing 1% albumin, 4% dextran, and papaverine (25 mg/l). High-frequency oscillation (tidal volume = 2.8 ml at 20 Hz, bias flow = 1 l/min) kept alveolar pressure (PA) nearly constant at 10 or 20 cmH2O. Pulmonary arterial pressure was set 2.5 cmH2O below or 5 cmH2O above PA (zones 1 and 2, respectively). Pulmonary venous pressure was kept at 0 cmH2O, with zero reference being the bottom of the lung. At PA of 10 cmH2O, flow was 64 +/- 40 and 5 +/- 3 ml/min (P < 0.05) and the mean VA/Q for perfusion was 1.1 +/- 0.4 and > 5 (P < 0.05) in zones 2 and 1, respectively. At PA of 20 cmH2O, flow was 89 +/- 36 and 22 +/- 13 ml/min (P < 0.05) and the mean VA/Q for perfusion was 0.8 +/- 0.3 and 3.7 +/- 2.4 (P < 0.05) in zones 2 and 1, respectively. Shunt averaged < 5% of total flow in all conditions. Blood flowing through vessels remaining open under zone 1 conditions 1) exchanges gas, 2) does not occur through anatomic or physiological shunts, and 3) may explain the high VA/Q seen with positive end-expiratory pressure.
Seven days of exercise increase GLUT-4 protein content in human skeletal muscle
Authors: Houmard J. A. , Hickey M. S. , Tyndall G. L. , Gavigan K. E. , Dohm G. L.
Published: December 2017

Insulin-responsive glucose transporter (GLUT-4) content increases by 1.8-fold in skeletal muscle with 14 wk of exercise training [Houmard et al. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E896-E901, 1993]. The purpose of this study was to determine whether more short-term training (7 days) increases GLUT-4 protein content in human skeletal muscle. Seven sedentary men [25.0 +/- 1.1 (SE) yr, 44.1 +/- 2.2 ml.kg-1.min-1 maximal O2 uptake, 14.9 +/- 2.1% body fat] were examined before and after 7 days of cycle ergometer training (1 h/day, 76 +/- 2% maximal heart rate). Needle biopsy samples from the vastus lateralis were used to determine GLUT-4 protein content. Muscle GLUT-4 increased (P < 0.05) by an average of 2.8 +/- 0.5-fold with 7 days of training. GLUT-4 content in skeletal muscle thus increases substantially with short-term exercise training.
Effect of anemia on intrapulmonary shunt during atelectasis in rabbits
Authors: Deem S. , Bishop M. J. , Alberts M. K.
Published: December 2017

To elucidate the effects of anemia on intrapulmonary shunt, we studied a model of left lung atelectasis in anesthetized rabbits. In 10 rabbits, isovolemic anemia was produced by sequential hemodilution. Seven control rabbits were followed over time, without hemodilution. Intrapulmonary shunt (Qs/QT) was measured by using blood gas analysis and by quantitation of the percentage of blood flow to the collapsed left lung (QLl/QT) using fluorescent microspheres. In control rabbits, Qs/QT and QLl/QT decreased over time, whereas arterial PO2 increased. In hemodiluted rabbits, there was a trend toward increased Qs/QT and QLl/QT. There were significant differences in the behavior of Qs/QT, QLl/QT, and arterial PO2 between control and hemodiluted rabbits. Hemodynamic parameters, including cardiac output and pulmonary artery pressure, were not different between groups. In a third group of rabbits with pharmacologically induced acidosis but no hemodilution, Qs/QT and QLl/QT decreased over time, and arterial PO2 increased. We conclude that acute isovolemic anemia has a deleterious effect on pulmonary gas exchange, possibly through attenuation of hypoxic pulmonary vasoconstriction.