bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction without impairing gas exchange
Authors: Pison U. , Lopez F. A. , Heidelmeyer C. F. , Rossaint R. , Falke K. J.
Published: December 2017

Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that participates in the regulation of vascular tone. We studied the effects of inhaled NO gas on transient hypoxic pulmonary vasoconstriction and normal lungs in mechanically ventilated sheep. We measured hemodynamics and pulmonary gas exchange. For gas exchange measurements we used conventional blood gas analysis and the multiple inert gas elimination technique to estimate ventilation-perfusion heterogeneity. Our hypotheses were 1) inhaled NO reverses hypoxic pulmonary vasoconstriction, 2) the hemodynamic effects of inhaled NO are limited to the pulmonary circulation, and 3) inhaled NO does not impair pulmonary gas exchange and may redistribute blood flow to better ventilated areas of the lungs. Hypoxic pulmonary vasoconstriction was induced by using a hypoxic inspiratory gas mixture. The addition of 20 ppm NO to the hypoxic inspiratory gases returned pulmonary arterial pressure to baseline values. Systemic hemodynamics and gas exchange indexes derived from conventional blood gas analysis remained constant. Gas exchange indexes for ventilation-perfusion ratios and gas dispersions improved. The addition of 20 ppm NO to medical air (21% O2) had no such significant effects on hemodynamics or pulmonary gas exchange. Our findings show that inhaled NO reverses transient hypoxic pulmonary vasoconstriction. The hemodynamic effects of NO are limited to the pulmonary circulation; it does not impair pulmonary gas exchange. Moreover, it redistributes blood flow to better ventilated alveoli. As such, NO has potential in the treatment of lung diseases associated with pulmonary hypertension.
Breathing volumes and gas exchange during simulated rapid free ascent from 100 msw
Authors: Linnarsson D. , Ornhagen H. , Gennser M. , Berg H.
Published: December 2017

The crew of a disabled submarine can be rescued by means of free ascent through the water to the surface. Pulmonary gas exchange was studied during simulated rapid free ascent in subjects standing immersed to the neck in a pressure chamber. The pressure was rapidly increased to 1.1 MPa [100 meters seawater (msw)] followed by decompression at 0.03 MPa/s (3 msw/s). Effective inspired tidal volume, as estimated by an Ar dilution method, fell gradually to zero during decompression from 20 to 0 msw. Directly determined expired tidal volumes were increased up to two to three times at the time of return to surface pressure compared with pre- and postdecompression volumes. End-tidal PCO2 was increased on compression and fell to a nadir of 3.4 kPa (25 Torr) at the time of return to surface pressure. Thus, intrapulmonary gas expansion caused simultaneous inspiratory hypoventilation and expiratory hyperventilation. If O2-enriched gas is to be used to reduce the risk of decompression sickness, it should be administered early during decompression to alter the intrapulmonary gas composition. The time course of arterial PCO2 changes as reflected by end-tidal values during short-lasting compression/decompression would act to promote inert gas supersaturation in the brain.
Physical and cytochemical properties of neutrophils activated in situ in the lung during ZAP infusion in sheep
Authors: Albertine K. H. , Rosolia D. L. , Schuhl R. A. , Peters S. P. , Gee M. H.
Published: December 2017

Increased retention of activated neutrophils in the lungs contributes to endothelial cell injury. However, characterization of the morphological changes that occur in neutrophils during activation in the pulmonary microcirculation has not been fully determined in vivo. Therefore, the present study was designed to determine structural and cytochemical properties of neutrophils in situ in pulmonary arterioles and alveolar capillaries during the infusion of zymosan-activated plasma (ZAP) or plasma (control) in anesthetized sheep. Quantitative morphological methods showed that ZAP infusion caused significant retention of neutrophils in alveolar capillaries [2.19 +/- 0.40 (SD) x 10(8) neutrophils/ml of capillary blood volume] and pulmonary arterioles (1.02 +/- 0.46 x 10(8) neutrophils/ml of arterial blood volume) compared with plasma infusion (1.03 +/- 0.15 and 0.30 +/- 0.10 x 10(8) neutrophils/ml, respectively; P < 0.05). Harmonic mean diameter of ZAP-activated neutrophils in situ (7.19 +/- 0.44 microns) was significantly greater than the diameter of neutrophils in plasma-treated sheep (6.29 +/- 0.17 microns; P < 0.05). Neutrophil cross-sectional area (54 +/- 3 microns2) and volume (248 +/- 27 microns3) in situ in alveolar capillaries were also significantly greater in ZAP-treated sheep than in control sheep (41 +/- 4 microns2 and 184 +/- 9 microns3, respectively; P < 0.05). Similarly, microvascular neutrophils in ZAP-treated sheep were vacuolated and elongated, filamentous actin was redistributed peripherally, and the cells were degranulated. We conclude that during ZAP infusion, neutrophils become enlarged and degranulated in pulmonary microvessels, especially in alveolar capillaries. The structural and cytochemical changes that occur are consistent with the hypothesis that neutrophil activation is accompanied by alterations in neutrophil physical properties, alterations that may facilitate retention and contribute to endothelial cell injury.
Abdominal compliance, parasternal activation, and chest wall motion
Authors: Cala S. J. , Edyvean J. , Engel L. A.
Published: December 2017

We measured abdominal compliance (Cab) and rib cage displacement (delta Vrc) relative to abdominal displacement (delta Vab) during relaxation and tidal breathing in upright (U) and supine (S) postures in five normal subjects. In S, an abdominal binder was used to decrease Cab in two to five increments. We also measured the electrical activity of the parasternal muscle (EMGps) with the use of fine-wire intramuscular electrodes during CO2 rebreathing in U and in supine unbound (SU) and supine bound (SB) postures. During maximum binding (SB2), Cab decreased to 39 +/- 7% of the SU value (P = 0.01), matching Cab in U (P = 0.16). In the SB condition, the ratio of tidal delta Vrc/delta Vab to relaxation delta Vrc/delta Vab increased as Cab decreased, matching the data in U. For the group, this ratio decreased during SU to 47 +/- 10% (P = 0.02) but increased during SB2 to 86 +/- 7% (P = 0.18) of the value in U. During CO2 rebreathing, EMGps increased linearly with tidal volume (r > 0.727, P < 0.01). However, at any given tidal volume, the SU and SB2 EMGps were not significantly different (P = 0.12), and both were less than that in U (P < 0.02). The results suggest that the differences in chest wall motion between U and S may be due to the difference in Cab and not to different patterns of respiratory muscle recruitment. The mechanism may relate to changes in mechanical coupling between the diaphragm and the rib cage.
Effect of nebulized lidocaine on ventilatory response to CO2 in healthy subjects
Authors: Mador M. J.
Published: December 2017

Partial vagal blockade produced by inhalation of a local anesthetic aerosol has enhanced CO2 responsiveness in some studies but not in others. The effect of inhaled local anesthetic may depend on the amount of drug depositing in the central airways, i.e., the degree of airway anesthesia. We examined the ventilatory response to CO2 rebreathing in 11 healthy subjects before and after inhalation of 4% lidocaine and a normal saline control solution. Lidocaine and control solutions were aerosolized via two different nebulizers: one produced particles with a mass median aerodynamic diameter of 5.28 microns, and the other produced particles with a mass median aerodynamic diameter of 1.76 microns. The ventilatory response to CO2 was not affected by the control solution. In contrast, the ventilatory response to CO2 was significantly increased after aerosolized lidocaine when administered via the moderate-particle-size nebulizer (2.13 +/- 0.66 vs. 1.83 +/- 0.54 l.min-1.Torr-1 during control, P = 0.01) but not via the small-particle-size nebulizer (1.96 +/- 0.82 vs. 1.94 +/- 0.84 l.min-1.Torr-1 during control, P = NS). The increase in ventilation was achieved predominantly by an increase in frequency (P = 0.01) while tidal volume was unchanged. In conclusion, airway receptors accessible to inhaled local anesthetic play a role in the control of breathing during CO2 rebreathing. Previous negative studies may be due to differences in nebulizer technique, affecting the amount of drug depositing within the central airways.
Multielectrode mapping of slow-wave activity in the isolated rabbit duodenum
Authors: Lammers W. J. , al-Kais A. , Singh S. , Arafat K. , el-Sharkawy T. Y.
Published: December 2017

The technique of multiple simultaneous recordings from a large number of extracellular electrodes (> 100) is currently used in the study of normal and abnormal electrical conduction in the heart and the genesis of cardiac arrhythmias. To investigate whether such a system could also be applied in gastrointestinal electrophysiology, several studies were performed with this technique on segments of isolated rabbit duodenum. A multiple-electrode assembly consisting of 240 silver wires was positioned on the serosal surface of the duodenum, and the recorded signals were, after suitable processing, stored. Thereafter, analysis of all simultaneously recorded slow waves during a selected period of time was performed to reconstruct the pattern of conduction in the duodenum. The first results show that there is a considerable variation in conduction pattern, which is determined by the site of the natural pacemaker. Several experiments were performed to rule out possible deleterious effects of positioning the multiple-electrode assembly on the duodenum. Furthermore, prolonged periods of recording did not influence propagation speed and pattern provided that the positioning of the multiple electrode assembly was performed with care. Entrainment of the natural pacemaker was possible by applying electrical stimuli through 2 of the 240 extracellular electrodes during simultaneous recordings. In conclusion, multisite extracellular mapping of gastrointestinal smooth muscle is possible and can be used to study origin and spread of slow-wave activity.
Early and late respiratory-related cortical potentials evoked by pressure pulse stimuli in humans
Authors: Strobel R. J. , Daubenspeck J. A.
Published: December 2017

Although respiratory-related cortical evoked potentials (CEPs) have been obtained in humans, early-latency responses have been obtained only with direct electrical stimulation of respiratory afferents. We have recorded both early and late cortical activity in response to a relatively novel stimulus consisting of a 300-ms negative pressure pulse applied to the mouth near the start of selected inspirations, when mouth pressure attained a predetermined threshold. This stimulus caused highly reproducible and rapid changes in mouth pressure and was effective in eliciting CEPs to a wide range of applied pressures. Using pulses of approximately -2 to -25 cmH2O, we obtained an early positive component with a mean latency of approximately 20 ms and a subsequent negative component at approximately 30 ms in normal subjects. Peak-to-peak amplitude varied directly, and component latencies inversely, as a function of pulse magnitude. Using -5- to -10-cmH2O stimuli, we also measured a later positive-negative-positive response with mean component latencies of 96.7 +/- 15.1, 147 +/- 14.8, and 237.6 +/- 23.5 ms, respectively. The early-latency activity was resistant to manipulations of stimulus predictability, whereas the later waves were attenuated or disappeared when load presentation was made completely predictable. We validated our method by eliminating the possibility of tactile stimulation of the lips and teeth as the origin of the evoked responses. We propose that early-latency activity derives from precortical structures and may provide a window on the functioning of respiratory afferents in normal subjects and in patients with respiratory disease.
Left ventricular performance during continuous endotoxin-induced hyperdynamic endotoxemia in sheep
Authors: Noshima S. , Noda H. , Herndon D. N. , Traber L. D. , Traber D. L.
Published: December 2017

Cardiac function was studied in an unanesthetized ovine model of hyperdynamic endotoxemia. Sixteen sheep were instrumented with ultrasonic crystals on the left ventricle to measure changes in its external diameter, a pressure transducer in the left ventricle, and aortic and Swan-Ganz catheters. The animals received either Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1; LPS group, n = 10] or an equivalent amount of 0.9% NaCl (sham group, n = 6). Between 1 and 8 h after LPS, a hypodynamic state with low cardiac output ensued (LPS 5.0 +/- 0.2 vs. sham 6.3 +/- 0.4 l.min-1.m-2). During this period, the end-systolic pressure-diameter relationship, a sensitive index of myocardial contractility, was reduced (LPS 10.4 +/- 1.2 vs. sham 17.2 +/- 0.8 mmHg/mm). After this first phase, the sheep developed a persistent hyperdynamic state characterized by a significant increase in cardiac output. By 24 h after LPS administration, the cardiac output was 10.1 +/- 0.5 l.min-1.m-2 (sham 6.3 +/- 0.3). Despite the marked elevation of cardiac output, the end-systolic pressure-diameter relationship had fallen to 8.5 +/- 0.9 mmHg/mm (sham 16.0 +/- 1.2). In a model of hyperdynamic state, an increased cardiac output occurs despite a significant depression in myocardial contractility.
Effect of soleus unweighting on stimulation of insulin-independent glucose transport activity
Authors: Henriksen E. J. , Ritter L. S.
Published: December 2017

Unweighting of the rat soleus by tail-cast suspension results in increased insulin action on stimulation of glucose transport, which can be explained, at least in part, by increased insulin binding and enhanced glucose transporter protein levels. Glucose transport is also activated by an insulin-independent mechanism stimulated by in vitro muscle contractions or hypoxia. Therefore, the purpose of this study was to determine if soleus unweighting leads to an enhanced response of the insulin-independent pathway for stimulation of glucose transport. The hindlimbs of juvenile male Wistar rats were suspended by a tail-cast system for 3 or 6 days. Glucose transport activity in isolated soleus strips (approximately 18 mg) was then assessed by using 2-deoxy-[1,2–3H]glucose (2-DG) uptake. Insulin (2 mU/ml) had a progressively enhanced effect on 2-DG uptake after 3 and 6 days of unweighting (+44 and +72% vs. control, respectively; both P < 0.001). At these same times, there was no difference between groups for activation of 2-DG uptake by maximally effective treatments with contractions (10 tetanuses), hypoxia (60 min), or caffeine (5 mM). These results indicate that the enhanced capacity for stimulation of glucose transport after soleus unweighting is restricted to the insulin pathway, with no apparent enhancement of the insulin-independent pathway.
Excitatory amino acid neurotransmission in superior laryngeal nerve-evoked inspiratory termination
Authors: Karius D. R. , Ling L. , Speck D. F.
Published: December 2017

Superior laryngeal nerve (SLN) stimulation elicits a transient inhibition of inspiration (single shocks) or inspiratory termination (stimulus trains). The neural pathways mediating these responses are unknown, but the medial nucleus tractus solitarius (mNTS) has been implicated in the termination reflex. This study tested the hypothesis that SLN-evoked inspiratory termination requires excitatory amino acid (EAA) neurotransmission in medial aspects of the NTS. Experiments were conducted in decerebrate, vagotomized, and paralyzed adult cats. Inspiratory motor output was recorded from the phrenic nerve. After control responses to SLN stimulation were recorded, a unilateral injection of the EAA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 mM) was made into the mNTS. The transient inhibitions were not altered by DNQX. Inspiratory termination elicited by stimulation of the SLN contralateral to the injection persisted after DNQX (n = 4). Stimulation of the ipsilateral SLN no longer elicited termination (5 of 9 animals) or did so only at greatly elevated thresholds (4 of 9). We conclude that EAA neurotransmission in the mNTS is not required in the transient reflex but is necessary for the production of the SLN-evoked inspiratory termination.
Effects of chronic hypoxia and exercise on plasma erythropoietin in high-altitude residents
Authors: Schmidt W. , Spielvogel H. , Eckardt K. U. , Quintela A. , Penaloza R.
Published: December 2017

The present study was performed to evaluate the effects of chronic inspiratory hypoxia and its combination with physical exercise on plasma erythropoietin concentration ([EPO]). Eight natives from the Bolivian Plateau were investigated at 3,600 m above sea level at rest as well as during and up to 48 h after exhaustive exercise (EE) and 60 min of submaximal (60%) cycle ergometer exercise (SE). Ten sea-level subjects were used as a control group for resting values. The mean resting plasma [EPO] of the high-altitude group (19.5 +/- 0.7 mU/ml) did not differ from that of the sea-level group (18.1 +/- 0.4 mU/ml) but was higher than would be expected from the relationship between [EPO] and hematocrit at sea level. Five hours after both types of exercise, [EPO] decreased by 2.1 +/- 0.8 (EE, P < 0.01) and 1.6 +/- 0.8 mU/ml (SE, P < 0.05); 48 h after SE, [EPO] increased by 2.6 +/- 0.9 mU/ml (P < 0.05). It is concluded that 1) high-altitude natives need relatively high [EPO] to maintain their high hematocrit and 2) exercise at low basal arterial PO2 does not directly increase plasma [EPO] in high-altitude residents but seems to exert suppressive effects.
Interaction of iberiotoxin with beta-adrenoceptor agonists and sodium nitroprusside on guinea pig trachea
Authors: Jones T. R. , Charette L. , Garcia M. L. , Kaczorowski G. J.
Published: December 2017

Airway smooth muscle plasma membranes contain a variety of functional K+ channels. In particular, there is a predominance of Ca(2+)-activated K+ channels (maxi-K). Inhibition of these K+ channels has been postulated to account for the ability of charybdotoxin (ChTX) to produce contraction of airway smooth muscle and to modify the relaxant effects of beta-adrenoceptor agonists and sodium nitroprusside (SNP). Iberiotoxin (IbTX) is more selective and more potent than ChTX at blocking maxi-K channels. In this study, pharmacological experiments were performed on guinea pig trachea to determine whether IbTX produced effects similar to ChTX. The concentration-response curves to salbutamol were markedly affected by IbTX, with a > 60-fold rightward shift being produced with 20 nM IbTX. The maximal relaxation to salbutamol was reduced to 49.3 +/- 0.9, 22.3 +/- 4.7, and 15.0 +/- 2.7% of control maximum in the presence of 20, 60, and 180 nM IbTX, respectively. Similar to salbutamol, the maximal relaxation to SNP was reduced to 80 +/- 1.6, 19 +/- 1.7, and 12 +/- 2.1% of control maximum in the presence of 20, 60, and 180 nM IbTX, respectively. IbTX (180 nM) failed to produce a significant alteration of relaxation to the ATP-dependent K+ channel agonist BRL-34915. Exposure of tissues to K(+)-rich medium (80 mM) inhibited responses to salbutamol > or = SNP > isoproterenol. These results confirm and extend our earlier observations that maxi-K channels may be involved in regulating tone and relaxation of carbachol-contracted guinea pig tracheal smooth muscle. This mechanism is of particular importance for beta 2-adrenoceptor- and SNP-induced relaxation.
Role of muscle fiber hypertrophy and hyperplasia in intermittently stretched avian muscle
Authors: Antonio J. , Gonyea W. J.
Published: December 2017

In the chronic stretch model, muscle fiber hyperplasia precedes fiber hypertrophy [Alway et al. Am. J. Physiol. 259 (Cell Physiol. 28): C92-C102, 1990]. This study was undertaken to determine if an intermittent stretch protocol would induce fiber hypertrophy without fiber hyperplasia. A weight equalt to 10% of the bird's mass was attached to the right wing of seven adult quail while the left wing served as the intra-animal control. The weight was attached to the wing for 24-h periods interspersed with a 48- to 72-hr rest interval. The actual stretch time was 5 days while the length of the treatment period was 15 days. Muscle mass and length increased significantly 53.1 +/- 9.0 and 26.1 +/- 7.3% in the stretched anterior latissimus dorsi. Fiber number, which was determined from a histological section in the midregion of the muscle, did not change (control 1,651.6 +/- 94.8; stretch 1,626.0 +/- 70.9). The slow tonic fiber areas increased significantly an average of 28.6 +/- 5.7%, whereas the fast fibers increased 18.5 +/- 8.4% when compared with control values. Mean fiber area (average of slow and fast fibers) increased significantly by 27.8 +/- 6.0% in the stretched anterior latissimus dorsi. There were no differences in the percentage of slow fibers or volume density of noncontractile tissue. These data indicate that muscle adapts differently to intermittent stretch than it does to chronic stretch despite an equivalent load and stretch duration. In contrast to chronic stretch, 5 days of intermittent stretch produces muscle fiber hypertrophy without fiber hyperplasia.
Staphylococcal alpha-toxin induced ventilation-perfusion mismatch in isolated blood-free perfused rabbit lungs
Authors: Walmrath D. , Scharmann M. , Konig R. , Pilch J. , Grimminger F. , Seeger W.
Published: December 2017

Gas exchange conditions in blood-free perfused isolated rabbit lungs were assessed by the use of the multiple inert gas elimination technique. Under baseline conditions, unimodal narrow distribution of perfusion and ventilation to midrange-ventilation-perfusion (VA/Q) areas was noted. Intravascular challenge with staphylococcal alpha-toxin caused a rapid increase in pulmonary arterial pressure (to > 40 mmHg within approximately 15 min) and delayed-onset (> 10–15 min) lung edema formation, with unaltered ventilation pressures. The vasoconstrictor response was paralleled by a progressive, severe leftward shift of perfusion to areas with low-VA/Q ratios, accompanied by a minor fraction of shunt flow. At pulmonary arterial pressures > 40 mmHg, extreme VA/Q mismatch with near absence of perfusate flow to midrange-VA/Q areas was registered. Vasoconstrictor response and VA/Q mismatch, but not the progressive edema formation, were virtually completely suppressed in lungs pretreated with acetylsalicylic acid or the thromboxane receptor antagonist BM 13505. Moreover, "rescue" application of BM 13505 after onset of alpha-toxin-induced pressor response and gas exchange abnormalities completely reversed pressure elevation and loss of VA/Q matching. We conclude that the marked vasoconstrictor response to staphylococcal alpha-toxin is paralleled by severe VA/Q mismatch with predominant perfusion of low-VA/Q areas independent of lung edema formation. Pressor response and VA/Q mismatch, but not vascular leakage, are suppressed by thromboxane inhibition.
Estimation of ventilatory capacity during submaximal exercise
Authors: Babb T. G. , Rodarte J. R.
Published: December 2017

There is presently no precise way to determine ventilatory capacity for a given individual during exercise; however, this information would be helpful in evaluating ventilatory reserve during exercise. Using schematic representations of maximal expiratory flow-volume curves and individual maximal expiratory flow-volume curves from four subjects, we describe a technique for estimating ventilatory capacity. In these subjects, we measured maximal expiratory flow-volume loops at rest and tidal flow-volume loops and inspiratory capacity (IC) during submaximal cycle ergometry. We also compared minute ventilation (VE) during submaximal exercise with calculated ventilatory maxima (VEmaxCal) and with maximal voluntary ventilation (MVV) to estimate ventilatory reserve. Using the schematic flow-volume curves, we demonstrated the theoretical effect of maximal expiratory flow and lung volume on ventilatory capacity and breathing pattern. In the subjects, we observed that the estimation of ventilatory reserve with use of VE/VEmaxCal was most helpful in indicating when subjects were approaching maximal expiratory flow over a large portion of tidal volume, especially at submaximal exercise levels where VE/VEmaxCal and VE/MVV differed the most. These data suggest that this technique may be useful in estimating ventilatory capacity, which could then be used to evaluate ventilatory reserve during exercise.
Cell and sarcomere contractile performance from the same cardiocyte using video microscopy
Authors: Mukherjee R. , Crawford F. A. , Hewett K. W. , Spinale F. G.
Published: December 2017

The relationship between whole cell and sarcomere contractile performance from within the same myocyte remains unclear. In the present study, the dynamic properties of whole cell and sarcomere contractile performance were examined from the same myocyte by computer-assisted video microscopy. Isolated canine left ventricular myocytes were field stimulated at 1 Hz, and whole cell and sarcomere contractile performance was measured in the unloaded unattached state (n = 16) and after attachment to a basement membrane substrate (n = 18). Whole cell and sarcomere contractile measurements were obtained immediately on initiation of electrical stimulation as well as at steady state, after which measurements were repeated in the presence of 25 nM isoproterenol. Video-microscopic images of whole cell and sarcomere contractions were obtained at final magnifications of x1,100 and x5,500, respectively. By use of a 240-Hz high-scan-rate charge-coupled device camera and a video-based edge-detection system synchronized with the camera video output, the myocyte and sarcomere motion data were digitized. Steady-state percentage and velocity of shortening for whole cells and sarcomeres were 4.75 +/- 0.30% and 56.50 +/- 2.37 microns/s and 8.63 +/- 0.60% and 2.24 +/- 0.46 microns/s, respectively, for the attached myocytes and 8.63 +/- 0.48% and 71.38 +/- 6.14 microns/s and 11.73 +/- 3.22% and 2.72 +/- 0.62 microns/s, respectively, for the unattached myocytes. With the initiation of electrical stimulation, the extent of the shortening-velocity of relengthening relationship increased in a linear fashion for the attached (whole cell, r = 0.87; sarcomere, r = 0.90; both P < 0.001) and unattached myocytes (whole cell, r = 0.83; sarcomere, r = 0.88; both P < 0.001). In all experiments, isoproterenol significantly increased the slope of these linear relationships (P < 0.01). Furthermore, the relationship between whole cell and sarcomere velocity of shortening was highly linear (r > 0.91, P < 0.001). In summary, this study demonstrated that the video-based edge-detection technique could be adapted to measure cell and sarcomere contractile performance from the same myocyte. Furthermore, a significant linear relationship exists between whole cell and sarcomere contractile dynamics with alterations in both load and inotropic state.
Estimation of body composition changes during weight cycling by bioelectrical impedance analysis in rats
Authors: Ilagan J. , Bhutani V. , Archer P. , Lin P. K. , Jen K. L.
Published: December 2017

The effects of body weight cycling (WC) in rats on body composition (BC) and feeding efficiency were studied. The usefulness of estimating BC by bioelectrical impedance analysis (BIA) was also examined. Female Sprague-Dawley rats were divided into high-fat ad libitum feeding, either noncycling or cycling, or restricted feeding (75% of control feed) cycling groups. Control rats were fed a regular laboratory ad libitum diet and did not cycle. All rats were killed at the end of week 61. A BIA unit was used at each stage of WC to obtain resistance and reactance readings. Final BC was determined by chemical analysis. On the basis of the final chemical analysis and BIA measurements, an equation was established and applied to estimate BC at each stage of WC: fat-free mass (g) = 0.38 x body wt (g) + 13.8 x [length (cm)2/resistance] + 70.9 (r = 0.95, P < 0.001). High-fat ad libitum feeding induced rapid body weight and fat gains as well as an elevated feeding efficiency and an internal fat-to-subcutaneous fat ratio, regardless of whether the rats cycled. This change in fat mass was clearly detected by the BIA. Although rats fed restricted diets had similar body weights as did control rats, they had a significantly higher internal fat-to-subcutaneous fat ratio. Thus, not only the amount of food but also the composition of the diet is important for proper weight management. The BIA method is capable of detecting the body fat mass change during WC.
Increased negativity of interstitial fluid pressure in rat trachea after mast cell degranulation
Authors: Koller M. E. , Woie K. , Reed R. K.
Published: December 2017

The present study was performed to investigate whether the increased negativity of interstitial fluid pressure (Pif) observed after intravenous injection of dextran could be mediated via mast cell degranulation induced by C48/80 and polymyxin B sulfate. Increased negativity of Pif, concomitant with edema formation and increased albumin extravasation, was seen with both substances. However, the two substances differed in that polymyxin B sulfate induced less negativity in Pif and a larger but transient increase in capillary albumin extravasation and interstitial fluid volume. Total tissue water (TTW) increased from 2.11 to 2.71 ml/g dry wt 10 min after polymyxin B and returned to control level at 30 and 60 min. Injection of C48/80 increased TTW to 2.68 ml/g dry wt at 30 min, and TTW was still elevated at 60 min. Albumin extravasation followed a similar pattern; polymyxin B sulfate increased albumin extravasation from < 0.08 to 1.18 ml/g dry wt during the first 5 min after administration. C48/80 was less potent, and maximal albumin leakage was seen after 10–25 min (0.25 ml/g dry wt). The observations demonstrate the importance of the interstitium and the loose connective tissues as "active" participants in the edema-generating process and suggest an interaction with the structural components of the interstitium, as well as an important role for the mast cells in the chain of events creating increased negativity of Pif.
No evidence of oxidant stress during high-intensity rowing training
Authors: Dernbach A. R. , Sherman W. M. , Simonsen J. C. , Flowers K. M. , Lamb D. R.
Published: December 2017

In untrained subjects, strenuous exercise provokes the appearance of oxidant stress markers in blood and muscle. On the other hand, trained muscle is resistant to oxidant stress unless exercise challenges the muscle glycogen supply. It is not known whether chronic high-intensity exercise alters the susceptibility of skeletal muscle to oxidant stress, whether there are gender-related differences in markers of oxidant stress, or whether elevating muscle glycogen stores by increasing dietary carbohydrate can minimize any exercise-related oxidant stress. To address these issues, collegiate rowers (12 men, 11 women) were randomly assigned to a moderate-(MOD, 5 g/kg body wt) or high-carbohydrate (HI, 10 g/kg) diet in a double-blind design and underwent strenuous training for 4 wk. Training in the A.M. was 40 min at 70% maximal O2 consumption (VO2); in the P.M. it was either three 2,500-m time trials (to assess power output) or aerobic and lactate tolerance training. Total daily training time was 65 min at 70% maximal VO2 and 38 min at > or = 90% maximal VO2. Thrice-weekly morning blood samples were assayed for serum creatine kinase (CK), plasma thiobarbituric acid-reactive substances (TBARS), and serum beta-glucuronidase (beta-Gluc). Weekly muscle biopsies were obtained for analysis of glycogen and, when tissue sample quantity allowed, TBARS. HI rowers produced more power and improved power more (10.7 +/- 1.0 vs. 1.6 +/- 1.6%) over the 4 wk than did the MOD rowers. Preexercise muscle glycogen concentration was maintained at 119 mmol/kg in MOD but increased 65% in HI rowers (P < 0.05).
Regional coupling between chest wall and lung expansion during HFV: a positron imaging study
Authors: Venegas J. G. , Tsuzaki K. , Fox B. J. , Simon B. A. , Hales C. A.
Published: December 2017

Apparently conflicting differences between the regional chest wall motion and gas transport have been observed during high-frequency ventilation (HFV). To elucidate the mechanism responsible for such differences, a positron imaging technique capable of assessing dynamic chest wall volumetric expansion, regional lung volume, and regional gas transport was developed. Anesthetized supine dogs were studied at ventilatory frequencies (f) ranging from 1 to 15 Hz and eucapnic tidal volumes. The regional distribution of mean lung volume was found to be independent of f, but the apex-to-base ratio of regional chest wall expansion favored the lung bases at low f and became more homogeneous at higher f. Regional gas transport per unit of lung volume, assessed from washout maneuvers, was homogeneous at 1 Hz, favored the bases progressively as f increased to 9 Hz, and returned to homogeneity at 15 Hz. Interregional asynchrony (pendelluft) and right-to-left differences were small at this large regional scale. Analysis of the data at a higher spatial resolution showed that the motion of the diaphragm relative to the excursions of the rib cage decreased as f increased. These differences from apex to base in regional chest wall expansion and gas transport were consistent with a simple model including lung, rib cage, and diaphragm regional impedances and a viscous coupling between lungs and chest wall caused by the relative sliding between pleural surfaces. To further test this model, we studied five additional animals under open chest conditions. These studies resulted in a homogeneous and f-independent regional gas transport. We conclude that the apex-to-base distribution of gas transport observed during HFV is not caused by intrinsic lung heterogeneity but rather is a result of chest wall expansion dynamics and its coupling to the lung.
Effect of metabolic acidosis on pulmonary gas exchange of artificially ventilated dogs
Authors: Frans A. , Clerbaux T. , Willems E. , Kreuzer F.
Published: December 2017

It is well established that metabolic acidosis induces a reduction in alveolar-arterial O2 difference [(A-a)Do2] in artificially ventilated dogs by shifting the oxyhemoglobin dissociation curve (ODC) and/or by improving the distribution of the ventilation-to-perfusion ratio (VA/Q) throughout the lung. To assess the influence of these two factors we examined eight artificially ventilated dogs before and after induction of metabolic acidosis by a perfusion of 0.3 mol HCl. We measured classic indexes of cardiopulmonary function. VA/Q distribution was estimated using the multiple inert gas elimination technique (MIGET). ODC and Bohr effect of each dog were obtained by a dynamic method. Acidosis increased CO2 excretion, respiratory quotient, blood PO2 at 50% saturation, and arterial PCO2 and PO2 with a simultaneous decrease in (A-a)DO2. In seven dogs, the distribution of VA and Q, as assessed by MIGET, was not substantially modified by HCl perfusion. In the eighth dog the distribution of Q and VA became more homogeneous after acidosis. This led us to conclude that the Bohr effect is the most important and most consistently observed factor responsible for the decrease in (A-a)DO2 found in metabolic acidosis. In rare cases the increase in pulmonary arterial pressure may complement this action by improving the distribution of the VA/Q ratio.
Energetics of best performances in middle-distance running
Authors: Di Prampero P. E. , Capelli C. , Pagliaro P. , Antonutto G. , Girardis M. , Zamparo P. , Soule R. G.
Published: December 2017

Oxygen consumption (VO2) and blood lactate concentration were determined during constant-speed track running on 16 runners of intermediate level competing in middle distances (0.8–5.0 km). The energy cost of track running per unit distance (Cr) was then obtained from the ratio of steady-state VO2, corrected for lactate production, to speed; it was found to be independent of speed, its overall mean being 3.72 +/- 0.24 J.kg-1 x m-1 (n = 58; 1 ml O2 = 20.9 J). Maximal VO2 (VO2max) was also measured on the same subjects. Theoretical record times were then calculated for each distance and subject and compared with actual seasonal best performances as follows. The maximal metabolic power (Er max) a subject can maintain in running is a known function of VO2max and maximal anaerobic capacity and of the effort duration to exhaustion (te). Er max was then calculated as a function of te from VO2max, assuming a standard value for maximal anaerobic capacity. The metabolic power requirement (Er) necessary to cover a given distance (d) was calculated as a function of performance time (t) from the product Crdt-1 = Er. The time values that solve the equality Er max(te) = Er(t), assumed to yield the theoretical best t, were obtained by an iterative procedure for any given subject and distance and compared with actual records.
Tumor necrosis factor-alpha inhibits endothelium-dependent relaxation
Authors: Greenberg S. , Xie J. , Wang Y. , Cai B. , Kolls J. , Nelson S. , Hyman A. , Summer W. R. , Lippton H.
Published: December 2017

Tumor necrosis factor-alpha (TNF-alpha) stimulates nitric oxide (NO) in vascular endothelium by induction of the enzyme NO synthase II (NOS II). We examined the effects of TNF-alpha on 1) endothelium-dependent (EDR) and endothelium-independent (EIR) relaxation and 2) contraction of bovine intralobar pulmonary arteries (BPA) and veins (BPV) in vitro. Acetylcholine (ACh), bradykinin (BK), histamine, and A23187 produced EDR of BPA contracted with a 50% effective concentration of U-46619 (15 nM), because relaxation was abolished by endothelium-rubbing and attenuated by L-NG-mono-methylarginine (L-NMMA; 300 microM). TNF-alpha (0.00417, 0.0417, 0.417, and 1.25 micrograms/ml) incubated with BPA for 60 min inhibited EDR of the BPA to ACh, BK, and histamine. The effects of TNF required 30 min for onset. Recovery of EDR occurred 3–4 h after washout of TNF-alpha. Pentoxifylline (1 microM) did not affect ACh-induced EDR but selectively reversed TNF-alpha-mediated inhibition of ACh-induced EDR. TNF-alpha-mediated inhibition of EDR was not reversible by L-NMMA, an inhibitor of NOS I and NOS II, the cyclooxygenase inhibitor ibuprofen, or CV-3908 (1 microM), a platelet-activating factor antagonist. The inhibitory effect of TNF-alpha on EDR was not mediated by nonspecific sensitization of the endothelium to human protein because recombinant human granulocyte colony-stimulating factor (10, 50, and 500 x 10(3) U/ml) did not affect EDR of BPA. The effect of TNF-alpha was specific for release of NO from the endothelium of BPA because TNF-alpha did not affect 1) EDR of BPV to ACh, BK, or ATP; 2) EIR of BPA or BPV to nitroprusside; and 3) contraction of either BPA or BPV to KCl, U-46619, histamine, norepinephrine, or serotonin. Thus TNF-alpha appears to selectively inhibit receptor-mediated EDR and NO release in BPA. TNF-alpha-mediated inhibition of EDR differs from that of L-arginine-based inhibitors and may represent an endogenous physiological mechanism of regulation of NO in the endothelium.
Heparin-protamine reactions in pigs: role of oxygen-derived free radicals
Authors: Vollmar B. , Conzen P. F. , Habazettl H. , Yekebas E. , Peter K.
Published: December 2017

We tested the hypothesis that pulmonary hypertension and thromboxane A2 release after heparin neutralization by protamine are mediated by oxygen free radicals. Forty-five pigs in five groups were studied during general anesthesia. Group I animals received 250 IU heparin followed by 100 mg protamine after 15 min. Group II and group III animals received dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU) 30 min before heparin infusion. Group IV animals were given superoxide dismutase (SOD) 5 min before protamine. Group V served for testing the pulmonary vascular reactivity in DMTU-treated animals to a thromboxane A2 analogue (U-46619). Generation of oxygen free radicals by polymorphonuclear granulocytes (PMNs) was measured in vitro by chemiluminescence. Severe pulmonary hypertension and thromboxane A2 release after protamine were not prevented by either DMSO or SOD. DMTU reduced pulmonary vasoconstriction to U-46619 and protamine but not to TxA2 release, indicating that DMTU had unspecific vascular effects in group III. Heparin-protamine released no oxygen free radicals from isolated PMNs. The results indicate that oxygen free radicals do not have a key role in mediating pulmonary vasoconstriction after protamine neutralization of heparin.
Interstitial space and collagen alterations of the developing rat diaphragm
Authors: Gosselin L. E. , Martinez D. A. , Vailas A. C. , Sieck G. C.
Published: December 2017

The effect of growth on the relative interstitial space [%total cross-sectional area (CSA)] and collagen content of the rat diaphragm muscle was examined at postnatal ages of 0, 7, 14, and 21 days as well as in adult males. The proportion of interstitial space relative to total muscle CSA was determined by computerized image analysis of lectin-stained cross sections of diaphragm muscle. To assess collagen content and extent of collagen maturation (i.e., cross-linking), high-pressure liquid chromatography analysis was used to measure hydroxyproline concentration and the nonreducible collagen cross-link hydroxylysylpyridinoline (HP), respectively. At birth, interstitial space accounted for approximately 47% of total diaphragm muscle CSA. During postnatal growth, the relative contribution of interstitial space decreased such that by adulthood the interstitial space accounted for approximately 18% of total muscle CSA. The change in relative interstitial space occurred without a concomitant change in hydroxyproline concentration. However, the concentration of HP markedly increased with age such that the adult diaphragm contained approximately 17 times more HP than at birth. These results indicate that during development the relative CSA occupied by interstitial space decreases as muscle fiber size increases. However, the reduction in relative interstitial space is not associated with a change in collagen concentration. Thus collagen density in the interstitial space may increase with age. It is possible that the observed changes in relative interstitial space and collagen influence the passive length-force properties of the diaphragm.
Segmental vascular pressures in lung embolism
Authors: Ehrhart I. C. , Hofman W. F.
Published: December 2017

Average microvascular filtration pressure and vascular permeability measures were obtained in 100-microns glass bead-embolized dog lung lobes randomly assigned to groups in which isolated perfusion was designed to produce weight gain (edema groups) or no weight gain (isogravimetric groups). The solvent drag reflection coefficient (sigma), an index of vascular permeability, was obtained during edema formation, whereas isogravimetric capillary pressure was obtained during isogravimetry. Vascular permeability increased in response to embolism, because sigma was 0.53 +/- 0.03 vs. 0.80 +/- 0.05 (P < 0.005) in embolized and control lobes, respectively. Vascular occlusion methods indicated the greatest resistance increase in response to embolism in the vascular segment represented by Pao--Pdo (arterial occlusion pressure--double occlusion pressure). Because papaverine vasodilation reduced total vascular resistance (RT; P < 0.05) by decreasing Pao (P < 0.01) without altering Pdo, the RT increase in response to embolism was likely due to both vasoconstriction and obstruction. Because Pdo approximated capillary pressure at isogravimetry, Pdo appears to estimate average filtration pressure in both embolized (n = 6) and control lungs (n = 6). Arterial pressure was 56.2 +/- 13.6 vs. 17.6 +/- 1.5 cmH2O (P < 0.01) in embolized (n = 5) and control lobes (n = 6), respectively, whereas Pdo values of 16.1 +/- 1.5 vs. 12.4 +/- 0.8 (P < 0.05) suggested relatively little increase in filtration pressure in response to embolism. If the beads obstructed 100-microns vessels, the vascular segment represented by Pao--Pdo, the major site of vasoconstriction as well as mechanical obstruction, likely includes 100-microns arteries.
Influence of nasal airflow and resistance on nasal dilator muscle activities during exercise
Authors: Connel D. C. , Fregosi R. F.
Published: December 2017

Our purpose was to assess the separate effects of nasal airflow and resistance on the activity of the nasal dilator [alae nasi (AN)] muscles. Nasal airflow and the AN electromyogram were recorded at rest and during progressive-intensity exercise at 60, 120, and 150–180 W in 10 healthy subjects who breathed nasally under all conditions. The activity of the AN muscles increased linearly as a function of the increase in nasal minute ventilation evoked by progressive-intensity exercise (r = 0.99, P < 0.002). Reciprocal changes in nasal airflow and resistance were produced by surreptitious substitution of 12–15 breaths of 79% He-21% O2 for air at rest and during exercise. The switch to He-O2 decreased airway resistance (anterior rhinomanometry) by approximately 30% at rest and 40–60% during exercise. He-O2 did not change nasal flow or AN activities significantly under resting conditions. In contrast, He-O2 increased nasal flow and decreased the AN electromyogram by 25–50% during exercise (P < 0.05). The results suggest that AN muscle activities during nasal breathing are regulated by mechanisms that track airway resistance or the level of flow turbulence. The increase in AN activities during exercise probably helps ensure nasal airway patency in the face of the considerable collapsing pressures that prevail under these conditions.
Echocardiographic evaluation of size, function, and mass of normal and hypertrophied rat ventricles
Authors: Pawlush D. G. , Moore R. L. , Musch T. I. , Davidson W. R.
Published: December 2017

The noninvasive evaluation of cardiac structure and function in small animals would provide a means for investigators to repeatedly evaluate treatment effects at various stages of experimental protocols. In this study, commercially available echocardiographic and Doppler equipment was utilized to evaluate hypertrophied (HYP) and normal (SH) rat hearts. Surgically induced renovascular hypertension was used to produce a 35% increase in left ventricular (LV) weight in HYP relative to SH hearts. A commercially available echocardiographic system with integral Doppler capabilities and a 7.5-mHz single-crystal mechanical transducer was used to obtain parasternal long- and short-axis images of HYP and SH hearts in anesthetized animals. HYP hearts were found to have normal systolic function, as evidenced by preserved LV systolic and diastolic dimensions and volumes as well as fractional shortening and ejection fraction. HYP hearts demonstrated a 62% increase in their echocardiographically measured LV posterior wall thicknesses and a 44% increase in calculated ventricular mass. Both parameters were reliable in predicting the presence and degree of left ventricular hypertrophy. Doppler flow velocities through the aortic root and pulmonic valve did not differ between groups, again suggesting preserved LV systolic performance. These results indicate that two-dimensional echocardiography provides a useful means to noninvasively evaluate cardiac structure and function in rats.