bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of skeletal muscle dihydropyridine receptor gene expression by biomechanical unloading
Authors: Kandarian S. , O'Brien S. , Thomas K. , Schulte L. , Navarro J.
Published: December 2017

Biomechanical unloading of the rat soleus by hindlimb unweighting is known to induce atrophy and a slow- to fast-twitch transition of skeletal muscle contractile properties, particularly in slow-twitch muscles such as the soleus. The purpose of this study was to determine whether the expression of the dihydropyridine (DHP) receptor gene is upregulated in unloaded slow-twitch soleus muscles. A rat DHP receptor cDNA was isolated by screening a random-primed cDNA lambda gt10 library from denervated rat skeletal muscle with oligonucleotide probes complementary to the coding region of the rabbit DHP receptor cDNA. Muscle mass and DHP receptor mRNA expression were assessed 1, 4, 7, 14, and 28 days after hindlimb unweighting in rats by tail suspension. Isometric twitch contraction times of soleus muscles were measured at 28 days of unweighting. Northern blot analysis showed that tissue distribution of DHP receptor mRNA was specific for skeletal muscle and expression was 200% greater in control fast-twitch extensor digitorum longus (EDL) than in control soleus muscles. A significant stimulation (80%) in receptor message of the soleus was induced as early as 24 h of unloading without changes in muscle mass. Unloading for 28 days induced marked atrophy (control = 133 +/- 3 vs. unweighted = 62.4 +/- 1.8 mg), and expression of the DHP receptor mRNA in the soleus was indistinguishable from levels normally expressed in EDL muscles. These changes in mRNA expression are in the same direction as the 37% reduction in time to peak tension and 28% decrease in half-relaxation time 28 days after unweighting. Our results suggest that muscle loading necessary for weight support modulates the expression of the DHP receptor gene in the soleus muscle.
High lung volume increases stress failure in pulmonary capillaries
Authors: Fu Z. , Costello M. L. , Tsukimoto K. , Prediletto R. , Elliott A. R. , Mathieu-Costello O. , West J. B.
Published: December 2017

We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.
K+ channel pulmonary vasodilation in fetal lambs: role of endothelium-derived nitric oxide
Authors: Chang J. K. , Moore P. , Fineman J. R. , Soifer S. J. , Heymann M. A.
Published: December 2017

To define the role and mechanism of action of K+ channels in regulating fetal pulmonary vascular tone, we studied the hemodynamic effects of pinacidil (a K+ channel activator) and glibenclamide (a K+ channel blocker). The effects of pinacidil were compared with those of acetylcholine [an endothelium-derived relaxing factor- (EDRF) dependent pulmonary vasodilator] and 8-bromoguanosine 3′,5′-cyclic monophosphate (8-bromo-cGMP, an EDRF-independent pulmonary vasodilator) before and after treatment with N omega-nitro-L-arginine [a competitive inhibitor of an EDRF, endothelium-derived nitric oxide (EDNO), synthesis], or L-arginine (the substrate for the formation of EDNO). In 14 unanesthetized fetal lambs in utero, catheters were inserted into the fetal pulmonary artery, descending aorta, left atrium, and superior vena cava to measure pressures and administer drugs. An ultrasonic flow transducer was placed around the left pulmonary artery to measure flow (QP) continuously. In eight animals, pinacidil, acetylcholine, and 8-bromo-cGMP caused similar acute maximal increases in QP of 128, 137, and 155 ml/min, respectively. After a 60-min infusion of N omega-nitro-L-arginine (2.07 +/- 0.27 mg.kg-1.min-1), the increase in QP caused by acetylcholine and pinacidil was significantly attenuated, by 84 and 68%, respectively, with only a 10% attenuation of the increase in QP caused by 8-bromo-cGMP. In six additional N omega-nitro-L-arginine-pretreated fetal lambs, infusion of L-arginine (32.2 +/- 4.3 mg.kg-1.min-1) restored the vasodilatory effects of acetylcholine and pinacidil. A 20-min infusion of glibenclamide (n = 6; 0.64 +/- 0.07 mg.kg-1.min-1) blocked the vasodilation by pinacidil but not acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of age and physical activity status on the speed-aerobic demand relationship of walking
Authors: Martin P. E. , Rothstein D. E. , Larish D. D.
Published: December 2017

Older adults tend to show lower preferred walking speeds and higher aerobic demands per distance walked than young adults. It has been suggested that a more sedentary life-style contributes to diminished musculoskeletal functioning, which in turn contributes to poorer economy of motion in the aged and sedentary adults. The purpose of this study was to quantify the speed-aerobic demand relationship during walking for old (greater than 65 yr of age) and young adults and to determine whether physical activity status affects this relationship. Aerobic demands for 30 young and 30 old individuals representing sedentary and physically active groups were measured as the subjects performed treadmill walking at seven speeds ranging from 0.67 to 2.01 m/s. All four age/physical activity groups displayed U-shaped speed-aerobic demand curves with minimum gross oxygen consumption per unit distance walked (ml.kg-1.km-1) at 1.34 m/s. A statistically significant age effect on walking aerobic demand was observed, with old subjects showing an 8% higher mean aerobic demand than the young subjects. This age-related effect was not associated with shifts in the speed at which aerobic demand was minimized or with the preferred walking speed of older individuals falling on a less economical portion of the speed-aerobic demand curve. Rather, it was speculated that declines in force-generating capacity of muscle in the aged may require recruitment of additional motor units and perhaps an additional proportion of less economical fast twitch muscle fibers to generate necessary forces. Physical activity status had no significant effect on walking aerobic demand.(ABSTRACT TRUNCATED AT 250 WORDS)
Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis
Authors: Meyer J. , Traber L. D. , Nelson S. , Lentz C. W. , Nakazawa H. , Herndon D. N. , Noda H. , Traber D. L.
Published: December 2017

Septic shock is characterized by an increase in cardiac output and a fall in systemic vascular resistance index and mean arterial pressure. Endotoxin alters the smooth muscle function of blood vessels, probably by means of an increased production of the potent vasodilator nitric oxide (NO). The present study was accomplished to determine how the inhibition of NO synthesis influences cardiovascular performance in an ovine model of hyperdynamic endotoxemia. Endotoxemia was induced in five range ewes (41 +/- 2 kg) by continuous infusion of Escherichia coli endotoxin (LPS, 10 ng.kg-1.min-1) over the entire study period. After 24 h of LPS infusion, cardiac output increased from 5.2 +/- 0.3 to 7.9 +/- 0.6 (SE) 1/min (P less than 0.05) and mean arterial pressure and systemic vascular resistance index fell from 92 +/- 5 to 79 +/- 6 mmHg (P = 0.08) and from 1,473 +/- 173 to 824 +/- 108 dyn.s.cm-5.m2 (P less than 0.05), respectively. The pulmonary shunt fraction increased from 0.23 +/- 0.03 to 0.32 +/- 0.03 (P less than 0.05). The intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (25 mg/kg) 24 h after the start of the LPS infusion changed these values to approximately baseline levels over the subsequent 4 h. Although N omega-nitro-L-arginine methyl ester increased pulmonary arterial pressure and pulmonary vascular resistance (P less than 0.05), right and left ventricular stroke volume index showed no significant changes. It is concluded that NO has a major function in cardiovascular performance in endotoxemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of leukopenia on pulmonary hypertension after heparin-protamine in pigs
Authors: Habazettl H. , Conzen P. F. , Vollmar B. , Yekebas E. , Peter K.
Published: December 2017

Heparin neutralization by protamine after cardiac surgery and cardiopulmonary bypass may be associated with complement activation, transient leukopenia, thromboxane A2 release, and severe pulmonary hypertension. The role of leukocytes in the heparin-protamine reaction was studied in leukopenic pigs (n = 9) and a control group (n = 8). Leukopenia was induced by pretreatment with cyclophosphamide (30 mg.kg-1.day-1) for 6–7 days. During general anesthesia and after catheterization, baseline recordings of hemodynamics were performed and blood samples were withdrawn. Heparin (250 IU/kg) was injected and measurements were repeated after 10 min. Protamine sulfate (100 mg) was then infused over 2 min and measurements were performed after 2, 5, and 15 min. Prostanoid concentrations were measured by radioimmunoassays. In additional in vitro experiments, the release of thromboxane B2 from washed platelets and leukocytes after heparin-protamine stimulation was measured. Pretreatment with cyclophosphamide reduced leukocyte counts by 95.5% and the number of neutrophils by greater than 99.9%. Protamine infusion increased mean pulmonary arterial pressure by 74 and 46% and pulmonary vascular resistance by 185 and 384% in control and leukopenic animals, respectively. Thromboxane B2 concentrations increased in both groups. Stimulation by heparin, protamine, or heparin and protamine in sequence did not induce any thromboxane A2 release from washed blood cells. It is concluded that leukocytes do not contribute to pulmonary hypertension after heparin-protamine.
Hypertrophic response to unilateral concentric isokinetic resistance training
Authors: Housh D. J. , Housh T. J. , Johnson G. O. , Chu W. K.
Published: December 2017

The purposes of this study were to 1) determine the effect of concentric isokinetic training on strength and cross-sectional area (CSA) of selected extensor and flexor muscles of the forearm and leg, 2) examine the potential for preferential hypertrophy of individual muscles within a muscle group, 3) identify the location (proximal, middle, or distal level) of hypertrophy within an individual muscle, and 4) determine the effect of unilateral concentric isokinetic training on strength and hypertrophy of the contralateral limbs. Thirteen untrained male college students [mean age 25.1 +/- 6.1 (SD) yr] volunteered to perform six sets of 10 repetitions of extension and flexion of the nondominant limbs three times per week for 8 wk, using a Cybex II isokinetic dynamometer. Pretraining and posttraining peak torque and muscle CSA measurements for both the dominant and nondominant limbs were determined utilizing a Cybex II isokinetic dynamometer and magnetic resonance imaging scanner, respectively. The results indicated significant (P less than 0.0008) hypertrophy in all trained muscle groups as well as preferential hypertrophy of individual muscles and at specific levels. None of the muscles of the contralateral limbs increased significantly in CSA. In addition, significant (P less than 0.0008) increases in peak torque occurred for trained forearm extension and flexion as well as trained leg flexion. There were no significant increases in peak torque, however, for trained leg extension or for any movement in the contralateral limbs. These data suggest that concentric isokinetic training results in significant strength and hypertrophic responses in the trained limbs.
Mechanical impedances of lungs and chest wall in the cat
Authors: Hantos Z. , Adamicza A. , Govaerts E. , Daroczy B.
Published: December 2017

In nine anesthetized and paralyzed cats, the mechanical impedances of the total respiratory system (Zrs) and the lungs (ZL) were measured with small-volume pseudorandom forced oscillations between 0.2 and 20 Hz. ZL was measured after thoracotomy, and chest wall impedance (Zw) was calculated as Zw = Zrs-ZL. All impedances were determined by using input airflow [input impedance (Zi)] and output flow measured with a body box [transfer impedance (Zt)]. The differences between Zi and Zt were small for Zrs and negligible for ZL. At 0.2 Hz, the real and imaginary parts of ZL amounted to 33 +/- 4 and 35 +/- 3% (SD), respectively, of Zrs. Up to 8 Hz, all impedances were consistent with a model containing a frequency-independent resistance and inertance and a constant-phase tissue part (G-jH)/omega alpha, where G and H are coefficients for damping and elastance, respectively, omega is angular frequency, and alpha determines the frequency dependence of the real and imaginary parts. G/H was higher for Zw than for ZL (0.29 +/- 0.05 vs. 0.22 +/- 0.04, P less than 0.01). In four cats, the amplitude dependence of impedances was studied: between oscillation volumes of 0.8 and 3 ml, GL, HL, Gw, and Hw decreased on average by 3, 9, 26, and 29%, respectively, whereas the change in G/H was small for both ZL (7%) and Zw (-4%). The values of H were two to three times higher than the quasistatic elastances estimated with greater volume changes (greater than 20 ml).
Regional differences in myosin heavy chain isoforms and enzyme activities of the rat diaphragm
Authors: Sugiura T. , Morita S. , Morimoto A. , Murakami N.
Published: December 2017

Myosin heavy chain isoforms and enzyme activities were compared between the costal and crural regions of the rat diaphragm. The percentage of heavy chain (HC) IIb in the crural region of the diaphragm was significantly (P less than 0.05) higher than that in the costal region (mean 7.3 vs. 3.0%), and the percentage of HCI was significantly lower in the crural than in the costal diaphragm (22.7 vs. 27.9%). The distributions of HCIIa and HCIId were relatively homogeneous in both regions. Succinate dehydrogenase activity in the costal diaphragm was 21% greater (P less than 0.01) than in the crural diaphragm. In contrast, there was no significant difference in the activity of phosphofructokinase in the crural and costal diaphragms. These results demonstrate that a difference in myosin heavy chain isoforms and oxidative capacity exists between the costal and crural regions of the rat diaphragm.
Analysis of pharyngeal resistance and genioglossal EMG activity using a model of orifice flow
Authors: Leiter J. C.
Published: December 2017

A model of orifice flow has been used to analyze the relationships among pressure, flow, and genioglossal electromyographic activity in the human pharynx during inspiration. The orifice flow model permits one to assess the character of airflow (laminar or turbulent) and to estimate the cross-sectional area of the orifice from pressure and flow measurements. On the basis of other data (J. Appl. Physiol. 73: 584–590, 1992), this analysis suggests that pharyngeal airflow is turbulent. Furthermore the area of the pharynx appears to increase as flow increases, but the actual change in pharyngeal diameter necessary to fit the pressure-flow data is quite small (0.11–0.87 cm, depending on the assumptions in the model). The flow-related increase in orifice area can be attributed, in part, to the activation of the genioglossus muscle. However, other flow-related factors may also contribute to pharyngeal dilation as airflow increases. Different airway shapes (circular and elliptical) and orientations (major axis anteroposterior and lateral) were incorporated into the model calculations; these factors modify considerably the apparent efficiency of genioglossal electromyographic activity. Genioglossal muscle shortening increases pharyngeal area and reduces pharyngeal resistance more effectively when the pharynx is elliptical, with the long axis of the ellipse oriented laterally. Hence the genioglossus may operate at a significant mechanical disadvantage in those patients with obstructive sleep apnea with a small sagittally oriented pharyngeal lumen.
Parenchymal stability
Authors: Stamenovic D. , Wilson T. A.
Published: December 2017

Both continuum and micromechanical models have been used to describe the mechanics of lung parenchyma. Different authors, using different models, have come to different conclusions about parenchymal stability. We show that the continuum model, augmented by bounds on the elastic moduli obtained from recent micromechanical modeling, yields the same conclusions about stability that have been obtained from purely micromechanical modeling: if the lung were homogeneous, it would be stable; local atelectasis would not occur at positive transpulmonary pressure. However, the same analysis yields the prediction that if the surface-to-volume ratio is not uniform throughout the lung, regions of higher surface density collapse if surface tension is large and insensitive to surface area. A micromechanical model that illustrates regional collapse is described.
Short-duration spaceflight impairs human carotid baroreceptor-cardiac reflex responses
Authors: Fritsch J. M. , Charles J. B. , Bennett B. S. , Jones M. M. , Eckberg D. L.
Published: December 2017

Orthostatic intolerance is a predictable but poorly understood consequence of space travel. Because arterial baroreceptors modulate abrupt pressure transients, we tested the hypothesis that spaceflight impairs baroreflex mechanisms. We studied vagally mediated carotid baroreceptor-cardiac reflex responses (provoked by neck pressure changes) in the supine position and heart rate and blood pressure in the supine and standing positions in 16 astronauts before and after 4- to 5-day Space Shuttle missions. On landing day, resting R-R intervals and standard deviations, and the slope, range, and position of operational points on the carotid transmural pressure-sinus node response relation were all reduced relative to preflight. Stand tests on landing day revealed two separate groups (one maintained standing arterial pressure better) that were separated by preflight slopes, operational points, and supine and standing R-R intervals and by preflight-to-postflight changes in standing pressures, body weights, and operational points. Our results suggest that short-duration spaceflight leads to significant reductions in vagal control of the sinus node that may contribute to, but do not account completely for, orthostatic intolerance.
Autoresuscitation: a survival mechanism in piglets
Authors: Sanocka U. M. , Donnelly D. F. , Haddad G. G.
Published: December 2017

Piglets were studied to determine 1) the cardiovascular and neurophysiological effects of prolonged laryngeal-induced respiratory inhibition (n = 7) and 2) whether these effects were modulated by autonomic blockade (n = 6). Respiration, electrocardiogram, electroencephalogram (EEG), and blood pressure were recorded, and blood gases were measured. During continuous laryngeal stimulation in the presence of light anesthesia, apnea was interrupted every 1–2.5 min by clusters of two to six breaths. Compared with control, these breaths had a significantly greater tidal volume (430 +/- 30% of control), shorter inspiratory time (87 +/- 5%), and longer expiratory time (124 +/- 15%) and, thus, were of a gasping nature. With each cluster of gasps, arterial PO2 increased from 15 +/- 2 to 56 +/- 5 Torr, heart rate from 84 +/- 7 to 161 +/- 5 beats/min, and mean blood pressure from 48 +/- 4 to 106 +/- 6 mmHg. The EEG became flat by 1 min after the onset of apnea and remained isoelectric throughout the stimulus period. Cyclical gasps were not affected by sympathetic or parasympathetic blockade. These data show that, despite EEG silence, piglets can autoresuscitate by initiating gasps that are not dependent on autonomic integrity. These gasps markedly improve cardiovascular status and may sustain animals for a prolonged period of time.
Effects of microgravity or simulated launch on testicular function in rats
Authors: Amann R. P. , Deaver D. R. , Zirkin B. R. , Grills G. S. , Sapp W. J. , Veeramachaneni D. N. , Clemens J. W. , Banerjee S. D. , Folmer J. , Gruppi C. M. , et al.
Published: December 2017

Testes from flight rats on COSMOS 2044 and simulated-launch, vivarium, or caudal-elevation control rats (5/group) were analyzed by subjective and quantitative methods. On the basis of observations of fixed tissue, it was evident that some rats had testicular abnormalities unassociated with treatment and probably existing when they were assigned randomly to the four treatment groups. Considering rats without preexisting abnormalities, diameter of seminiferous tubules and numbers of germ cells per tubule cross section were lower (P less than 0.05) in flight than in simulated-launch or vivarium rats. However, ratios of germ cells to each other or to Sertoli cells and number of homogenization-resistant spermatids did not differ from values for simulated-launch or vivarium controls. Expression of testis-specific gene products was not greatly altered by flight. Furthermore, there was no evidence for production of stress-inducible transcripts of the hsp70 or hsp90 genes. Concentration of receptors for rat luteinizing hormone in testicular tissue and surface density of smooth endoplasmic reticulum in Leydig cells were similar in flight and simulated-launch rats. However, concentrations of testosterone in testicular tissue or peripheral blood plasma were reduced (P less than 0.05) in flight rats to less than 20% of values for simulated-launch or vivarium controls. Thus spermatogenesis was essentially normal in flight rats, but production of testosterone was severely depressed. Exposure to microgravity for greater than 2 wk might result in additional changes. Sequelae of reduced androgen production associated with microgravity on turnover of muscle and bone should be considered.
Rat soleus muscle fiber responses to 14 days of spaceflight and hindlimb suspension
Authors: Ohira Y. , Jiang B. , Roy R. R. , Oganov V. , Ilyina-Kakueva E. , Marini J. F. , Edgerton V. R.
Published: December 2017

Morphological and enzymatic responses in fibers expressing fast, slow, or both types of myosin heavy chain (MHC) were studied in rats after 14 days of spaceflight (COSMOS 2044) or hindlimb suspension. Although the percentage of slow-twitch fibers was unchanged, a higher percentage of fibers that expressed both slow and fast MHC was observed in flight and suspended rats than in synchronous ground-based controls. The soleus was 25 and 34% smaller than control after 14 days of flight and suspension, with the reduction in fiber cross-sectional area (CSA) being greater in slow- than in fast-twitch fibers in both experimental groups. The activities of succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPD) were not significantly affected by flight or suspension. The total SDH activity (i.e., SDH activity x CSA) decreased significantly in the slow-twitch fibers of the flight and the fast-twitch fibers of the suspended rats, in large part due to fiber atrophy. A shift in MHC expression in 14 and 9% of the fibers in flight and suspended rats occurred without a change in myosin adenosinetriphosphatase activity. The SDH and GPD activities of the fibers that expressed both slow and fast MHC were slightly higher than the slow-twitch fibers and slightly lower than the fast-twitch fibers. These data indicate that events were initiated within 14 days of spaceflight or suspension that began to reconfigure the protein profiles of 9–14% of the slow-twitch fibers from typical slow-twitch toward those of fast-twitch fibers, while all fibers were dramatically losing total protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Periodic hemodynamics in skeletal muscle during local arterial pressure reduction
Authors: Schmidt J. A. , Intaglietta M. , Borgstrom P.
Published: December 2017

The time-dependent features of red blood cell flow were evaluated with laser-Doppler flowmetry (LDF) in the left gastrocnemius muscle of 31 anesthetized New Zealand White rabbits during stepwise arterial occlusion. During the control period with a median femoral pressure of 72 mmHg, 29 animals showed minor irregular fluctuations in LDF blood flow, and only two animals displayed periodic variations of blood flow. Lowering femoral arterial pressure induced maximal periodic blood flow variations at a median pressure of 35 mmHg in all animals with a median frequency of 1.5 cycles/min (termed “slow-wave flow motion”). The median amplitude was 48% of the corresponding average flow. These slow waves disappeared at a median femoral pressure of 20 mmHg. The median LDF flow value was 4.00 arbitrary units (AU) at control pressure and 2.05 AU at maximum slow-wave flow motion. When slow-wave flow motion was seen at several pressure levels, their frequency was identical, which supports the local pacemaker concept. This study promotes a novel concept for the role and physiological significance of periodic hemodynamics in that it is a condition not characteristic for normal control situations but is activated below a specific local arterial blood pressure and flow threshold, which is known to be the lower end of autoregulation in the microcirculation of rabbit skeletal muscle. This also suggests that slow-wave flow motion is primarily under local control mechanisms.
Neutral endopeptidase inhibitor potentiates endothelin-1-induced airway smooth muscle contraction
Authors: Yamaguchi T. , Kohrogi H. , Kawano O. , Ando M. , Araki S.
Published: December 2017

To study the role of neutral endopeptidase (NEP) on endothelin-1-induced contraction of the airway smooth muscle, we examined the contractile effect of endothelin-1 in the isolated guinea pig trachea and human bronchus in the presence or absence of NEP inhibitor phosphoramidon. After incubation with phosphoramidon (10(-8) to 10(-5) M), we added endothelin-1 cumulatively from 10(-11) to 10(-7) M to the airway tissues in organ baths. Phosphoramidon significantly potentiated the endothelin-1-induced contraction in a concentration-dependent fashion in both guinea pig trachea and human bronchus, and it shifted the concentration-response curves to the left. Because NEP is known to cleave tachykinins, we next studied whether endothelin-1 contracts airway tissues by releasing endogenous tachykinins from bronchial C-fibers. After incubation with phosphoramidon (10(-5) M), we added endothelin-1 cumulatively from 10(-11) to 10(-7) M to the tissues that were treated with capsaicin to deplete the tachykinins. Phosphoramidon significantly potentiated the endothelin-1-induced contraction in the capsaicin-treated tissues, suggesting that endothelin-1 causes the contraction, at least in part, without releasing tachykinins. In contrast to the effect of phosphoramidon, captopril (an angiotensin-converting enzyme inhibitor), leupeptin (a serine protease inhibitor), and bestatin (an aminopeptidase inhibitor) did not modulate the effect of endothelin-1-induced contraction in both guinea pig trachea and human bronchus. From these results, we conclude that NEP plays an important role in regulating endothelin-1-induced contraction in the guinea pig trachea and human bronchus.
Accumulated oxygen deficit increases with inclination of uphill running
Authors: Olesen H. L.
Published: December 2017

This study examined whether accumulated oxygen deficit depends on treadmill grade during uphill running. Oxygen uptake was measured during steady-state submaximal running. By linear extrapolation at each grade, energy demand was estimated for short exhaustive runs. Oxygen deficit was the difference between this estimate and accumulated oxygen uptake. Six subjects ran at grades of 1, 15, and 20% (study I), and five males trained for anaerobic metabolism ran at 1, 10.5, and 15% (study II). Accumulated oxygen deficit was 40 +/- 11 (SD), 72 +/- 20, and 69 +/- 8 ml O2/kg, respectively (study I), and 57 +/- 8, 78 +/- 10, and 100 +/- 7 ml O2/kg (study II). The finding that accumulated oxygen deficit became larger with treadmill inclination could reflect involvement of an increasing muscle mass. However, variation in accumulated oxygen deficit was too large to make this possibility the only explanation. More likely at small treadmill inclinations energy demand for high-intensity running is underestimated by extrapolation from oxygen uptake during submaximal exercise. At high grades of uphill running, accumulated oxygen deficit reached a maximum that may reflect the subjects' anaerobic capacity for running. This hypothesis was substantiated by an enhanced accumulated oxygen deficit in the anaerobically trained subjects during 15%, but not during 1%, uphill running.
Sensitivity to endotoxin in rabbits is increased after hemorrhagic shock
Authors: Mileski W. J. , Winn R. K. , Harlan J. M. , Rice C. L.
Published: December 2017

The immunoinflammatory response following trauma and hemorrhage may predispose to the development of sepsis and multiple-organ failure syndrome. Cardiac output (CO), arterial pressure, arterial PO2, and pulmonary permeability index were measured. We examined the sensitivity of rabbits to infusions of lipopolysaccharide (LPS) after hemorrhagic shock. Shock was produced by reducing CO to 40% of baseline for 90 min, followed by resuscitation with shed blood and then with lactated Ringer solution to maintain CO near baseline. Animals were assigned to three groups: 1) hemorrhagic shock only, 2) LPS only, and 3) hemorrhagic shock + LPS. Groups 1 and 3 were subjected to hemorrhagic shock on day 1. Escherichia coli LPS was infused (1.0 microgram/kg i.v.) into groups 2 and 3 on day 2. Fluid resuscitation with lactated Ringer solution was continued in an effort to maintain CO at baseline. Five hours after LPS infusion, 125I-albumin was injected intravenously, and rabbits were killed 1 h later for measurement of pulmonary permeability index. LPS infusion after shock (group 3) caused significant decreases in CO, arterial pressure, and PO2 and an increase in pulmonary permeability. These changes were not seen in the groups 1 and 2. We conclude that hemorrhagic shock and resuscitation result in a proinflammatory state, leading to increased sensitivity to subsequent exposure to LPS.
Optimized estimation of respiratory impedance by signal averaging in the time domain
Authors: Farre R. , Rotger M. , Navajas D.
Published: December 2017

The spontaneous breathing of a subject during measurements of respiratory impedance (Zrs) by the forced oscillation technique (FOT) induces errors that result in biased impedance estimates, especially at low frequencies. Although in standard measurements this bias may be avoided by using special impedance estimators, there are two applications of FOT for which such estimators are not useful: when a head generator is used and when measurements are made during intubation. In this paper we describe a data-processing procedure for unbiased impedance estimation for all FOT setups. The proposed estimator (Z) was devised for pseudorandom excitation and is based on time-domain signal averaging before frequency analysis. The performance of estimator Z was first analyzed by computer simulation of a head generator setup and a setup including an endotracheal tube to measure (2–32 Hz) a resistance-inertance-elastance model mimicking Zrs of a healthy subject. Second, Z was assessed during real measurements in 16 healthy subjects. The results obtained in the simulation (e.g., error in elastance was reduced from 15.6% with most conventional estimators to 3.3% with Z in simulation of head generator setup) and in the measurements in subjects (differences of less than 1.6% between Z and a reference) confirmed the theoretical lack of bias of Z and its practical suitability for the different FOT setups. In addition to its applicability in the situations in which no other unbiased estimators are available, estimator Z is also advantageous in most conventional applications of FOT, since it requires much less computing time and thus allows on-line Zrs measurements.
On the purported discovery of the bronchial circulation by Leonardo da Vinci
Authors: Mitzner W. , Wagner E.
Published: December 2017

Among modern physiologists and anatomists, there has been a nearly universal acceptance that Leonardo da Vinci was the first to identify the anatomy of the bronchial circulation. However, because of certain ambiguities in both his anatomic drawing that was supposed to have shown this circulation and the accompanying descriptive text, we questioned whether he really could have been the first to discover this small but important vasculature. To address this question, we set out to repeat Leonardo's dissections in the ox. We reasoned that perhaps the normally tiny bronchial vessels would be considerably more noticeable in this very large species. Our dissections, however, failed to provide any evidence that Leonardo's drawing was that of the bronchial circulation. Furthermore we observed a set of distinct small pulmonary veins to the left upper and right middle lobes that Leonardo, given his lack of understanding of the function of the lung and its circulation, could have easily mistaken for a separate circulation. We thus conclude that Leonardo da Vinci did not describe the anatomy of the bronchial circulation. We believe that the first person to clearly and unequivocally describe the anatomy of this circulation was the Dutch Professor of Anatomy and Botany, Frederich Ruysch.
Decrease in lung volume-related feedback enhances laryngeal reflexes to negative pressure
Authors: Zhang S. , Mathew O. P.
Published: December 2017

Negative pressure applied to the upper airway has an excitatory effect on the activity of upper airway muscles and an inhibitory effect on thoracic inspiratory muscles. The role of lung volume feedback in this response was investigated in 10 anesthetized spontaneously breathing adult rabbits. To alter lung volume feedback, the lower airway was exposed to SO2 (250 ppm for 15 min), thereby blocking slowly adapting receptors (SARs). Negative pressure pulses (5, 10, and 20 cmH2O, 300-ms duration) were applied to the functionally isolated upper airway before and after SAR blockade. Tracheal airflow and electromyogram (EMG) of the genioglossus and alae nasi were recorded. Peak EMG, peak inspiratory flow, tidal volume, and respiratory timing of control breaths (3 breaths immediately preceding test) and test breaths were determined. Analysis of variance was used to determine the significance of the effects. Negative pressure pulses increased peak EMG of genioglossus and alae nasi and inspiratory duration and decreased peak inspiratory flow. These effects were larger after SAR blockade. We conclude that a decrease in volume feedback from the lung augments the response to upper airway pressure change.
Relative contribution of bronchial flow to subpleural region in dog lung
Authors: Gilbert E. , Hakim T. S.
Published: December 2017

The bronchial flow is approximately 1% of the total pulmonary flow. Anastomosis between the bronchial and pulmonary vessels occurs primarily at the microcirculatory level. It is assumed that bronchopulmonary anastomoses are present in a homogeneous manner throughout lung parenchyma. To investigate this issue, an in situ blood-perfused left lower lung lobe (500 ml/min) was prepared in a live dog. The bronchial flow rate in the entire lobe was monitored using the rate of volume gain in the reservoir while the pulmonary and bronchial flow in the subpleural region was monitored using laser-Doppler flowmetry. The results were expressed as ratio of bronchial to pulmonary flow rate for the entire lobe and for the subpleural region. We found that, for the entire lobe, bronchial flow was 1.0% of pulmonary flow, while for the subpleural region this ratio was much higher, with an average of 12%. In two different experimental conditions that were imposed to affect the global bronchial flow, these ratios changed in the same direction as the global bronchial flow. After transfusion of blood into the animal, bronchial flow increased to 1.7%, while the subpleural bronchial flow increased to 18% of the subpleural pulmonary flow. During elevation of venous pressure, bronchial flow decreased to 0.6%, while the subpleural bronchial flow decreased to 10% of the subpleural pulmonary flow. The differences in the ratios between the global and subpleural region may be explained by having low pulmonary blood flow in the periphery compared with the interior regions of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in afferent and efferent phrenic activities with electrically induced diaphragmatic fatigue
Authors: Jammes Y. , Balzamo E.
Published: December 2017

In anesthetized artificially ventilated cats, diaphragmatic fatigue was produced by direct muscle stimulation with trains of pulses for 30 min. Failure of contraction was assessed from decrease in the maximal relaxation rate of transdiaphragmatic pressure twitches. Motor activities (electromyogram and motor phrenic neurogram) were processed by fast-Fourier transform analysis, which provided the power spectrum density function (PSDF). The discharge frequency of diaphragmatic afferents was also measured. In control conditions (before fatigue), intra-arterial bolus injection of lactic acid enhanced tonically active diaphragmatic afferents, whereas it reduced the firing rate of afferent fibers activated in phase with diaphragmatic contraction or relaxation. The same sensory response pattern was observed with the development of diaphragmatic fatigue. Leftward shift in PSDFs of motor phrenic neurogram also occurred, but it preceded the failure of diaphragmatic contraction as well as the changes in the electromyogram's PSDF and afferent paths, which were closely associated with lengthening of both inspiratory and total breath durations. After section of the phrenic nerves, the motor phrenic response disappeared during the fatigue trial. This demonstrates the existence of complex reflex-induced changes in the ventilatory control during diaphragmatic fatigue. They seem to involve the participation of several types of phrenic afferents.
Effect of downhill running on motoneuron pool excitability
Authors: Bulbulian R. , Bowles D. K.
Published: December 2017

The purpose of this study was to compare alterations in motoneuron pool excitability after eccentric-biased (ECC-B) downhill running exercise with non-biased (NO-B) level running exercise. Six male subjects (25–34 yr) participated in the study, which included ECC-B exercise (-10% grade) and NO-B exercise (0% grade) at 50% of maximal O2 uptake for 20 min. The control trial consisted of 20 min of quiet rest with all subjects participating in all conditions (repeated measures). Motoneuron pool excitability was measured by the Hoffman reflex (H-wave), which was expressed as a ratio (H/M ratio) of the maximal electrically stimulated muscle action potential (M-wave). NO-B exercise resulted in a 9.3 +/- 2.7% (SE) reduction in the H/M ratio. ECC-B exercise resulted in a 24.6 +/- 5.7% reduction in the ratio (P less than 0.05 for both). The two exercise treatment conditions were also significantly different from one another (P less than 0.05). Twenty-four-hour postexercise H/M ratios were similar to baseline (P greater than 0.05). Postexercise subjective muscle soreness assessment (DOMS) produced significant increases in DOMS of 36 and 166% immediately and 24 h after exercise, respectively, for the ECC-B trial only (P less than 0.001). The data show that ECC-B exercise results in greater postexercise H/M ratio reductions than NO-B exercise and that H/M ratio changes post-ECC-B exercise are not solely associated with DOMS.
Effect of acute nutritional deprivation on diaphragm structure and function in adolescent rats
Authors: Lewis M. I. , Sieck G. C.
Published: December 2017

The influence of 90 h of acute nutritional deprivation (ND; water ad libitum only) on in vitro contractile and fatigue properties, muscle fiber type proportions, and cross-sectional areas (CSA) of the adolescent rat diaphragm was determined. Diaphragm muscle properties in the ND rats were compared with those in control rats (CTL; food and water ad libitum). Acute ND resulted in a 32% reduction in body mass, whereas the body mass of CTL rats increased by 29%. Acute ND resulted in a significant reduction in the mass of the diaphragm (costal, 36%; crural, 43%), soleus (36%), and medial gastrocnemius (45%) muscles. Isometric twitch characteristics of the diaphragm muscle (contraction and half-relaxation times) were prolonged in the ND animals. Peak twitch and maximum tetanic forces were unaffected by ND. Fatigue resistance of the diaphragm muscle was improved in ND animals. Diaphragm muscle fiber type proportions were similar in ND and CTL groups. The CSA of type I and II diaphragm muscle fibers were reduced by 22 and 40%, respectively, in ND animals compared with CTL. We conclude that, whereas an identical protocol of acute ND had no significant effects on diaphragm muscle structure and function in adult rats, adolescent animals exhibit significantly less nutritional reserve. These differences may be due to curtailment of the rapid anabolic rate in growing animals.
Mapping of electrical muscle stimulation using MRI
Authors: Adams G. R. , Harris R. T. , Woodard D. , Dudley G. A.
Published: December 2017

The purpose of this study was to map the pattern of muscle contractile activity elicited by electromyostimulation (EMS). A secondary interest was to determine whether EMS evoked a different pattern of contractile activity than voluntary (VOL) efforts. These objectives were addressed by examining the pattern and extent of contrast shift in magnetic resonance (MR) images after isometric actions of the left m. quadriceps of seven subjects had been elicited by EMS (1-s train of 500-microseconds sine wave pulses at 50 Hz) or by VOL means. For both conditions, five sets of 10 muscle actions were executed at each of the three force levels equal to 25, 50, and 75% of maximal VOL isometric torque. There were 1-s, 1.5-min, and 30-min rests between muscle actions, sets, and torque levels, respectively. Transaxial proton MR images (TR/TE = 2,000/30, 60) of m. quadriceps femoris were obtained with a 1.5-T imager at rest and after completion of the five sets of isometric actions at each force level. MR image contrast shift, as indicated by T2 values > 1 SD above the mean resting muscle T2, was calculated per pixel. Torque declined approximately 18% (P < 0.05) during each EMS set independent of the preset relative force level but recovered between sets. EMS increased T2 values above rest (29 +/- 0.2 to 36 +/- 0.5, P < 0.05) in regions of muscle dispersed throughout a given cross section. The pattern of muscle stimulation, as reflected by increased T2 values, varied markedly among subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Peripheral pulmonary vascular resistance
Authors: Schrijen F. , Saunier C. , Chabot F.
Published: December 2017

The pressure-flow relationship has been studied in a peripheral portion of the lung vasculature in anesthetized dogs with use of a double-lumen catheter wedged in a distal pulmonary artery. One lumen was used to infuse mixed venous blood in the wedged area and the other to measure the corresponding perfusion pressure. Flow ranged from 0 to 9.2 ml/min, and the mean volume of the wedged area (n = 59) was 0.75 +/- 0.05 (SE) ml. In the areas where the distal pulmonary artery was in the same direction as the catheter ("coaxial"), the mean pressure-flow curve showed a negligible gamma-intercept and no significant difference between ascending and descending flow. The slope of the initial part of the ascending limb (peripheral pulmonary vascular resistance) varied from site to site and did not show a significant correlation with the overall pulmonary vascular resistance; it was inversely correlated with the volume of the wedged area (r = -0.35, P < 0.05) and directly, as expected, correlated with the y-intercept (r = 0.78, P < 0.001) and hysteresis (r = 0.48, P < 0.001). The results of two consecutive pressure-flow runs in the same site showed similar results, with no difference exceeding the error of measurement. In contrast, the slope increased by 71% during hypoxia (fraction of inspired O2 was 0.10, n = 5). This procedure seems suitable to determine the effects of physiological or pharmacological interventions on the pulmonary vessels, without interference of the systemic circulation.
Diaphragmatic activity induced by cortical stimulation: surface versus esophageal electrodes
Authors: Gea J. , Espadaler J. M. , Guiu R. , Aran X. , Seoane L. , Broquetas J. M.
Published: December 2017

Evoked responses of the diaphragm can be induced by magnetic cortical stimulation and recorded by either surface or esophageal electrodes. The former recording system is tolerated better by the patient but has potential problems with the specificity of the diaphragmatic signal. This study compares the responses of the diaphragm to cortical stimulation that were recorded simultaneously with surface and esophageal electrodes on seven patients (61 +/- 4 yr) with chronic obstructive pulmonary diseases. Stimuli were delivered in three ventilatory conditions: at baseline, during deep breathing, and during voluntary panting. No differences were observed between results recorded by surface and esophageal electrodes [amplitude of the compound motor of the action potential (CMAP), 0.8 +/- 0.1 vs. 0.8 +/- 0.1 mV, NS; latency, 13.1 +/- 0.4 vs. 12.6 +/- 0.5 ms, NS]. In addition, significant correlations were found (CMAP, r = 0.77, P < 0.001; latency, r = 0.71, P = 0.002). The concordance analysis, however, indicated some dissimilarity between the recordings of the electrodes (CMAP, R1 = 0.31; latency, R1 = 0.26). These differences may be due to the area of the muscle mainly recorded by each electrode and/or to the additional activity from other muscles recorded by surface electrodes. On the other hand, the diaphragmatic responses observed in these patients with chronic obstructive pulmonary diseases were similar to those previously reported in healthy subjects.