bluuebunny/crossref_metadata_2025 huggingface dataset:
Volume of activation of the Hering-Breuer inflation reflex in the newborn infant
Authors: Hassan A. , Gossage J. , Ingram D. , Lee S. , Milner A. D.
Published: December 2017

Although the Hering-Breuer inflation reflex (HBIR) is active within tidal breathing range in the neonatal period, there is no information regarding whether a critical volume has to be exceeded before any effect can be observed. To explore this, effects of multiple airway occlusions on inspiratory and expiratory timing were measured throughout tidal breathing range using a face mask and shutter system. In 20 of the 22 healthy infants studied, there was significant shortening of inspiration because the volume at which occlusion occurred rose from functional residual capacity (FRC) to end-inspiratory volume [14.9% reduction in inspiratory time (per ml/kg increase in lung volume at occlusion)]. All infants showed a significant increase in expiratory time [17.1% increase (per ml/kg increase in lung volume at occlusion)]. Polynomial regression analyses revealed a progressive increase in strength of HBIR from FRC to ∼4 ml/kg above FRC. Eighteen infants showed no further shortening of inspiratory time and 10 infants no further lengthening of expiratory time with increasing occlusion volumes, indicating maximal stimulation of the reflex had been achieved. There was a significant relationship between strength of HBIR and respiratory rate, suggesting that HBIR modifies the breathing pattern in the neonatal period.
Heterogeneity of metabolic activity in the canine parasternal intercostals during breathing
Authors: Legrand Alexandre , Goldman Serge , Damhaut Philippe , De Troyer André
Published: December 2017

In the dog, the inspiratory mechanical advantage of the parasternal intercostals shows a marked spatial heterogeneity, whereas the expiratory mechanical advantage of the triangularis sterni is relatively uniform. The contribution of a particular respiratory muscle to lung volume expansion during breathing, however, depends both on the mechanical advantage of the muscle and on its neural input. To evaluate the distribution of neural input across the canine parasternal intercostals and triangularis sterni, we have examined the distribution of metabolic activity among these muscles in seven spontaneously breathing animals by measuring the uptake of the glucose tracer analog [18F]fluorodeoxyglucose (FDG). FDG uptake in any given parasternal intercostal was greatest in the medial bundles and decreased rapidly toward the costochondral junctions. In addition, FDG uptake in the medial parasternal bundles increased from the first to the second interspace, plateaued in the second through fifth interspaces, and then decreased progressively toward the eighth interspace. In contrast, uptake in the triangularis sterni showed no significant rostrocaudal gradient. These results overall strengthen the idea that the spatial distribution of neural input within a particular set of respiratory muscles is closely matched with the spatial distribution of mechanical advantage.
Effects of perfluorochemical distribution and elimination dynamics on cardiopulmonary function
Authors: Miller Thomas F. , Milestone Bart , Stern Robert , Shaffer Thomas H. , Wolfson Marla R.
Published: December 2017

Based on a physicochemical property profile, we tested the hypothesis that different perfluorochemical (PFC) liquids may have distinct effects on intrapulmonary PFC distribution, lung function, and PFC elimination kinetics during partial liquid ventilation (PLV). Young rabbits were studied in five groups [healthy, PLV with perflubron (PFB) or with perfluorodecalin (DEC); saline lavage injury and conventional mechanical ventilation (CMV); saline lavage injury PLV with PFB or with DEC]. Arterial blood chemistry, respiratory compliance (Cr), quantitative computed tomography of PFC distribution, and PFC loss rate were assessed for 4 h. Initial distribution of PFB was more homogenous than that of DEC; over time, PFB redistributed to dependent regions whereas DEC distribution was relatively constant. PFC loss rate decreased over time in all groups, was higher with DEC than PFB, and was lower with injury. In healthy animals, arterial Po2(PaO2) and Cr decreased with either PFC; the decrease was greater and sustained with DEC. Lavaged animals treated with either PFC demonstrated increased PaO2, which was sustained with PFB but deteriorated with DEC. Lavaged animals treated with PFB demonstrated increased Cr, higher PaO2, and lower arterial Pco2than with CMV or PLV with DEC. The results indicate that 1) initial distribution and subsequent intrapulmonary redistribution of PFC are related to PFC properties; 2) PFC distribution influences PFC elimination, gas exchange, and Cr; and 3) PFC elimination, gas exchange, and Cr are influenced by PFC properties and lung condition.
A self-correcting indirect calorimeter system for the measurement of energy balance in small animals
Authors: Jensen Dalan R. , Gayles Ellis C. , Ammon Stefen , Phillips Robert , Eckel Robert H.
Published: December 2017

Indirect calorimetry involves measurement of CO2 produced and O2 consumed by an organism. These measurements are then used to calculate energy output, metabolic rate (MR), and respiratory quotient (RQ), a relative assessment of carbohydrate and lipid oxidation. By far the most difficult aspect of indirect calorimetry is measurement of O2. Moreover, the abundance of O2 (20.95%) relative to CO2 (0.03%) in ambient conditions dictates that measurement errors of O2 have greater implications on calculations of MR and RQ. Because compressed air is not feasible for use with animals in long-term experiments, changes in ambient conditions are nearly unavoidable. A self-correcting indirect calorimetry system was designed and constructed utilizing differential O2 and CO2 analyzers and a blank cage to monitor ambient conditions periodically. The system was validated by changing ambient O2 and CO2 concentrations by infusing N2 into the system during a test butane burn. MR and RQ were largely unaffected by these changes in ambient conditions, and inclusion of a blank cage in the system accounted for slight calibration offsets. MR and RQ were measured in mice ( n= 95) with and without correction for any small changes in ambient conditions measured in the blank cage. Coefficients of variation for MR and RQ were significantly decreased by taking into account ambient conditions measured in the blank cage ( P < 0.001), which resulted in a 2.3% increase in precision for measurement of MR. This system will be used to more accurately assess long-term measurements of energy balance in the many murine models of leanness and obesity to gain better insights into pathophysiology and treatment of human obesity.
Basophils and exercise-induced hypoxemia in extreme athletes
Authors: Mucci Patrick , Durand Fabienne , Lebel Bernard , Bousquet Jean , Préfaut Christian
Published: December 2017

This study examined whether the increase in histamine release (%H, i.e., plasma histamine expressed as a percentage of whole blood histamine) associated with exercise-induced hypoxemia (EIH) is related to high training-induced changes in basophil and osmolarity factors in arterial blood. All parameters were measured in 20 endurance athletes, 11 of whom presented an EIH (HThyp) and 9 of whom were nonhypoxemic (HTnor), and in 10 untrained control subjects (UT). Measurements were made at rest, at the maximal workload of an incremental exhaustive exercise test, and at the fifth minute of recovery. %H increased during exercise in HThyp( P < 0.01) but did not increase significantly in HTnorand UT controls. The results indicated that 1) osmolarity and Na+and K+concentrations did not differ between the two trained groups and 2) the basophil count and basophil histamine content did not differ among groups. We concluded that the %H increase associated with EIH was not due to a training effect on these parameters. The relatively low increase in histamine content during exercise in HThypin comparison to HTnor( P < 0.05) and UT ( P < 0.01) and the low recovery vs. resting basophil count only in HThyp( P < 0.01) suggested an accentuated exercise-induced basophil degranulation in the hypoxemic athletes.
Effect of long-duration spaceflight on postural control during self-generated perturbations
Authors: Layne Charles S. , Mulavara Ajitkumar P. , McDonald P. Vernon , Pruett Casey J. , Kozlovskaya Innessa B. , Bloomberg Jacob J.
Published: December 2017

This report is the first systematic evaluation of the effects of prolonged weightlessness on the bipedal postural control processes during self-generated perturbations produced by voluntary upper limb movements. Spaceflight impacts humans in a variety of ways, one of which is compromised postflight postural control. We examined the neuromuscular activation characteristics and center of pressure (COP) motion associated with arm movement of eight subjects who experienced long-duration spaceflight (3–6 mo) aboard the Mir space station. Surface electromyography, arm acceleration, and COP motion were collected while astronauts performed rapid unilateral shoulder flexions before and after spaceflight. Subjects generally displayed compromised postural control after flight, as evidenced by modified COP peak-to-peak anterior-posterior and mediolateral excursion, and pathlength relative to preflight values. These changes were associated with disrupted neuromuscular activation characteristics, particularly after the completion of arm acceleration (i.e., when subjects were attempting to maintain upright posture in response to self-generated perturbations). These findings suggest that, although the subjects were able to assemble coordination modes that enabled them to generate rapid arm movements, the subtle control necessary to maintain bipedal equilibrium evident in their preflight performance is compromised after long-duration spaceflight.
CNTF genotype is associated with muscular strength and quality in humans across the adult age span
Authors: Roth Stephen M. , Schrager Matthew A. , Ferrell Robert E. , Riechman Steven E. , Metter E. Jeffrey , Lynch Nicole A. , Lindle Rosemary S. , Hurley Ben F.
Published: December 2017

The relationship between ciliary neurotrophic factor (CNTF) genotype and muscle strength was examined in 494 healthy men and women across the entire adult age span (20–90 yr). Concentric (Con) and eccentric (Ecc) peak torque were assessed using a Kin-Com isokinetic dynamometer for the knee extensors (KE) and knee flexors (KF) at slow (0.52 rad/s) and faster (3.14 rad/s) velocities. The results were covaried for age, gender, and body mass or fat-free mass (FFM). Individuals heterozygous for the CNTF null (A allele) mutation (G/A) exhibited significantly higher Con peak torque of the KE and KF at 3.14 rad/s than G/G homozygotes when age, gender, and body mass were covaried ( P < 0.05). When the dominant leg FFM (estimated muscle mass) was used in place of body mass as a covariate, Con peak torque of the KE at 3.14 rad/s was also significantly greater in the G/A individuals ( P < 0.05). In addition, muscle quality of the KE (peak torque at 3.14 rad · s−1 · leg muscle mass−1) was significantly greater in the G/A heterozygotes ( P < 0.05). Similar results were seen in a subanalysis of subjects 60 yr and older, as well as in Caucasian subjects. In contrast, A/A homozygotes demonstrated significantly lower Ecc peak torque at 0.52 rad/s for both KE and KF compared with G/G and G/A groups ( P < 0.05). No significant relationships were observed at 0.52 rad/s between genotype and Con peak torque. These data indicate that individuals exhibiting the G/A genotype possess significantly greater muscular strength and muscle quality at relatively fast contraction speeds than do G/G individuals. Because of high positive correlations between fast-velocity peak torque and muscular power, these findings suggest that further investigations should address the relationship between CNTF genotype and muscular power.
Interdependence of bronchial circulation and clearance of99mTc-DTPA from the airway surface
Authors: Wagner Elizabeth M. , Foster W. Michael
Published: December 2017

The extent to which the systemic vasculature is involved in soluble-particle uptake in the conducting airways has not been studied extensively. In anesthetized, ventilated sheep, 6–10 μl of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) was delivered through a microspray nozzle to a fourth-generation airway. Perfusion of the cannulated bronchial artery was varied between control flow (0.6 ml · min−1 · kg−1), high flow (1.8 ml · min−1 · kg−1) or no flow (the infusion pump was stopped). Airway retention of the radioactive tracer was monitored using gamma camera imaging, and venous blood was sampled. During control perfusion, tracer retention at the site of deposition at 30 min averaged 20 ± 6% ( n= 7). With no flow, retention was significantly elevated to 32 ± 8% ( P = 0.03). In another group of sheep ( n = 5) with a control retention of 13 ± 4%, high flow resulted in an increase in tracer (25 ± 4%; P = 0.04). Maximum blood uptake of tracer was calculated by estimating circulating blood volume and averaged 16% of total activity during control flow. Only during high-flow conditions was 99mTc-DTPA in the blood decreased (10%; P = 0.04). Most of the tracer was cleared by mucociliary clearance as visualized by imaging. This component was substantially decreased during no flow. The results demonstrate that both decreased and increased airway perfusion limit removal of soluble tracer applied to the conducting airways.
Relationship between fat-to-fat-free mass ratio and decrements in leg strength after downhill running
Authors: Hickner R. C. , Mehta P. M. , Dyck D. , Devita P. , Houmard J. A. , Koves T. , Byrd P.
Published: December 2017

The purpose of this study was to determine whether greater body fat mass (FM) relative to lean mass would result in more severe muscle damage and greater decrements in leg strength after downhill running. The relationship between the FM-to-fat-free mass ratio (FM/FFM) and the strength decline resulting from downhill running (−11% grade) was investigated in 24 male runners [age 23.4 ± 0.7 (SE) yr]. The runners were divided into two groups on the basis of FM/FFM: low fat (FM/FFM = 0.100 ± 0.008, body mass = 68.4 ± 1.3 kg) and normal fat (FM/FFM = 0.233 ± 0.020, body mass = 76.5 ± 3.3 kg, P < 0.05). Leg strength was reduced less in the low-fat (−0.7 ± 1.3%) than in the normal-fat individuals (−10.3 ± 1.5%) 48 h after, compared with before, downhill running ( P < 0.01). Multiple linear regression analysis revealed that the decline in strength could be predicted best by FM/FFM ( r2= 0.44, P < 0.05) and FM-to-thigh lean tissue cross-sectional area ratio ( r2= 0.53, P < 0.05), with no additional variables enhancing the prediction equation. There were no differences in muscle glycogen, creatine phosphate, ATP, or total creatine 48 h after, compared with before, downhill running; however, the change in muscle glycogen after downhill running was associated with a higher FM/FFM ( r = −0.56, P < 0.05). These data suggest that FM/FFM is a major determinant of losses in muscle strength after downhill running.
Scoring of surface parameters of physiological relevance to surfactant therapy in respiratory distress syndrome
Authors: Banerjee R. , Bellare Jayesh R
Published: December 2017

The Wilhelmy balance was used for in vitro testing of surface parameters of surfactants used for respiratory distress syndrome therapy. Two commercial protein-free surfactants, ALEC and Exosurf, were compared with pure forms of the three main phospholipids in natural surfactants, dipalmitoyl phosphatidylcholine (PC), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE), and their binary mixtures, PC with PE and PG each in the ratio 2:3. Surface excess films (15 Å2/molecule) were compressed at 1.2 cycles/min past collapse to a compression ratio of 4:1. The maximum surface pressure, spreading time, compressibility, respreading ratio, recruitment index, and hysteresis area were compared. A consolidated list of criteria for selection of suitable surfactants was compiled from the literature. A relative scoring system was devised for comparison based on these criteria. PC/PG (2:3) performed the best as it fulfilled all the criteria and obtained the highest relative score. Exosurf also performed well, except on the respreading criterion. ALEC and PC/PE were equivalent in their performance and performed well, except on two criteria: hysteresis area and recruitment index. Thus the scoring system proposed here proved valuable to rate the overall efficacy as well as relative merits of surfactant formulations.
Role of nitric oxide during hyperventilation-induced bronchoconstriction in the guinea pig
Authors: Suman Oscar E. , Beck Kenneth C.
Published: December 2017

Airway function is largely preserved during exercise or isocapnic hyperventilation in humans and guinea pigs despite likely changes in airway milieu during hyperpnea. It is only on cessation of a hyperpneic challenge that airway function deteriorates significantly. We tested the hypothesis that nitric oxide, a known bronchodilator that is produced in the lungs and bronchi, might be responsible for the relative bronchodilation observed during hyperventilation (HV) in guinea pigs. Three groups of anesthetized guinea pigs were given saline and three groups given 50 mg/kg NG-monomethyl-l-arginine (l-NMMA), a potent nitric oxide synthase inhibitor. Three isocapnic ventilation groups included normal ventilation [40 breaths/min, 6 ml/kg tidal volume (Vt)], increased respiratory rate only (150 breaths/min, 6 ml/kg Vt), and increased respiratory rate and increased volume (100 breaths/min, 8 ml/kg Vt). l-NMMA reduced expired nitric oxide in all groups. Expired nitric oxide was slightly but significantly increased by HV in the saline groups. However, inhibition of nitric oxide production had no significant effect on rate of rise of respiratory system resistance (Rrs) during HV or on the larger rise in Rrs seen 6 min after HV. We conclude that nitric oxide synthase inhibition has no effect on changes in Rrs, either during or after HV in guinea pigs.
Static and dynamic operating characteristics of a pericardial balloon
Authors: Hamilton Douglas R. , Devries Gwyneth , Tyberg John V.
Published: December 2017

Previously, we developed a balloon transducer to measure the constraint of the pericardium (i.e., pericardial pressure) on the surface of the heart. It was validated physiologically in that it was shown to measure a pressure equal to the difference between the left ventricular end-diastolic pressure measured before and after pericardiectomy at the same left ventricular volume. To define its static operating characteristics, we loaded the balloon nonuniformly with weights that covered fractions of the balloon surface and found that the balloon accurately recorded the average stress if the stress was applied over at least 23% of its surface. To test its performance when curved, we placed it in large and small cylinders (minimum diameter 31 mm) and found that the balloon accurately recorded the stress. To define its dynamic operating characteristics, we applied sinusoidal stresses and found that its frequency response was limited only by that of the connecting catheter. When better dynamic response is required, we introduce a micromanometer-tipped catheter to obtain a unity-gain frequency response that is flat to 200 Hz.
Inconsistent link between low-frequency oscillations: R-R interval responses to augmented Mayer waves
Authors: Hamner J. W. , Morin Raymond J. , Rudolph James L. , Taylor J. Andrew
Published: December 2017

Low-frequency oscillations in arterial blood pressure (Mayer waves) and R-R interval are thought to be linked through the arterial baroreflex. To delve into this relationship, we applied low (10 mmHg) and moderate (30 mmHg) lower body negative pressure (LBNP) in 10-s cycles to 18 healthy young male subjects. They showed no change in average blood pressure with this oscillatory stimulus but did show a significant decrease in R-R interval ( P < 0.05) during both levels of LBNP. In addition, we succeeded in augmenting low-frequency blood pressure oscillations in a graded response to oscillatory LBNP level ( P < 0.05) while significantly increasing low-frequency R-R interval oscillations ( P < 0.05). However, cross-spectral coherence between these increased oscillations was highly variable across individuals and stimulus level. Although nearly all subjects showed significant coherence during basal conditions ( n = 17), only seven subjects maintained significant coherence during both levels of LBNP. These results suggest that a complex interaction of regulatory mechanisms determines the link between low-frequency oscillations and the responses to even low levels of LBNP.
Airway branching morphology of mature and immature rabbit lungs
Authors: Ramchandani R. , Bates J. H. T. , Shen X. , Suki B. , Tepper R. S.
Published: December 2017

The scheme of Horsfield et al. for describing the pulmonary airway tree ( J Appl Physiol 52: 21–26, 1982) catalogs each airway according to its order and the difference in order of its two daughters (denoted Δ). Although this scheme captures the natural asymmetry in the airway tree, it is still deterministic, because it assumes that all airways of a given order are the same; yet such variability is extremely important in determining the overall behavior of the lungs. We therefore analyzed complete lung lobes from three mature and two immature rabbits and determined the Horsfield order and Δ of every airway down to the terminal bronchioles. We also measured the diameter of each airway. This allowed us to determine the average structure of the rabbit airway tree, the variation about this average, and also how the structures of mature and immature airway trees compare. We found some variation in branching asymmetry and airway diameter at a given order between animals but no evidence of systematic differences in structure between mature and immature lungs. We found evidence of a difference in the branching structure of the peripheral vs. the central part of the airway tree (the break point being around order 20). We also determined the nature of the variation in Δ and diameter as a function of order, which should be valuable for the development of computer models seeking to encapsulate the naturally occurring regional variation in airway geometry in the normal rabbit lung.
Oxygen binding by single red blood cells from the red-eared turtleTrachemys scripta
Authors: Frische Sebastian , Bruno Stefano , Fago Angela , Weber Roy E. , Mozzarelli Andrea
Published: December 2017

Oxygen-binding properties of single red blood cells from the red-eared turtle Trachemys scripta were measured by microspectrophotometry to describe the variation in oxygen affinity of red blood cells and to gain insight into the distribution of functionally different hemoglobins among red blood cells. Methodologically, this study represents the first report on the cell-to-cell variation in oxygen-binding properties based on oxygen-binding curves of single vertebrate red blood cells. The cells differed significantly with respect to oxygen affinity. Mean oxygen pressure at half saturation of the cells in a blood sample was found to be 20.1 ± 3.3 (SD) Torr. The distribution of oxygen affinities among red blood cells is unimodal, indicating that the two hemoglobins found in turtle blood are not segregated in distinct cells. Therefore, the functional interaction shown by these hemoglobins in vitro is likely to take place in vivo. The considerable variation in oxygen affinity between individual red blood cells calls for its incorporation in models of tissue oxygenation.
Saline aerosol bolus dispersion. I. The effect of acinar airway alteration
Authors: Verbanck Sylvia , Schuermans Daniël , Vincken Walter , Paiva Manuel
Published: December 2017

We explored the possibility of using a saline aerosol for bolus dispersion measurements to detect peripheral airway alterations in smokers. Indexes of ventilation inhomogeneity in conductive ( S cond) and acinar ( S acin) lung zones, as derived from the multiple-breath N2 washout (Verbanck S, Schuermans D, Van Muylem A, Noppen M, Paiva M, and Vincken W, J Appl Physiol 83: 1807–1816, 1997), were also measured. The saline bolus test consisted of inhaling 60-ml saline aerosol boluses to different volumetric lung depths (VLD) in the 1.1 liter volume above functional residual capacity. In the never-smoker group ( n = 12), saline boluses showed bolus dispersion values consistent with normal values reported in the literature for 0.5- to 1-μm aerosols. In the smoker group ( n = 12; 28 ± 9 pack years, mean ± SD), significant increases were seen on dispersion and skew of the most peripherally inhaled saline boluses (VLD = 800 ml; P < 0.05) as well as on S acin ( P = 0.007) with respect to never-smokers. Shallow inhaled boluses (VLD = 200 ml) and S cond did not reveal any significant differences between smokers and never-smokers. This study shows the consistent response of two conceptually independent tests, in which both saline aerosol and gas-derived indexes point to a heterogeneous distribution of smoking-induced structural alterations in the lung periphery.
Saline aerosol bolus dispersion. II. The effect of conductive airway alteration
Authors: Verbanck Sylvia , Schuermans Daniël , Paiva Manuel , Vincken Walter
Published: December 2017

In a companion study (Verbanck S, Schuermans D, Vincken W, and Paiva M, J Appl Physiol 90: 1754–1762, 2001), we investigated whether saline aerosol bolus tests could also be used to detect proximal, as opposed to peripheral, airway alterations. We studied 10 never-smokers before and after histamine challenge, obtaining, for various volumetric lung depths (VLD), saline bolus-derived indexes computed by discarding aerosol concentrations below either 50% of the exhaled bolus maximum (half-width, H) or below cutoffs ranging from 5 to 25% (standard deviation, ς5%–ς25%) and skew (sk5–sk25%). Multiple-breath N2washout-derived indexes of conductive ( Scond) and acinar ( Sacin) ventilation inhomogeneity were also determined. After histamine, Scondsignificantly increased ( P = 0.008) whereas Sacinremained unaffected, indicating purely conductive airway alteration. Consistent with this observation, sk5%(or sk25%) was increased to the same extent at all VLD, and ς5%was increased preferentially at low VLD. By contrast, H and ς25%displayed preferential increases at high VLD, a pattern similar to that induced by peripheral alterations. The present work shows that proximal airway alteration can be reliably identified by saline bolus tests only if these include measurements at low and high VLD and if bolus dispersion is quantified as a standard deviation with a low cutoff.
Plasticity of monkey triceps muscle fibers in microgravity conditions
Authors: Kischel P. , Stevens L. , Montel V. , Picquet F. , Mounier Y.
Published: December 2017

We examined the changes in functional properties of triceps brachii skinned fibers from monkeys flown aboard the BION 11 satellite for 14 days and after ground-based arm immobilization. The composition of myosin heavy chain (MHC) isoforms allowed the identification of pure fibers containing type I (slow) or type IIa (fast) MHC isoforms or hybrid fibers coexpressing predominantly slow (hybrid slow; HS) or fast (hybrid fast) MHC isoforms. The ratio of HS fibers to the whole slow population was higher after flight (28%) than in the control population (7%), and the number of fast fibers was increased (up to 86% in flight vs. 12% in control). Diameters and maximal tensions of slow fibers were decreased after flight. The tension-pCa curves of slow and fast fibers were modified, with a decrease in pCa threshold and an increase in steepness. The proper effect of microgravity was distinguishable from that of immobilization, which induced less marked slow-to-fast transitions (only 59% of fast fibers) and changed the tension-pCa relationships.
Evidence that the renin decrease during hypoxia is adenosine mediated in conscious dogs
Authors: Höhne Claudia , Krebs Martin Otto , Boemke Willehad , Arntz Elisabeth , Kaczmarczyk Gabriele
Published: December 2017

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol · kg body wt−1 · day−1). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O2); second and third hours, hypoxia (10% inspiratory concentration of O2). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A1-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg · kg−1 · h−1). In theophylline experiments, PRA (5.9 ± 0.8 ng ANG I · ml−1 · h−1) and ANG II plasma concentration (15.9 ± 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 ± 63 to 132 ± 23 pg/ml ( P < 0.05). In control experiments, PRA decreased from 6.8 ± 0.8 during normoxia to 3.0 ± 0.5 ng ANG I · ml−1 · h−1 during hypoxia, ANG II decreased from 13.3 ± 1.9 to 7.3 ± 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 ± 50 to 70 ± 13 pg/ml ( P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.
β-Receptor agonist activity of phenylephrine in the human forearm
Authors: Torp Klaus D. , Tschakovsky Michael E. , Halliwill John R. , Minson Christopher T. , Joyner Michael J.
Published: December 2017

Phenylephrine is generally regarded as a “pure” α1-agonist. However, after treatment of the forearm with the α-adrenergic-blocking drug phentolamine, brachial artery infusion of phenylephrine can cause transient forearm vasodilation. To determine whether this response was β-receptor mediated, phenylephrine, phentolamine, and propranolol were infused into the brachial arteries of six healthy volunteers. Forearm vascular conductance (FVC) was also calculated and expressed as arbitrary units (units). Infusion of phenylephrine by itself (0.5 μg · dl forearm volume−1 · min−1) caused a sustained decrease ( P < 0.05) in FVC from 3.5 ± 0.7 to 0.9 ± 0.2 units ( P < 0.05). Infusion of the α-blocker phentolamine increased ( P < 0.05) baseline FVC to 5.7 ± 1.3 units. Subsequent infusion of phenylephrine after α-blockade caused FVC to increase ( P < 0.05) for ∼1 min from 5.7 ± 1.3 to a peak of 13.1 ± 1.8 units. Propranolol had no effect on baseline flow, and subsequent phenylephrine infusion after α- and β-blockade caused a small, but significant, sustained decrease in FVC from 5.1 ± 1.0 to 3.6 ± 0.8 units. There were no systemic effects from the infusions, and saline infusion at the same rate (1–2 ml/min) had no forearm vasoconstrictor or dilator effects. These data indicate that in humans phenylephrine can exert transient β2-vasodilator activity when its predominant α-constrictor effects are blocked.
Muscle capillary supply in harbor seals
Authors: Kanatous Shane B. , Elsner Robert , Mathieu-Costello Odile
Published: December 2017

The purpose of this study was to examine muscle capillary supply in harbor seals. Locomotory and nonlocomotory muscles of four harbor seals (mass = 17.5–41 kg) were glutaraldehyde-perfusion fixed and samples processed for electron microscopy and analyzed by morphometry. Capillary-to-fiber number and surface ratios were 0.81 ± 0.05 and 0.16 ± 0.01, respectively. Capillary length and surface area per volume of muscle fiber were 1,495 ± 83 mm/mm3and 22.4 ± 1.6 mm2/mm3, respectively. In the locomotory muscles, we measured capillary length and surface area per volume mitochondria (20.1 ± 1.7 km/ml and 2,531 ± 440 cm2/ml). All these values are 1.5–3 times lower than in muscles with similar or lower volume densities of mitochondria in dogs of comparable size. Compared with terrestrial mammals, the skeletal muscles of harbor seals do not match their increased aerobic enzyme capacities and mitochondrial volume densities with greater muscle capillary supply. They have a smaller capillary-to-fiber interface and capillary supply per fiber mitochondrial volume than terrestrial mammals of comparable size.
Myogenin and oxidative enzyme gene expression levels are elevated in rat soleus muscles after endurance training
Authors: Siu Parco M. , Donley David A. , Bryner Randall W. , Alway Stephen E.
Published: December 2017

The intent of this study was to determine whether endurance exercise training regulates increases in metabolic enzymes, which parallel modulations of myogenin and MyoD in skeletal muscle of rats. Adult Sprague-Dawley rats were endurance trained (TR) 5 days weekly for 8 wk on a motorized treadmill. They were killed 48 h after their last bout of exercise. Sedentary control (Con) rats were killed at the same time as TR animals. Myogenin, MyoD, citrate synthase (CS), cytochrome- c oxidase (COX) subunits II and VI, lactate dehydrogenase (LDH), and myosin light chain mRNA contents were determined in soleus muscles by using RT-PCR. Myogenin mRNA content was also estimated by using dot-blot hybridization. Protein expression levels of myogenin and MyoD were measured by Western blots. CS enzymatic activity was also measured. RT-PCR measurements showed that the mRNA contents of myogenin, CS, COX II, COX VI, and LDH were 25, 20, 17, 16, and 18% greater, respectively, in TR animals compared with Con animals ( P < 0.05). The ratio of myogenin to MyoD mRNA content estimated by RT-PCR in TR animals was 28% higher than that in Con animals ( P < 0.05). Myosin light chain expression was similar in Con and TR muscles. Results from dot-blot hybridization to a riboprobe further confirmed the increase in myogenin mRNA level in TR group. Western blot analysis indicated a 24% greater level of myogenin protein in TR animals compared with Con animals ( P < 0.01). The soleus muscles from TR animals had a 25% greater CS enzymatic activity than the Con animals ( P < 0.01). Moreover, myogenin mRNA and protein contents were positively correlated to CS activity and mRNA contents of CS, COX II, and COX VI ( P < 0.05). These data are consistent with the hypothesis that myogenin is in the pathway for exercise-induced changes in mitochondrial enzymes.
Functional alterations in adult rat myocytes after overexpression of phospholamban with use of adenovirus
Authors: DAVIA KERRY , HAJJAR ROGER J. , TERRACCIANO CESARE M. N. , KENT NATASHA SINGH , RANU HARDEEP K. , O'GARA PETER , ROSENZWEIG ANTHONY , HARDING SIAN E.
Published: December 2017

Davia, Kerry, Roger J. Hajjar, Cesare M. N. Terracciano, Natasha Singh Kent, Hardeep K. Ranu, Peter O'Gara, Anthony Rosenzweig, and Sian E. Harding. Functional alterations in adult rat myocytes after overexpression of phospholamban with use of adenovirus. Physiol. Genomics 1: 41–50, 1999.—An increased phospholamban (PLB)-to-sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) ratio has been suggested to contribute to the slowing of relaxation in failing human ventricle. We have used an adenoviral vector carrying the sequence for PLB to increase this ratio in isolated adult rat ventricular myocytes, and we have examined the functional consequences. With use of adenoviral vectors, the PLB content of adult rat myocytes was increased 2.73-fold, with SERCA2a levels unchanged. Maximum contraction amplitude of PLB-overexpressing myocytes was decreased to 6.9 ± 0.3% shortening compared with 11.2 ± 0.8% for 24-h controls (Con; P < 0.001, 5 preparations, 103 myocytes). Maximum rates of shortening and relengthening were also significantly decreased. Ca2+ transient amplitudes were slightly depressed, and time to 50% decay of the transients was significantly increased: 237 ± 18 ( n = 14 myocytes) and 432 ± 32 ms in Con and PLB ( n = 15) myocytes, respectively ( P < 0.001). The amount of Ca2+ in the sarcoplasmic reticulum stores was reduced by 21% ( P < 0.05). Relaxation was significantly slower in PLB than in Con myocytes when the Na+/Ca2+ exchanger was blocked but not when sarcoplasmic reticulum Ca2+ uptake was inhibited. Adenovirus infection with Ad.RSV.PLB was therefore able to produce functional changes in adult cardiac myocytes within 24 h, consistent with overexpression of PLB and similar to those seen in failing human heart.
nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle
Authors: LAU KIM S. , GRANGE ROBERT W. , ISOTANI EIJI , SARELIUS INGRID H. , KAMM KRISTINE E. , HUANG PAUL L. , STULL JAMES T.
Published: December 2017

Lau, Kim S., Robert W. Grange, Eiji Isotani, Ingrid H. Sarelius, Kristine E. Kamm, Paul L. Huang, and James T. Stull. nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle. Physiol. Genomics 2: 21–27, 2000.—Nitric oxide (NO) from Ca2+-dependent neuronal nitric oxide synthase (nNOS) in skeletal muscle fibers may modulate vascular tone by a cGMP-dependent pathway similar to NO derived from NOS in endothelial cells (eNOS). In isolated fast-twitch extensor digitorum longus (EDL) muscles from control mice, cGMP formation increased ∼166% with electrical stimulation (30 Hz, 15 s). cGMP levels were not altered in slow-twitch soleus muscles. The NOS inhibitor Nω-nitro-l-arginine abolished the contraction-induced increase in cGMP content in EDL muscles, and the NO donor sodium nitroprusside (SNP) increased cGMP content ∼167% in noncontracting EDL muscles. SNP treatment but not electrical stimulation increased cGMP formation in muscles from nNOS−/− mice. cGMP formation in control and stimulated EDL muscles from eNOS−/− mice was less than that obtained with similarly treated muscles from control mice. Arteriolar relaxation in contracting fast-twitch mouse cremaster muscle was attenuated in muscles from mice lacking either nNOS or eNOS. These findings suggest that increases in cGMP and NO-dependent vascular relaxation in contracting fast-twitch skeletal muscle may require both nNOS and eNOS.
Blood pressure QTL that differentiate Dahl salt-sensitive and spontaneously hypertensive rats
Authors: GARRETT MICHAEL R. , SAAD YASSER , DENE HOWARD , RAPP JOHN P.
Published: December 2017

Garrett, Michael R., Yasser Saad, Howard Dene, and John P. Rapp. Blood pressure QTL that differentiate Dahl salt-sensitive and spontaneously hypertensive rats. Physiol Genomics 3: 33–38, 2000.—Our purpose was to define quantitative trait loci (QTL) for blood pressure that differ between two widely used hypertensive rat strains, the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR). A genome scan was done on an F2(S × SHR) population fed 8% NaCl for 4 wk. Three blood pressure QTL were detected, one on each of rat chromosomes (chr) 3, 8, and 9. For the chr 3 QTL the SHR allele increased blood pressure, and for chr 8 and 9 the S allele increased blood pressure. The QTL on chr 9 was exceptionally strong, having a LOD score of 7.3 and accounting for 30% of the phenotypic variance and a difference of 40 mmHg between homozygotes. A review of the literature in conjunction with the present data suggests that S and SHR are not different for the previously described prominent blood pressure QTL on chr 1, 2, 10, and 13. QTL for body weight on chr 4, 12, 18, and 20, each with an effect of about 30 g, were incidentally observed.
Genetic variation inLMNAmodulates plasma leptin and indices of obesity in aboriginal Canadians
Authors: HEGELE ROBERT A. , CAO HENIAN , HARRIS STEWART B. , ZINMAN BERNARD , HANLEY ANTHONY J. , ANDERSON CAROL M.
Published: December 2017

Hegele, Robert A., Henian Cao, Stewart B. Harris, Bernard Zinman, Anthony J. Hanley, and Carol M. Anderson. Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians. Physiol Genomics 3: 39–44, 2000.—We previously showed that a rare mutation in LMNA, which encodes lamins A and C, underlies autosomal dominant Dunnigan-type familial partial lipodystrophy (FPLD). Because FPLD is an extreme example of genetically disturbed adipocyte differentiation, it is possible that common variation in LMNA is associated with obesity-related phenotypes. We therefore analyzed the relationships between the common LMNA 1908T/C single nucleotide polymorphism (SNP) and plasma leptin and anthropometric indices in 306 nondiabetic Canadian Oji-Cree. We found that subjects with the LMNA 1908T/1908T genotype had significantly higher plasma leptin than the subjects with either the 1908C/1908T or 1908C/1908C genotypes, after adjustment for age and sex. Physical indices of obesity, such as body mass index, percent body fat, and ratio of waist-to-hip circumference, were also higher among Oji-Cree subjects with the LMNA 1908T/1908T genotype than the subjects with either the 1908C/1908T or 1908C/1908C genotypes. The results suggest that common genetic variation in LMNA may be an important determinant of plasma leptin and obesity-related quantitative traits.
ANP in regulation of arterial pressure and fluid-electrolyte balance: lessons from genetic mouse models
Authors: MELO LUIS G. , STEINHELPER MARK E. , PANG STEPHEN C. , TSE YAT , ACKERMANN UWE
Published: December 2017

Melo, Luis G., Mark E. Steinhelper, Stephen C. Pang, Yat Tse, and Uwe Ackermann. ANP in the regulation of arterial pressure and fluid-electrolyte balance: lessons from genetic mouse models. Physiol Genomics 3: 45–58, 2000.—The recent development of genetic mouse models presenting life-long alterations in expression of the genes for atrial natriuretic peptide (ANP) or its receptors (NPR-A, NPR-C) has uncovered a physiological role of this hormone in chronic blood pressure homeostasis. Transgenic mice overexpressing a transthyretin-ANP fusion gene are hypotensive relative to the nontransgenic littermates, whereas mice harboring functional disruptions of the ANP or NPR-A genes are hypertensive compared with their respective wild-type counterparts. The chronic hypotensive action of ANP is determined by vasodilation of the resistance vasculature, which is probably mediated by attenuation of vascular sympathetic tone at one or several prejunctional sites. Under conditions of normal dietary salt consumption, the hypotensive action of ANP is dissociated from the natriuretic activity of the hormone. However, during elevated dietary salt intake, ANP-mediated antagonism of the renin-angiotensin system is essential for maintenance of blood pressure constancy, inasmuch as the ANP gene “knockout” mice (ANP −/−) develop a salt-sensitive component of hypertension in association with failure to adequately downregulate plasma renin activity. These findings imply that genetic deficiencies in ANP or natriuretic receptor activity may be underlying causative factors in the etiology of salt-sensitive variants of hypertensive disease and other sodium-retaining disorders, such as congestive heart failure and cirrhosis.
Interaction of genetic and environmental programming of the leptin system and of obesity disposition
Authors: SCHMIDT INGRID , SCHOELCH CORINNA , ZISKA THOMAS , SCHNEIDER DARIUS , SIMON ECKHART , PLAGEMANN ANDREAS
Published: December 2017

Schmidt, Ingrid, Corinna Schoelch, Thomas Ziska, Darius Schneider, Eckhart Simon, and Andreas Plagemann. Interaction of genetic and environmental programming for disturbances of the leptin system and for obesity. Physiol Genomics 3: 113–120, 2000.—Possible adverse interactions between an usually inconspicuous genetic trait and early environmental factors favoring the development of obesity were investigated in rats heterozygous for the leptin receptor defect “ fatty” ( fa). Pups were exposed to early postnatal overfeeding by reducing litter size from normally 10–12 to only 4. Rearing +/+ and +/ fa pups from day 3 to 21 in small litters increased fat-free dry mass and body fat, but only in the latter did a significant interaction with genotype occur. Pronounced differences in the responsiveness of +/+ and +/ fa pups to “prophylactic” leptin treatment (from day 1 to 21) were observed, with +/ fa females from small litters being nearly as fat and unresponsive as previously reported for normally reared fa/ fa pups. Clear heterozygous differences in total hypothalamic leptin binding, but no litter size effect, paralleling the differences in leptin responsiveness, were observed. By early postnatal overfeeding an usually inconspicuous genetic trait may thus become etiologic for the development of obesity via physiological changes other than the decreased leptin binding characterizing the genetic defect.
Microsatellite marker panels for use in high-throughput genotyping of mouse crosses
Authors: IAKOUBOVA OLGA A. , OLSSON CHRISTINE L. , DAINS KATHERINE M. , CHOI JIM , KALCHEVA IVETTA , BENTLEY L. GORDON , CUNANAN MADALYNE , HILLMAN DAVID , LOUIE JUDI , MACHRUS MIGDAD , WEST DAVID B.
Published: December 2017

Iakoubova, Olga A., Christine L. Olsson, Katherine M. Dains, Jim Choi, Ivetta Kalcheva, L. Gordon Bentley, Madalyne Cunanan, David Hillman, Judi Louie, Migdad Machrus, and David B. West. Microsatellite marker panels for use in high-throughput genotyping of mouse crosses. Physiol Genomics 3: 145–148, 2000.—Several microsatellite genotyping panel sets have been developed that are polymorphic between C57BL/6J and CAST/Ei mice, or C57BL/6J and DBA/2J. One set of markers for each strain pair has an intermarker distance of ∼20 cM, and a second set has an intermarker distance of 5 cM. The 20-cM set contains 105 markers for C57BL/6J × DBA/2J and 108 for C57BL/6J × CAST/Ei, divided into 13 panels. Each 5-cM set includes 350 markers arranged into 45 panels. A panel contains a number of primer pairs whose fluorescently labeled PCR products can be pooled together and separated on one lane of a polyacrylamide gel. The sets are arranged by the size of the PCR product and by the type of fluorescent dye; 5-cM sets are also arranged by chromosomal region. The 20-cM sets are most useful for full-genome scans, the 5-cM sets are useful for full-genome and/or for region-specific chromosome screens. Both sets were proven as useful tools for speed congenic development, quantitative trait loci (QTL) analysis and physical mapping. These panel sets provide a throughput of 1,536–2,304 mouse genotypes daily per one gel-based system. Whole genome scans of one animal require 13 or 48 gel lanes, with 20 cM or 5 cM density, respectively.