bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver asialoglycoprotein receptor levels correlate with severity of alcoholic liver damage in rats
Authors: Casey Carol A. , McVicker Benita L. , Donohue Terrence M. , McFarland Melinda A. , Wiegert Robert L. , Nanji Amin A.
Published: January 2004

It has been demonstrated that the oral administration of ethanol (Lieber-DeCarli liquid diet) to rats results in a decreased expression and content of the asialoglycoprotein receptor (ASGP-R) in the resultant fatty liver. In the present study, we wanted to determine whether the extent of impaired receptor content was correlated with the severity of liver pathology by using the intragastric feeding model. When ASGP-R protein and mRNA levels were measured in animals infused with ethanol or dextrose in the presence of fish oil (FO) or medium-chain triglyceride as the source of fat, more significant impairments to the ASGP-R were observed in the FO-ethanol group compared with the medium-chain triglyceride-ethanol group. Furthermore, only the FO-ethanol group showed pathological liver changes. These results demonstrate that a correlation exists between the progression of alcohol-associated liver injury, as defined by the severity of liver pathology, and an ethanol-induced decline in ASGP-R content.
Mechanical state of airway smooth muscle at very short lengths
Authors: Meiss Richard A. , Pidaparti Ramana M.
Published: January 2004

Although the shortening of smooth muscle at physiological lengths is dominated by an interaction between external forces (loads) and internal forces, at very short lengths, internal forces appear to dominate the mechanical behavior of the active tissue. We tested the hypothesis that, under conditions of extreme shortening and low external force, the mechanical behavior of isolated canine tracheal smooth muscle tissue can be understood as a structure in which the force borne and exerted by the cross bridge and myofilament array is opposed by radially disposed connective tissue in the presence of an incompressible fluid matrix (cellular and extracellular). Strips of electrically stimulated tracheal muscle were allowed to shorten maximally under very low afterload, and large longitudinal sinusoidal vibrations (34 Hz, 1 s in duration, and up to 50% of the muscle length before vibration) were applied to highly shortened (active) tissue strips to produce reversible cross-bridge detachment. During the vibration, peak muscle force fell exponentially with successive forced elongations. After the episode, the muscle either extended itself or exerted a force against the tension transducer, depending on external conditions. The magnitude of this effect was proportional to the prior muscle stiffness and the amplitude of the vibration, indicating a recoil of strained connective tissue elements no longer opposed by cross-bridge forces. This behavior suggests that mechanical behavior at short lengths is dominated by tissue forces within a tensegrity-like structure made up of connective tissue, other extracellular matrix components, and active contractile elements.
Effects of carbohydrate availability on sustained shivering II. Relating muscle recruitment to fuel selection
Authors: Haman François , Legault Stéphane R. , Rakobowchuk Mark , Ducharme Michel B. , Weber Jean-Michel
Published: January 2004

The purpose of this study was to quantify how shivering activity would be affected by large changes in fuel metabolism (see Haman F, Peronnet F, Kenny GP, Doucet E, Massicotte D, Lavoie C, and Weber J-M, J Appl Physiol 96: 000–000, 2004). Adult men were exposed to 10°C for 2 h after a low-carbohydrate diet and exercise (Lo) and after high-carbohydrate diet without exercise (Hi). Using simultaneous metabolic and electromyographic (EMG) measurements, we quantified the effects of changes in fuel selection on the shivering activity of eight large muscles representing >90% of total shivering muscle mass. Contrary to expectation, drastic changes in fuel metabolism [carbohydrates 28 vs. 65% of total heat production (Ḣprod), lipids 53 vs. 23% Ḣprod, and proteins 19 vs. 12% Ḣprodfor Lo and Hi, respectively] are achieved without altering the EMG signature of shivering muscles. Results show that total shivering activity and the specific contribution of each muscle to total shivering activity are not affected by large changes in fuel selection. In addition, we found that changes in burst shivering rate (∼4 bursts/min), relative contribution of burst activity to total shivering (∼10% of total shivering activity), and burst shivering intensity (∼12% of maximal voluntary contraction) are the same between Lo and Hi. Spectral analysis of EMG signals also reveals that mean frequencies of the power spectrum remained the same under all conditions (whole body average of 78 ± 5 Hz for Lo and 83 ± 7 Hz for Hi). During low-intensity shivering, humans are therefore able to sustain the same thermogenic rate by oxidizing widely different fuel mixtures within the same muscle fibers.
The respiratory change in preejection period: a new method to predict fluid responsiveness
Authors: Bendjelid Karim , Suter Peter M. , Romand Jacques A.
Published: January 2004

The accuracy and clinical utility of preload indexes as bedside indicators of fluid responsiveness in patients after cardiac surgery is controversial. This study evaluates whether respiratory changes (Δ) in the preejection period (PEP; ΔPEP) predict fluid responsiveness in mechanically ventilated patients. Sixteen postcoronary artery bypass surgery patients, deeply sedated under mechanical ventilation, were enrolled. PEP was defined as the time interval between the beginning of the Q wave on the electrocardiogram and the upstroke of the radial arterial pressure. ΔPEP (%) was defined as the difference between expiratory and inspiratory PEP measured over one respiratory cycle. We also measured cardiac output, stroke volume index, right atrial pressure, pulmonary arterial occlusion pressure, respiratory change in pulse pressure, systolic pressure variation, and the Δdown component of SPV. Data were measured without positive end-expiratory pressure (PEEP) and after application of a PEEP of 10 cmH2O (PEEP10). When PEEP10 induced a decrease of >15% in mean arterial pressure value, then measurements were re-performed before and after volume expansion. Volume loading was done in eight patients. Right atrial pressure and pulmonary arterial occlusion pressure before volume expansion did not correlate with the change in stroke volume index after the fluid challenge. Systolic pressure variation, ΔPEP, Δdown, and change in pulse pressure before volume expansion correlated with stroke volume index change after fluid challenge ( r2 = 0.52, 0.57, 0.68, and 0.83, respectively). In deeply sedated, mechanically ventilated patients after cardiac surgery, ΔPEP, a new method, can be used to predict fluid responsiveness and hemodynamic response to PEEP10.
Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle
Authors: Morris R. Tyler , Spangenburg Espen E. , Booth Frank W.
Published: January 2004

Various cellular signaling pathways, such as phosphatidylinositol 3-kinase, calcineurin, Janus kinase 2/signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) have been suggested to play an important role in skeletal muscle growth. Old muscle, compared with young muscle, lacks the ability to completely regrow its muscle mass after an atrophy-induced stimulus. it is hypothesized that defects and/or delays in the activation of specific cell signaling pathways of aged soleus muscle limit the potential for growth. To test this, 42 male Fischer 344 × Brown Norway rats, 30 mo old, were hindlimb immobilized for 10 days, and their muscle samples were compared with muscle samples analyzed from 3- to 4-mo-old rats in a previous report (Childs TE, Spangenburg EE, Vyas DR, and Booth FW. Am J Physiol Cell Physiol: 285: C391–C398, 2003). After 10 days, the immobilization was removed and rats were allowed to ambulate for a series of days. Alterations in the activation or deactivation status of specific signaling pathways were determined by comparing the phosphorylation (phos) and total concentration of specific signaling proteins (pan) through Western blotting with the 10-day immobilization group. Various cell signals and their respective time groups of the old rats were shown to be significantly different compared with the 10-day immobilization group. For example, peak increases during recovery from the immobilization were observed at 1) the third recovery day for calcineurin B-pan and 2) the sixth recovery day for glycogen synthase kinase-3β-phos, p70 S6 kinase (p70S6k) -phos and -pan, calcineurin A-pan, STAT3-phos and -pan, p44 MAPK-pan, and p42 MAPK-pan. In contrast, Akt-pan, c-Jun NH2-terminal kinase-phos, and p38 MAPK-phos were observed to decrease from 10-day immobilization values to control levels. Also, Aktphos was unchanged among all groups. In a follow-up experiment in which muscle samples from both the present study and a previous study (Childs TE, Spangenburg EE, Vyas DR, and Booth FW. Am J Physiol Cell Physiol: 285: C391–C398, 2003) were reanalyzed together, the recovery-induced increase in p70S6k-phos from immobilization-atrophy was significantly attenuated in soleus muscles of the old group.
Effects of intravenous N-acetylcysteine infusion on time to fatigue and potassium regulation during prolonged cycling exercise
Authors: Medved Ivan , Brown Malcolm J. , Bjorksten Andrew R. , McKenna Michael J.
Published: January 2004

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated whether the antioxidant compound N-acetylcysteine (NAC) augments time to fatigue during prolonged, submaximal cycling exercise. Seven men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling exercise, comprising 45 min at 70% of peak oxygen consumption (V̇o2 peak) and then to fatigue at 90% V̇o2 peak. NAC was intravenously infused at 125 mg·kg-1·h-1 for 15 min and then 25 mg·kg-1·h-1 for 20 min before and throughout exercise, which was continued until fatigue. Arterialized venous blood was analyzed for NAC concentration, hematology, and plasma electrolytes. NAC induced no serious adverse reactions and did not affect hematology, acid-base status, or plasma electrolytes. Time to fatigue was reproducible in preliminary trials (coefficient of variation 7.4 ± 1.2%) and was not augmented by NAC (NAC 14.6 ± 4.5 min; control 12.8 ± 5.4 min). However, time to fatigue during NAC trials was correlated with V̇o2 peak ( r = 0.78; P < 0.05), suggesting that NAC effects on performance may be dependent on training status. The rise in plasma K+ concentration at fatigue was attenuated by NAC ( P < 0.05). The ratio of rise in K+ concentration to work and the percentage change in time to fatigue tended to be inversely related ( r = -0.71; P < 0.07). Further research is required to clarify a possible training status-dependent effect of NAC on muscle performance and K+ regulation.
β2- and β3-Adrenergic receptor polymorphisms and exercise hemodynamics in postmenopausal women
Authors: McCole Steve D. , Shuldiner Alan R. , Brown Michael D. , Moore Geoffrey E. , Ferrell Robert E. , Wilund Kenneth R. , Huberty Andrea , Douglass Larry W. , Hagberg James M.
Published: January 2004

We sought to determine whether common genetic variations at the β2 (β2-AR, Gln27Glu) and β3 (β3-AR, Trp64Arg) adrenergic receptor gene loci were associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise. CV hemodynamics were assessed in 62 healthy postmenopausal women (20 sedentary, 22 physically active, and 20 endurance athletes) during treadmill exercise at 40, 60, 80, and 100% maximal O2 uptake using acetylene rebreathing to quantify cardiac output. The β2-AR genotype and habitual physical activity (PA) levels interacted to significantly associate with arteriovenous O2 difference (a-vDo2) during submaximal exercise ( P = 0.05), with the highest submaximal exercise a-vDo2 in sedentary women homozygous for the β2-AR Gln allele and no genotype-dependent differences in submaximal exercise a-vDo2 in physically active and athletic women. The β2-AR genotype also was independently associated with a-vDo2 during submaximal ( P = 0.004) and ∼100% maximal O2 uptake exercise ( P = 0.006), with a 1.2-2 ml/100 ml greater a-vDo2 in the Gln/Gln than in the Glu/Glu genotype women. The β3-AR genotype, independently or interacting with habitual PA levels, was not significantly associated with any CV hemodynamic variables during submaximal or maximal exercise. Thus it appears that the β2-AR genotype, both independently and interacting with habitual PA levels, is significantly associated with a-vDo2 during exercise in postmenopausal women, whereas the β3-AR genotype does not appear to be associated with any maximal or submaximal exercise CV hemodynamic responses in postmenopausal women.
Deep breath reversal and exponential return of methacholine-induced obstruction in asthmatic and nonasthmatic subjects
Authors: Jackson Andrew C. , Murphy Margaret M. , Rassulo John , Celli Bartolome R. , Ingram Roland H.
Published: January 2004

A deep breath (DB) during induced obstruction results in a transient reversal with a return to pre-DB levels in both asthmatic and nonasthmatic subjects. The time course of this transient recovery has been reported to be exponential by one group but linear by another group. In the present study, we estimated airway resistance (Raw) from measurements of respiratory system transfer impedance before and after a DB. Nine healthy subjects and nine asthmatic subjects were studied at their maximum response during a methacholine challenge. In all subjects, the DB resulted in a rapid decrease in Raw, which then returned to pre-DB levels. This recovery was well fit with a monoexponential function in both groups, and the time constant was significantly smaller in the asthmatic than the nonasthmatic subjects (11.6 ± 5.0 and 35.1 ± 15.9 s, respectively). Obstruction was completely reversed in the nonasthmatic subjects (pre- and postchallenge mean Raw immediately after the DB were 2.03 ± 0.66 and 2.06 ± 0.68 cmH2O·l-1·s, respectively), whereas in the asthmatic subjects complete reversal did not occur (2.29 ± 0.78 and 4.84 ± 2.64 cmH2O·l-1·s, respectively). Raw after the DB returned to postchallenge, pre-DB values in the nonasthmatic subjects (3.78 ± 1.56 and 3.97 ± 1.63 cmH2O·l-1·s, respectively), whereas in the asthmatic subjects it was higher but not significantly so (9.19 ± 4.95 and 7.14 ± 3.56 cmH2O·l-1·s, respectively). The monoexponential recovery suggests a first-order process such as airway wall-parenchymal tissue interdependence or renewed constriction of airway smooth muscle.
Hypoxia-mediated prolonged elevation of sympathetic nerve activity after periods of intermittent hypoxic apnea
Authors: Cutler Michael J. , Swift Nicolette Muenter , Keller David M. , Wasmund Wendy L. , Smith Michael L.
Published: January 2004

Obstructive sleep apnea (OSA) is associated with transient elevation of muscle sympathetic nerve activity (MSNA) during apneic events, which often produces elevated daytime MSNA in OSA patients. Hypoxia is postulated to be the primary stimulus for elevated daytime MSNA in OSA patients. Therefore, we studied the effects of 20 min of intermittent voluntary hypoxic apneas on MSNA during 180 min of recovery. Also, we compared MSNA during recovery after either 20 min of intermittent voluntary hypoxic apneas, hypercapnic hypoxia, or isocapnic hypoxia. Consistent with our hypothesis, both total MSNA and MSNA burst frequency were elevated after 20 min of intermittent hypoxic apnea compared with baseline ( P < 0.05). Both total MSNA and MSNA burst frequency remained elevated throughout the 180-min recovery period and were statistically different from time control subjects throughout this period ( P < 0.05). Finally, MSNA during recovery from intermittent hypoxic apnea, hypercapnic hypoxia, and isocapnic hypoxia were not different ( P = 0.50). Therefore, these data support the hypothesis that short-term exposure to intermittent hypoxic apnea results in sustained elevation of MSNA and that hypoxia is the primary mediator of this response.
Mathematical modeling of airway epithelial wound closure during cyclic mechanical strain
Authors: Savla Ushma , Olson Lars E. , Waters Christopher M.
Published: January 2004

The repair of airway epithelium after injury is crucial in restoring epithelial barrier integrity. Because the airways are stretched and compressed due to changes in both circumferential and longitudinal dimensions during respiration and may be overdistended during mechanical ventilation, we investigated the effect of cyclic strain on the repair of epithelial wounds. Both cyclic elongation and compression significantly slowed repair, with compression having the greatest effect. We developed a mathematical model of the mechanisms involved in airway epithelial cell wound closure. The model focuses on the differences in spreading, migration, and proliferation with cyclic strain by using separate parameters for each process and incorporating a time delay for the mitotic component. Numerical solutions of model equations determine the shape of the diffusive wave solutions of cell density that correspond to the influx of cells into the wound during the initial phase of reepithelialization. Model simulations were compared with experimental measurements of cell density and the rate of wound closure, and parameters were determined based on measurements from airway epithelial cells from several different sources. The contributions of spreading, migration, and mitosis were investigated both numerically and experimentally by using cytochalasin D to inhibit cell motility and mitomycin C to inhibit proliferation.
Respiratory muscle strength training with nonrespiratory maneuvers
Authors: DePalo Vera A. , Parker Annie Lin , Al-Bilbeisi Fadi , McCool F. Dennis
Published: January 2004

The diaphragm and abdominal muscles can be recruited during nonrespiratory maneuvers. With these maneuvers, transdiaphragmatic pressures are elevated to levels that could potentially provide a strength-training stimulus. To determine whether repeated forceful nonrespiratory maneuvers strengthen the diaphragm, four healthy subjects performed sit-ups and biceps curls 3-4 days/wk for 16 wk and four subjects served as controls. The maximal transdiaphragmatic pressure was measured at baseline and after 16 wk of training. Maximum static inspiratory and expiratory mouth pressures and diaphragm thickness derived from ultrasound were measured at baseline and 8 and 16 wk. After training, there were significant increases in diaphragm thickness [2.5 ± 0.1 to 3.2 ± 0.1 mm (mean ± SD) ( P < 0.001)], maximal transdiaphragmatic pressure [198 ± 21 to 256 ± 23 cmH2O ( P < 0.02)], maximum static inspiratory pressure [134 ± 22 to 171 ± 16 cmH2O ( P < 0.002)], maximum static expiratory pressure [195 ± 20 to 267 ± 40 cmH2O ( P < 0.002)], and maximum gastric pressure [161 ± 5 to 212 ± 40 cmH2O ( P < 0.03)]. These parameters were unchanged in the control group. We conclude that nonrespiratory maneuvers can strengthen the inspiratory and expiratory muscles in healthy individuals. Because diaphragm thickness increased with training, the increase in maximal pressures is unlikely due to a learning effect.
Electrical stimulation of the posteromedial thalamus modulates breathing in unanesthetized fetal sheep
Authors: Koos Brian J. , Kawasaki Yoshikazu , Hari Ashwinii , Bohorquez Fanor , Jan Calvin , Roostaeian Jason , Wilson Charles L. , Kruger Lawrence
Published: January 2004

Having previously shown that lesions in the posteromedial group of thalamic nuclei abolish hypoxic inhibition of fetal breathing, we devised this study to identify thalamic loci that depress breathing by focal stimulation of specific sectors of the caudal thalamus and adjacent structures. Multipolar electrode arrays consisting of a series of eight stimulation contacts at 1.25-mm intervals were implanted vertically through guide cannulae into the caudal diencephalon of 12 chronically catheterized fetal sheep (>0.8 term), and central neural tissue was stimulated between adjacent contacts. Each site was stimulated repeatedly with increasing current searching for spatial and stimulus strength parameters for a reliable alteration in respiratory rate. Respiratory period increased when stimulation involved areas of the parafascicular nuclear complex (Pf), which more than doubled the mean period compared with the baseline of 0.90 ± 0.19 s. The change in respiratory period was due to an increase in expiratory time, whereas inspiratory time and breath amplitude were not significantly affected. Breathing period and expiratory time were also increased when the stimulations involved the intralaminar wing surrounding the mediodorsal nucleus, the rostral central gray, zona incerta, and ventral tegmental area. Reductions in respiratory frequency occurred less consistently, with stimulation involving surrounding zones including the sub-Pf, ventromedial nucleus, and ventrobasal nuclear complex. These findings support the hypothesis that a restricted area of the posteromedial thalamus (principally Pf) constitutes part of a neuronal circuitry that modulates respiratory motoneurons.
A thin, flexible multielectrode grid for high-density surface EMG
Authors: Lapatki B. G. , van Dijk J. P. , Jonas I. E. , Zwarts M. J. , Stegeman D. F.
Published: January 2004

Although the value of high-density surface electromyography (sEMG) has already been proven in fundamental research and for specific diagnostic questions, there is as yet no broad clinical application. This is partly due to limitations of construction principles and application techniques of conventional electrode array systems. We developed a thin, highly flexible, two-dimensional multielectrode sEMG grid, which is manufactured by using flexprint techniques. The material used as electrode carrier (Polyimid, 50 μm thick) allows grids to be cut out in any required shape or size. One universal grid version can therefore be used for many applications, thereby reducing costs. The reusable electrode grid is attached to the skin by using specially prepared double-sided adhesive tape, which allows the selective application of conductive cream only directly below the detection surfaces. To explore the practical possibilities, this technique was applied in single motor unit analysis of the facial musculature. The high mechanical flexibility allowed the electrode grid to follow the skin surface even in areas with very uneven contours, resulting in good electrical connections in the whole recording area. The silverchloride surfaces of the electrodes and their low electrode-to-skin impedances guaranteed high baseline stability and a low signal noise level. The electrode-to-skin attachment proved to withstand saliva and great tensile forces due to mimic contractions. The inexpensive, universally adaptable and minimally obstructive sensor allows the principal advantages of high-density sEMG to be extended to all skeletal muscles accessible from the skin surface and may lay the foundation for more broad clinical application of this noninvasive, two-dimensional sEMG technique.
Active recovery attenuates the fall in sweat rate but not cutaneous vascular conductance after supine exercise
Authors: Wilson Thad E. , Carter Robert , Cutler Michael J. , Cui Jian , Smith Michael L. , Crandall Craig G.
Published: January 2004

The purpose of this study was to identify whether baroreceptor unloading was responsible for less efficient heat loss responses (i.e., skin blood flow and sweat rate) previously reported during inactive compared with active recovery after upright cycle exercise (Carter R III, Wilson TE, Watenpaugh DE, Smith ML, and Crandall CG. J Appl Physiol 93: 1918-1929, 2002). Eight healthy adults performed two 15-min bouts of supine cycle exercise followed by inactive or active (no-load pedaling) supine recovery. Core temperature (Tcore), mean skin temperature (Tsk), heart rate, mean arterial blood pressure (MAP), thoracic impedance, central venous pressure ( n = 4), cutaneous vascular conductance (CVC; laser-Doppler flux/MAP expressed as percentage of maximal vasodilation), and sweat rate were measured throughout exercise and during 5 min of recovery. Exercise bouts were similar in power output, heart rate, Tcore, and Tsk. Baroreceptor loading and thermal status were similar during trials because MAP (90 ± 4, 88 ± 4 mmHg), thoracic impedance (29 ± 1, 28 ± 2 Ω), central venous pressure (5 ± 1, 4 ± 1 mmHg), Tcore(37.5 ± 0.1, 37.5 ± 0.1°C), and Tsk(34.1 ± 0.3, 34.2 ± 0.2°C) were not significantly different at 3 min of recovery between active and inactive recoveries, respectively; all P > 0.05. At 3 min of recovery, chest CVC was not significantly different between active (25 ± 6% of maximum) and inactive (28 ± 6% of maximum; P > 0.05) recovery. In contrast, at this time point, chest sweat rate was higher during active (0.45 ± 0.16 mg·cm-2·min-1) compared with inactive (0.34 ± 0.19 mg·cm-2·min-1; P < 0.05) recovery. After exercise CVC and sweat rate are differentially controlled, with CVC being primarily influenced by baroreceptor loading status while sweat rate is influenced by other factors.
A GABAergic inhibitory microcircuit controlling cholinergic outflow to the airways
Authors: Moore Constance T. , Wilson Christopher G. , Mayer Catherine A. , Acquah Sandra S. , Massari V. John , Haxhiu Musa A.
Published: January 2004

GABA is the main inhibitory neurotransmitter that participates in the regulation of cholinergic outflow to the airways. We have tested the hypothesis that a monosynaptic GABAergic circuit modulates the output of airway-related vagal preganglionic neurons (AVPNs) in the rostral nucleus ambiguus by using a dual-labeling electron microscopic method combining immunocytochemistry for glutamic acid decarboxylase (GAD) with retrograde tracing from the trachea. We also determined the effects of blockade of GABAA receptors on airway smooth muscle tone. The results showed that retrogradely labeled AVPNs received a significant GAD-immunoreactive (GAD-IR) terminal input. Out of a pooled total of 3,161 synaptic contacts with retrogradely labeled somatic and dendritic profiles, 20.2% were GAD-IR. GAD-IR terminals formed significantly more axosomatic synapses than axodendritic synapses ( P < 0.02). A dense population of GABAergic synaptic contacts on AVPNs provides a morphological basis for potent physiological effects of GABA on the excitability of AVPNs. GAD-IR terminals formed exclusively symmetric synaptic specializations. GAD-IR terminals were significantly larger ( P < 0.05) in both length and width than unlabeled terminals synapsing on AVPNs. Therefore, the structural characteristics of certain nerve terminals may be closely correlated with their function. Pharmacological blockade of GABAA receptors within the rostral nucleus ambiguus increased activity of putative AVPNs and airway smooth muscle tone. We conclude that a tonically active monosynaptic GABAergic circuit utilizing symmetric synapses regulates the discharge of AVPNs.
Increased sensitivity of the ryanodine receptor to halothane-induced oligomerization in malignant hyperthermia-susceptible human skeletal muscle
Authors: Glover Louise , Heffron James J. A. , Ohlendieck Kay
Published: January 2004

Mutations in the skeletal muscle RyR1 isoform of the ryanodine receptor (RyR) Ca2+-release channel confer susceptibility to malignant hyperthermia, which may be triggered by inhalational anesthetics such as halothane. Using immunoblotting, we show here that the ryanodine receptor, calmodulin, junctin, calsequestrin, sarcalumenin, calreticulin, annexin-VI, sarco(endo)plasmic reticulum Ca2+-ATPase, and the dihydropyridine receptor exhibit no major changes in their expression level between normal human skeletal muscle and biopsies from individuals susceptible to malignant hyperthermia. In contrast, protein gel-shift studies with halothane-treated sarcoplasmic reticulum vesicles from normal and susceptible specimens showed a clear difference. Although the α2-dihydropyridine receptor and calsequestrin were not affected, clustering of the Ca2+-ATPase was induced at comparable halothane concentrations. In the concentration range of 0.014–0.35 mM halothane, anesthetic-induced oligomerization of the RyR1 complex was observed at a lower threshold concentration in the sarcoplasmic reticulum from patients with malignant hyperthermia. Thus the previously described decreased Ca2+-loading ability of the sarcoplasmic reticulum from susceptible muscle fibers is probably not due to a modified expression of Ca2+-handling elements, but more likely a feature of altered quaternary receptor structure or modified functional dynamics within the Ca2+-regulatory apparatus. Possibly increased RyR1 complex formation, in conjunction with decreased Ca2+uptake, is of central importance to the development of a metabolic crisis in malignant hyperthermia.
The two mechanisms of intercostal muscle action on the lung
Authors: Wilson Theodore A. , De Troyer Andre
Published: January 2004

The mechanisms of respiratory action of the intercostal muscles were studied by measuring the effect of external forces (F) applied to the ribs and by modeling the effect of F exerted by the intercostal muscles. In five dogs, with the airway occluded, cranial F were applied to individual rib pairs, from the 2nd to the 11th rib pair, and the change in airway opening pressure (Pao) was measured. The ratio Pao/F increases with increasing rib number in the upper ribs (2nd to 5th) and decreases in the lower ribs (5th to 11th). These data were incorporated into a model for the geometry of the ribs and intercostal muscles, and Pao/F was calculated from the model. For interspaces 2-8, the calculated values agree reasonably well with previously measured values. From the modeling, two mechanisms of intercostal muscle action are identified. One is the well-known Hamberger mechanism, modified to account for the three-dimensional geometry of the rib cage. This mechanism depends on the slant of an intercostal muscle relative to the ribs and on the resulting difference between the moments applied to the upper and lower ribs that bound each interspace. The second is a new mechanism that depends on the difference between the values of Pao/F for the upper and lower ribs.
Airway diffusing capacity of nitric oxide and steroid therapy in asthma
Authors: Shin Hye-Won , Rose-Gottron Christine M. , Cooper Dan M. , Newcomb Robert L. , George Steven C.
Published: January 2004

Exhaled nitric oxide (NO) concentration is a noninvasive index for monitoring lung inflammation in diseases such as asthma. The plateau concentration at constant flow is highly dependent on the exhalation flow rate and the use of corticosteroids and cannot distinguish airway and alveolar sources. In subjects with steroid-naive asthma ( n = 8) or steroid-treated asthma ( n = 12) and in healthy controls ( n = 24), we measured flow-independent NO exchange parameters that partition exhaled NO into airway and alveolar regions and correlated these with symptoms and lung function. The mean (±SD) maximum airway flux (pl/s) and airway tissue concentration [parts/billion (ppb)] of NO were lower in steroid-treated asthmatic subjects compared with steroid-naive asthmatic subjects (1,195 ± 836 pl/s and 143 ± 66 ppb compared with 2,693 ± 1,687 pl/s and 438 ± 312 ppb, respectively). In contrast, the airway diffusing capacity for NO (pl·s-1·ppb-1) was elevated in both asthmatic groups compared with healthy controls, independent of steroid therapy (11.8 ± 11.7, 8.71 ± 5.74, and 3.13 ± 1.57 pl·s-1·ppb-1for steroid treated, steroid naive, and healthy controls, respectively). In addition, the airway diffusing capacity was inversely correlated with both forced expired volume in 1 s and forced vital capacity (%predicted), whereas the airway tissue concentration was positively correlated with forced vital capacity. Consistent with previously reported results from Silkoff et al. (Silkoff PE, Sylvester JT, Zamel N, and Permutt S, Am J Respir Crit Med 161: 1218-1228, 2000) that used an alternate technique, we conclude that the airway diffusing capacity for NO is elevated in asthma independent of steroid therapy and may reflect clinically relevant changes in airways.
Increasing blood flow before exercise in spinal cord-injured individuals does not alter muscle fatigue
Authors: Olive Jennifer L. , Slade Jill M. , Bickel C. Scott , Dudley Gary A. , McCully Kevin K.
Published: January 2004

Previous studies have shown increased fatigue in paralyzed muscle of spinal cord-injured (SCI) patients (Castro M, Apple D Jr, Hillegass E, and Dudley GA. Eur J Appl Physiol 80: 373-378, 1999; Gerrits H, Hopman MTE, Sargeant A, and de Haan A. Clin Physiol 21: 105-113, 2001). Our purpose was to determine whether the increased muscle fatigue could be due to a delayed rise in blood flow at the onset of exercise in SCI individuals. Isometric electrical stimulation was used to induce fatigue in the quadriceps femoris muscle of seven male, chronic (>1 yr postinjury), complete (American Spinal Injury Association, category A) SCI subjects. Cuff occlusion was used to elevate blood flow before electrical stimulation, and the magnitude of fatigue was compared with a control condition of electrical stimulation without prior cuff occlusion. Blood flow was measured in the femoral artery by Doppler ultrasound. Prior cuff occlusion increased blood flow in the first 30 s of stimulation compared with the No-Cuff condition (1,350 vs. 680 ml/min, respectively; P < 0.001), although blood flow at the end of stimulation was the same between conditions (1,260 ± 140 vs. 1,160 ± 370 ml/min, Cuff and No-Cuff condition, respectively; P = 0.511). Muscle fatigue was not significantly different between prior cuff occlusion and the control condition (32 ± 13 vs. 35 ± 10%; P = 0.670). In conclusion, increased muscle fatigue in SCI individuals is not associated with the prolonged time for blood flow to increase at the onset of exercise.
Interstitial albumin concentration measured during growth of perivascular cuffs in liquid-filled rabbit lung
Authors: Moe Sonja M. , Conhaim Robert L. , Lai-Fook Stephen J.
Published: January 2004

The growth rate and albumin concentration of interstitial fluid cuffs were measured in isolated rabbit lungs inflated with albumin solution (3 g/dl) to constant airway (Paw) and vascular pressures for up to 10 h. Cuff size was measured from images of frozen lung sections, and cuff albumin concentration (Cc) was measured from the fluorescence of Evans blue labeled albumin that entered the cuffs from the alveolar space. At 5-cmH2O Paw, cuff size peaked at 1 h and then decreased by 75% in 2 h. The decreased cuff size was consistent with an osmotic absorption into the albumin solution that filled the vascular and alveolar spaces. At 15-cmH2O Paw, cuff size peaked at 0.25 h and then remained constant. Cc rose continuously at both pressures, but was greater at the higher pressure. The increasing Cc with a constant cuff size was modeled as diffusion through epithelial pores. Initial Cc-to-airway albumin concentration ratio was 0.1 at 5-cmH2O Paw and increased to 0.3 at 15 cmH2O, a behavior that indicated an increased permeability with lung inflation. Estimated epithelial reflection coefficient was 0.9 and 0.7, and equivalent epithelial pore radii were 4.5 and 6.1 nm at 5- and 15-cmH2O Paw, respectively. The initial cuff growth occurred against an albumin colloid osmotic pressure gradient because a high interstitial resistance reduced the overall epithelial-interstitial reflection coefficient to the low value of the interstitium.
Superior performance of African runners in warm humid but not in cool environmental conditions
Authors: Marino Frank E. , Lambert Mike I. , Noakes Timothy D.
Published: January 2004

The purpose of this study was to examine the running performances and associated thermoregulatory responses of African and Caucasian runners in cool and warm conditions. On two separate occasions, 12 ( n = 6 African, n = 6 Caucasian) well-trained men ran on a motorized treadmill at 70% of peak treadmill running velocity for 30 min followed by an 8-km self-paced performance run (PR) in cool (15°C) or warm (35°C) humid (60% relative humidity) conditions. Time to complete the PR in the cool condition was not different between groups (∼27 min) but was significantly longer in warm conditions for Caucasian (33.0 ± 1.6 min) vs. African (29.7 ± 2.3 min, P < 0.01) runners. Rectal temperatures were not different between groups but were higher during warm compared with cool conditions. During the 8-km PR, sweat rates for Africans (25.3 ± 2.3 ml/min) were lower compared with Caucasians (32.2 ± 4.1 ml/min; P < 0.01). Relative rates of heat production were less for Africans than Caucasians in the heat. The finding that African runners ran faster only in the heat despite similar thermoregulatory responses as Caucasian runners suggests that the larger Caucasians reduce their running speed to ensure an optimal rate of heat storage without developing dangerous hyperthermia. According to this model, the superior running performance in the heat of these African runners can be partly attributed to their smaller size and hence their capacity to run faster in the heat while storing heat at the same rate as heavier Caucasian runners.
Carbohydrate intake during endurance exercise increases natural killer cell responsiveness to IL-2
Authors: McFarlin Brian K. , Flynn Michael G. , Stewart Laura K. , Timmerman Kyle L.
Published: January 2004

The purpose of this study was to evaluate the effect of high-intensity endurance exercise and carbohydrate consumption on in vitro responsiveness of natural killer (NK) to IL-2 (2.5 U/ml for 24 h). Thirteen male subjects (18-26 yr old; peak O2consumption = 59.79 ± 5.13 ml·kg-1·ml-1) were recruited to complete two 1-h (75-80% peak O2consumption) cycling trials in a random counterbalanced order: carbohydrate (CHO) and placebo (Pla). Venous blood samples were collected before (Pre), immediately (Post), 2 h (2H), and 4 h (4H) after exercise. All resting samples were taken after 15 min of seated rest. NK (CD3-/56+), activated NK (CD3-/56+/69+), helper T cell (Th; CD3+/4+), and cytotoxic T cell (Tc; CD3+/8+) number were measured by using flow cytometry. NK cell activity (NKCA) was determined by using both a51Cr release assay (NKCA-51) and activated NK cell number (NKCA-69). Immune system variables were not different between CHO and Pla, with the exception of NK cell responsiveness to IL-2, where Post (116.2%) and 4H (48.4%) was significantly greater in CHO ( P < 0.05). NK, Th, and Tc were significantly higher Post (40.7, 102.7, and 82.0%, respectively) and lower at 2H (-51.9, -53.3, and -53.2%, respectively) than Pre (time effect). 4H was not different from Pre for NK, Th, and Tc. NKCA was significantly lower 2H (NKCA-51, NKCA-69) and 4H (NKCA-69) than Pre. CHO consumption during exercise did not prevent disruptions in unstimulated immune system function, but it did enhance NK responsiveness to IL-2.
Susceptibility to sarcomere injury induced by single stretches of maximally activated muscles ofmdxmice
Authors: Consolino Christina M. , Brooks Susan V.
Published: January 2004

The purpose was to investigate the contribution of mechanical damage to sarcomeres to the greater susceptibility of dystrophic muscle fibers to contraction-induced injury. Single stretches provide an effective method for studying mechanical factors that contribute to the initiation of contraction-induced injury. We hypothesized that, after single stretches, the deficits in isometric force would be greater for muscles of mdx than C57BL/10 mice, whereas membrane damage would be minimal for all muscles. Extensor digitorum longus (EDL) and soleus muscles of mice were removed under anesthesia with Avertin (tribromoethanol). During the plateau of a maximum isometric contraction in vitro, muscles were stretched through single strains of 20-60% fiber length. Isometric force was remeasured 1 min later, and muscles were then incubated in procion orange dye to identify fibers with membrane damage. Force deficits at 1 min were two- to threefold greater for EDL muscles of mdx compared with C57BL/10 mice, whereas no significant differences were observed between soleus muscles of mdx and C57BL/10 mice. For all muscles, membrane damage was minimal and not significantly increased by single stretches for either strain of mice. These data support a critical role of dystrophin maintaining sarcomere stability in EDL muscles, whereas soleus muscles retain abilities, in the absence of dystrophin, not different from control muscles to resist sarcomere damage.
Sensing vascular distension in skeletal muscle by slow conducting afferent fibers: neurophysiological basis and implication for respiratory control
Authors: Haouzi Philippe , Chenuel Bruno , Huszczuk Andrew
Published: January 2004

This review examines the evidence that skeletal muscles can sense the status of the peripheral vascular network through group III and IV muscle afferent fibers. The anatomic and neurophysiological basis for such a mechanism is the following: 1) a significant portion of group III and IV afferent fibers have been found in the vicinity and the adventitia of the arterioles and the venules; 2) both of these groups of afferent fibers can respond to mechanical stimuli; 3) a population of group III and IV fibers stimulated during muscle contraction has been found to be inhibited to various degrees by arterial occlusion; and 4) more recently, direct evidence has been obtained showing that a part of the group IV muscle afferent fibers is stimulated by venous occlusion and by injection of vasodilatory agents. The physiological relevance of sensing local distension of the vascular network at venular level in the muscles is clearly different from that of the large veins, since the former can directly monitor the degree of tissue perfusion. The possible involvement of this sensing mechanism in respiratory control is discussed mainly in the light of the ventilatory effects of peripheral vascular occlusions during and after muscular exercise. It is proposed that this regulatory system anticipates the chemical changes that would occur in the arterial blood during increased metabolic load and attempts to minimize them by adjusting the level of ventilation to the level of muscle perfusion, thus matching the magnitudes of the peripheral and pulmonary gas exchange.
Effects of simulated microgravity on closed-loop cardiovascular regulation and orthostatic intolerance: analysis by means of system identification
Authors: Xiao Xinshu , Mukkamala Ramakrishna , Sheynberg Natalie , Grenon S. Marlene , Ehrman Michael D. , Mullen Thomas J. , Ramsdell Craig D. , Williams Gordon H. , Cohen Richard J.
Published: January 2004

Microgravity-induced orthostatic intolerance (OI) continues to be a primary concern for the human space program. To test the hypothesis that exposure to simulated microgravity significantly alters autonomic nervous control and, thus, contributes to increased incidence of OI, we employed the cardiovascular system identification (CSI) technique to evaluate quantitatively parasympathetic and sympathetic regulation of heart rate (HR). The CSI method analyzes second-to-second fluctuations in noninvasively measured HR, arterial blood pressure, and instantaneous lung volume. The coupling mechanisms between these signals are characterized by using a closed-loop model. Parameters reflecting parasympathetic and sympathetic responsiveness with regard to HR regulation can be extracted from the identified coupling mechanisms. We analyzed data collected from 29 human subjects before and after 16 days of head-down-tilt bed rest (simulated microgravity). Statistical analyses showed that parasympathetic and sympathetic responsiveness was impaired by bed rest. A lower sympathetic responsiveness and a higher parasympathetic responsiveness measured before bed rest identified individuals at greater risk of OI before and after bed rest. We propose an algorithm to predict OI after bed rest from measures obtained before bed rest.
Regulation of brain water during acute glucose-induced hyperosmolality in ovine fetuses, lambs, and adults
Authors: Stonestreet Barbara S. , Petersson Katherine H. , Sadowska Grazyna B. , Patlak Clifford S.
Published: January 2004

We tested the hypothesis that, during acute glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and that brain volume regulation is present in fetuses, premature and newborn lambs. Brain water responses to glucose-induced hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, and adult sheep. After exposure of the sheep to increases in osmolality with glucose plus NaCl, brain water and electrolytes were measured. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. In the absence of volume regulation, brain solute remains constant as osmolality changes. The osmotically active solute demonstrated direct linear correlations with plasma osmolality in the cerebral cortex of the fetuses at 60% of gestation ( r = 0.72, n = 24, P = 0.0001), premature lambs ( r = 0.58, n = 22, P = 0.005), newborn lambs ( r = 0.57, n = 24, P = 0.004), and adult sheep ( r = 0.70, n = 18, P = 0.001). Similar findings were observed in the cerebellum and medulla. Increases in the quantity of osmotically active solute over the range of plasma osmolalities indicate that volume regulation was present in the brain regions of the fetuses, premature lambs, newborn lambs, and adult sheep during glucose-induced hyperosmolality. We conclude that, during glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and exhibits volume regulation in fetuses at 60% of gestation, premature lambs, newborn lambs, and adult sheep.
Considerations on the history dependence of muscle contraction
Authors: Rassier Dilson E. , Herzog Walter
Published: January 2004

When a skeletal muscle that is actively producing force is shortened or stretched, the resulting steady-state isometric force after the dynamic phase is smaller or greater, respectively, than the purely isometric force obtained at the corresponding final length. The cross-bridge model of muscle contraction does not readily explain this history dependence of force production. The most accepted proposal to explain both, force depression after shortening and force enhancement after stretch, is a nonuniform behavior of sarcomeres that develops during and after length changes. This hypothesis is based on the idea of instability of sarcomere lengths on the descending limb of the force-length relationship. However, recent evidence suggests that skeletal muscles may be stable over the entire range of active force production, including the descending limb of the force-length relationship. The purpose of this review was to critically evaluate hypotheses aimed at explaining the history dependence of force production and to provide some novel insight into the possible mechanisms underlying these phenomena. It is concluded that the sarcomere nonuniformity hypothesis cannot always explain the total force enhancement observed after stretch and likely does not cause all of the force depression after shortening. There is evidence that force depression after shortening is associated with a reduction in the proportion of attached cross bridges, which, in turn, might be related to a stress-induced inhibition of cross-bridge attachment in the myofilament overlap zone. Furthermore, we suggest that force enhancement is not associated with instability of sarcomeres on the descending limb of the force-length relationship and that force enhancement has an active and a passive component. Force depression after shortening and force enhancement after stretch are likely to have different origins.