bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paradoxical effect of oxygen administration on breathing stability following post‐hyperventilation apnoea in lambs
Authors: Wilkinson M. H. , Berger P. J. , Blanch N. , Brodecky V. , Jones C. A. 
Published: September 2004

Oxygen administration is thought to suppress periodic breathing (PB) by reducing carotid body activity, and yet earlier experiments in neonates have shown that PB incidence may be increased following the application of hyperoxia. To clarify this paradox, we studied the changes in the pattern of PB that occur following administration of oxygen in a lamb model of PB.
PB was induced in eleven of seventeen anaesthetized lambs following passive hyper‐ventilation with air. When oxygen was administered during PB, the pattern was first enhanced, as evidenced by a sudden decrease in the ratio of the ventilatory duration to the apnoeic pause duration, and then suppressed, as evidenced by a progressive return to stable breathing which was associated with an increase in minute ventilation.
Five of the six lambs that did not show PB following passive hyperventilation with air could be made to do so if oxygen was substituted for air as the inspired gas following passive hyperventilation.
Five of the eleven lambs that showed PB following hyperventilation with air responded to the application of oxygen during PB by switching to a gross form of episodic breathing consisting of long apnoeic pauses followed by equally long periods of breathing during which minute ventilation fell progressively with time.
We conclude that when applied against a background of arterial hypoxaemia, oxygen has a destabilizing influence on ventilation in that (a) it accentuates the unstable breathing that occurs during PB, (b) it induces PB in lambs that exhibited stable breathing in air, and (c) it may precipitate episodic breathing.
A Comparison of the Ventilatory Response of Sleeping Newborn Lambs to Step and Progressive Hypoxaemia
Authors: Cohen Gary , Malcolm Girvan , Henderson‐Smart David 
Published: September 2004

Slight variations in the rate at which hypoxaemia develops may significantly alter the ventilatory response (VR) elicited. Here we have developed a technique to compare the VRs elicited from sleeping newborn lambs by specific (stepversusprogressive), short‐duration (≥ 5 min) episodes of hypoxaemia. The results may help us understand the limitations of using tests which deliver poorly defined stimuli to evaluate the postnatal development of the oxygen chemoreflex.The VRs of five lambs elicited by a 5 min step or progressive reduction in the arterial oxygen saturation (Sa,O2) during quiet sleep were compared. Minute ventilation (V̇i, face mask) andSa,O2(pulse oximeter) were measured continuously. Alternate step (Sa,O2reduced to 80–85 % within 60 s and maintained for a further 4 min) and progressive tests (progressive reduction inSa,O2to 80 % over 5 min) were administered daily between postnatal days 2–14.There was a significant difference between the mean VR to stepversusprogressive hypoxaemia. The VR to a step challenge was biphasic (ΔV̇i=+32 ± 5% at 1 min and −1 ± 4% at 5 min; mean ±s.e.m.). Progressive hypoxaemia elicited a more subdued but sustained hyperpnoea (ΔV̇i=+11 ± 2% at 1 min and +11 ± 4% at 5 min). The difference between these two response profiles was statistically significant (P< 0.001).Mean responses of lambs aged ≤ 5 days (4 ± 0.2 days) and ≥ 9 days (10 ± 0.3 days) were also compared. There was an upward shift in the position of step and progressive response curves of older lambs, reflecting primarily the increased vigour of the initial hyperpnoea elicited by step (ΔV̇iat 1 min =+20 ± 4% at 4 daysvs.+40 ± 11 % at 10 days) as well as progressive (ΔV̇iat 1 min =+6 ± 2% at 4 daysvs.+17 ± 5%at 10 days) hypoxaemia.Qualitatively different VRs may be elicited from the newborn, depending upon the specific hypoxaemic profile administered. Therefore, to evaluate the significance of VRs elicited in response to classical, steady‐state hypoxia at different postnatal ages properly, the stimulus must be accurately described.
Energetics of lengthening in mouse and toad skeletal muscles
Authors: Constable J. K. , Barclay C. J. , Gibbs C. L. 
Published: September 2004

The energetics of lengthening were studied in amphibian and mammalian skeletal muscle. The aims were to determine whether energy absorption during stretch is a general property of skeletal muscle and to investigate the influence of lengthening velocity on energy absorption.
Experiments were performed in vitro (21 °C) using bundles of muscle fibres from fast‐twitch extensor digitorum longus and slow‐twitch soleus muscles of the mouse and tibialis anterior muscles of a toad, Bufo marìnus. Initial heat production and mechanical work done on muscles were measured during isovelocity lengthening. Enthalpy output during lengthening was calculated as the difference between the amount of heat produced and the work done.
For all three muscle types, more energy was put into muscles as work than was produced as heat. Thus, part of the energy put into muscles to stretch them must have been absorbed.
For all three muscle types, the amount of energy absorbed was constant at velocities exceeding ∼0.5Vmax (Vmax is the maximum shortening velocity), but was significantly lower at slow velocities of lengthening. The same amount of energy was absorbed by all three muscles when lengthened at ≥ 0.5 Vmax.
It was concluded that absorption of energy during lengthening occurs in mammalian as well as amphibian muscle and that lengthening velocity has only a small effect on the amount of energy absorbed.
Energetic cost of activation processes during contraction of swine arterial smooth muscle
Authors: Wingard Christopher J. , Paul Richard J. , Murphy Richard A. 
Published: September 2004

The objective of this study was to partition the increase in ATP consumption during contraction of swine carotid arterial smooth muscle estimated from suprabasal oxygen consumption (suprabasal JO2) and lactate release (Jlactate) into a component associated with cross‐bridge cycling (Jx) and one reflecting activation (JA).
Two experimental approaches – varying length under constant activation, and varying activation at a long length (1.8 times the optimal length for force development (L0)) where force generation is minimal – revealed a linear dependence of J0 and activation energy (JA) on cross‐bridge phosphorylation. Protocols inducing a large increase in myosin regulatory light chain (MRLC) phosphorylation at 1.8L0 resulted in significant elevations of JO2 and marked reductions in the economy of force maintenance. Our evidence suggests that this is primarily due to the increased cost of cross‐bridge phosphorylation.
The extrapolated estimate of JA during maximal K+‐induced depolarization made by varying length was 16%, while at 1.8LO it was 33% of the suprabasal JO2 at L0. Calculated activation energies ranged from 17 to 45% of the suprabasal JO2 at L0 and from 72 to 87% of the suprabasal JO2 at 1.8L0 under stimulation conditions that varied steady‐state MRLC phosphorylation from 15 to 50%.
The results suggest that the kinetics of cross‐bridge phosphorylation‐dephosphorylation can rival those of cross‐bridge cycling during isometric contractions in swine arterial smooth muscle.
The Effects of Breathing He–O2 Mixtures on Maximal Oxygen Consumption in Normoxic and Hypoxic Men
Authors: Esposito Fabio , Ferretti Guido 
Published: September 2004

The hypothesis that the ventilatory resistance to O2 flow (RV) does limit maximal O2 consumption (V̇O2 max) in hypoxia, but not in normoxia, at least in non‐athletic subjects, was tested. RV was reduced by using He–O2 mixtures.
V̇O2, max was measured during graded cyclo‐ergometric exercise in eight men (aged 30 ± 3 years) who breathed N2–O2 and He–O2 mixtures in normoxia (inspired oxygen fraction (FI,O2= 0.21) and hypoxia (FI,O2= 0.11). O2 consumption, expired and alveolar ventilations (V̇E and V̇A, respectively), blood lactate and haemoglobin concentrations, heart rate and arterial oxygen saturation (Sa,O2) were determined at the steady state of each work load. Arterial O2 and CO2 partial pressures (Pa,O2) and Pa,CO2, respectively) were measured at rest and at the end of the highest work load.
Maximal V̇E and V̇A were significantly increased by He—O2 breathing in normoxia (+27 and +18%, respectively), without significant changes in Pa, O2, Sa, O2V̇O2, max In hypoxia, V̇E and V̇A increased (+31 and +24%, respectively), together with Pa,O2 (+17%), Sa, O2 (+6%) and V̇O2, max (+14%).
The results support the hypothesis that the role of RV in limiting V̇O2,max is negligible in normoxia. In hypoxia, the finding that higher V̇E and V̇A values during He–O2 breathing led to higher V̇O2,max values suggests a greater role of RV as a limiting factor. It is unclear whether the finding that the V̇O2 max values were the same during He–O2 and N2–O2 breathing in normoxia is due to a non‐linear response of the O2 transfer system, as previously proposed.
Perception and gut reflexes induced by stimulation of gastrointestinal thermoreceptors in humans
Authors: Villanova Nicola , Azpiroz Fernando , Malagelada Juan‐R. 
Published: September 2004

Experimental studies in animals suggest the existence of thermoreceptors in the gastrointestinal tract. Our aim was to investigate the distribution and specificity of upper gut thermoreceptors in humans.
In healthy subjects, thermal stimulation of the stomach (n= 8) and the small intestine (n= 6) was produced by means of a thermostat, which recirculates water at adjusted temperatures through an ultrathin intraluminal bag. Progressively warm (42, 47 and 52 °C) and cold (32, 22 and 12 °C) stimuli of 3 min duration were alternately applied at 13 min intervals. Perception was scored on a scale of 0–6 and gastric tone responses were measured with a barostat.
Thermal stimuli induced specific responses: cold stimuli induced abdominal cold sensation and a reflex contraction of the stomach, whereas warm stimuli induced warm sensation and a reflex gastric relaxation.
Thermal stimuli induced similar stimulus‐related perception in the stomach and small intestine (temperatures between 12 and 49.5 ± 0.5 °C were tolerated).
The reflex responses were site specific. Warm and cold stimulation of the stomach induced gastric reflexes (76 ± 26 ml isobaric expansion at 47 °C, and 68 ± 10 ml contraction at 12°C; P > 0.05 for both). However, only warm, not cold, stimulation of the intestine induced enterogastric reflexes.
These results indicate that in humans, warm and cold receptors are distributed along the gastrointestinal tract and project afferent input both into perception and reflex circuits with specific topographic organization.
Mechanism of action of endothelin in rat cardiac muscle: cross‐bridge kinetics and myosin light chain phosphorylation
Authors: Rossmanith Gunther H. , Hoh Joseph F. Y. , Turnbull Lynne , Ludowyke Russell I. 
Published: September 2004

The molecular mechanism of inotropic action of endothelin was investigated in rat ventricular muscle by studying its effects on characteristics of isometric twitch, barium‐induced steady contracture and the level of incorporation of 32Pi into myosin light chain 2.
Exposure of rat papillary muscle to endothelin caused an increase in isometric twitch force but did not alter the twitch‐time parameters.
Endothelin did not significantly change the maximum contracture tension but did cause an increase in contracture tension at submaximal levels of activation, without changes in the tension‐to‐stiffness ratio and kinetics of attached cross‐bridges. Kinetics of attached cross‐bridges were deduced during steady contracture from complex‐stiffness values, and in particular from the frequency at which muscle stiffness assumes a minimum value, fmin. Endothelin did not alter fmin.
Endothelin caused an increase in the level of incorporation of 32Pi into myosin light chain 2 without a concurrent change in the level of incorporation of 32Pi into troponin I.
We conclude that the inotropic action of endothelin is not due to an increase in the kinetics of attached cross‐bridges, nor due to a change in the force per unit cross‐bridge, but may result from an increased divalent cation sensitivity caused by elevated myosin light chain 2 phosphorylation, resembling post‐tetanic potentiation in fast skeletal muscle fibres.
Discharge of human muscle spindle afferents innervating ankle dorsiflexors during target isometric contractions
Authors: Wilson Linda R , Gandevia Simon C , Burke David 
Published: September 2004

There are discrepancies in the literature about the reproducibility of forces at which human muscle spindle afferents accelerate their discharge during isometric voluntary contractions. The aim of this study was to determine for single muscle spindle afferents both the reproducibility of the ‘acceleration threshold’ and the factors contributing to variability of ‘acceleration threshold’.
Microneurographic recordings were made from muscle spindle afferents innervating tibialis anterior while subjects performed isometric ankle dorsiflexions. Subjects matched the force of their contractions with a visually displayed ‘ramp‐and‐hol? template. Template parameters were determined by the force of maximal isometric ankle dorsiflexion (MVC), and expressed as per cent MVC. The required ‘ramp’ rate and ‘hold’ force was adjusted between trials (range, 0.5‐5% MVC s− and 0.5‐20% MVC, respectively). The duration of the hold phase was 4 s and, following each contraction, stretch was applied transversely to the tendon to minimize the influence of any ‘after‐effects’ on spindle afferent responses in subsequent contractions.
For each contraction, the force at which the rate of muscle spindle discharge increased was defined as the ‘acceleration threshold’. Of twenty‐six muscle spindle afferents innervating tibialis anterior, all but two increased their discharge in the test contractions. In 90% of contractions, acceleration thresholds were less than 3.2% MVC (range, 0.01–11.9% MVC).
Individual muscle spindle afferents increased their discharge at similar but not identical forces in repeated contractions. There was a positive correlation between the rate of contraction and the acceleration threshold (P < 0.001), but the strength of the target contraction had no effect on the threshold, and there was no trend for thresholds to change over time.
The results suggest, first, that most muscle spindle endings in the human pretibial muscles receive a significant increase in fusimotor drive during relatively weak isometric efforts and secondly, that when fusimotor after‐effects are controlled, much of the residual variability in ‘acceleration threshold’ for any one spindle in repeated contractions is due to extrafusal factors, particularly variability in contraction rate.
Lymph Flow Pattern in the Intact Thoracic Duct in Sheep
Authors: Onizuka Masataka , FlatebØ Torun , Nicolaysen Gunnar 
Published: September 2004

To study the lymph flow dynamics in the intact thoracic duct, we applied an ultrasound transit‐time flow probe in seven anaesthetized and four unanaesthetized adult sheep (.60 kg). In unanaesthetized non‐fasting animals we found that lymph flow in the thoracic duct was always regular pulsatile (pulsation frequency, 5.2 ± 0.8 min−1) with no relation to heart or respiratory activity. At baseline the peak level of the thoracic duct pulse flow was 11.6–20.7 ml min−1 with a nadir of 0–3.6 ml min−1. Mean lymph flow was 5.4 ± 3.1 ml min−1. The flow pattern of lymph in the thoracic duct was essentially the same in the anaesthetized animals.
In both the anaesthetized and unanaesthetized animals, the lymph flow response to a stepwise increase in the outflow venous pressure showed interindividual variation. Some were sensitive to any increase in outflow venous pressure, but others were resistant in that lymph flow did not decrease until outflow venous pressure was increased to higher levels. This resistance was also observed in the high lymph flow condition produced by fluid infusion in the anaesthetized animal and mechanical constriction of the caudal vena cava in the unanaesthetized animals. Pulsation frequency of the thoracic duct flow initially increased and then decreased with a stepwise increase in the outflow venous pressure. This initial increase might be a compensatory response to maintain lymph flow against elevated outflow venous pressure.
To test the effect of long‐term outflow venous pressure elevation in unanaesthetized sheep, outflow venous pressure was increased by inflation of a cuff around the cranial vena cava for 1, 5 or 25 h. The cuff was inflated to a level where lymph flow was reduced. Lymph flow remained low or decreased further during the entire cuff‐inflation period. We calculated the lymph debt caused by the outflow venous pressure elevation and the amount ‘repaid’ when venous pressure returned to normal. Lymph debt for 25 h was 6400 ml but only 200 ml was repaid. Since we observed no visible oedema formation in the lower body of the sheep, the non‐colloidal components of the lymph must have been reabsorbed into the bloodstream, most likely in the lymph nodes.
Lymph flow dynamics in exercising human skeletal muscle as detected by scintography
Authors: Havas Eino , Parviainen Tapani , Vuorela Juha , Toivanen Jarmo , Nikula Tuomo , Vihko Veikko 
Published: September 2004

The effects of dynamic and isometric muscle contractions on the lymph flow dynamics in human skeletal muscle were studied with a scintographic method.
Radioactively labelled human serum albumin (99mTc‐HSA) was injected bilaterally into the vastus lateralis muscles of eight men (n= 16), four of whom had had an endurance training background. The subjects performed 100 submaximal contractions in 10 min as (i) dynamic knee extensions (CONS), (ii) isometric contractions with the knees at full extension (IMExt), or (iii) isometric contractions with knees fixed at 90 deg angle flexion (IMFlex). The exercises were separated by 65 min periods in supine rest. The level of radioactivity at the injection site was monitored by a gamma‐camera, and the clearance rate of radioactivity (CR) was calculated as the fractional decrease during the periods of interest (CR unit =% min−).
The clearance rate was low during the rest periods (0.04 ± 0.05% min−1), though higher in the trained than in the sedentary subjects (0.06 ± 0.05 vs. 0.03 ± 0.03% min−1; P= 0.008). Exercise increased the clearance rate three‐ to sixfold, to 0.16 ± 0.16% min−1 during CONS, 0.20 ± 0.15% min− during IMExt and 0.09 ± 0.11 % min−1 during IMFlex. There were no differences between the subject subgroups.
The higher clearance rate during IMExt than during IMFlex (P= 0.02) demonstrates the importance of muscle deformations on lymph propulsion and experimentally confirms the current concepts of lymph formation and propulsion in voluntarily active skeletal muscle. It is suggested that lymph propulsion by working muscle is most efficient when the muscle is able to shorten close to its minimum length.
Extracellular divalent cations block a cation non‐selective conductance unrelated to calcium channels in rat cardiac muscle
Authors: Mubagwa Kanigula , Stengl Milan , Flameng Willem 
Published: September 2004

The effect of removing extracellular divalent cations on resting potential (Vrest) and background conductance of rat cardiac muscle was studied. Vrest was measured with 3 M KCl‐filled microelectrodes in papillary muscles, or with a patch electrode in ventricular myocytes. Whole‐cell membrane currents were measured in myocytes using step or ramp voltage commands.
In both muscles and single cells, decrease or removal of Ca2+o and Mg2+o caused a nifedipine‐resistant depolarization, which was reversed upon readmission of Ca2+o or Mg2+o (half‐maximal effect at 0.8 mM Ca2+o or 3 mM Mg2+o in muscles).
In single myocytes, removal of Ca2+o and Mg2+o had no effect on the seal resistance in non‐ruptured cell‐attached recordings, but reversibly induced a current with a reversal potential (Vrev) of −8 ± 3.4 mV (with internal Cs+; mean. s.e.m., n= 23) during whole‐cell recordings. The current was insensitive to nifedipine (3–100 μM) or amiloride (1 mM). Vrev was insensitive to changes in the equilibrium potential for chloride ions (Ecl.
The current induced in the absence of extracellular divalent cations was blocked in a concentration‐dependent manner by Ca2+o. (At −80 mV, the affinity constant Kca was 60 μM with a Hill coefficient of 0.9.) KCa was voltage dependent at positive but not negative potentials. Mg2+o, Ni2+o, Sr2+o, Ba2+o, Cd2+o and Gd3+o also blocked the current.
In 0 mM Na+ (145 mM NMDG+), the inward component of the divalent cation‐sensitive current was decreased and Vrev shifted to more negative potentials.
These results suggest that a novel conductance pathway, permeable to monovalent cations but not to OF and blocked by divalent cations, exists in ventricular myocytes.
Effects of Extracellular pH on Receptor‐Mediated Ca2+ Influx in A7r5 Rat Smooth Muscle Cells: Involvement of Two Different Types of Channel
Authors: Iwasawa Kuniaki , Nakajima Toshiaki , Hazama Hisanori , Goto Atsuro , Shin Wee Soo , Toyo‐oka Teruhiko , Omata Masao 
Published: September 2004

The effects of extracellular pH (pHo) on receptor (vasopressin or endothelin‐l)‐mediated Ca2+ entry and Ca2+‐permeable channels were investigated in aortic smooth muscle cells (A7r5) from rat embryonic thoracic aorta. Intracellular Ca2+ ([Ca2+]i) was measured using fura‐2 AM and whole‐cell voltage clamp techniques were employed.
Vasopressin and endothelin‐1 (100 nM) in the presence of nicardipine (10 μM) evoked a sustained rise in [Ca2+]i due to calcium entry. Extracellular acidosis decreased receptor (vasopressin or endothelin‐l)‐mediated Ca2+ entry, while extracellular alkalosis potentiated it.
Depletion of intracellular Ca2+ stores with thapsigargin (1 μM) also evoked Ca2+ entry activated by emptying of intracellular Ca2+ stores (capacitative Ca2+ entry). Extracellular acidosis decreased this capacitative Ca2+ entry, while extracellular alkalosis potentiated it.
Under voltage‐clamp conditions with Cs+ internal solution, vasopressin and endothelin‐1 activated non‐selective cation currents (Icat). Ba2+ or Ca2+ were also charge carriers of Icat. Reducing the pHo inhibited Icat, while increasing pHo potentiated it in a reversible manner.
Intracellular pH (pHi) changes did not cause the same marked effects as pHo changes, and a high concentration of Hepes (50 mM) in the patch pipette did not inhibit the effects of pHo on Icat.
Similar results were obtained when Icat was activated by GTPγS (1 mM) applied through the patch pipette, even in the absence of agonists, probably because of direct activation of GTP‐binding proteins coupled to the receptors.
In cells treated with thapsigargin, addition of Ca2+ to the bath solution induced Ca2+‐dependent K+ currents activated by capacitative Ca2+ entry. However, no measurable ionic currents activated by capacitative Ca2+ entry (ICRAC) were observed under conditions with Cs+ internal solution and EGTA (5 mM), although vasopressin still activated Icat.
These results suggest that the contractile agonists vasopressin and endothelin‐1 evoke Ca2+ entry through two different types of Ca2+‐permeable channel (Icat and ICRAC) and pHo affects these channels, which may modulate receptor‐mediated Ca2+ influx in A7r5 cells. Thus, pH‐induced changes of these channels may play a pathophysiological role in the control of receptor‐mediated contractions.