Differential activation among five human inspiratory motoneuron pools during tidal breathing.

Neural drive to inspiratory pump muscles is increased under many pathological conditions. This study determined for the first time how neural drive is distributed to five different human inspiratory pump muscles during tidal breathing. The discharge of single motor units (n = 280) from five healthy subjects in the diaphragm, scalene, second parasternal intercostal, third dorsal external intercostal, and fifth dorsal external intercostal was recorded with needle electrodes. All units increased their discharge during inspiration, but 41 (15%) discharged tonically throughout expiration. Motor unit populations from each muscle differed in the timing of their activation and in the discharge rates of their motor units. Relative to the onset of inspiratory flow, the earliest recruited muscles were the diaphragm and third dorsal external intercostal (mean onset for the population after 26 and 29% of inspiratory time). The fifth dorsal external intercostal muscle was recruited later (43% of inspiratory time; P < 0.05). Compared with the other inspiratory muscles, units in the diaphragm and third dorsal external intercostal had the highest onset (7.7 and 7.1 Hz, respectively) and peak firing frequencies (12.6 and 11.9 Hz, respectively; both P < 0.05). There was a unimodal distribution of recruitment times of motor units in all muscles. Neural drive to human inspiratory pump muscles differs in timing, strength, and distribution, presumably to achieve efficient ventilation.     

A model of the central and reflex inhibition of inspiration in the cat

An attempt is made to summarize the results obtained in previous work from this and other laboratories on the steady state and transient relationships between the mechanical and neural events in breathing and their precise timing in the breathing cycle at different blood chemical demands for ventilation and at different body temperatures, and to fit these results into a functional and realistic model of the bulbo-pontine inspiratory off-switch mechanisms. The experimentally based requirements for the model are briefly described and listed. After a presentation of the model in qualitative terms its functional properties are considered quantitatively and compared with the performance of the real, biological system. This has been achieved by assuming some simple mathematical approximations for the activities of the introduced physiological parameters and their chemical “drive” dependence. The gaps in our present knowledge are pointed out and some key experiments suggested. The proposed model is consistent with the main conclusions reached in previous work from this laboratory that there are three neural submechanisms which are mainly responsible for the effects of increased CO₂ on ventilation: 1) a rise in the inspiratory off-switch threshold, 2) an increased rate of rise of the centrally generated inspiratory activity that projects to the off-switch mechanism (and to the spinal respiratory motoneurons), and 3) the vagal volume feed-back. Of these 1) and 2) are mainly responsible for the increase in tidal volume, whereas the vagal volume feed-back is mainly responsible for the increase in respiratory rate. The comparison between the model behaviour and experimental data suggest that the slight CO₂ sensitivity of the pulmonary stretch receptors recently reported on, has to be taken into account. The model studies have suggested the increase in respiratory rate with increased temperature may be due either to an increased rate of rise of inspiratory activity or to a decreased off-switch threshold, or both in combination. The mechanism controlling the expiratory durations are briefly discussed.     

No evidence for long-term facilitation after episodic hypoxia in spontaneously breathing, anesthetized rats.

Repeated electrical or hypoxic stimulation of peripheral chemoreceptors has been shown to cause a persistent poststimulus increase in respiratory motoneuron activity, termed long-term facilitation (LTF). LTF after episodic hypoxia has been demonstrated most consistently in anesthetized, vagotomized, paralyzed, artificially ventilated rats. Evidence for LTF in spontaneously breathing animals and humans after episodic hypoxia is equivocal and may have been influenced by the awake state of the subjects in these studies. The present study was designed to test the hypothesis that LTF is evoked in respiratory-related tongue muscle and inspiratory pump muscle activities after episodic hypoxia in 10 spontaneously breathing, anesthetized, vagotomized rats. The animals were exposed to three (5-min) episodes of isocapnic hypoxia, separated by 5 min of hyperoxia (50% inspired oxygen). Genioglossus, hyoglossus, and inspiratory intercostal EMG activities, along with respiratory-related tongue movements and esophageal pressure, were recorded before, during, and for 60 min after the end of episodic isocapnic hypoxia. We found no evidence for LTF in tongue muscle (genioglossus, hyoglossus) or inspiratory pump muscle (inspiratory intercostal) activities after episodic hypoxia. Rather, the primary poststimulus effect of episodic hypoxia was diminished respiratory frequency, which contributed to a reduction in ventilatory drive.     

Load compensation and respiratory muscle function during sleep.

The sleeping state places unique demands on the ventilatory control system. The sleep-induced increase in airway resistance, the loss of consciousness, and the need to maintain the sleeping state without frequent arousals require the presence of complex compensatory mechanisms. The increase in upper airway resistance during sleep represents the major effect of sleep on ventilatory control. This occurs because of a loss of muscle activity, which narrows the airway and also makes it more susceptible to collapse in response to the intraluminal pressure generated by other inspiratory muscles. The magnitude and timing of the drive to upper airway vs. other inspiratory pump muscles determine the level of resistance and can lead to inspiratory flow limitation and complete upper airway occlusion. The fall in ventilation with this mechanical load is not prevented, as it is in the awake state, because of the absence of immediate compensatory responses during sleep. However, during sleep, compensatory mechanisms are activated that tend to return ventilation toward control levels if the load is maintained. Upper airway protective reflexes, intrinsic properties of the chest wall, muscle length-compensating reflexes, and most importantly chemoresponsiveness of both upper airway and inspiratory pump muscles are all present during sleep to minimize the adverse effect of loading on ventilation. In non-rapid-eye-movement sleep, the high mechanical impedance combined with incomplete load compensation causes an increase in arterial PCO2 and augmented respiratory muscle activity. Phasic rapid-eye-movement sleep, however, interferes further with effective load compensation, primarily by its selective inhibitory effects on the phasic activation of postural muscles of the chest wall. The level and pattern of ventilation during sleep in health and disease states represent a compromise toward the ideal goal, which is to achieve maximum load compensation and meet the demand for chemical homeostasis while maintaining sleep state.     

Oxygen cost of breathing during fatiguing inspiratory resistive loads

When a subject breathes against an inspiratory resistance, the inspiratory pressure, the inspiratory flow, and the lung volume at which the breathing task takes place all interact to determine the length of time the task can be sustained (Tlim). We hypothesized that the mechanism actually limiting tasks in which these parameters were varied involved the rate of energy utilization by the inspiratory muscles. To test this hypothesis, we studied four experienced normal subjects during fatiguing breathing tasks performed over a range of pressures and flows and at two different lung volumes. We assessed energy utilization by measuring the increment in the rate of whole body O2 consumption due to the breathing task (VO2 resp). Power and mean esophageal pressure correlated with Tlim but depended also on lung volume and inspiratory flow rate. In contrast, VO2 resp closely correlated with Tlim, and this relationship was not systematically altered by inspiratory flow or lung volume. The shape of the VO2 resp vs. Tlim curve was approximately hyperbolic, with high rates of VO2 resp associated with short endurance times and lower rates of VO2 resp approaching an asymptotic value at high Tlim. These findings are consistent with a mechanism whereby a critical rate of energy utilization determines the endurance of the inspiratory pump, and that rate varies with pressure, flow, and lung volume.     

Fluctuation in timing of upper airway and chest wall inspiratory muscle activity in obstructive sleep apnea

An imbalance in the amplitude of electrical activity of the upper airway and chest wall inspiratory muscles is associated with both collapse and reopening of the upper airway in obstructive sleep apnea (OSA). The purpose of this study was to examine whether timing of the phasic activity of these inspiratory muscles also was associated with changes in upper airway caliber in OSA. We hypothesized that activation of upper airway muscle phasic electrical activity before activation of the chest wall pump muscles would help preserve upper airway patency. In contrast, we anticipated that the reversal of this pattern with delayed activation of upper airway inspiratory muscles would be associated with upper airway narrowing or collapse. Therefore the timing and amplitude of midline transmandibular and costal margin moving time average (MTA) electromyogram (EMG) signals were analyzed from 58 apnea cycles in stage 2 sleep in six OSA patients. In 86% of the postapnea breaths analyzed the upper airway MTA peak activity preceded the chest wall peak activity. In 86% of the obstructed respiratory efforts the upper airway MTA peak activity followed the chest wall peak activity. The onset of phasic electrical activity followed this same pattern. During inspiratory efforts when phasic inspiratory EMG amplitude did not change from preapnea to apnea, the timing changes noted above occurred. Even within breaths the relative timing of the upper airway and chest wall electrical activities was closely associated with changes in the pressure-flow relationship. We conclude that the relative timing of inspiratory activity of the upper airway and chest wall inspiratory muscles fluctuates during sleep in OSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Movement of tropomyosin during regulation of vertebrate skeletal muscle: a simple physical model.

Using data obtained from (a) X-ray diffraction patterns of vertebrate skeletal muscle (b) three dimensional reconstructions from electron micrographs of in vitro aggregates of the thin filament proteins in the switched “on” and “off” positions (c) the analysis of the sequence of tropomyosin, a simple model can be proposed which may explain the geometrical arrangement of actin, tropomyosin and troponin during regulation. The “cooperative” behaviour exhibited by the thin filament can also be explained in terms of this arrangement.     

Geometry for mutualistic and selfish herds: the limited domain of danger

We present a two-dimensional individual-based model of aggregation behaviour in animals by introducing the concept of a "limited domain of danger", which represents either a limited detection range or a limited attack range of predators. The limited domain of danger provides a suitable framework for the analysis of individual movement rules under real-life conditions because it takes into account the predator's prey detection and capture abilities. For the first time, a single geometrical construct can be used to analyse the predation risk of both peripheral and central individuals in a group. Furthermore, our model provides a conceptual framework that can be equally applied to aggregation behaviour and refuge use and thus presents a conceptual advance on current theory that treats these antipredator behaviours separately. An analysis of individual movement rules using limited domains of danger showed that the time minimization strategy outcompetes the nearest neighbour strategy proposed by Hamilton's (J. Theor. Biol. 31 (1971) 295) selfish herd model, whereas a random strategy confers no benefit and can even be disadvantageous. The superior performance of the time minimization strategy highlights the importance of taking biological constraints, such as an animal's orientation relative to its neighbours, into account when searching for efficient movement rules underlying the aggregation process.     

Cell fusion generates an inhomogeneous distribution of elasticity and rigidity in plasma membranes

The post-electrofusion oscillation cycle of human erythrocytes (doublets) was evaluated for the first four pump events in order to quantify the spectrin-network rearrangement in the fusion zone. Experiments were carried out on control cells and on cells that received a 40 degree C and a 45 degree C 20-min heat treatment. The amplitude of the geometrical changes depended on the heat-treatment procedure, whereas the roundness on entering the pump event was always identical. The rigid influence of the fusion zone prevented the doublets from adopting a spherical shape. The fusion zone was characterized by a linear elongation modulus that could be calculated from geometrical measurements and earlier findings on erythrocyte membrane mechanics, and that ranged between 1.44E6 Nm(-2) for control doublets and 0.99E6 Nm(-2) after 45 degrees C heat treatment. The membrane composition of the fusion zone differs greatly from that of the other membrane parts not involved in fusion processes and evidence is given that this inhomogeneity stems from a rearrangement of the triangulated spectrin network and other membrane skeletal proteins in the fusion zone.     

Fatigue of the inspiratory muscle pump in humans: an isoflow approach

A new method is described for measurement of inspiratory muscle endurance in humans that is based on isokinetic principles of muscle testing (i.e., measurement of maximum force during a constant velocity of shortening). Subjects inspired maximally while their lungs were inflated at a constant rate during each breath for 10 min. Inspiratory and expiratory time, flow rate, tidal volume, and end-tidal CO2 were maintained constant. In each subject, maximum inspiratory mouth pressure exponentially decayed over the first few minutes to an apparent sustainable value. Repeated tests in experienced subjects showed high reproducibility of sustainable pressure measurements. To determine the effects of flow, endurance tests were repeated in four subjects at flows of 0.75, 1.0, and 1.25 l/s, with a constant duty cycle. As flow increased, the maximum pressures that could be attained at rest and the maximum sustainable pressures decreased. At each flow, the sustainable pressure remained a constant fraction of the maximum pressure attainable at rest. We interpret the decay in mouth pressure during isoflow endurance tests to directly reflect the loss of net inspiratory muscle force available by maximum voluntary activation of the inspiratory pump.     

Upper airway afferents are sufficient to evoke the early components of respiratory-related cortical potentials in humans.

Repeated inspiratory occlusions in humans elicit respiratory-related cortical potentials, the respiratory counterpart of somatosensory-evoked potentials. These potentials comprise early components (stimulus detection) and late components (cognitive processing). They are considered as the summation of several afferent activities from various part of the respiratory system. This study assesses the role of the upper airway as a determinant of the early and late components of the potentials, taking advantage of the presence of a tracheotomy in patients totally or partially deafferented. Eight patients who could breathe either through the mouth or through a tracheotomy orifice (whole upper airway bypassed) were studied (4 quadriplegic patients with phrenic pacing, 4 patients with various sources of inspiratory pump dysfunction). Respiratory-related evoked potentials were recorded in CZ-C3 and CZ-C4. They were consistently present after mouth occlusions, with a first positive P1 and a first negative N1 components of normal latencies (P1: 40.4 +/- 6.1 ms in CZ-C3 and 47.6 +/- 7.6 ms in CZ-C4; N1: 84.4 +/- 27.1 ms in CZ-C3 and 90.2 +/- 17.4 ms in CZ-C4) and amplitudes. Tracheal occlusions did not evoke any cortical activity. Therefore, in patients with inspiratory pump dysfunction, the activation of upper airway afferents is sufficient to produce the early components of the respiratory-related evoked cortical potentials. Per contra, in this setting, pulmonary afferents do not suffice to evoke these components.     

Consequences of periodic augmented breaths on tongue muscle activities in hypoxic rats.

This study was designed to investigate the influence of hypoxia-evoked augmented breaths (ABs) on respiratory-related tongue protrudor and retractor muscle activities and inspiratory pump muscle output. Genioglossus (GG) and hyoglossus (HG) electromyogram (EMG) activities and respiratory-related tongue movements were compared with peak esophageal pressure (Pes; negative change in pressure during inspiration) and minute Pes (Pes x respiratory frequency = Pes/min) before and after ABs evoked by sustained poikilocapnic, isocapnic, and hypercapnic hypoxia in spontaneously breathing, anesthetized rats. ABs evoked by poikilocapnic and isocapnic hypoxia triggered long-lasting (duration at least 10 respiratory cycles) reductions in GG and HG EMG activities and tongue movements relative to pre-AB levels, but Pes was reduced transiently (duration of <10 respiratory cycles) after ABs. Adding 7% CO(2) to the hypoxic inspirate had no effect on the frequency of evoked ABs, but this prevented long-term declines in tongue muscle activities. Bilateral vagotomy abolished hypoxia-induced ABs and stabilized drive to the tongue muscles during each hypoxic condition. We conclude that, in the rat, hypoxia-evoked ABs 1) elicit long-lasting reductions in protrudor and retractor tongue muscle activities, 2) produce short-term declines in inspiratory pump muscle output, and 3) are mediated by vagal afferents. The more prolonged reductions in pharyngeal airway vs. pump muscle activities may lead to upper airway narrowing or collapse after spontaneous ABs.     

How does the geometry affect the internal biomechanics of a lumbar spine bi-segment finite element model? Consequences on the validation process

Numerical modelling can provide a thorough understanding of the mechanical influence on the spinal tissues and may offer explanations to mechanically linked pathologies. Such objective might be achieved only if the models are carefully validated. Sensitivity study must be performed in order to evaluate the influence of the approximations inherent to modelling. In this study, a new geometrically accurate L3-L5 lumbar spine bi-segmental finite-element model was acquired by modifying a previously existing model. The effect of changes in bone geometry, ligament fibres distribution, nucleus position and disc height was investigated in flexion and extension by comparison of the results obtained from the model before and after the geometrical update. Additional calculations were performed in axial rotation and lateral bending in order to compare the computed ranges of motion (ROM) with experimental results. It was found that the geometrical parameters affected the stress distribution and strain energy in the zygapophysial joints, the ligaments, and the intervertebral disc, changing qualitatively and quantitatively their relative role in resisting the imposed loads. The predicted ROM were generally in good agreement with the experimental results, independently of the geometrical changes. Hence, although the model update affected its internal biomechanics, no conclusions could be drawn from the experimental data about the validation of a particular geometry. Hence the validation of the lumbar spine model should be based on the relative role of its structural components and not only on its global mobility.     

Breathing strategy of the adult horse (Equus caballus) at rest

To investigate the mechanism underlying the polyphasic airflow pattern of the equine species, we recorded airflow, tidal volum, rib cage and abdominal motion, and the sequence of activation of the diaphragm, intercostal, and abdominal muscles during quiet breathing in nine adult horses standing at rest. In addition, esophageal, abdominal, and transdiaphragmatic pressures were simultaneously recorded using balloon-tipped catheters. Analysis of tidal flow-volume loops showed that, unlike humans, the horse at rest breathes around, rather than from, the relaxed volume of the respiratory system (Vrx). Analysis of the pattern of electromyographic activities and changes in generated pressures during the breathing cycle indicate that the first part of expiration is passive, as in humans, with deflation toward Vrx, but subsequent abdominal activity is responsible for a second phase of expiration: active deflation to below Vrx. From this end-expiratory volume, passive inflation occurs toward Vrx, followed by a second phase of inspiration: active inflation to above Vrx, brought about by inspiratory muscle contraction. Under these conditions the abdominal muscles appear to share the principal pumping duties with the diaphragm. Adoption of this breathing strategy by the horse may relate to its peculiar thoracoabdominal anatomic arrangement and to its very low passive chest wall compliance. We conclude that there is a passive and active phase to both inspiration and expiration due to the coordinated action of the respiratory pump muscles responsible for the resting adult horse's biphasic inspiratory and expiratory airflow pattern. This unique breathing pattern perhaps represents a strategy of minimizing the high elastic work of breathing in this species, at least at resting breathing frequencies.     

A network model for control of inspiratory cutoff by the pneumotaxic center with supportive experimental data in cats

A network model for the control of inspiratory cutoff by the pneumotaxic center (PC) in cats, based on a previously described anatomical model, is proposed. It is postulated that in vagotomized cats early expiratory cells in the PC produce the inspiratory cutoff. The firing patterns of neurons derived from the model were similar to those observed in the PC. Systematic changes in any one of several parameters in the model resulted in a marked change in inspiratory amplitude with no significant change in inspiratory duration; this response is similar to that already observed in vagotomized cats during changes in ventilatory drive. The basic conformation of the model was tested experimentally in the isolated respiratory center preparation of the cat. Discharges of 48 cells in the PC were recorded and the firing patterns analyzed to determine the change in frequency and temporal pattern of activity associated with spontaneous changes in the amplitude and/or duration of inspiration. 47 of the 48 cells exhibited changes in firing pattern that were consistent with the model.     

A mathematical description of a pump/leak/buffer model for plant nitrate uptake

A pump/leak/buffer model of nitrate in plants is presented in the form of a differential equation, based on the computer simulation model of Scaife (1989). The equation is solved, and the long-term behaviour of the rate of nitrate uptake of the plants described.     

Removal of excessive bronchial secretions by asymmetric high-frequency oscillations

The present study evaluated whether high-frequency oscillations (HFO) with biased flow profiles applied at the airway opening are capable of altering mucus clearance. In eight anesthetized sheep, artificial mucus (100 P) was infused continuously (1 ml/min) into the left main bronchus via a cannula inserted through the dorsal wall of the left main bronchus after thoracotomy. Outcoming mucus was collected every 10 min from the end of a cuffed orotracheal tube. Animals were ventilated with a Harvard respirator at a low frequency with superimposed HFO at 14 Hz with asymmetrical waveforms generated by a digitally controlled electromagnetic piston pump (expiratory bias: peak expiratory flow 3.8 l/s, peak inspiratory flow 1.3 l/s; inspiratory bias: reverse of expiratory bias). The influence of posture and of HFO airflow bias on mucus clearance was determined. In the horizontal position, mucus clearance with expiratory biased HFO was 3.5 +/- 2 (SD) ml/10 min. Head-down tilt produced a clearance of 3.1 +/- 3 ml/10 min; addition of HFO with expiratory bias increased clearance to 11.0 +/- 2.0 ml/10 min (P less than 0.05). No clearance occurred with inspiratory biased HFO during head-down tilt. These results indicate that expiratory biased HFO at the airway opening can clear excessive airway secretions and augment clearance by postural drainage.     

Compensatory Effect between Aortic Stiffening and Remodelling during Ageing

The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases.