Effect of mechanical loading on breathing patterns in women

First-breath ventilatory responses to graded inspiratory elastic and resistive loads were obtained from 80 women unfamiliar with respiratory experimentation. For each load 1) responses from different subjects ranged from a weak tidal volume defense coupled with an increased breathing frequency to a strong tidal volume defense coupled with a decreased frequency; 2) strong tidal volume defenders employed longer inspirations than did weak tidal volume defenders; and 3) individual respiratory frequency responses were mediated by changes in inspiratory and/or expiratory timing. Thus the group response was qualitatively the same as that reported for 80 men. Quantitatively, however, mean inspiratory airflow responses of women exceeded those of men by an amount attributable to women's higher intrinsic respiratory elastance. Tidal volume responses, on the other hand, did not differ significantly, suggesting that men and women produce different neural adjustments to loads. In support of this hypothesis, analysis of respiratory timing responses revealed that 1) men actively prolonged inspiration more than women during resistive loading; and 2) women actively shortened inspiration more than men during elastic loading. These findings indicate that the load-compensating behavior exhibited by men and women is similar but not identical.     

Respiratory load compensation in neuromuscular disorders

First-breath ventilatory responses to graded elastic (delta E) and resistive (delta R) loads from 10 people with spinal muscular atrophy (SMA), 15 people with Duchenne muscular dystrophy (DMD), and 80 able-bodied people were compared. The SMA and DMD groups produced equal tidal volume, respiratory frequency, inspiratory duration (TI), expiratory duration, mean inspiratory airflow, and duty cycle responses to both delta E and delta R. Thus SMA (primarily a motoneuron disorder) and DMD (primarily a muscle disorder) have the same net effect on loaded breathing responses. The SMA and DMD groups failed to duplicate the normal group's short expirations during delta E, long inspirations during delta R, and thus, extended duty cycles during both delta E and delta R. The deficit in load compensation therefore was due to impaired regulation of respiratory timing (reflecting neural mechanisms) but not airflow defense (reflecting mechanical and neural mechanisms). One-fifth of the normal but none of the SMA or DMD subjects actively generated an "optimal" TI response (defined theoretically as TI greater than 160% control during large delta R and TI less than 75% control during large delta E). This lack of optimal responses, which is the same abnormality exhibited by quadriplegic people, suggests that SMA and DMD also impair human ability to discriminate between large delta R and delta E. These findings support the hypothesis that neuromuscular disorders can lead to disturbances in respiratory perception.     

Reflex control of inspiratory duration in newborn infants

We applied graded resistive and elastic loads and total airway occlusions to single inspirations in six full-term healthy infants on days 2-3 of life to investigate the effect on neural and mechanical inspiratory duration (TI). The infants breathed through a face mask and pneumotachograph, and flow, volume, airway pressure, and diaphragm electromyogram (EMG) were recorded. Loads were applied to the inspiratory outlet of a two-way respiratory valve using a manifold system. Application of all loads resulted in inspired volumes decreased from control (P less than 0.001), and changes were progressive with increasing loads. TI measured from the pattern of the diaphragm EMG (TIEMG) was prolonged from control by application of all elastic and resistive loads and by total airway occlusions, resulting in a single curvilinear relationship between inspired volume and TIEMG that was independent of inspired volume trajectory. In contrast, when TI was measured from the pattern of airflow, the effect of loading on the mechanical time constant of the respiratory system resulted in different inspired volume-TI relationships for elastic and resistive loads. Mechanical and neural inspired volume and duration of the following unloaded inspiration were unchanged from control values. These findings indicate that neural inspiratory timing in infants depends on magnitude of phasic volume change during inspiration. They are consistent with the hypothesis that termination of inspiration is accomplished by an "off-switch" mechanism and that inspired volume determines the level of vagally mediated inspiratory inhibition to trigger this mechanism.     

Effects of expiratory loading on respiration in humans

We examined the effects of expiratory resistive loads of 10 and 18 cmH2O.l-1.s in healthy subjects on ventilation and occlusion pressure responses to CO2, respiratory muscle electromyogram, pattern of breathing, and thoracoabdominal movements. In addition, we compared ventilation and occlusion pressure responses to CO2 breathing elicited by breathing through an inspiratory resistive load of 10 cmH2O.l-1.s to those produced by an expiratory load of similar magnitude. Both inspiratory and expiratory loads decreased ventilatory responses to CO2 and increased the tidal volume achieved at any given level of ventilation. Depression of ventilatory responses to Co2 was greater with the larger than with the smaller expiratory load, but the decrease was in proportion to the difference in the severity of the loads. Occlusion pressure responses were increased significantly by the inspiratory resistive load but not by the smaller expiratory load. However, occlusion pressure responses to CO2 were significantly larger with the greater expiratory load than control. Increase in occlusion pressure observed could not be explained by changes in functional residual capacity or chemical drive. The larger expiratory load also produced significant increases in electrical activity measured during both inspiration and expiration. These results suggest that sufficiently severe impediments to breathing, even when they are exclusively expiratory, can enhance inspiratory muscle activity in conscious humans.     

Effects of volume history and vagotomy on pulmonary and chest wall mechanics in cats

Using the technique of rapid airway occlusion during constant-flow inflation, we studied the effects of inflation volume, different baseline tidal volumes (10, 20, and 30 ml/kg), and vagotomy on the resistive and elastic properties of the lungs and chest wall in six anesthetized tracheotomized paralyzed mechanically ventilated cats. Before vagotomy, airway resistance decreased significantly with increasing inflation volume at all baseline tidal volumes. At any given inflation volume, airway resistance decreased with increasing baseline tidal volume. After vagotomy, airway resistance decreased markedly and was no longer affected by baseline tidal volume. Prevagotomy, pulmonary tissue resistance increased progressively with increasing lung volume and was not affected by baseline tidal volume. Pulmonary tissue resistance decreased postvagotomy. Chest wall tissue resistance increased during lung inflation but was not affected by either baseline tidal volume or vagotomy. The static volume-pressure relationships of the lungs and chest wall were not affected by either baseline tidal volume or vagotomy. The data were interpreted in terms of a linear viscoelastic model of the respiratory system (J. Appl. Physiol. 67: 2276-2285, 1989).     

Model analysis of respiratory responses to inspiratory resistive loads

Based on experimental inspiratory driving pressure waveforms and active respiratory impedance data of anesthetized cats, we made model predictions of the factors that determine the immediate (first loaded breath) intrinsic (i.e., nonneural) tidal volume compensation to added inspiratory resistive loads. The time course of driving pressure (P) was given by P = atb, where a is the pressure at 1 s from onset of inspiration and represents the intensity of neuromuscular drive, t is time, and b is a dimensionless index of the shape of the driving pressure wave. For a given value of active respiratory impedance, tidal volume compensation to added resistive loads increases with increasing inspiratory duration and decreasing value of b but is independent of a. Model predictions of load compensation are compared to experimental results.     

Effects of aging on sensation of respiratory force and displacement

The psychophysical technique of magnitude production was used to evaluate the sensation of inspiratory force and inspired volume in young and older subjects. Inspiratory force was generated during a static inspiratory maneuver against a closed airway. The exponent of the power function relationship between airway pressure and sensation intensity during force scaling was not significantly different between young and older subjects. In contrast, the exponents for the magnitude production of inspired volume were significantly greater in the older compared with the young group. We also assessed the effects of age on the relative importance of force and displacement signals on the sensation of inspired volume. Subjects attempted to reproduce a control tidal volume while breathing against a series of inspiratory resistive and elastic loads. In both groups error in tidal volume reproduction increased progressively as the severity of the load increased. During moderate and severe loading the error in the older subjects was significantly greater than in the young group. Correspondingly, the peak inspiratory airway pressures at tidal volume reproduction against these loads were significantly smaller in the older compared with the young subjects. The results suggest that in older subjects cues related to respiratory muscle force are more important than volume in the sensation of lung volume changes. In young subjects the sensation of lung volume changes is based to a greater degree on signals of volume or displacement.     

Relationships between forced vital capacity and subjective responses to added resistive load to inspiration

1. 1. This study was conducted to investigate the effects of forced vital capacity on breathing pattern and subjective responses to inspiratory resistance.

2. 2. The subjects were divided into two groups according to their %FVC [large (L) and small (S) group; five subjects in each].

3. 3. Added inspiratory resistances were 0.6 (control), 1.5 (R1), 2.5 (R2), 3.1 (R3) cmH₂O · 1⁻¹ · s.

4. 4. Breathing pattern was analyzed by personal computer during rest and exercise with bicycle ergometer.

5. 5. The degree of sensation of breathing difficulty was expressed in SNS reported in our previous study.

6. 6. SNS in S group increased with resistance while no tendency was observed in L group. SNS in S group was significantly greater than that in L group at R3 condition.

7. 7. The breathing pattern of S group was characterized in smaller tidal volume and faster respiratory frequency compared to those of L group with no resistive load.

8. 8. However, outstanding changes in breathing pattern were observed in S group with longer inspiratory time and lower mean inspiratory flow rate when resistive loads were added, which led to increased tidal volume and decreased respiratory frequency.

Respiratory responses to microinjections of leptin into the solitary tract nucleus

Regulatory polypeptide leptin, apart from its well-known hypothalamic effects, stimulates ventilation. The present study on anaesthetised rats was undertaken to elucidate the respiratory effects of 10(-10)-10(-4) M leptin microinjected into the solitary tract nucleus, containing a high concentration of leptin receptors. Injections of 10(-8)-10(-4) M leptin induced dose-dependent increase in ventilation, tidal volume and electric activity of inspiratory muscles; 10(-6) M leptin additionally induced a short-term increase in respiratory frequency and a shortening of both inspiratory and expiratory duration. The respiratory responses to leptin is also characterised by appearance of sighs: deep and prolonged inspirations associated with an augmented burst in the activity of the inspiratory muscles and prolonged post-sigh inter-burst interval. The results taken together with evidence of high concentration of specific leptin ObRb-receptor in the solitary tract nucleus suggest involvement of endogenous leptin in the control of breathing via dorsal structures of the respiratory center.     

Effect of resistive loading on inspiratory work output in anesthetized cats

In five spontaneously breathing anesthetized cats, we determined the inspiratory elastic (Wel), resistive (Wres), and total (WI) mechanical work rates (power) during control and first loaded inspirations through graded linear resistances (delta R) by "Campbell diagrams" based on measurement of esophageal pressure. WI did not change with delta R's up to 0.31 cmH2O X ml-1 X s, the concomitant decrease in Wel being balanced by an increase in Wres. The stability of WI in the face of delta R's was due to the vagally mediated prolongation of inspiration and the intrinsic properties of the respiratory system and of the contracting inspiratory muscles. To assess the separate contributions of volume-related and flow-related intrinsic mechanisms to the stability of WI, we made model predictions of the immediate effects of delta R's on inspiratory mechanical work output based on measurements of inspiratory driving pressure waves and passive and active respiratory resistance and elastance on the same five cats. The results suggest that the intrinsic stability of WI in the face of delta R's is provided primarily by the active elastance.     

Pulmonary mechanics during rapid mechanical ventilation in rabbits with saline-lavaged lungs

Infants with respiratory failure are frequently mechanically ventilated at rates exceeding 60 breaths/min. We analyzed the effect of ventilatory rates of 30, 60, and 90 breaths/min (inspiratory times of 0.6, 0.3, and 0.2 s, respectively) on the pressure-flow relationships of the lungs of anesthetized paralyzed rabbits after saline lavage. Tidal volume and functional residual capacity were maintained constant. We computed effective inspiratory and expiratory resistance and compliance of the lungs by dividing changes in transpulmonary pressure into resistive and elastic components with a multiple linear regression. We found that mean pulmonary resistance was lower at higher ventilatory rates, while pulmonary compliance was independent of ventilatory rate. The transpulmonary pressure developed by the ventilator during inspiration approximated a linear ramp. Gas flow became constant and the pressure-volume relationship linear during the last portion of inspiration. Even at a ventilatory rate of 90 breaths/min, 28-56% of the tidal volume was delivered with a constant inspiratory flow. Our findings are consistent with the model of Bates et al. (J. Appl. Physiol. 58: 1840-1848, 1985), wherein the distribution of gas flow within the lungs depends predominantly on resistive factors while inspiratory flow is increasing, and on elastic factors while inspiratory flow is constant. This dynamic behavior of the surfactant-depleted lungs suggests that, even with very short inspiratory times, distribution of gas flow within the lungs is in large part determined by elastic factors. Unless the inspiratory time is further shortened, gas flow may be directed to areas of increased resistance, resulting in hyperinflation and barotrauma.     

Chest wall and trunk muscle activity during inspiratory loading.

We measured the electromyographic (EMG) activity in four chest wall and trunk (CWT) muscles, the erector spinae, latissimus dorsi, pectoralis major, and trapezius, together with the parasternal, in four normal subjects during graded inspiratory efforts against an occlusion in both upright and seated postures. We also measured CWT EMGs in six seated subjects during inspiratory resistive loading at high and low tidal volumes [1,280 +/- 80 (SE) and 920 +/- 60 ml, respectively]. With one exception, CWT EMG increased as a function of inspiratory pressure generated (Pmus) at all lung volumes in both postures, with no systematic difference in recruitment between CWT and parasternal muscles as a function of Pmus. At any given lung volume there was no consistent difference in CWT EMG at a given Pmus between the two postures (P > 0.09). However, at a given Pmus during both graded inspiratory efforts and inspiratory resistive loading, EMGs of all muscles increased with lung volume, with greater volume dependence in the upright posture (P < 0.02). The results suggest that during inspiratory efforts, CWT muscles contribute to the generation of inspiratory pressure. The CWT muscles may act as fixators opposing deflationary forces transmitted to the vertebral column by rib cage articulations, a function that may be less effective at high lung volumes if the direction of the muscular insertions is altered disadvantageously.     

Effect of pyracetam on fatigue of inspiratory muscles in cats

The aim of the work was to study the influence of pyracetam on respiratory muscles fatigue and ventilatory disorders caused by inspiratory resistive load in cats. The experiments have show that after the use of pyracetam in conditions of fatigue total bioelectric activities of inspiratory muscles and of the phrenic nerve and transdiaphragmal pressure restore; duty cycle, respiratory rate and tidal volume per minute decrease. The conclusion is drawn that pyracetam in the dose 300 mg/kg, in intravenous administration, compensates inspiratory muscle fatigue at the expense of its central mechanism of action.     

Increased lung volume limits endurance of inspiratory muscles

We examined the influence of lung volume on the ability of normal subjects to sustain breathing against inspiratory resistive loading. Four normal subjects breathed on a closed circuit in which inspiration was loaded by a flow resistor. Subjects were assigned a series of breathing tasks over a range of pressures and flows. In each task there was a specified resistor and also targets for either mean esophageal or airway opening pressure, respiratory frequency, and duty cycle. Endurance was assessed as the length of time to failure of the assigned task. The prime experimental variable was lung volume, which was increased by approximately 1 liter during some tasks; 8 cmH2O continuous positive airway pressure was applied to increase lung volume without increasing elastic load. As previously shown (McCool et al.J. Appl. Physiol. 60: 299-303, 1986), for tasks that could be sustained for the same time, there was an inverse linear relationship of mean esophageal pressure with inspiratory flow rate. This trade-off of pressure and flow was apparent both with and without the increase of lung volume. Comparable tasks, however, could not be sustained as long at the higher lung volumes. This effect of volume on endurance was greater for tasks characterized by high inspiratory pressures and low flow rates than for tasks that could be sustained for the same time but that had lower inspiratory pressures and higher flow rates. This is probably due to the effects of shortening of the sarcomere on fatiguability. Increased lung volume, per se, may contribute to respiratory failure because of increased inspiratory muscle fatiguability by mechanisms independent of elastic load.     

Response of normal subjects to inspiratory resistive unloading

The purpose of this study was to examine the role of the normal inspiratory resistive load in the regulation of respiratory motor output in resting conscious humans. We used a recently described device (J. Appl. Physiol. 62: 2491-2499, 1987) to make mouth pressure during inspiration positive and proportional to inspiratory flow, thus causing inspiratory resistive unloading (IRUL); the magnitude of IRUL (delta R = -3.0 cmH2O.1(-1).s) was set so as to unload most (approximately 86% of the normal inspiratory resistance. Six conscious normal humans were studied. Driving pressure (DP) was calculated according to the method of Younes et al. (J. Appl. Physiol. 51: 963-1001, 1981), which provides the equivalent of occlusion pressure at functional residual capacity throughout the breath. IRUL resulted in small but significant changes in minute ventilation (0.6 1/min) and in end-tidal CO2 concentration (-0.11%) with no significant change in tidal volume or respiratory frequency. There was a significant shortening of the duration (neural inspiratory time) of the rising phase of the DP waveform and the shape of the rising phase became more convex to the time axis. There was no change in the average rate of rise of DP or in the duration or shape of the declining phase. We conclude that 1) the normal inspiratory resistance is an important determinant of the duration and shape of the rising phase of DP and 2) the neural responses elicited by the normal inspiratory resistance are similar to those observed with added inspiratory resistive loads.     

O2 cost of inspiratory and expiratory resistive breathing in humans

In six normal male subjects we compared the O2 cost of resistive breathing (VO2 resp) between equivalent external inspiratory (IRL) and expiratory loads (ERL) studied separately. Each subject performed four pairs of runs matched for tidal volume, breathing frequency, flow rates, lung volume, pressure-time product, and work rate. Basal O2 uptake, measured before and after pairs of loaded runs, was subtracted from that measured during resistive breathing to obtain VO2 resp. For an equivalent load, the VO2 resp during ERL (184 +/- 17 ml O2/min) was nearly twice that obtained during IRL (97 +/- 9 ml O2/min). This twofold difference in efficiency between inspiratory and expiratory resistive breathing may reflect the relatively lower mechanical advantage of the expiratory muscles in overcoming respiratory loads. Variable recruitment of expiratory muscles may explain the large variation of results obtained in studies of respiratory muscle efficiency in normal subjects.     

Chest wall distortion during resistive inspiratory loading

We studied six (1 naive and 5 experienced) subjects breathing with added inspiratory resistive loads while we recorded chest wall motion (anteroposterior rib cage, anteroposterior abdomen, and lateral rib cage) and tidal volumes. In the five experienced subjects, transdiaphragmatic and pleural pressures, and electromyographs of the sternocleidomastoid and abdominal muscles were also measured. Subjects inspired against the resistor spontaneously and then with specific instructions to reach a target pleural or transdiaphragmatic pressure or to maximize selected electromyographic activities. Depending on the instructions, a wide variety of patterns of inspiratory motion resulted. Although the forces leading to a more elliptical or circular configuration of the chest wall can be identified, it is difficult to analyze or predict the configurational results based on insertional and pressure-related contributions of a few individual respiratory muscles. Although overall chest wall respiratory motion cannot be readily inferred from the electromyographic and pressure data we recorded, it is clear that responses to loading can vary substantially within and between individuals. Undoubtedly, the underlying mechanism for the distortional changes with loading are complex and perhaps many are behavioral rather than automatic and/or compensatory.     

Significance of airway resistance for the pattern of breathing and lung volumes in exercising humans

The effects of increased airway resistance on lung volumes and pattern of breathing were studied in eight subjects performing leg exercise on a cycle ergometer. Airway resistance was changed 1) by increasing the density (D) of the respired gas by a factor of 4.2 and changing the inspired gas from O2 at 1.3 bar to air at 6 bar and 2) by increasing airway flow rates by exposing the subjects to incremental work loads of 0-200 W. Increased gas D caused a slower and deeper respiration at rest and during exercise and, at work loads greater than 120 W, depressed the responses of ventilation and mean inspiratory flow. Raised airway resistance induced by increases in D and/or airway flow rates altered respiratory timing by increasing the ratio of inspiratory time (TI) to total breath duration. Furthermore, analyses of the relationships between tidal volume and TI and between end-inspiratory volume and TI revealed elevation of Hering-Breuer inspiratory volume thresholds. We propose that this elevation, and hence exercise-induced increases of tidal volume, can largely be explained by previous observations that the threshold of the inspiratory off-switch mechanisms depends on central inspiratory activity (cf. C. von Euler, J. Appl. Physiol. 55: 1647-1659, 1983), which in turn increases with airway resistance (Acta Physiol. Scand. 120: 557-565, 1984).     

Respiratory volume perception through the nose and mouth determined noninvasively

The relative importance of the nose vs. the mouth in the perception of respiratory volumes has never been assessed, nor have previous respiratory perception studies been performed noninvasively. Using respiratory inductive plethysmography, we monitored 12 normal subjects noninvasively when breathing either exclusively through the nose or mouth. The sensation of inspired volume mouth breathing was compared with that of nose breathing over a wide range of the inspiratory capacity. The psychophysical techniques of tidal volume duplication, tidal volume doubling, and magnitude estimation were utilized. A just noticeable difference was calculated from the constant error of the tidal volume duplication trials. The exponents for magnitude estimation were 1.06 and 1.07 for nose and mouth breathing, respectively. The other psychophysical techniques also revealed no differences in nose and mouth volume perception. These results suggest that tidal volume changes are perceived equally well through the nose and mouth. Furthermore, the location of the receptors, important in volume perception, is probably at a distal point common to the nose and mouth.     

Flow and volume dependence of expiratory resistance in anesthetized cats

In five anesthetized paralyzed cats, mechanically ventilated with tidal volumes of 36-48 ml, the isovolume pressure-flow relationships of the lung and respiratory system were studied. The expiratory pressure was altered between 3 and -12 cmH2O for single tidal expirations. Isovolume pressure-flow plots for three lung volumes showed that the resistive pressure-flow relationships were curvilinear in all cases, fitting Rohrer's equation: P = K1V + K2V2, where P is the resistive pressure loss, K1 and K2 are Rohrer's coefficients, and V is flow. Values of K1 and K2 declined with lung inflation, consistent with the volume dependence of pulmonary (RL) and respiratory system resistances (Rrs). During lung deflation against atmospheric pressure, RL and Rrs tended to remain constant through most of expiration, resulting in a nearly linear volume-flow relationship. In the presence of a fixed respiratory system elastance, the shape of the volume-flow profile depended on the balance between the volume and the flow dependence of RL and Rrs. However, the flow dependence of RL and Rrs indicates that their measured values will be affected by all factors that modify expiratory flow, e.g., respiratory system elastance, equipment resistance, and the presence of respiratory muscle activity.