Respiratory elastic load compensation in anesthetized patients with kyphoscoliosis

To evaluate the effects of abnormal respiratory mechanics and neuromuscular drive on the various components of elastic load compensation, we studied 16 anesthetized patients with kyphoscoliosis whose mean passive and active respiratory elastance (Ers and E'rs, respectively), active respiratory resistance, and peak inspiratory occlusion pressure were, respectively, 89, 84, 100, and 37% greater and inspiratory duration (TI) 13% less than corresponding values in 13 anesthetized controls. Ers comprised approximately 66% of effective elastance (E*rs) in both groups. E'rs, reflecting the role of the force-length properties of the active inspiratory muscles in increasing the internal impedance, comprised 83.8 and 86.1% of E*rs in the kyphoscoliosis patients and controls, respectively (P less than 0.001). This demonstrates the influence of increased intrinsic elastance and resistance and decreased TI on tidal volume defense in kyphoscoliosis patients in the absence of vagal modulation. In some patients the difference between Ers and E*rs was substantial, despite an unchanged or even shortened TI, suggesting that the Hering-Breuer reflex may affect stability through ways other than altering TI (e.g., via graded volume-dependent "terminal inhibition"). Characteristics of elastic load compensation in anesthetized kyphoscoliosis patients are similar to those of anesthetized normal subjects.     

Active and passive respiratory mechanics in anesthetized dogs

In six spontaneously breathing anesthetized dogs (pentobarbital sodium, 30 mg/kg) airflow, volume, and tracheal and esophageal pressures were measured. The active and passive mechanical properties of the total respiratory system, lung, and chest wall were calculated. The average passive values of respiratory system, lung, and chest wall elastances amounted to, respectively, 50.1, 32.3, and 17.7 cmH2O X l-1. Resistive pressure-vs.-flow relationships for the relaxed respiratory system, lung, and chest wall were also determined; a linear relationship was found for the former (the total passive intrinsic resistance averaged 4.1 cmH2O X l-1 X s), whereas power functions best described the others: the pulmonary pressure-flow relationship exhibited an upward concavity, which for the chest wall presented an upward convexity. The average active elastance and resistance of the respiratory system were, respectively, 64.0 cmH2O X l-1 and 5.4 cmH2O X l-1 X s. The greater active impedance reflects pressure losses due to force-length and force-velocity properties of the inspiratory muscles and those due to distortion of the respiratory system from its relaxed configuration.     

Effect of hypoxia on immediate ventilatory load response in dogs.

The effective elastance of the respiratory system (which has been previously shown to provide an index of the ability of the respiratory musculature to compensate rapidly for transient mechanical ventilatory loads) was measured in six hypoxic dogs to determine whether hypoxia hindered immediate load-compensatory mechanisms. The effective elastance value was computed from measurements of control tidal volume and the pressure developed at the airway opening during the first inspiratory effort following airway occlusion at FRC. The mean effective elastance was 197 cmH2O/l while the animals were breathing room air and did not change significantly when the animals were rendered hypoxic by reducing the inspired oxygen concentration, in five dogs, or by controlled hemorrhage, in two dogs. It was concluded that inasmuch as effective elastance measurements remain constant during hypoxia, the stability of ventilation is not significantly impaired in this situation.     

Interrupter technique for measurement of respiratory mechanics in anesthetized cats

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg ip), airflow, changes in lung volume, and tracheal and esophageal pressures were measured. Airflow was interrupted by brief airway occlusions during relaxed expirations (elicited via the Breuer-Hering inflation reflex) and throughout spontaneous breaths. A plateau in tracheal pressure occurred throughout relaxed expirations and the latter part of spontaneous expirations indicating respiratory muscle relaxation. Measurement of tracheal pressure, immediately preceding airflow, and corresponding volume enabled determination of respiratory system elastance and flow resistance. These were partitioned into lung and chest wall components using esophageal pressure. Respiratory system elastance was constant over the tidal volume range, divided approximately equally between the lung and chest wall. While the passive pressure-flow relationship for the respiratory system was linear, those for the lung and chest wall were curvilinear. Volume dependence of chest wall flow resistance was demonstrated. During inspiratory interruptions, tracheal pressure increased progressively; initial tracheal pressure was estimated by backward extrapolation. Inspiratory flow resistance of the lung and total respiratory system were constant. Force-velocity properties of the contracting inspiratory muscles contributed little to overall active resistance.     

Respiratory mechanics during halothane anesthesia and anesthesia-paralysis in humans

In six spontaneously breathing anesthetized subjects [halothane approximately 1 maximum anesthetic concentration (MAC), 70% N2O-30% O2], we measured flow (V), volume (V), and tracheal pressure (Ptr). With airway occluded at end-inspiration tidal volume (VT), we measured Ptr when the subjects relaxed the respiratory muscles. Dividing relaxed Ptr by VT, total respiratory system elastance (Ers) was obtained. With the subject still relaxed, the occlusion was released to obtain the V-V relationship during the ensuing relaxed expiration. Under these conditions, the expiratory driving pressure is V X Ers, and thus the pressure-flow relationship of the system can be obtained. By subtracting the flow resistance of equipment, the intrinsic respiratory flow resistance (Rrs) is obtained. Similar measurements were repeated during anesthesia-paralysis (succinylcholine). Ers averaged 23.9 +/- 4 (+/- SD) during anesthesia and 21 +/- 1.8 cmH2O X 1(-1) during anesthesia-paralysis. The corresponding values of intrinsic Rrs were 1.6 +/- 0.7 and 1.9 +/- 0.9 cmH2O X 1(-1) X s, respectively. These results indicate that Ers increases substantially during anesthesia, whereas Rrs remains within the normal limits. Muscle paralysis has no significant effect on Ers and Rrs. We also provide the first measurements of inspiratory muscle activity and related negative work during spontaneous expiration in anesthetized humans. These show that 36-74% of the elastic energy stored during inspiration is wasted in terms of negative inspiratory muscle work.     

Ontogeny of respiratory control and pulmonary mechanics in newborn rabbits

Maturation of the respiratory pattern and the active and passive mechanical properties of the respiratory system were assessed in 19 tracheotomized rabbits (postnatal age range: 1-26 days) placed in a body plethysmograph. With maturation both minute ventilation and tidal volume significantly increased, whereas respiratory frequency decreased. When normalized for body weight (kg) both the passive (Rrs X kg) and active (R'rs X kg) resistances of the respiratory system significantly increased with age, whereas the corresponding passive (Crs X kg-1) and active (C'rs X kg-1) compliances significantly decreased. At any given age R'rs X kg only slightly exceeded Rrs X kg, whereas C'rs X kg-1 was significantly lower than Crs X kg-1. Moreover, the maturational increases in Rrs X kg and R'rs X kg exceeded the corresponding decreases in Crs X kg-1 and C'rs X kg-1, resulting in significant age-related increases in both the passive (tau rs) and active (tau'rs) time constants of the respiratory system. Due to the age-related increases in tau'rs, producing a delayed volume response to any given inspiratory driving pressure, the relative volume loss obtained at any time during inspiration was greater in the maturing rabbit. On the other hand, because of concomitant compensatory changes in respiratory pattern, evidenced by increases in inspiratory duration with age, the end-inspiratory tidal volume loss in the maturing animal was maintained generally less than 10% at all postnatal ages. Thus maturational changes in respiratory pattern appear coupled to changes in the active mechanical properties of the respiratory system. The latter coupling serves to optimize the transduction of inspiratory pressure into volume change in a manner consistent with establishing the minimum inspiratory work of breathing during postnatal development.     

Inspiratory muscle forces and endurance in maximum resistive loading

The ability of the respiratory muscles to sustain ventilation against increasing inspiratory resistive loads was measured in 10 normal subjects. All subjects reached a maximum rating of perceived respiratory effort and at maximum resistance showed signs of respiratory failure (CO2 retention, O2 desaturation, and rib cage and abdominal paradox). The maximum resistance achieved varied widely (range 73-660 cmH2O X l-1 X s). The increase in O2 uptake (delta Vo2) associated with loading was linearly related to the integrated mouth pressure (IMP): delta Vo2 = 0.028 X IMP + 19 ml/min (r = 0.88, P less than 0.001). Maximum delta Vo2 was 142 ml/min +/- SD 68 ml/min. There were significant (P less than 0.05) relationships between the maximum voluntary inspiratory pressure against an occluded airway (MIP) and both maximum IMP (r = 0.80) and maximum delta Vo2 (r = 0.76). In five subjects, three imposed breathing patterns were used to examine the effect of different patterns of respiratory muscle force deployment. Increasing inspiratory duration (TI) from 1.5 to 3.0 and 6.0 s, at the same frequency of breathing (5.5 breaths/min) reduced peak inspiratory pressure and increased the maximum resistance tolerated (190, 269, and 366 cmH2O X l-1 X s, respectively) and maximum IMP (2043, 2473, and 2913 cmH2O X s X min-1, but the effect on maximum delta Vo2 was less consistent (166, 237, and 180 ml/min). The ventilatory endurance capacity and the maximum O2 uptake of the respiratory muscles are related to the strength of the inspiratory muscles, but are also modified through the pattern of force deployment.     

Analysis of behavior of the respiratory system in ARDS patients: effects of flow, volume, and time

The effects of inspiratory flow (V) and inflation volume (delta V) on the mechanical properties of the respiratory system in eight ARDS patients were investigated using the technique of rapid airway occlusion during constant-flow inflation. We measured interrupter resistance (Rint,rs), which in humans represents airway resistance, the additional resistance (delta Rrs) due to viscoelastic pressure dissipations and time constant inequalities, and static (Est,rs) and dynamic (Edyn,rs) elastance. The results were compared with a previous study on 16 normal anesthetized paralyzed humans (D'Angelo et al. J. Appl. Physiol. 67: 2556-2564, 1989). We observed that 1) resistance and elastance were higher in ARDS patients; 2) with increasing V, Rint,rs and Est,rs did not change, delta Rrs decreased progressively, and Edyn,rs increased progressively; 3) with increasing delta V, Rint,rs decreased slightly, delta Rrs increased progressively, and Est,rs and Edyn,rs showed an initial decrease followed by a secondary increase noted only in the ARDS patients. The above findings could be explained in terms of a model incorporating a standard resistance in parallel with a standard elastance and a series spring-and-dashpot body that represents the stress adaptation units within the tissues of the respiratory system.     

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.     

Activity of bulbar respiratory neurones during cough and other respiratory tract reflexes in cats

Changes evoked by mechanical stimulation of the relevant parts of the respiratory tract in the activity of inspiratory and expiratory neurones in the ventral respiratory group of the medulla oblongata, and in pleural pressure and the diaphragmatic electromyogram, were determined during cough, sneeze and the aspiration and expiration reflexes in 17 anaesthetized (but not paralysed) cats. The results of 72 tests of elicitation of the given reflexes showed that: Compared with the control inspiration, both the mean and the maximum discharge frequency of spontaneously active inspiratory neurones rose during the inspiratory phase of cough, sneeze and the aspiration reflex. Regular recruitment of new inspiratory units was also observed in the inspiratory phase of cough and the aspiration reflex. Compared with the control expiration, both the mean and the maximum discharge frequency of spontaneously active expiratory neurones rose during the cough, sneeze and expiration reflex effort. Recruitment of latent expiratory neurones was always observed in the expulsive phase of the given respiratory processes. The recruitment of latent expiratory neurones was accompanied by reciprocal inhibition of the activity of inspiratory units and recruitment of latent inspiratory neurones by inhibition of the activity of expiratory units and recruitment of latent inspiratory neurones by inhibition of the activity of expiratory units. Regular recruitment of the same expiratory neurones in all expulsive respiratory processes, together with the similar incidence of inspiratory neurones in the inspiratory phase of sneeze and the aspiration reflex, indicates that they are "nonspecific" in character.     

Decay of inspiratory muscle pressure during expiration in anesthetized cats

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg) we studied the antagonistic pressure developed by the inspiratory muscles during expiration (PmusI). This was accomplished in two ways: 1) with our previously reported method (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 1266-1271, 1982) based on the measurement of changes in lung volume and airflow during spontaneous expiration, together with determination of the total passive respiratory system elastance and resistance; and 2) measurement of the time course of changes in tracheal/pressure after airway occlusion at end inspiration, up to the moment when the inspiratory muscles become completely relaxed. The agreement between the two methods is generally good, both in the amplitude of PmusI and in its time course. We also applied the first method to spontaneous expirations through added linear resistive loads. These did not alter the relative decay of PmusI. Thus in anesthetized cats the braking action of the inspiratory muscles does not decrease when expiratory resistive loads are added, i.e., when such braking is clearly not required.     

关于复合呼吸机械负荷生理、心理效应的观察与分析

以12名男性成年为被试者,观察了外加死腔(V_(ADS))与吸气阻力(RI)对呼吸型式、通气功能以及呼吸不适感觉的联合影响。结果表明:(1)V_(ADS)及R_I对吸气相面罩腔(口腔)压力(P_I)及外呼吸功率(W_I)具有协同的增强作用;复合呼吸机械负荷的强度越大,此种协同作用也越加明显。(2)无论V_(ADS)及R_I的比例关系如何,反应呼吸不适感觉强度的类别量值(S)与P_I(或W_I)之间,总是符合共同的线性关系,故可以P_I(或W_I)作为复合呼吸机械负荷的综合强度指标。(3)在所观察范围内,V_(ADS)并不影响对阻力性机械负荷的呼吸调节功能。以上结果对制订呼吸防护装备生理标准有一定意义。     

Chest wall and respiratory system mechanics in cats: effects of flow and volume

The effects of inspiratory flow rate and inflation volume on the resistive properties of the chest wall were investigated in six anesthetized paralyzed cats by use of the technique of rapid airway occlusion during constant flow inflation. This allowed measurement of the intrinsic resistance (Rw,min) and overall dynamic inspiratory impedance (Rw,max), which includes the additional pressure losses due to time constant inequalities within the chest wall tissues and/or stress adaptation. These results, together with our previous data pertaining to the lung (Kochi et al., J. Appl. Physiol. 64: 441-450, 1988), allowed us to determine Rmin and Rmax of the total respiratory system (rs). We observed that 1) Rw,max and Rrs,max exhibited marked frequency dependence; 2) Rw,min was independent of flow (V) and inspired volume (delta V), whereas Rrs,min increased linearly with V and decreased with increasing delta V; 3) Rw,max decreased with increasing V, whereas Rrs,max exhibited a minimum value at a flow rate substantially higher than the resting range of V; 4) both Rw,max and Rrs,max increased with increasing delta V. We conclude that during resting breathing, flow resistance of the chest wall and total respiratory system, as conventionally measured, includes a significant component reflecting time constant inequalities and/or stress adaptation phenomena.     

Dose effect of pentobarbital sodium on control of breathing in cats

The dose effect of pentobarbital sodium on integrated ("moving time average") phrenic activity (EPHR), transdiaphragmatic pressure (Pdi), gastric pressure (Pga), changes in lung volume (V), and mechanical properties of the respiratory system was studied in six cats breathing room air. Increased pentobarbital dose from an initial value of 35 mg/kg ip, had no substantial effect on the relationship between EPHR and Pdi during both unoccluded and occluded inspirations, indicating that the diaphragmatic excitation-contraction coupling was not affected. Similarly, increased anesthetic dose had no effect on the relationship between EPHR and delta Pga during both occluded and unoccluded breaths, suggesting that the contribution of the diaphragm to the breathing movements did not change with increasing depth of anesthesia. Although the time course of phrenic activity showed substantial interanimal differences, the shape of the phrenic neurogram did not change substantially with increased pentobarbital dose in any of the cats studied. Increased anesthetic dose depressed, in the same proportion, the rate of rise of EPHR, Pdi, and V, but the mechanical properties of the respiratory system remained unchanged. The depression of ventilation with increased anesthetic dose was not proportional to the drop in central inspiratory activity, as quantified in terms of rate of rise of EPHR.     

Medullary neurons mediating the inhibition of inspiration by intercostal muscle tendon organs?

Studies were conducted to test the hypothesis that nonrespiratory-modulated units are last-order interneurons mediating the effects of intercostal muscle tendon organs on medullary inspiratory neuron activity. Vagotomized, anesthetized, or decerebrate cats were used. Results show the following. 1) Afferents from different receptor types (i.e., intercostal tendon organs and chest wall cutaneous receptors) that inhibit medullary inspiratory neuron activities evoke the same units. 2) Gastrocnemius muscle group I afferent fibers evoke some of the same units as intercostal afferents but do not alter respiratory activity. 3) The "pneumotaxic center" and laryngeal nerve afferents, which inhibit medullary inspiratory activity, evoke different medullary units than intercostal afferents. 4) Evoked units are not active in spontaneously breathing cats. Additional results suggest that a few respiratory neurons near the retrofacial nucleus may be involved in the mediation of the inspiratory inhibitory effects of intercostal tendon organs. These results do not establish the mechanism by which intercostal muscle tendon organs reduces medullary inspiratory activity.     

Decay of inspiratory muscle pressure during expiration in conscious humans

In eight conscious spontaneously breathing adults we studied the decay of pressure developed by the inspiratory muscles during expiration (PmusI). PmusI was obtained according to the following equation: PmusI(t) = Ers X V(t) - Rrs X V(t), where V is volume and V is flow at any instant t during spontaneous expiration, and Ers and Rrs are, respectively, the passive elastance and resistance of the total respiratory system. Ers was determined with the relaxation method, and resistance with the interrupter method. All subjects showed marked braking of expiratory flow by PmusI. The mean time for PmusI to reduce to 50 and 0% amounted, respectively, to 23 and 79% of expiratory time. During expiration, 24-55% of the elastic energy stored during inspiration was used as resistive work and the remainder (45-76%) as negative work.     

Immediate response to resistive loading in anesthetized humans

In eight spontaneously breathing anesthetized subjects (halothane: approximately 1 minimal alveolar concn; 70% N2O-30% O2), we determined 1) the inspiratory driving pressure by analysis of the pressure developed at the airway opening (Poao) during inspiratory efforts against airways occluded at end expiration; 2) the active inspiratory impedance; and 3) the immediate (first loaded breath) response to added inspiratory resistive loads (delta R). Based on these data we made model predictions of the immediate tidal volume response to delta R. Such predictions closely fitted the experimental results. The present investigation indicates that 1) in halothane-anesthetized humans the shape of the Poao wave differs from that in anesthetized animals, 2) the immediate response to delta R is not associated with appreciable changes in intensity, shape, and timing of inspiratory neural drive but depends mainly on intrinsic (nonneural) mechanisms; 3) the flow-dependent resistance of endotracheal tubes must be taken into account in studies dealing with increased neuromuscular drive in intubated subjects; and 4) in anesthetized humans Poao reflects the driving pressure available to produce the breathing movements.     

Influence of lung volume on oxygen cost of resistive breathing

We examined the relationship between the O2 cost of breathing (VO2 resp) and lung volume at constant load, ventilation, work rate, and pressure-time product in five trained normal subjects breathing through an inspiratory resistance at functional residual capacity (FRC) and when lung volume (VL) was increased to 37 +/- 2% (mean +/- SE) of inspiratory capacity (high VL). High VL was maintained using continuous positive airway pressure of 9 +/- 2 cmH2O and with the subjects coached to relax during expiration to minimize respiratory muscle activity. Six paired runs were performed in each subject at constant tidal volume (0.62 +/- 0.2 liters), frequency (23 +/- 1 breaths/min), inspiratory flow rate (0.45 +/- 0.1 l/s), and inspiratory muscle pressure (45 +/- 2% of maximum static pressure at FRC). VO2 resp increased from 109 +/- 15 ml/min at FRC by 41 +/- 11% at high VL (P less than 0.05). Thus the efficiency of breathing at high VL (3.9 +/- 0.2%) was less than that at FRC (5.2 +/- 0.3%, P less than 0.01). The decrease in inspiratory muscle efficiency at high VL may be due to changes in mechanical coupling, in the pattern of recruitment of the respiratory muscles, or in the intrinsic properties of the inspiratory muscles at shorter length. When the work of breathing at high VL was normalized for the decrease in maximum inspiratory muscle pressure with VL, efficiency at high VL (5.2 +/- 0.3%) did not differ from that at FRC (P less than 0.7), suggesting that the fall in efficiency may have been related to the fall in inspiratory muscle strength. During acute hyperinflation the decreased efficiency contributes to the increased O2 cost of breathing and may contribute to the diminished inspiratory muscle endurance.     

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.     

Decay of inspiratory muscle pressure during expiration in anesthetized kyphoscoliosis patients.

The decay of pressure developed by the inspiratory muscles during expiration (PmusI) has not been studied in subjects with increased respiratory impedance such as in kyphoscoliosis. PmusI was compared in 11 anesthetized patients with kyphoscoliosis with that in 11 anesthetized normal subjects. PmusI was obtained according to the following equation: PmusI(t) = Ers.V(t) - K1V(t) - K2V2(t), where V is volume and V is airflow at any instant t during spontaneous expiration, Ers is the passive elastance, and K1V + K2V2 is the flow resistance (curvilinear in both groups because of the endotracheal tube and the intrinsic resistance in the kyphoscoliotics) of the total respiratory system. Ers was determined by the relaxation method and resistance from the ensuing V-V relationships during the ensuing relaxed expiration. Changes in impedance due to pliometric work done by the inspiratory muscles during relaxation were neglected. Subjects in both groups showed marked braking of expiratory flow by PmusI. The mean time for PmusI to decrease to 50 and 0% amounted to 17 and 8% less, respectively, in the kyphoscoliosis group. Average values for flow-resistive work in the control and kyphoscoliosis groups both amounted to approximately 40% of the elastic energy stored during inspiration. The remaining portion, used as negative work, amounted to approximately 60% in both groups. Expiratory braking in anesthetized kyphoscoliotic patients appears to be in proportion to their magnitude of elastic recoil and intrinsic flow resistance.