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.     

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.     

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.     

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.     

Mechanisms of respiratory elastic load compensation in anesthetized humans

In anesthetized humans the nature of tidal volume (VT) compensation during elastic loading (as reflected in the difference between passive and effective respiratory elastances (Ers) and (E*rs), respectively) has not been fully elucidated. We assessed the relative contribution of various mechanisms contributing to VT compensation during linear elastic loading in 10 young anesthetized adults free of cardiorespiratory disease. Ers averaged 22.0 cmH2O X 1(-1), representing 64% of E*rs. Most of E*rs (84%) was comprised of the active elastance (E'rs), reflecting the major role played by the addition of force-length properties of inspiratory muscles to the internal impedance, and chest wall distortion played in the defense of VT. Of the remaining 16% of E*rs, the difference between E*rs and isotime E*rs, representing the contribution of prolongation of inspiratory time (TI) via the Hering-Breuer reflex, amounted to only 9%. Finally, the remainder of E*rs, which reflects the difference between E*rs and E'rs in the absence of vagal modulation, and attributed to several factors [shape of driving pressure wave, duration of control TI, and magnitude of E'rs and intrinsic flow resistance plus external resistances (Zin, Rossi, Zocchi, and Milic-Emili. J. Appl. Physiol. 57: 271-277, 1984)], amounted to less than 7%.     

Respiratory volume-time relationships during resistive loading in the cat.

The first-breath (neural) effects of graded resistive loads added separately during inspiration and expiration was studied in seven anesthetized cats before and after bilateral vagotomy. Additions of airflow resistance during inspiration reduced the volume inspired (VI) and increased inspiratory duration (TI). The duration of the ensuing unloaded expiration (TE) was unchanged. Vagotomy eliminated the TI modulation with inspiratory loads. Tracheal occlusion at the onset of inspiration yielded TI values similar to the fixed values observed following vagotomy. Resistive loads added during expiration produced similar results. Expired volume (VE) decreased and (TE) increased approaching the values obtained after vagotomy. Unlike the inspiratory resistive loads, loading during expiration results in an upward shift in the functional residual capacity (FRC). The FRC shift produces a time lag between the onset of diaphragmatic (EMG) activity and the initiation of airflow of the next (unloaded) inspiration. These studies suggest separate volume-time relationships for the inspiratory and expiratory phases of the breathing cycle. Both relationships are dependent upon vagally mediated volume feedback.     

Interrupter technique for measurement of respiratory mechanics in anesthetized humans

Flow (V), volume (V), and tracheal pressure (Ptr) were measured throughout a series of brief (100 ms) interruptions of expiratory V in six patients during anesthesia (halothane-N2O) and anesthesia-paralysis (succinylcholine). For the latter part of spontaneous expiration and throughout passive deflation during muscle paralysis, a plateau in postinterruption Ptr was observed, indicating respiratory muscle relaxation. Under these conditions, passive elastance of the total respiratory system (Ers) was determined as the plateau in postinterruption Ptr divided by the corresponding V. The pressure-flow relationship of the total system was determined by plotting the plateau in Ptr during interruption against the immediately preceding V. Ers averaged 23.5 +/- 1.9 (SD) cmH2O X l-1 during anesthesia and 25.5 +/- 5.4 cmH2O X l-1 during anesthesia-paralysis. Corresponding values of total respiratory system resistance were 2.0 +/- 0.8 and 1.9 +/- 0.6 cmH2O X l-1 X s, respectively. Respiratory mechanics determined during anesthesia paralysis using the single-breath method (W.A. Zin, L. D. Pengelly, and J. Milic-Emili, J. Appl. Physiol. 52: 1266-1271, 1982) were also similar. Early in spontaneous expiration, however, Ptr increased progressively during the period of interruption, reflecting the presence of gradually decreasing antagonistic (postinspiratory) pressure of the inspiratory muscles. In conclusion, the interrupter technique allows for simultaneous determination of the passive elastic as well as flow-resistive properties of the total respiratory system. The presence of a plateau in postinterruption Ptr may be employed as a useful and simple criterion to confirm the presence of respiratory muscle relaxation.     

Respiratory function of hyoid muscles and hyoid arch

The position of the hyoid arch suggests that it supports soft tissue surrounding the upper airway (UA) and can act to maintain UA patency. We also suspected that muscles inserting on the hyoid arch might show respiratory patterns of activity that could be affected by respiratory stimuli. To test these possibilities, we moved the hyoid arch ventrally in six anesthetized dogs either by traction on it or by stimulation of hyoid muscles. UA resistance was decreased 73 +/- (SE) 6% and 72 +/- 6% by traction and stimulation during expiration and 57 +/- 15% and 52 +/- 8% during inspiration. Moving averages of the geniohyoid (GH) and thyrohyoid (TH) obtained in six other dogs breathing 100% O2 showed phasic respiratory activity while the sternohyoid (SH) showed phasic respiratory activity in only two of these animals and no activity in four. With progressive hypercapnia, GH and TH increased as did SH when activity was already present. Airway occlusion at end expiration augmented and prolonged inspiratory activity in the hyoid muscles but did not elicit SH activity if not already present. Occlusion at end inspiration suppressed phasic activity in hyoid muscles for as long as in the diaphragm. After vagotomy activity increased and became almost exclusively inspiratory. Activity appeared in SH when not previously present. Duration and amplitude of hyoid muscle activity were increased with negative UA pressure and augmented breaths. We conclude that the hyoid arch and muscles can strongly affect UA flow resistance. Hyoid muscles show responses to chemical, vagal, and negative pressure stimuli similar to other UA muscles.     

Inspiratory and expiratory patterns of the pectoralis major muscle during pulmonary defensive reflexes

Experiments wereconducted to determine the discharge pattern of the pectoralis majormuscle during pulmonary defensive reflexes in anesthetized cats(n = 15). Coughs andexpiration reflexes were elicited by mechanical stimulation of theintrathoracic trachea or larynx. Augmented breaths occurredspontaneously or were evoked by the same mechanical stimuli.Electromyograms (EMGs) were recorded from the diaphragm, rectusabdominis, and pectoralis major muscles. During augmented breaths, thepectoralis major had inspiratory EMG activity similar to that of thediaphragm, but during expiration reflexes the pectoralis major also hadpurely expiratory EMG activity similar to the rectus abdominis. Duringtracheobronchial cough, the pectoralis major had an inspiratory patternsimilar to that of the diaphragm in 10 animals, an expiratory patternsimilar to that of the rectus abdominis in 3 animals, and a biphasicpattern in 2 animals. The pectoralis major was active during both the inspiratory and expiratory phases during laryngeal cough. We conclude that, in contrast to the diaphragm or rectus abdominis muscles, thepectoralis major is active during both inspiratory and expiratory pulmonary defensive reflexes.

     

Nasal and oral airway pressure-flow relationships.

We examined the inspiratory and expiratory pressure-flow relationships of both the oral and nasal airways before and after exercise in normal upright subjects. With the use of a partitioned facemask, nasal resistance was measured using posterior rhinomanometry, and oral resistance was measured by recording transoral pressure during oral breathing. Both the nasal and oral pressure-flow relationships for inspiration and expiration were curvilinear and were well described by a power function of the form delta P = aVb (where P is pressure, V is flow, a and b are constants) (r2 = 0.96 +/- 0.01). The exponent b describes the curvilinearity of the pressure-flow curve and can be used to infer the flow regimen. At rest, the inspiratory nasal and oral curves suggested a similar degree of turbulence (b = 1.77 +/- 0.06 and 1.83 +/- 0.04, respectively). However, inspiratory flow regimens were inferred to be more turbulent than those during expiration both before and after exercise. After exercise, decreases in inspiratory nasal resistance at low flows were associated with a change in flow regimen from fully turbulent to orifice flow over the entire flow range. Thus the application of a power function to nasal and oral pressure-flow data permits representation of the whole relationship and allows insight into the nature of the flow regimens.     

Effects of upper airway anesthesia on pharyngeal patency during sleep

Pharyngeal patency depends, in part, on the tone and inspiratory activation of pharyngeal dilator muscles. To evaluate the influence of upper airway sensory feedback on pharyngeal muscle tone and thus pharyngeal patency, we measured pharyngeal airflow resistance and breathing pattern in 15 normal, supine subjects before and after topical lidocaine anesthesia of the pharynx and glottis. Studies were conducted during sleep and during quiet, relaxed wakefulness before sleep onset. Maximal flow-volume loops were also measured before and after anesthesia. During sleep, pharyngeal resistance at peak inspiratory flow increased by 63% after topical anesthesia (P less than 0.01). Resistance during expiration increased by 40% (P less than 0.01). Similar changes were observed during quiet wakefulness. However, upper airway anesthesia did not affect breathing pattern during sleep and did not alter awake flow-volume loops. These results indicate that pharyngeal patency during sleep is compromised when the upper airway is anesthetized and suggest that upper airway reflexes, which promote pharyngeal patency, exist in humans.     

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.     

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.     

Effects of negative upper airway pressure on pattern of breathing in sleeping infants

Negative upper airway (UAW) pressure inhibits diaphragm inspiratory activity in animals, but there is no direct evidence of this reflex in humans. Also, little is known regarding reflex latency or effects of varying time of stimulation during the breathing cycle. We studied effects of UAW negative pressure on inspiratory airflow and respiratory timing in seven tracheostomized infants during quiet sleep with a face mask and syringe used to produce UAW suction without changing lower airway pressure. Suction trials lasted 2-3 s. During UAW suction, mean and peak inspiratory airflow as well as tidal volume was markedly reduced (16-68%) regardless of whether stimulation occurred in inspiration or expiration. Reflex latency was 42 +/- 3 ms. When suction was applied during inspiration or late expiration, the inspiration and the following expiration were shortened. In contrast, suction applied during midexpiration prolonged expiration and tended to prolong inspiration. The changes in flow, tidal volume, and timing indicate a marked inhibitory effect of UAW suction on thoracic inspiratory muscles. Such a reflex mechanism may function in preventing pharyngeal collapse by inspiratory suction pressure.     

Effects of hypercapnia on inspiratory and expiratory muscle activity during expiration

Persistence of inspiratory muscle activity during the early phase of expiratory airflow slows the rate of lung deflation, whereas heightened expiratory muscle activity produces the opposite effect. To examine the influence of increased chemoreceptor drive and the role of vagal afferent activity on these processes, the effects of progressive hypercapnia were evaluated in 12 anesthetized tracheotomized dogs before and after vagotomy. Postinspiratory activity of inspiratory muscles (PIIA) and the activity of expiratory muscles were studied. During resting breathing, the duration of PIIA correlated with the duration of inspiration but not with expiration. Parasternal intercostal PIIA was directly related to that of the diaphragm. Based on their PIIA, dogs could be divided into two groups: one with prolonged PIIA (mean 0.57 s) and the other with brief PIIA (mean 0.16 s). Hypercapnia caused progressive shortening of the PIIA in the dogs with prolonged PIIA during resting breathing. The electrical activity of the external oblique and internal intercostal muscles increased gradually during CO2 rebreathing in all dogs both pre- and postvagotomy. After vagotomy, abdominal activity continued to increase with hypercapnia but was less at all levels of PCO2. The internal intercostal response to hypercapnia was not affected by vagotomy. The combination of shorter PIIA and augmented expiratory activity with hypercapnia might, in addition to changes in lung recoil pressure and airway resistance, hasten exhalation.     

Dynamics of breathing in the hypoxic awake lamb

Newborn mammals respond to hypoxia with an immediate hyperventilation that is rapidly dampened. Changes in mechanical properties of the respiratory system during hypoxia have been considered an important reason for this fall in minute ventilation (VE). We have studied the dynamic mechanical behavior of the respiratory system in eight unanesthetized intact newborn lambs (mean age 2 days) during normoxia and hypoxia (FIO2 = 0.08). Mouth pressure (P), airflow (V), and volume (V) were recorded while lambs were breathing through a leak-proof face mask and a pneumotachograph. Active compliance (C') and resistance (R') of the respiratory system were computed from P developed during an inspiratory effort against airway closure at end expiration and V and V of the preceding breaths. Tidal expiratory V-V curves were analyzed to estimate the elevation in functional residual capacity (FRC) over resting volume (Vr). After hypoxia, there was an immediate increase in VE in the first 2 min, from 0.49 to 1.13 l.kg-1.min-1, followed by a rapid decrease to 0.80. After 8 min of hypoxia, C' was unchanged. The inspiratory R' decreased during hypoxia, probably reflecting a drop in inspiratory laryngeal resistance. The expiratory V-V curves during hypoxia showed considerable braking, often with a double peak in expiratory V. This pattern was only occasionally seen during normoxia. In animals with a linear segment of the expiratory V-V curves the FRC-Vr difference could be calculated and averaged 1.93 ml/kg during normoxia and 3.47 during hypoxia. The recoil P of the respiratory system at end expiration was 0.75 cmH2O during normoxia vs. 1.63 cmH2O during hypoxia (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory phasic effects of inspiratory loading on left ventricular hemodynamics in vagotomized dogs.

Exaggerated inspiratory swings in intrathoracic pressure have been postulated to increase left ventricular (LV) afterload. These predictions are based on measurements of LV afterload by use of esophageal or lateral pleural pressure. Using direct measurements of pericardial pressure, we reexamined respiratory changes in LV afterload. In 11 anesthetized vagotomized dogs, we measured arterial pressure, LV end-systolic (ES) and end-diastolic transmural (TM) pressures, stroke volume (SV), diastolic left anterior descending blood flow (CBF-D), and coronary resistance. Dogs were studied before and while breathing against an inspiratory threshold load of -20 to -25 cmH2O compared with end expiration. Relative to end expiration, SV and LVES TM pressures decreased during inspiration and increased during early expiration, effects exaggerated during inspiratory loading. In all cases, LV afterload (LVES TM pressure) changed in parallel with SV. LV end-diastolic TM pressure did not change. CBF-D paralleled arterial pressure, and there were no changes in coronary resistance. In two dogs, regional LVES segment length paralleled calculated changes in LVES TM pressure. We conclude that 1) LV afterload decreases during early inspiration and increases during early expiration, changes secondary to those in SV; 2) changes in CBF-D are secondary to changes in perfusion pressure during the respiratory cycle; and 3) the use of esophageal or lateral pleural pressure to estimate LV surface pressure overestimates changes in LV TM pressures during respiration.     

Effect of expiratory loading on glottic dimensions in humans

We examined the effects of external mechanical loading on glottic dimensions in 13 normal subjects. When flow-resistive loads of 7, 27, and 48 cmH2O X l-1 X s, measured at 0.2 l/s, were applied during expiration, glottic width at the mid-tidal volume point in expiration (dge) was 2.3 +/- 12, 37.9 +/- 7.5, and 38.3 +/- 8.9% (means +/- SE) less than the control dge, respectively. Simultaneously, mouth pressure (Pm) increased by 2.5 +/- 4, 3.0 +/- 0.4, and 4.6 +/- 0.6 cmH2O, respectively. When subjects were switched from a resistance to a positive end-expiratory pressure at comparable values of Pm, both dge and expiratory flow returned to control values, whereas the level of hyperinflation remained constant. Glottic width during inspiration (unloaded) did not change on any of the resistive loads. There was a slight inverse relationship between the ratio of expiratory to inspiratory glottic width and the ratio of expiratory to inspiratory duration. Our results show noncompensatory glottic narrowing when subjects breathe against an expiratory resistance and suggest that the glottic dimensions are influenced by the time course of lung emptying during expiration. We speculate that the glottic constriction is related to the increased activity of expiratory medullary neurons during loaded expiration and, by increasing the internal impedance of the respiratory system, may have a stabilizing function.     

Airway resistance due to alveolar gas compression measured by barometric plethysmography in mice.

We developed a method for measuring airway resistance (R(aw)) in mice that does not require a measurement of airway flow. An analysis of R(aw) induced by alveolar gas compression showed the following relationship for an animal breathing spontaneously in a closed box: R(aw) = A(bt)V(b)/[V(t) (V(e) + 0.5V(t))]. Here A(bt) is the area under the box pressure-time curve during inspiration or expiration, V(b) is box volume, V(t) is tidal volume, and V(e) is functional residual capacity (FRC). In anesthetized and conscious unrestrained mice, from experiments with both room temperature box air and body temperature humidified box air, the contributions of gas compression to the box pressure amplitude were 15 and 31% of those due to the temperature-humidity difference between box and alveolar gas. We corrected the measured A(bt) and V(t) for temperature-humidity and gas compression effects, respectively, using a sinusoidal analysis. In anesthetized mice, R(aw) averaged 4.3 cmH(2)O.ml(-1).s, fourfold greater than pulmonary resistance measured by conventional methods. In conscious mice with an assumed FRC equal to that measured in the anesthetized mice, the corrected R(aw) at room temperature averaged 1.9 cmH(2)O.ml(-1).s. In both conscious mice and anesthetized mice, exposure to aerosolized methacholine with room temperature box air significantly increased R(aw) by around eightfold. Here we assumed that in the conscious mice both V(t) and FRC remained constant. In both conscious and anesthetized mice, body temperature humidified box air reduced the methacholine-induced increase in R(aw) observed at room temperature. The method using the increase in A(bt) with bronchoconstriction provides a conservative estimate for the increase in R(aw) in conscious mice.