Respiratory activity of posterior cricoarytenoid muscle and vocal cords in humans

We examined the respiratory activity of the posterior cricoarytenoid muscle (PCA) simultaneously with the movements of the vocal cords during tidal breathing and panting in four normal seated subjects. A bipolar electrode was constructed to record the surface electromyogram (EMG) of the PCA. The glottis was visualized with a fiberoptic bronchoscope, and the glottic image was recorded simultaneously with tidal volume and a digital time marker on video tape. During quiet breathing the integrated EMG signal (EPCA) showed consistent phasic variations in each subject. The inspiratory onset of EPCA in the four subjects preceded inspiratory flow by 170 +/- 80, 650 +/- 310, 130 +/- 80, and 130 +/- 90 ms (mean +/- SD), respectively. This lead time of the PCA was similar to that between the onset of glottic widening and inspiration in each subject. The proportion of each cycle during which EPCA increased (the duty cycle) was 31 +/- 3% (mean +/- SE), whereas the inspiratory portion of the respiratory cycle constituted 37 +/- 2% (mean +/- SE), respectively. The duty cycle of the PCA remained relatively constant in the same subject on different days. During panting at functional residual capacity, the EPCA increased to 142 +/- 11% of the peak activity recorded during the preceding control breaths. This was accompanied by a sustained increase in the glottic width to 91 +/- 9% of the peak value in the preceding breaths. These results confirm the role of the PCA as a principal abductor of the vocal cords and indicate a temporal relationship between PCA activation and the inspiratory phase of the respiratory cycle during tidal breathing in humans.     

Posterior cricoarytenoid activity in normal adults during involuntary and voluntary hyperventilation

The effect of isocapnic hypoxia and hyperoxic hypercapnia on the electrical activity of the posterior cricoarytenoid (PCA) muscle was determined in eight normal adult humans by use of standard rebreathing techniques and was compared with PCA activity during voluntary hyperventilation performed under isocapnic and hypocapnic conditions. PCA activity was recorded with intramuscular hooked-wire electrodes implanted through a fiberoptic nasopharyngoscope. During quiet breathing in all subjects, the PCA was phasically active on inspiration and tonically active throughout the respiratory cycle. At comparable increments in respiratory output, hypercapnia, hypoxia, and voluntary hyperventilation appeared to be associated with similar increases in phasic or tonic PCA activity. During quiet breathing, the onset of phasic PCA activity usually occurred before inspiratory airflow and extended beyond the start of expiratory airflow. The duration of phasic PCA preactivation and postinspiratory phasic PCA activity remained unchanged during progressive hypercapnia and progressive hypoxia. The results, in combination with recent findings for vocal cord adductors, suggest that vocal cord position throughout the respiratory cycle during hyperpnea is actively controlled by simultaneously acting and antagonistic intrinsic laryngeal muscles.     

Regulation of end-expiratory lung volume during exercise

We determined the effects of exercise on active expiration and end-expiratory lung volume (EELV) during steady-state exercise in 13 healthy subjects. We also addressed the questions of what affects active expiration during exercise. Exercise effects on EELV were determined by a He-dilution technique and verified by changes in end-expiratory esophageal pressure. We also used abdominal pressure-volume loops to determine active expiration. EELV was reduced with increasing exercise intensity. EELV was reduced significantly during even mild steady-state exercise and during heavy exercise decreased an average of 0.71 +/- 0.3 liter. Dynamic lung compliance was reduced 30-50%; EELV remained greater than closing volume. Changing the resistance to airflow (via SF6-O2 or He-O2 breathing) during steady-state exercise changed the peak gastric and esophageal pressure generation during expiration but did not alter EELV; breathing through the mouthpiece produced similar effects during exercise. EELV was significantly reduced in the supine position. With supine exercise active expiration was not elicited, and EELV remained the same as in supine rest. With CO2-driven hyperpnea (7-70 l/min), EELV remained unchanged from resting levels, whereas during exercise, at similar minute ventilation (VE) values EELV was consistently decreased. At the same VE, treadmill running caused an increase in tonic gastric pressure and greater reductions in EELV than either walking or cycling. We conclude that both the exercise stimulus and the resultant hyperpnea stimulate active expiration and a reduced FRC. This new EELV is preserved in the face of moderate changes in mechanical time constants of the lung. This reduced EELV during exercise aids inspiration by optimizing diaphragmatic length and permitting elastic recoil of the chest wall.     

Posterior cricoarytenoid muscle activity during wakefulness and sleep in normal adults

Six normal adults were studied 1) to compare respiratory-related posterior cricoarytenoid (PCA) muscle activity during wakefulness and sleep and 2) to determine the effect of upper airway occlusions during non-rapid-eye-movement (NREM) sleep on PCA activity. A new electromyographic technique was developed to implant hooked-wire electrodes into the PCA by using a nasopharyngoscope. A previously described technique was used to induce upper airway occlusions during NREM sleep (Kuna and Smickley, J. Appl. Physiol. 64: 347-353, 1988). The PCA exhibited phasic inspiratory activity during quiet breathing in wakefulness and sleep in all subjects. Discounting changes in tonic activity, peak amplitude of PCA inspiratory activity during stage 3-4 NREM sleep decreased to 77% of its value in wakefulness. Tonic activity throughout the respiratory cycle was present in all subjects during wakefulness but was absent during state 3-4 NREM sleep. In this sleep stage, PCA phasic activity abruptly terminated near the end of inspiration. During nasal airway occlusions in NREM sleep, PCA phasic activity did not increase significantly during the first or second occluded effort. The results, in combination with recent findings for vocal cord adductors in awake and sleeping adults, suggest that vocal cord position during quiet breathing in wakefulness is actively controlled by simultaneously acting antagonistic intrinsic laryngeal muscles. In contrast, the return of the vocal cords toward the midline during expiration in stage 3-4 NREM sleep appears to be a passive phenomenon.     

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.     

Posterior cricoarytenoid and diaphragm activities during tidal breathing in neonates

To investigate airflow regulation in newborn infants, we recorded airflow, volume, diaphragm (Di), and laryngeal electromyogram (EMG) during spontaneous breathing in eight supine unsedated sleeping full-term neonates. Using an esophageal catheter electrode, we recorded phasic respiratory activity consistent with that of the principal laryngeal abductors, the posterior cricoarytenoids (PCA). Sequential activation of PCA and Di preceded inspiration. PCA activity typically peaked early in inspiration followed by either a decrescendo or tonic EMG activity of variable amplitude during expiration. Expiratory airflow retardation, or braking, accompanied by expiratory prolongation and reduced ventilation, was commonly observed. In some subjects we observed a time interval between PCA onset and a sudden increase in expiratory airflow just before inspiration, suggesting that release of the brake involved an abrupt loss of antagonistic adductor activity. Our findings suggest that airflow in newborn infants is controlled throughout the breathing cycle by the coordinated action of the Di and the reciprocal action of PCA and laryngeal adductor activities. We conclude that braking mechanisms in infants interact with vagal reflex mechanisms that modulate respiratory cycle timing to influence both the dynamic maintenance of end-expiratory lung volume and ventilation.     

Phasic respiratory modulation of pharyngeal collapsibility via neuromuscular mechanisms in rats

Obstructive sleep apnea patients experience recurrent upper airway (UA) collapse due to decreases in the UA dilator muscle activity during sleep. In contrast, activation of UA dilators reduces pharyngeal critical pressure (Pcrit, an index of pharyngeal collapsibility), suggesting an inverse relationship between pharyngeal collapsibility and dilator activity. Since most UA muscles display phasic respiratory activity, we hypothesized that pharyngeal collapsibility is modulated by respiratory drive via neuromuscular mechanisms. Adult male Sprague-Dawley rats were anesthetized, vagotomized, and ventilated (normocapnia). In one group, integrated genioglossal activity, Pcrit, and maximal airflow (V(max)) were measured at three expiration and five inspiration time points within the breathing cycle. Pcrit was closely and inversely related to phasic genioglossal activity, with the value measured at peak inspiration being the lowest. In other groups, the variables were measured during expiration and peak inspiration, before and after each of five manipulations. Pcrit was 26% more negative (-15.0 ± 1.0 cmH(2)O, -18.9 ± 1.2 cmH(2)O; n = 23), V(max) was 7% larger (31.0 ± 1.0 ml/s, 33.2 ± 1.1 ml/s), nasal resistance was 12% bigger [0.49 ± 0.05 cmH(2)O/(ml/s), 0.59 ± 0.05 cmH(2)O/(ml/s)], and latency to induced UA closure was 14% longer (55 ± 4 ms, 63 ± 5 ms) during peak inspiration vs. expiration (all P < 0.005). The expiration-inspiration difference in Pcrit was abolished with neuromuscular blockade, hypocapnic apnea, or death but was not reduced by the superior laryngeal nerve transection or altered by tracheal displacement. Collectively, these results suggest that pharyngeal collapsibility is moment-by-moment modulated by respiratory drive and this phasic modulation requires neuromuscular mechanisms, but not the UA negative pressure reflex or tracheal displacement by phasic lung inflation.     

Factors influencing glottic dimensions during forced expiration

To examine the relationship between expiratory effort, expiratory flow, and glottic aperture, we compared the effects of actively and passively produced changes in flow in six normal subjects. During flow transients of 1.08 +/- 0.08 l/s produced by voluntary expiratory effort, glottic width (dg) increased by 54 +/- 13% (mean +/- SE). In contrast transient increases in expiratory flow, produced passively by chest compression, were not accompanied by increases in glottic dimensions. Similarly, when subjects expired through a resistance, transient passive increases in mouth pressure of 8.1 +/- 0.8 cmH2O failed to increase glottic width. However, when similar positive-pressure transients were produced actively, dg increased by 97 +/- 36% even though the expiratory efforts were accompanied by relatively small increases in flow (0.20 +/- 0.05 l/s). During tidal breathing glottic widening commenced 160 +/- 60 ms before the onset of inspiratory flow, whereas the widening associated with active flow and pressure transients did not measurably precede the onset of the change in flow or pressure. Our results indicate that transient expulsive efforts are associated with synchronous increases in dg, regardless of whether expiratory flow increases. The findings are most readily explained by a centrally determined synchronous recruitment of intrinsic laryngeal and expiratory muscles that facilitates lung emptying by minimizing airway resistance during forced exhalation.     

Responses to chemical stimulation of upper airway muscles diaphragm in awake cats

The steady-state and transient effects of hyperoxic hypercapnia on the electromyographic activities of the genioglossus (GG), posterior cricoarytenoid (PCA), and diaphragm (D) were studied in conscious unsedated cats with chronically implanted electrodes. Hypercapnia (inhalation of 3.4 and 7.4% CO2 in O2) increased the phasic electrical activity occurring during inspiration in all three muscles and also increased tonic activity of the GG. The GG responded to steady-state CO2 inhalation alinearly and with larger increases in activity than the PCA and D. Phasic GG activity was present in only 4 of 10 cats breathing 100% O2, whereas phasic PCA and D activity could be observed in all animals studied. When gas mixtures containing CO2 were given, the GG reached its new steady-state level more slowly than the D or PCA, and when CO2 was rapidly removed from the inspired gas mixture, the GG attained its steady state sooner than either the PCA or D. These results suggest that in awake unsedated animals, chemical stimuli do not affect either transient or steady-state responses of the GG in the same way as the D. These differences seem to be explained mainly by different threshold characteristics of hypoglossal and phrenic neurons but also in part by dissimilarities in their steady-state responses.     

Transverse abdominis length changes during eupnea, hypercapnia, and airway occlusion

The abdominal muscles accelerate airflow during expiration and may also influence the end-expiratory volume and configuration of the thorax. Although much is known about their electrical activity, the degree to which they change length during the respiratory cycle has not been previously assessed. In the present study we measured respiratory changes in transverse abdominis length using sonomicrometry in 14 pentobarbital sodium-anesthetized supine dogs and compared length changes to simultaneously recorded tidal volume and transverse abdominis electromyograms (EMG). To determine muscle resting length at passive functional residual capacity (LFRC), the animals were hyperventilated to apnea. The transverse abdominis was electrically active in all animals during resting O2 breathing (eupnea). During inspiration the transverse abdominis lengthened above resting length in all 14 dogs by a mean of 3.7 +/- 1.1% LFRC; during expiration the transverse abdominis shortened below resting length in 13 of 14 dogs by a mean of 4.2 +/- 0.9% LFRC. Increasing hyperoxic hypercapnia (produced in 9 animals) progressively heightened transverse abdominis EMG and progressively increased the extent of muscle shortening below resting length (to 12.6 +/- 3.2% LFRC at a PCO2 of 90 Torr). During single-breath airway occlusion substantial inspiratory lengthening of the transverse abdominis occurred, both during O2 breathing and during CO2 rebreathing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroarytenoid muscle activity during hypoxia, hypercapnia, and voluntary hyperventilation in humans

Intramuscular electromyographic activity of the thyroarytenoid (TA) muscle, a vocal cord adductor, was recorded in nine normal adult humans during progressive isocapnic hypoxia and hyperoxic hypercapnia. Four of the nine subjects also performed voluntary isocapnic hyperventilation. During quiet breathing of room air, the TA exhibited phasic activity in expiration and often tonic activity throughout the respiratory cycle. Both phasic and tonic TA activity progressively decreased with either increasing hypoxia or hypercapnia. Tonic activity appeared to decrease more rapidly than phasic activity with increasing chemical stimulation. At comparable tidal volume increments, the relative decrease in phasic TA activity appeared to be greater under hypoxic than under hypercapnic conditions. During voluntary isocapnic hyperventilation, phasic TA activity decreased without significant change in tonic activity. At tidal volumes approximately double those of base line, the relative decrease in TA activity was similar during both hypercapnia and voluntary hyperventilation, although differences appeared at higher tidal volumes. The results, in combination with recent findings in humans regarding the posterior cricoarytenoid muscle, a vocal cord abductor, suggest that vocal cord position is dependent on the net balance of counteracting forces not only during quiet breathing but also during involuntary and voluntary hyperpnea.     

Respiratory activities of intralaryngeal branches of the recurrent laryngeal nerve

To distinguish experimentally between motor nerve activity destined for vocal cord abductor muscles and that bound for muscles that adduct the cords, we recorded efferent activities of intralaryngeal branches of the recurrent laryngeal nerve (RLN) in decerebrate, vagotomized, paralyzed, ventilated cats. Activities of the whole RLN and phrenic nerve were also recorded. Nerve activities were assessed at several steady-state end-tidal O2 and CO2 concentrations. The nerve to the thyroarytenoid (TA) muscle, a vocal cord adductor, was only slightly active under base-line (normocapnic, hyperoxic) conditions but in most cats developed strong activity during expiration in hypocapnia or hypoxia. In severe hypocapnia, phasic expiratory TA activity persisted even during phrenic apnea, indicating continuing activity of the respiratory rhythm generator. The nerve to the posterior cricoarytenoid (PCA) muscle, the vocal cord abductor, was always active in inspiration but often showed expiratory activity as well. This expiratory activity was usually enhanced by hypercapnia and often inhibited by hypoxia. The results are consistent with previous electromyographic findings and emphasize the importance of distinguishing abductor from adductor activity in studies of laryngeal control.     

Influence of posterior cricoarytenoid muscle activity on pressure-flow relationship of the larynx

We examined the effect of posterior cricoarytenoid (PCA) muscle activity on the pressure-flow (PV) relationship of the larynx in five anesthetized tracheostomized dogs. The PCA activity was recorded using bipolar fine-wire electrodes, expressed as a percentage of the quiet breathing level and altered by mechanical ventilation, changes in lung volume, and chest wall compression. Subglottic pressure was recorded while a constant flow of air was passed through the upper airway. In the absence of PCA activity the PV relationship was alinear and could be described by a power function (P = K0Va, where K0 and a are constants). The slope of the log P-log V plots in the absence of PCA and thyroarytenoid activity was 1.83 +/- 0.02 (SD), whereas with increasing PCA activity it was 1.88 +/- 0.11. An effective hydraulic diameter (DH) was calculated for 20% increments of PCA activity, and in two dogs glottic diameter (Dg) was calculated from glottic area measurements obtained by fiber-optic laryngoscopy. Both DH and Dg increased linearly with increasing PCA activity. Denervation of the cricothyroid muscle had no systematic effect on laryngeal resistance. The results indicate that the PV relationship of the larynx may be described by a power function with a single exponent, the magnitude of which is independent of glottic dilator muscle activity and consistent with orifice flow. However, laryngeal diameter increases linearly with PCA activity in the range studied.     

Numerical 3D analysis of oscillatory flow in the time-varying laryngeal channel

Three-dimensional flow through an anatomically representative model of the human larynx has been numerically simulated. This model includes the vestibular folds, the vocal cords and the glottic and subglottic areas. Pseudo-time-varying glottic aperture and flow conditions have been considered during quiet breathing, with a peak volume flow rate of 0.75 l/s and a frequency of 0.25 Hz. Because of the severe constriction, jet-like configurations have been observed. Minor differences have been outlined between the inspiration and expiration profiles. Simulations demonstrated the presence of a backflow region which may extend to 60 mm from the glottis at peak inspiration and occupy 20% of the tracheal cross section. Because of its rolling, this backflow region appears in the sagittal plane close to the anterior wall, only one diameter from the laryngeal constriction and extends over about 40 mm. The evolution of the streamwise velocity contours and of the corresponding secondary vector plots at six critical stations, including the glottic section, has also been described. A double pair of counter-rotating vortices develops shortly downstream/upstream from the orifice respectively at inspiration/expiration and merges near the frontal plane about 25 mm from the glottis. The effect of the incoming flow has been evaluated by including the pharyngeal channel; no major difference has been observed in the computed flow patterns.     

Facilitation of the diaphragm response to transcranial magnetic stimulation by increases in human respiratory drive.

The human respiratory neural drive has an automatic component (bulbospinal pathway) and a volitional component (corticospinal pathway). The aim of this study was to assess the effects of a hypercapnia-induced increase in the automatic respiratory drive on the function of the diaphragmatic corticospinal pathway as independently as possible of any other influence. Thirteen healthy volunteers breathed room air and then 5 and 7% hyperoxic CO2. Cervical (cms) and transcranial (tms) magnetic stimulations were performed during early inspiration and expiration. Transdiaphragmatic pressure (Pdi) and surface electromyogram of the diaphragm (DiEMG) and of the abductor pollicis brevis (apbEMG) were recorded in response to cms and tms. During inspiration, Pdi,cms was unaffected by CO2, but Pdi,tms increased significantly with 7% CO2. During expiration, Pdi,cms was significantly reduced by CO2, whereas Pdi,tms was preserved. DiEMG,tms latencies decreased significantly during early inspiration and expiration (air vs. 5% CO2 and air vs. 7% CO2). DiEMG,tms amplitude increased significantly in response to early expiration-tms (air vs. 5% CO2 and air vs. 7% CO2) but not in response to early inspiration-tms. DiEMG,cms latencies and amplitudes were not affected by CO2 whereas 7% CO2 significantly increased the apbEMG,cms latency. The apbEMG,tms vs. apbEMG,cms latency difference was unaffected by CO2. In conclusion, increasing the automatic drive to breathe facilitates the response of the diaphragm to tms, during both inspiration and expiration. This could allow the corticospinal drive to breathe to keep the capacity to modulate respiration in conditions under which the automatic respiratory control is stimulated.     

Thyroarytenoid muscle activity during hypoxia in awake lambs

It is generally accepted that hypoxia in early life results in active laryngeal braking of expiratory airflow via the recruitment of glottic adductor muscles. We examined the electromyogram expiratory activity of the thyroarytenoid muscle in seven 11- to 18-day-old awake nonsedated lambs exposed to an inspired O2 fraction of 0.08 for 18 min. The lambs breathed through a face mask and a pneumotachograph. During baseline prehypoxic breathing, the thyroarytenoid muscle was largely inactive in each awake lamb. Unexpectedly, no recruitment of the thyroarytenoid muscle was recorded during hypoxia in any of the seven lambs; simultaneous examination of the flow-volume curves revealed an absence of expiratory airflow braking. Also unexpectedly, marked expiratory activity of the thyroarytenoid muscle was recorded, with each expiration occurring within less than 10 s after the return to room air. The resulting delay of expiration was apparent in the flow-volume loops. Thus, in awake 11- to 18-day-old lambs, 1) active expiratory glottic adduction is absent during hypoxia and 2) a return from hypoxia to room air results in prolonged expiration as well as active glottic adduction that controls end-expiratory lung volume.     

Changes in respiratory movements of the human vocal cords during hyperpnea

Five healthy young subjects were studied to assess the changes in vocal cord movements that occur between resting breathing and hyperpnea. Both hypercapnia and exercise induced decreases in the extent of narrowing of the glottic aperture occurring during expiration. In addition, four of the subjects showed a significant positive rank correlation between the extent of narrowing of the glottis and the observed length of the expiratory phase of the respiratory cycle. These results indicate that the braking of expiratory airflow by movements of the vocal cords toward the midline is reduced during hyperpnea at the same time that expiratory time is decreased.     

Excitatory lung reflex may stress inspiratory muscle by suppressing expiratory muscle activity.

Recently, a vagally mediated excitatory lung reflex (ELR) causing neural hyperpnea and tachypnea was identified. Because ventilation is regulated through both inspiratory and expiratory processes, we investigated the effects of the ELR on these two processes simultaneously. In anesthetized, open-chest, and artificially ventilated rabbits, we recorded phrenic nerve activity and abdominal muscle activity to assess the breathing pattern when the ELR was evoked by directly injecting hypertonic saline (8.1%, 0.1 ml) into lung parenchyma. Activation of the ELR stimulated inspiratory activity, which was exhibited by increasing amplitude, burst rate, and duty cycle of the phrenic activity (by 22 +/- 4, 33 +/- 9, and 57 +/- 11%, respectively; n = 13; P < 0.001), but suppressed expiratory muscle activity. The expiratory muscle became silent in most cases. On average, the amplitude of expiratory muscle activity decreased by 88 +/- 5% (P < 0.002). The suppression reached the peak at 6.9 +/- 1 s and lasted for 200 s (median). Injection of H(2)O(2) into the lung parenchyma produced similar responses. By suppressing expiration, the ELR produces a shift in the workload from expiratory muscle to inspiratory muscle. Therefore, we conclude that the ELR may contribute to inspiratory muscle fatigue, not only by directly increasing the inspiratory activity but also by suppressing expiratory activity.     

Postinspiratory neuronal activities during behavioral control, sleep, and wakefulness.

Cells that discharge in early expiration and inhibit other respiratory cells purportedly cause a separate phase of the respiratory cycle that has been named "postinspiration." Our objective was to study these postinspiratory cells in the intact unanesthetized cat during sleep, wakefulness, and behavioral inhibition of inspiration, but we were unable to find cells with strong and consistent activity confined to early expiration. Instead, we found that various cell types were active in early expiration. They included inspiratory-expiratory phase-spanning cells, retrofacial augmenting expiratory cells with bursts in early expiration, retrofacial decrementing expiratory cells, tonic expiratory cells, and cells with variable activity in the early part of expiration. Just as the cell types active during early expiration were heterogeneous so too were their activities during behavioral inhibition of inspiration and during sleep. These results suggest that the state of early expiration is determined by many different cell types rather than a single class of postinspiratory cells.     

Total work rate of breathing optimization in CO-2 inhalation and exercise.

The hypothesis that respiratory frequency and the relative durations of inspiration and expiration are regulated according to a total cycle work rate minimization criterion was explored. Effects of negative work performed by the respiratory muscles and dead space variation as a function of tidal volume were included in a formulation which yielded a theoretically predictable optimal frequency and relative duration of inspiration and expiration at all levels of ventilation. Predicted cycle characteristics based on measured mechanical parameters were compared with data taken during CO-2 inhalation (3 and 5%) and moderate exercise (MRR = 3 and 6) in three normal human subjects. No major difference in breathing pattern was observed between CO-2 inhalation and exercise. Results suggest that conditions for minimization of total cycle work rate are achieved asympototically as the level of ventilation rises above the resting level. At rest and at low levels of hyperpnea complete work rate optimization is not achieved.