Relationship of transdiaphragmatic pressure and latencies for detecting added inspiratory loads.

The purpose of this investigation was to measure changes in transdiaphragmatic pressure (Pdi) developed during graded elastic (E) and resistive (R) loaded breaths and to correlate the emergence of such changes with the load-dependent alterations in latency for detection (Tdet). Five healthy adults were studied using three protocols, i.e., graded E, graded R, and graded R in the presence of elevated background R. In each protocol, loads were added for single inspirations, 10 times in random order and separated by three to five unloaded breaths. Subjects pressed a signal marker as soon as loads were detected. Inspiratory flow (VI), inspired volume (VI), mouth pressure, and Pdi of loaded breaths and the preceding unloaded breaths were recorded and computer averaged. Patterns of VI and VI were not altered prior to detection of the smallest added E and R loads but decreased with the higher loads. Group mean patterns of Pdi showed graded increases during loaded breaths. Augmentation of Pdi preceded Tdet and occurred earlier as Tdet decreased with graded E and R loads. Elevating the background R delayed both Tdet of added R and the augmentation of Pdi. Results are consistent with the hypothesis that load-induced changes in diaphragmatic tension may play a sensory role in detection of inspiratory loads.

Respiratory volume-timing relationship during sustained elevation of functional residual capacity.

In 7 spontaneously breathing dial-urethane anesthetized cats a negative pressure was produced around the thorax and abdomen to increase the functional residual capacity (FRC) by about 1 tidal volume for up to 60 min. A tracheal cannula was connected to a resistive manifold for selective loading of inspiration or expiration. Two resistive loads and tracheal occlusion were presented six times each at control FRC (FRCc), after 60 min at elevated FRC (FRCe) and 30 min after return to FRCc. Inspiratory and expiratory durations (TI and TE) were measured from diaphragmatic EMG. We observed that TI at FRCe (0.88 +/- 0.11 sec) was not significantly shorter than TI at FRCc (1.06 +/- 0.14 sec). Tracheal occlusion at FRCe caused a shorter TI (1.37 +/- 0.15 sec) than at FRCc (1.79 +/- 0.21 sec) (P less than 0.05). The slope (m) of the VI-TI relationship generated by the resistive loads at FRCe was steeper (m = -65 +/- 7 ml X sec-1) and shifted upward from the VI-TI curve at FRCc (-50 +/- 6 ml X sec-1) (P less than 0.05). The VE-TE relationship at FRCe was not significantly changed from control. Thirty minutes following return to FRCc, TI was still slightly shorter (0.96 +/- 0.11 sec) than the initial TI at FRCc. We conclude: (1) The slope of the VI-TI relationship is determined to a great extent by the total lung volume. However, under the conditions of sustained elevation of FRC, this relationship is influenced by the partial adaptation of slowly adapting pulmonary receptors SARs. (2) The increased SAR activity at end expiration during FRCe may not influence the control of TE.

Scaling of added loads to breathing: magnitude estimation vs. handgrip matching.

Six healthy male adults were studied at five levels of suprathreshold added resistance (delta R) applied three times to inspiration in a random sequence. Subjects squeezed an isometric handgrip dynamometer coincident with the breath to express the perceived magnitude of the load and also gave a numerical estimate after completing the loaded inspiration. Peak mouth pressure, grip deflection, and numerical estimate were analyzed to derive the exponents for Stevens' power law. The mean exponent and correlation coefficient obtained from numerical estimates were 1.11 +/- 0.16 and 0.94 +/- 0.04, respectively, while the exponent and correlation coefficient simultaneously obtained from handgrip matching was 0.73 +/- 0.10 and 0.91 +/- 0.05, respectively. Multiplying each subject's exponent obtained from handgrip matching by 1.7 yields a mean equated exponent of 1.23 +/- 0.17. The equated exponents were not statistically different (P greater than 0.05) from the exponents derived from numerical estimates. These results suggest that the use of cross-modality (handgrip) matching provides a reliable method for obtaining psychophysical magnitude functions of respiratory sensations and that exponents obtained using either technique can be equated for comparison.

Effect of background loading on perception of inspiratory loads.

The effect of background loading on magnitude estimation of added elastic and resistive inspiratory loads was determined. An analogous study involving estimation of the heaviness of weights in the hand was also performed. Perceptual performance was assessed using Stevens' power law psi = k phi n, where psi is the subjective magnitude, phi is the peak mouth pressure generated with an inspiratory load or the weight of the load in grams for the heaviness estimation, and the exponent n characterizes perceptual performance. The value of n was determined for the control and background conditions for each study. The results for both inspiratory loading studies and the heaviness estimation experiment indicate that background loading is associated with a significant increase in the exponent for magnitude estimation (P less than 0.05). Adjustment of the stimulus scale by subtracting the difference in peak mouth pressures generated during resting breathing between control and background-loaded conditions for the inspiratory loading studies, or the weight of the background load in the heaviness estimation experiment, converted the exponents obtained under background-loaded conditions to values that were not significantly different from those for control (P greater than 0.05). These results are consistent with the theory suggesting that an increase in detection threshold, produced by the background load, is responsible for the increase in exponent for magnitude estimation.

Comparison of subjects' perception of inspiratory and expiratory resistance.

Six healthy male adults were studied at five levels of suprathreshold added resistance (delta R) applied thrice to either inspiration (I) or expiration (E) in a random sequence. Subjects squeezed on isometric handgrip dynamometer to express the perceived magnitude of the load. Peak mouth pressure (Pm), flow, grip (G), and delta R were analyzed to derive the exponent for Steven's power law. We observed that the slope for log G vs. log delta R was significantly greater for I loads than for E loads (P less than 0.05), but the intercepts for E loads were significantly elevated. However, the slopes and intercepts for log G vs. log Pm during the same I and E loads were not significantly different. When subjects were instructed to target I or E flow to a preset level, we observed no difference between the slopes and intercepts for log G vs. log delta R during I and E loading. These results suggest that 1) the sensory information utilized in judging the magnitude of added resistance is more likely related to the force generated by the respiratory muscles (Pm) rather than delta R per se; and 2) similar muscle receptors and neural processing systems are utilized in the estimation of added loads involving either inspiratory or expiratory muscle groups.

Ventilatory responses to static handgrip exercise.

Previous research indicates that fatiguing static exercise causes hyperventilation and a decrease of end-tidal CO2 partial pressure PETCO2. The objectives of this study were 1) to examine the changes in pattern of breathing during static exercise, and 2) to define the isocapnic ventilatory response. Six healthy males were studied once a week at one of three levels of static handgrip exercise: 15, 25, or 30% maximum voluntary contraction (MVC) was sustained for 5 min while holding PETCO2 constant or allowing it to run free. During 25 and 30% MVC, we observed 1) progressive increases in mean tidal volume (VT), inspiratory ventilation (VI), VT/TI, heart rate (HR), and arterial BP, 2) increased breath-to-breath variability of VT, 3) no significant changes in respiratory frequency (f), and 4) progressive decreases in PETCO2. Keeping PETCO2 constant at preexercise levels did not change the pattern or magnitude of the ventilatory response to exercise. The time course and magnitude of the subjects' perceived effort resembled the time course and magnitude of the ventilatory response. The variability of VT during the response to static exercise suggests an element of control instability. The identical ventilatory responses during hypocapnic and isocapnic conditions may result from the slow response of the central chemoreceptors; an overriding influence of muscle afferents; and/or increased central command arising with fatigue.

The effects of airway anesthesia on magnitude estimation of added inspiratory resistive and elastic loads.

The effects of airway anesthesia on the magnitude estimation of added inspiratory loads were studied in 5 healthy normal subjects. The subjects assessed the magnitude of a given load by means of a handgrip dynamometer; 5 suprathreshold resistive loads. (range, 2.9 to 21.0 cmH2O/L/s) and 7 suprathreshold elastic loads (range, 4.6 to 24.0 cmH2O/L) were used. Anesthesia of the upper and lower airways was obtained by gargling and inhalation of 4% lidocaine solution; the adequacy of airway anesthesia was assessed by the inhalation of 20% citric acid solution. Studies were performed in the control state and during the airway anesthetized state. The relationship between log added load and log handgrip response, represented by the regression coefficient between these two variables, was in accord with the psychophysical power law of Stevens in all the studies. The regression coefficient during the control state of resistive loads (mean = 0.566) and elastic loads (mean = 0.516) did not alter significantly (p greater than 0.05) during the airway anesthetized state. These results indicate that the magnitude estimation of added inspiratory loads is not primarily mediated through receptors in the upper or lower airways.

Response of ventral respiratory group inspiratory neurons to mechanical loading.

The bursting patterns of 32 ventral respiratory group (VRG) medullary inspiratory neurons were studied in response to selected mechanical loads in 68 allobarbital-urethan-anesthetized cats. Mechanical loads consisted of three levels of resistive loads, one elastic load, and tracheal occlusion (TO). The application of each load was manipulated to oppose either inspiration or expiration. Loads were applied for only one inspiration or expiration to prevent changes in chemical drive. All loaded breath unit responses were analyzed and compared with control values for inspiratory time (TI), expiratory time (TE), spikes per burst (SPB), and average firing rate (FR). Inspiratory mechanical loads resulted in statistically significant increases in TI and SPB but only small nonsignificant increases in FR and TE. Expiratory resistive loading produced its predominant effect on TE. The higher expiratory mechanical loads also caused significant increases in the subsequent unloaded TI and SPB. In contrast to expiratory loading, large inspiratory loads did not significantly affect the next unloaded TE. Bilateral cervical vagotomy eliminated the observed neural responses to loading for both inspiratory and expiratory loads. All of the 71 neurons tested with lung inflations and TO at end inspiration showed inhibition (Ra type) rather than facilitation (R beta).

Ability of healthy men to discriminate between added inspiratory resistive and elastic loads.

Previous studies of the latencies for the detection of inspiratory resistive (R) and elastic (E) loads revealed that R loads were detected earlier in the loaded breath than E loads (Respir. Physiol. 34: 267--77, 1978). These results suggested that the load information generated by R and E loads have different temporal patterns. We hypothesized that these differences might provide a mechanism for subjects to accurately discriminate between R and E loads and secondly, that the R and E load sensations perceived by subjects should have different temporal characteristics. To test these hypotheses we studied six healthy subjects in a two-part study. In this first, two levels of R and E loads (near threshold and 4--5 times threshold) were randomly presented for single inspirations separated by 3--6 unloaded breaths for a total of 10 presentations each. Subjects indicated detection and type of load perceived by pressing R or E marker buttons. In the second part, using the same loading protocol, subjects squeezed a hand grip dynamometer to express the pattern of perceived load sensation. Results indicate that subjects cannot discriminate between near-threshold R and E load but can discriminate between R and E loads 4--5 times threshold with considerable accuracy. Mean grip responses show that perceived load sensations arise earlier and reach maximum values sooner during R loaded breaths. Grip responses are consistent with the previously reported differences in R and E detection latencies and support the hypothesis that load discrimination is mediated by differences in the temporal pattern of load information generated during R and E loaded breaths.

The effect of the resistive loading of inspiration and expiration on pulmonary stretch receptor discharge.

Anesthetized, spontaneously breathing cats were used to examine the hypothesized role of slowly adapting pulmonary stretch receptors (PSR) in the control of breath duration. Initially, graded inspiratory and expiratory resistive loads were added to elucidate the inspiratory and expiratory volume-time relationship with both vagi intact. Unilateral vagotomy increased the slope of the VI--TI relationship indicating a reduction of the volume related modulation of TI. PSR frequency (fPSR) at end-inspiration also progressively decreased resulting in a fPSR--TI relationship qualitatively similar to the VI--TI curve. Expiratory resistive loading also produced an increased slope for the VE--TE relationship when the right vagus nerve was severed. The prolongation of TE was associated with a progressive increase in the number of PSR discharges during the loaded expiration. These results support the hypothesized role of PSR in the vagally mediated prolongation of TI and TE during resistive loading. In a subsequent series of experiments, the changes in fPSR were correlated with the tidal volume and transpulmonary pressure (PTP) changes. The fPSR was linearly related to PTP during both eupnic and loaded breathing. When fPSR was plotted against volume, a clockwise hysteresis was observed. These results suggest that in the spontaneously breathing cat, intrathoracic PSR frequency varies as a function of the transmural pressure across the airways.

Behavior of expiratory neurons in response to mechanical and chemical loading.

The response of medullary expiratory neurons to added mechanical and chemical loads was studied in anesthetized cats. Alterations in burst characteristics and central timing were compared in the intact and bilaterally vagotomized cat. The following results were obtained: (1) Graded expiratory airflow resistances caused progressive increases in burst duration, spikes per burst and firing rate; similar effects were noted for end-inspiratory tracheal occlusions and continuous positive breathing; all facilitation was eliminated by vagotomy. (2) Graded inspiratory airflow resistances delayed the onset of an expiratory burst but did not change the overall burst characteristics. (3) Acute hypercapnia increased ventilation without noticeable changes in expiratory burst characteristics; acute hypoxia produced a reduction in burst duration concomitant with changes in ventilation. It is concluded that (1) expiratory neurons are responsive to vagally mediated volume information and (2) transient hypoxia and hypercapnia sufficient to increase ventilation does not increase the firing rate of expiratory neurons but exerts differential effects with respect to timing. It is suggested that expiratory duration is related to the time integral of expired volume and that the increase in FRC imposed by expiratory loads does not alter the central timing of the next inspiration.

Temporal differences in the detection of resistive and elastic loads to breathing.

Two series of experiments were conducted on 8 healthy subjects to test for temporal differences in the detection of added resistive and elastic loads. In one series of experiments, 5 resistive loads were presented for single inspirations for a total of 10 presentations each. Subjects pressed a signal marker as soon as possible if they detected the load. In the second series, 5 elastic loads were tested using the same protocol The detection time (Tdet) for threshold resistive loads (deltaR50) occurred in mid-inspiration near Vmax whereas the Tdet for threshold D loads (delta E50) occurred near the end of inspiration. The differences in the detection times were significant (P less than 0.001). With suprathreshold loads, detection times progressively decreased reaching a minimum value with total occlusion. These results demonstrate unique temporal differences in the patterns of sensory information generated by added resistive and elastic loads and suggest that the intensity of the information is flow dependent for resistive loads and volume dependent for elastic loads.

Effect of chest cage restriction on perception of added airflow resistance.

The effect of restricting chest expansion on the detection of resistive loads added to inspiration was assessed in 6 healthy male subjects. Restriction was accomplished using an adjustable chest clamping device. Load detection scores obtained with and without chest clamping were plotted against deltaR and the Weber Fraction (deltaR/Ro), where deltaR is the added load and Ro is the initial resistive load (i.e. subject's R plus minimal R of the apparatus). Results indicate that restricting chest expansion does not alter the ability of healthy subjects to detect added inspiratory resistive loads. It is concluded that perception of such loads is not dependent upon sensory information from the chest wall.

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.