Ventilatory responses to inspiratory threshold loading in humans

Normal alveolar ventilation tends to be maintained during external mechanical loading. The precise manner by which this occurs is unclear but may involve intrinsic mechanisms related to the muscular pump, neural influences, and chemoreceptor control. Recent observations suggest that submaximal threshold loads may result in hyperventilation. In this study we explicitly examined the respiratory effects of sustained threshold loading in normal subjects. We found that sustained threshold loading resulted in hyperventilation associated with high P100's (mouth pressure 100 ms after the start of an occluded breath) and increased tidal volumes but with little effect on duty cycle or respiratory rate. In addition, this increased respiratory motor output was sustained for 30-60 s after the load was removed. At very high threshold loads, hyperventilation failed to occur, despite increased P100's. We conclude that threshold loading results in increased respiratory motor output and hyperventilation, a response that is different from that observed with either resistive or elastic loads, and that the failure to hyperventilate at the higher loads may be the result of mechanical limitation.     

Breathing through an inspiratory threshold device improves stroke volume during central hypovolemia in humans.

Inspiratory resistance induced by breathing through an impedance threshold device (ITD) reduces intrathoracic pressure and increases stroke volume (SV) in supine normovolemic humans. We hypothesized that breathing through an ITD would also be associated with a protection of SV and a subsequent increase in the tolerance to progressive central hypovolemia. Eight volunteers (5 men, 3 women) were instrumented to record ECG and beat-by-beat arterial pressure and SV (Finometer). Tolerance to progressive lower body negative pressure (LBNP) was assessed while subjects breathed against either 0 (sham ITD) or -7 cmH(2)O inspiratory resistance (active ITD); experiments were performed on separate days. Because the active ITD increased LBNP tolerance time from 2,014 +/- 106 to 2,259 +/- 138 s (P = 0.006), data were analyzed (time and frequency domains) under both conditions at the time at which cardiovascular collapse occurred during the sham experiment to determine the mechanisms underlying this protective effect. At this time point, arterial blood pressure, SV, and cardiac output were higher (P < or = 0.005) when breathing on the active ITD rather than the sham ITD, whereas indirect indicators of autonomic activity (low- and high-frequency oscillations of the R-to-R interval) were not altered. ITD breathing did not alter the transfer function between systolic arterial pressure and R-to-R interval, indicating that integrated baroreflex sensitivity was similar between the two conditions. These data show that breathing against inspiratory resistance increases tolerance to progressive central hypovolemia by better maintaining SV, cardiac output, and arterial blood pressures via primarily mechanical rather than neural mechanisms.     

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.     

Detection threshold for inspiratory resistive loads and respiratory-related evoked potentials.

The relationship between detection threshold of inspiratory resistive loads and the peaks of the respiratory-related evoked potential (RREP) is unknown. It was hypothesized that the short-latency and long-latency peaks of the RREP would only be elicited by inspiratory loads that exceeded the detection threshold. The detection threshold for inspiratory resistive loads was measured in healthy subjects with inspiratory-interruption or onset load presentations. In a separate protocol, the RREPs were recorded with resistive loads that spanned the detection threshold. The loads were presented in stimulus attend and ignore sessions. Onset and interruption load presentations had the same resistive load detection threshold. The P(1), N(f), and N(1) peaks of the RREP were observed with loads that exceeded the detection threshold in both attend and ignore conditions. The P(300) was present with loads that exceeded the detection threshold only in the attend condition. No RREP components were elicited with subthreshold loads. The P(1), N(f), and P(300) amplitudes varied with resistive load magnitude. The results support the hypothesis that there is a resistive load threshold for eliciting the RREPs. The amplitude of the RREP peaks vary as a function of load magnitude. The cognitive P(300) RREP peak is present only for detectable loads and when the subject attends to the stimulus. The absence of the RREP with loads below the detection threshold and the presence of the RREP elicited by suprathreshold loads are consistent with the gating of these neural measures of respiratory mechanosensory information processing.     

Immediate diaphragmatic electromyogram responses to imperceptible mechanical loads in conscious humans.

We used an esophageal electrode to measure the amplitude and neural inspiratory and expiratory (N TE) timing responses of crural diaphragmatic electrical activity in response to flow-resistive (R) and elastic (E) loads at or below the threshold for conscious detection, applied pseudorandomly to the oral airway of eight normal subjects. We observed a rapid first-breath neural reflex that modified respiratory timing such that N TE lengthened significantly in response to R loads in six of eight subjects and shortened in response to E loading in six of seven subjects. The prolongation of N TE with R loading resulted primarily from lengthening the portion of N TE during which phasic activity in the diaphragm is absent (TE NDIA), whereas E loading shortened N TE mainly by reducing TE NDIA. Most subjects responded to both types of loading by decreasing mean tonic diaphragmatic activity, the average level of muscle activity that exists when no phasic changes are occurring, as well as its variability. The observed timing responses are consistent in direction with optimally adaptive pattern regulation, whereas the modulation of tonic activity may be useful in neural regulation of end-expiratory lung volume.     

Detection of inspiratory resistive loads in double-lung transplant recipients.

The afferent pathways mediating respiratory load perception are still largely unknown. To assess the role of lung vagal afferents in respiratory sensation, detection of inspiratory resistive loads was compared between 10 double-lung transplant (DLT) recipients with normal lung function and 12 healthy control (Nor) subjects. Despite a similar unloaded and loaded breathing pattern, the DLT group had a significantly higher detection threshold (2.91 +/- 0.5 vs. 1.55 +/- 0.3 cmH(2)O. l(-1). s) and Weber fraction (0.50 +/- 0.1 vs. 0.30 +/- 0.1) compared with the Nor group. These results suggest that inspiratory resistive load detection occurs in the absence of vagal afferent feedback from the lung but that lung vagal afferents contribute to inspiratory resistive load detection response in humans. Lung vagal afferents are not essential to the regulation of resting breathing and load compensation responses.     

Nonchemical influence of inspiratory pressure support on inspiratory activity in humans

To determinewhether nonchemical inhibition of respiratory activity occurs duringinspiratory pressure support (IPS) ventilation (IPSV), respiratorymotor output (in 9 subjects), obtained by calculatingtransdiaphragmatic pressure-time products, and central respiratoryoutput (in 5 subjects), obtained by integrating the electromyographicactivity of the diaphragm (EMGdi) during mechanical inspiratory time,EMGdi per minute, and electrical inspiratory time, asdetermined from onset to peak EMGdi, were compared during spontaneous ventilation (control) and IPSV with(IPS+CO₂) and without (IPS)correction of hypocapnia. Both IPS andIPS+CO₂ induced significantdecreases in transdiaphragmatic pressure-time products (46 ± 31 and53 ± 23%, respectively), EMGdi during mechanical inspiratory time(49 ± 12 and 57 ± 14%, respectively), EMGdi per minute (65 ± 22 and 69 ± 15%, respectively), andelectrical inspiratory time (73 ± 8 and 65 ± 6%,respectively). Because correction of hypocapnia failed to eliminate themarked inhibition of both respiratory and central motor output seenwith IPS, we conclude that nonchemical inhibition of respiratoryactivity occurs during IPSV.

     

Sympathetic responses to head-down rotations in humans.

Muscle sympathetic nerve activity (MSNA) increases with head-down neck flexion (HDNF). The present study had three aims: 1) to examine sympathetic and vascular responses to two different magnitudes of HDNF; 2) to examine these same responses during prolonged HDNF; and 3) to determine the influence of nonspecific pressure receptors in the head on MSNA. The first experiment tested responses to two static head positions in the vertical axis [HDNF and intermediate HDNF (I-HDNF; approximately 50% of HDNF)]. MSNA increased above baseline during both I-HDNF and HDNF (from 219 +/- 36 to 301 +/- 47 and from 238 +/- 42 to 356 +/- 59 units/min, respectively; P < 0.01). Calf blood flow (CBF) decreased and calf vascular resistance increased during both I-HDNF and HDNF (P < 0.01). Both the increase in MSNA and the decrease in CBF were linearly related to the magnitude of the downward head rotations (P < 0.01). The second experiment tested responses during prolonged HDNF. MSNA increased (from 223 +/- 63 to 315 +/- 79 units/min; P < 0.01) and CBF decreased (from 3.2 +/- 0.4 to 2.6 +/- 0.04 ml. 100 ml-1. min-1; P < 0.01) at the onset of HDNF. These responses were maintained throughout the 30-min period. Mean arterial blood pressure gradually increased during the 30 min of HDNF (from 94 +/- 4 to 105 +/- 3 mmHg; P < 0.01). In a third experiment, head-down neck extension was performed with subjects in the supine position. Unlike HDNF, head-down neck extension did not affect MSNA. The results from these studies demonstrate that MSNA: 1) increases in magnitude as the degree of HDNF increases; 2) remains elevated above baseline during prolonged HDNF; and 3) responses during HDNF are not associated with nonspecific receptors in the head activated by increases in cerebral pressure.     

Magnitude estimation of inspiratory resistive loads by double-lung transplant recipients.

The purpose of this study was to investigate the role of afferent input from the lung and lower airways in magnitude estimation of inspiratory resistive loads (R). To assess the role of lung vagal afferents in respiratory sensation, sensations related to inspiratory R, reflected by subjects' percentage of handgrip responses (HG%), were compared between double-lung transplant (DLT) recipients with normal lung function and healthy control (Nor) subjects. Perceptual sensitivity to the external load was measured as the slope of HG% as a function of peak mouth pressure (Pm), and the slope of HG% as a function of R, after a log-log transformation. The results showed that the DLT group had a similar HG% response, as well as the slopes of log HG%-log Pm and log HG%-log R, compared with the Nor group. Furthermore, the ventilatory responses to external loads were also similar between the two groups. These results suggest that lung vagal afferents do not play a significant role in magnitude estimation of inspiratory resistive loads in humans.     

Cardiovascular and splenic responses to exercise in humans.

To investigate splenic erythrocyte volume after exercise and the effect on hematocrit- and hemoglobin-based plasma volume equations, nine men cycled at an intensity of 60% maximal O(2) uptake for 5-, 10-, or 15-min duration, followed by an incremental ride to exhaustion. The reduction in spleen volume, calculated using (99m)Tc-labeled erythrocytes, was not significantly different among the three submaximal rides (5 min = 28%, 10 min = 30%, 15 min = 36%; P = 0.26). The incremental ride to exhaustion resulted in a 56% reduction in spleen volume, which recovered to baseline levels within 20 min. Plasma catecholamines were inversely related to spleen volume after exercise (r = 0.70-0.84; P < 0.0001). There were no differences in red cell or total blood volume pre- to postexercise; however, a significant reduction in plasma volume was observed (18.9%; P < 0.01). There was no difference between the iodinated albumin and the hematocrit and hemoglobin methods of assessing plasma volume changes. These results suggest that the spleen regulates its volume in response to an intensity-dependent signal, and plasma catecholamines appear partially responsible. Splenic release of erythrocytes has no effect on indirect measures of plasma volume.