Effects of aging on sensation of respiratory force and displacement

The psychophysical technique of magnitude production was used to evaluate the sensation of inspiratory force and inspired volume in young and older subjects. Inspiratory force was generated during a static inspiratory maneuver against a closed airway. The exponent of the power function relationship between airway pressure and sensation intensity during force scaling was not significantly different between young and older subjects. In contrast, the exponents for the magnitude production of inspired volume were significantly greater in the older compared with the young group. We also assessed the effects of age on the relative importance of force and displacement signals on the sensation of inspired volume. Subjects attempted to reproduce a control tidal volume while breathing against a series of inspiratory resistive and elastic loads. In both groups error in tidal volume reproduction increased progressively as the severity of the load increased. During moderate and severe loading the error in the older subjects was significantly greater than in the young group. Correspondingly, the peak inspiratory airway pressures at tidal volume reproduction against these loads were significantly smaller in the older compared with the young subjects. The results suggest that in older subjects cues related to respiratory muscle force are more important than volume in the sensation of lung volume changes. In young subjects the sensation of lung volume changes is based to a greater degree on signals of volume or displacement.     

Respiratory sinus arrhythmia in the denervated human heart

We performed this study to test whether the denervated human heart has the ability to manifest respiratory sinus arrhythmia (RSA). With the use of a highly sensitive spectral analysis technique (cross correlation) to define beat-to-beat coupling between respiratory frequency and heart rate period (R-R) and hence RSA, we compared the effects of patterned breathing at defined respiratory frequency and tidal volumes (VT), Valsalva and Mueller maneuvers, single deep breaths, and unpatterned spontaneous breathing on RSA in 12 normal volunteers and 8 cardiac allograft transplant recipients. In normal subjects R-R changes closely followed changes in respiratory frequency (P less than 0.001) but were little affected by changes in VT. On the R-R spectrum, an oscillation peak synchronous with respiration was found in heart transplant patients. However, the average magnitude of the respiration-related oscillations was 1.7-7.9% that seen in normal subjects and was proportionally more influenced by changes in VT. Changes in R-R induced by Valsalva and Mueller maneuvers were 3.8 and 4.9% of those seen in normal subjects, respectively, whereas changes in R-R induced by single deep breaths were 14.3% of those seen in normal subjects. The magnitude of RSA was not related to time since the heart transplantation, neither was it related to patient age or sex. Thus the heart has the intrinsic ability to vary heart rate in synchrony with ventilation, consistent with the hypothesis that changes, or rate of changes, in myocardial wall stretch might alter intrinsic heart rate independent of autonomic tone.     

Deep-breath frequency in bronchoconstricted monkeys (Macaca fascicularis).

Deep-breath frequency has been shown to increase in spontaneously obstructed asthmatic subjects. Furthermore, deep breaths are known to be regulated by lung rapidly adapting receptors, yet the mechanism by which these receptors are stimulated is unclear. This study tested the hypothesis that deep-breath frequency increases during experimentally induced bronchoconstriction, and the magnitude of the increased deep-breath frequency is dependent on the method by which bronchoconstriction is induced. Nine cynomolgus monkeys (Macaca fascicularis) were challenged with methacholine (MCh), Ascaris suum (AS), histamine, or an external mechanical resistance. Baseline (BL) and challenge deep-breath frequency were calculated from the number of deep breaths per trial period. Airway resistance (Raw) and tissue compliance (Cti), as well as tidal volume, respiratory rate, and minute ventilation, were analyzed for BL and challenged conditions. Transfer impedance measurements were fit with the DuBois model to determine the respiratory parameters (Raw and Cti). The flow at the airway opening was measured and analyzed on a breath-by-breath basis to obtain the ventilatory parameters (tidal volume, respiratory rate, and minute ventilation). Deep-breath frequency resulting from AS and histamine challenges [0.370 (SD 0.186) and 0.467 breaths/min (SD 0.216), respectively] was significantly increased compared with BL, MCh, or external resistance challenges [0.61 (SD 0.046), 0.156 (SD 0.173), and 0.117 breaths/min (SD 0.082), respectively]. MCh and external resistance challenges resulted in insignificant changes in deep-breath frequency compared with BL. All four modalities produced similar levels of bronchoconstriction, as assessed through changes in Raw and Cti, and had similar effects on the ventilatory parameters except that non-deep-breath tidal volume was decreased in AS and histamine. We propose that increased deep-breath frequency during AS and histamine challenge is the result of increased vascular permeability, which acts to increase rapidly adapting receptor activity.     

Gate mechanism in breathlessness caused by chest wall vibration in humans

The effects of bilateral alternating out-of-phase vibrations were studied in 10 normal healthy subjects and five asthmatic patients. The second or third intercostal spaces were vibrated during expiration, and the seventh to ninth intercostal spaces were vibrated during inspiration. Most subjects sensed breathlessness during such vibrations, and 100 Hz was most effective. The degree of breathlessness correlated positively with increased respiratory rate. Respiratory rate increased from 14.1 +/- 3.78 (mean +/- SD) to 22.3 +/- 7.14 breaths/min (P less than 0.05) during relatively severe breathlessness and to 20.39 +/- 5.66 breaths/min (P less than 0.05) during less uncomfortable sensation. Slight or negligible breathlessness induced no significant increase in rate (15.33 +/- 4.19 breaths/min). All asthma patients described the sensations during vibration as similar to those during asthma attacks, and their respiratory rates increased 20.7 +/- 11.03% during 100 Hz vibration (P less than 0.01). It is suggested that the uncomfortable sensation of breathlessness may be induced by muscle spindles in the intercostal muscles being activated out of phase with the respiratory cycle. The central mechanism that receives the intercostal afferents may have a certain gate that operates in relation to the sensation of breathlessness.     

The influence of hyperventilation on the measurement of stroke volume using a CO2 rebreathing method

The influence of different degrees of hyperventilation on stroke volume measured with a CO2 rebreathing method was studied in seven normal subjects and seven patients with aortic regurgitation. Hyperventilation was initially performed with a rebreathing rate of 30 min-1 and a tidal volume corresponding to 60% of the subject's vital capacity. The tidal volume was then randomly decreased or increased by 0.5 and 1.01 and the procedure was repeated with rebreathing rates of 25 and 35 min-1. The possible influence of habituation to repeated measurements was tested in seven of the subjects. No significant differences in response to hyperventilation of stroke volume, cardiac output or heart rate were found between normal subjects and patients. When the tidal volume was increased, there was a significant increase in heart rate and also an increase in cardiac output, which was significant when comparing measurements performed with the lowest and highest tidal volumes. When comparing initial and final measurements, there was a significant decrease in heart rate and a tendency to decrease in cardiac output. Stroke volume was not affected by variations in rebreathing rate from 25 to 35 min-1 or tidal volume changes of +/- 0.51 and was also unaffected by repeated measurements.     

The Prevalence and Magnitude of Impaired Cutaneous Sensation across the Hand in the Chronic Period Post-Stroke

Sensation is commonly impaired immediately post-stroke but little is known about the long-term changes in cutaneous sensation that have the capacity to adversely impact independence and motor-function. We investigated cutaneous sensory thresholds across the hand in the chronic post-stroke period. Cutaneous sensation was assessed in 42 community-dwelling stroke patients and compared to 36 healthy subjects. Sensation was tested with calibrated monofilaments at 6 sites on the hand that covered the median, ulnar and radial innervation territories and included both glabrous (hairless) and hairy skin. The motor-function of stroke patients was assessed with the Wolf Motor Function Test and the upper-limb motor Fugl-Meyer Assessment. Impaired cutaneous sensation was defined as monofilament thresholds >3 SD above the mean of healthy subjects and good sensation was ≤3 SD. Cutaneous sensation was impaired for 33% of patients and was 40–84% worse on the more-affected side compared to healthy subjects depending on the site (p<0.05). When the stroke patient data were pooled cutaneous sensation fell within the healthy range, although ∼1/3 of patients were classified with impaired sensation. Classification by motor-function revealed low levels of impaired sensation. The magnitude of sensory loss was only apparent when the sensory-function of stroke patients was classified as good or impaired. Sensation was most impaired on the dorsum of the hand where age-related changes in monofilament thresholds are minimal in healthy subjects. Although patients with both high and low motor-function had poor cutaneous sensation, overall patients with low motor-function had poorer cutaneous sensation than those with higher motor-function, and relationships were found between motor impairments and sensation at the fingertip and palm. These results emphasize the importance of identifying the presence and magnitude of cutaneous sensory impairments in the chronic period after stroke.     

Respiratory volume perception through the nose and mouth determined noninvasively

The relative importance of the nose vs. the mouth in the perception of respiratory volumes has never been assessed, nor have previous respiratory perception studies been performed noninvasively. Using respiratory inductive plethysmography, we monitored 12 normal subjects noninvasively when breathing either exclusively through the nose or mouth. The sensation of inspired volume mouth breathing was compared with that of nose breathing over a wide range of the inspiratory capacity. The psychophysical techniques of tidal volume duplication, tidal volume doubling, and magnitude estimation were utilized. A just noticeable difference was calculated from the constant error of the tidal volume duplication trials. The exponents for magnitude estimation were 1.06 and 1.07 for nose and mouth breathing, respectively. The other psychophysical techniques also revealed no differences in nose and mouth volume perception. These results suggest that tidal volume changes are perceived equally well through the nose and mouth. Furthermore, the location of the receptors, important in volume perception, is probably at a distal point common to the nose and mouth.     

Spectral analysis of breathing pattern in man

The periodic oscillations of breathing pattern parameters were studied in 34 healthy subjects. In a three minutes' resting spirometric recording we determined the duration of inspiration, expiration and tidal volume in successive breaths and computed autocorrelation functions and power spectral density. Ten of the subjects were re-examined 2 years later. Pulmonary functions were examined in all of them. Rhythmic changes lasting several respiratory cycles were found in the breathing pattern. Rhythmic changes in the duration of inspiration, expiration and tidal volume differed from one another in the same individual. The spectrograms of the individual breathing pattern parameters in the same individual changed during a 2-year period. Despite individual differences, the power spectral density correlations in the same subject and between different subjects two years later, and the mean curves for power spectral densities, show that in all the subjects the power fell at values of 0 to 0.05 Hz and was then maintained at a roughly constant level. Differences in the spectrograms of the various parameters in the same subject can hardly be attributed to a feedback between peripheral receptors and respiratory centres. Rhythmic changes are probably of central origin.     

Relationships between eupnoeic pattern of breathing and ventilatory control in man II. Early response to transient hypercapnia.

The individual importance of peripheral chemosensitive afferents was studied using a transient hypercapnia (inhalation of a 5% or a 10% CO2 in air gas mixture respectively during 4 or 2 breaths) in human conscious subjects chosen for their different eupnoeic ventilatory patterns. Calculation of the speed of change in end-tidal CO2 pressure in tracheal gas (sPETCO2) and of the rate of change in tidal volume (sVI) gave assessment for quantifying the sensitivity of arterial chemoreceptors to hypercapnia (sCO2=SVI/SPETCO2). Our results showed that, independently of any outside influence of the eupnoeic ventilatory pattern on the components of the chemical stimulus, sVI and sCO2 were found to be much smaller in subjects whose pattern of breathing was slow (i.e. having a large tidal volume). The possible causes of the weak importance of peripheral chemosensitive afferents in such subjects were discussed.     

Role of the carotid chemoreceptors in regulation of inspiratory onset

We studied the effect of intermittent tidal breaths of CO2-enriched air (3-9% CO2) on the duration of expiratory time (TE) in five trained dogs, before and after (3 dogs) bilateral surgical denervation of the carotid bodies (CBD). During studies the dogs lay quietly, either awake or in nonrapid-eye-movement sleep, and breathed through a cuffed endotracheal tube inserted via a chronic tracheostomy. Studies were conducted during bilateral blockade of the cervical vagus nerves (VB), achieved by circulating cold alcohol through radiators placed around exteriorized vagal skin loops. Prior to CBD, single breaths of CO2 significantly shortened TE and thus advanced the onset of the subsequent inspiration. Further, the decrease in TE induced by the CO2 stimulus was in direct proportion to the inspired CO2 concentration. Thus 3% CO2 shortened TE by 1.82 +/- 0.93 (SD) s, and 9% CO2 by 3.44 +/- 1.53 s. Changes in TE occurred in the absence of associated changes in either tidal volume or inspiratory time. After CBD, test breaths of CO2 failed to shorten TE during VB. We conclude that the carotid bodies have the ability to mediate changes in the timing of inspiratory onset in response to a transient CO2 stimulus.     

Respiratory load compensation in infants.

We have studied the respiratory compensation for elastic loads in 15 term and preterm infants. Elastic loads, approximately equal to the infant's effective elastance, were applied to the airway for five breaths while tidal volume and mask pressure were monitored. Motion of the rib cage and abdomen were monitored simultaneously with magnetometers. The studies were done both in active or REM sleep and in quiet or non-REM sleep. During quiet sleep the load immediately reduced the tidal volume by about 50% but a progressive increase in tidal volume occurred over the next four loaded breaths. During active sleep load compensation was disorganized with respect to both tidal volume and frequency, and compensation was significantly less. Active sleep was also characterized by marked rib cage distortion. We suggest that during active sleep there is tonic inhibition of the intercostal muscles, allowing the diaphragm to distort the rib cage. This distortion impairs load compensation by a direct mechanical effect and indirectly by initiating an intercostal-phrenic reflex.     

Respiratory Sinus Arrhythmia as an Index of Vagal Activity during Stress in Infants: Respiratory Influences and Their Control

Respiratory sinus arrhythmia (RSA) is related to cardiac vagal outflow and the respiratory pattern. Prior infant studies have not systematically examined respiration rate and tidal volume influences on infant RSA or the extent to which infants'' breathing is too fast to extract a valid RSA. We therefore monitored cardiac activity, respiration, and physical activity in 23 six-month old infants during a standardized laboratory stressor protocol. On average, 12.6% (range 0–58.2%) of analyzed breaths were too short for RSA extraction. Higher respiration rate was associated with lower RSA amplitude in most infants, and lower tidal volume was associated with lower RSA amplitude in some infants. RSA amplitude corrected for respiration rate and tidal volume influences showed theoretically expected strong reductions during stress, whereas performance of uncorrected RSA was less consistent. We conclude that stress-induced changes of peak-valley RSA and effects of variations in breathing patterns on RSA can be determined for a representative percentage of infant breaths. As expected, breathing substantially affects infant RSA and needs to be considered in studies of infant psychophysiology.     

Regional expiratory flow limitation studied with Technegas in asthma.

Regional expiratory flow limitation (EFL) may occur during tidal breathing without being detected by measurements of flow at the mouth. We tested this hypothesis by using Technegas to reveal sites of EFL. A first study (study 1) was undertaken to determine whether deposition of Technegas during tidal breathing reveals the occurrence of regional EFL in induced bronchoconstriction. Time-activity curves of Technegas inhaled during 12 tidal breaths were measured in four asthmatic subjects at control conditions and after exposure to inhaled methacholine at a dose sufficient to abolish expiratory flow reserve near functional residual capacity. A second study (study 2) was conducted in seven asthmatic subjects at control and after three increasing doses of methacholine to compare the pattern of Technegas deposition in the lung with the occurrence of EFL. The latter was assessed at the mouth by comparing tidal with forced expiratory flow or with the flow generated on application of a negative pressure. Study 1 documented enhanced and spotty deposition of Technegas in the central lung regions with increasing radioactivity during tidal expiration. This is consistent with increased impaction of Technegas on the airway wall downstream from the flow-limiting segment. Study 2 showed that both methods based on analysis of flow at the mouth failed to detect EFL at the time spotty deposition of Technegas occurred. We conclude that regional EFL occurs asynchronously across the lung and that methods based on mouth flow measurements are insensitive to it.     

Role of nitric oxide during hyperventilation-induced bronchoconstriction in the guinea pig.

Airway function is largely preserved during exercise or isocapnic hyperventilation in humans and guinea pigs despite likely changes in airway milieu during hyperpnea. It is only on cessation of a hyperpneic challenge that airway function deteriorates significantly. We tested the hypothesis that nitric oxide, a known bronchodilator that is produced in the lungs and bronchi, might be responsible for the relative bronchodilation observed during hyperventilation (HV) in guinea pigs. Three groups of anesthetized guinea pigs were given saline and three groups given 50 mg/kg N(G)-monomethyl-L-arginine (L-NMMA), a potent nitric oxide synthase inhibitor. Three isocapnic ventilation groups included normal ventilation [40 breaths/min, 6 ml/kg tidal volume (VT)], increased respiratory rate only (150 breaths/min, 6 ml/kg VT), and increased respiratory rate and increased volume (100 breaths/min, 8 ml/kg VT). L-NMMA reduced expired nitric oxide in all groups. Expired nitric oxide was slightly but significantly increased by HV in the saline groups. However, inhibition of nitric oxide production had no significant effect on rate of rise of respiratory system resistance (Rrs) during HV or on the larger rise in Rrs seen 6 min after HV. We conclude that nitric oxide synthase inhibition has no effect on changes in Rrs, either during or after HV in guinea pigs.     

Lung elastic recoil during breathing at increased lung volume.

During dynamic hyperinflation with induced bronchoconstriction, there is a reduction in lung elastic recoil at constant lung volume (R. Pellegrino, O. Wilson, G. Jenouri, and J. R. Rodarte. J. Appl. Physiol. 81: 964-975, 1996). In the present study, lung elastic recoil at control end inspiration was measured in normal subjects in a volume displacement plethysmograph before and after voluntary increases in mean lung volume, which were achieved by one tidal volume increase in functional residual capacity (FRC) with constant tidal volume and by doubling tidal volume with constant FRC. Lung elastic recoil at control end inspiration was significantly decreased by approximately 10% within four breaths of increasing FRC. When tidal volume was doubled, the decrease in computed lung recoil at control end inspiration was not significant. Because voluntary increases of lung volume should not produce airway closure, we conclude that stress relaxation was responsible for the decrease in lung recoil.     

Phonospirometry for noninvasive measurement of ventilation: methodology and preliminary results.

We measured tracheal flow from tracheal sounds to estimate tidal volume, minute ventilation (VI), respiratory frequency, mean inspiratory flow (VT/TI), and duty cycle (TI/Ttot). In 11 normal subjects, 3 patients with unstable airway obstruction, and 3 stable asthmatic patients, we measured tracheal sounds and flow twice: first to derive flow-sound relationships and second to obtain flow-volume relationships from the sound signal. The flow-volume relationship was compared with pneumotach-derived volume. When subjects were seated, facing forward and with neck rotation, flexion, and standing, flow-volume relationship was within 15% of pneumotach-derived volume. Error increased with neck extension and while supine. We then measured ventilation without mouthpiece or nose clip from tracheal sounds during quiet breathing for up to 30 min. Normal results +/- SD revealed tidal volume = 0.37 +/- 0.065 liter, respiratory frequency = 19.3 +/- 3.5 breaths/min, VI = 6.9 +/- 1.2 l/min, VT/TI = 0.31 +/- 0.06 l/s, and TI/Ttot = 0.37 +/- 0.04. Unstable airway obstruction had large VI due to increased VT/TI. With the exception of TI/Ttot, variations in ventilatory parameters were closer to log normal than normal distributions and tended to be greater in patients. We conclude that phonospirometry measures ventilation reasonably accurately without mouthpiece, nose clip, or rigid postural constraints.     

Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits

Shen, X., S. J. Gunst, and R. S. Tepper. Effect oftidal volume and frequency on airway responsiveness in mechanically ventilated rabbits. J. Appl. Physiol.83(4): 1202-1208, 1997.We evaluated the effects of the rate andvolume of tidal ventilation on airway resistance (Raw) duringintravenous methacholine (MCh) challenge in mechanically ventilatedrabbits. Five rabbits were challenged at tidal volumes of 5, 10, and 20 ml/kg at a frequency of 15 breaths/min and also under static conditions(0 ml/kg tidal volume). Four rabbits were subjected to MCh challenge atfrequencies of 6 and 30 breaths/min with a tidal volume of 10 ml/kg andalso under static conditions. In both groups, the increase in Raw with MCh challenge was significantly greater under static conditions thanduring tidal ventilation at any frequency or volume. Increases in thevolume or frequency of tidal ventilation resulted in significant decreases in Raw in response to MCh. We conclude that tidal breathing suppresses airway responsiveness in rabbits in vivo. The suppression ofnarrowing in response to MCh increases as the magnitude of the volumeor the frequency of the tidal oscillations is increased. Our findingssuggest that the effect of lung volume changes on airway responsivenessin vivo is primarily related to the stretch of airway smooth muscle.

     

Reflex compensation of voluntary inspiration when immersion changes diaphragm length

When immersion alters inspiratory muscle operating lengths, spontaneously breathing humans maintain a constant tidal volume by reflex adjustment of inspiratory muscle activation (Reid et al. J. Appl. Physiol. 58: 1136-1142, 1985). We term this the operational length compensation reflex. The present experiment demonstrates that similar adjustments occur during voluntary respiratory maneuvers. Each of seven naive subjects sat in a tank with water at hip level. We trained them to reproduce an inspired volume (+/- 10%) at constant inspiratory duration. They received verbal feedback during training but not during the experiment. We measured surface electromyograms (EMGs) of diaphragm and intercostal muscles and tidal volume. After the subjects were trained, we made repeated measurements of 10 trained breaths with water at the hip and then again after raising water level to the xiphoid (which decreases lung volume and increases operating length of the diaphragm). In 30 of 42 trials there was a substantial fall in peak diaphragm EMG. In 10 trials this was sufficient to prevent any change in tidal volume. Inspiratory flow was more closely regulated than tidal volume. Subjects were not aware of making adjustments in drive.     

Steady-state response of quadriplegic subjects to inspiratory resistive load

Normal subjects preserve tidal volume (VT) in the face of added inspiratory resistance by increasing maximal amplitude and duration of the rising phase of respiratory driving pressure (DP) and by changing the shape of this phase to one that is more concave to the time axis. To explore the possible role of chest wall afferents in mediating these responses, we determined averaged DP in eight quadriplegic subjects during steady-state unloaded breathing and while breathing through an inspiratory resistance (8.5 cmH2O X 1(-1) X s). As with normal subjects, quadriplegics preserved VT (loaded VT = 106% control) by utilizing all three mechanisms. However, prolongation of the inspiratory duration derived from the DP waveform (+22% vs. +42%) and shape response were significantly less in the quadriplegic subjects. Shape response was completely absent in subjects with C4 lesions. The results provide strong evidence that respiratory muscle spindles are responsible for shape response and that changes in afferent feedback from the chest wall play an important role in mediating inspiratory prolongation.     

Attenuation of induced bronchoconstriction in healthy subjects: effects of breathing depth.

The effects of breathing depth in attenuating induced bronchoconstriction were studied in 12 healthy subjects. On four separate, randomized occasions, the depth of a series of five breaths taken soon (approximately 1 min) after methacholine (MCh) inhalation was varied from spontaneous tidal volume to lung volumes terminating at approximately 80, approximately 90, and 100% of total lung capacity (TLC). Partial forced expiratory flow at 40% of control forced vital capacity (V(part)) and residual volume (RV) were measured at control and again at 2, 7, and 11 min after MCh. The decrease in V(part) and the increase in RV were significantly less when the depth of the five-breath series was progressively increased (P < 0.001), with a linear relationship. The attenuating effects of deep breaths of any amplitude were significantly greater on RV than V(part) (P < 0.01) and lasted as long as 11 min, despite a slight decrease with time when the end-inspiratory lung volume was 100% of TLC. In conclusion, in healthy subjects exposed to MCh, a series of breaths of different depth up to TLC caused a progressive and sustained attenuation of bronchoconstriction. The effects of the depth of the five-breath series were more evident on the RV than on V(part), likely due to the different mechanisms that regulate airway closure and expiratory flow limitation.