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Biomedical subjects

J A Dempsey

Publications and source records attributed to J A Dempsey.

At least 19 recordsLinked to original sources
PubMed1992

Respiratory muscle recruitment during selective central and peripheral chemoreceptor stimulation in awake dogs.

1. In four awake dogs we measured EMG activity of three inspiratory and four expiratory muscles during sustained central chemoreceptor stimulation (CO2 inhalation), and peripheral chemoreceptor stimulation (intravenous infusion of almitrine bismesylate (almitrine)). By using this selective pharmacological stimulation of the peripheral chemoreceptors and reversibly cold-blocking pulmonary stretch receptors, we were able to determine the effects of each type of stimulation on respiratory muscle recruitment in the absence of such complicating influences as pulmonary stretch receptor feedback, cerebral hypoxia or hypocapnia, and differences in breathing pattern. 2. During 10 min of steady-state hyperpnoea (minute ventilation VI, approximately twice eupnoea) caused by either hypercapnia or isocapnic stimulation of the carotid bodies with almitrine, all three inspiratory and all four expiratory muscles demonstrated significant and sustained elevations in EMG activity. 3. With both types of chemoreceptor stimulation, as tidal volume, VT, increased, so did the mean electrical activities of the crural diaphragm (r = 0.88), costal diaphragm (r = 0.93), parasternals (r = 0.82), triangularis sterni (r = 0.74), transversus abdominis (r = 0.77), external obliques (r = 0.68) and internal intercostals (r = 0.75). 4. In each dog, the response of ventilation and of the diaphragmatic EMG to a given level of central or peripheral chemoreceptor stimulation is highly reproducible from one test day to the next. On the other hand, accessory inspiratory and expiratory abdominal and rib cage muscles in two of the four dogs showed highly significant changes from day to day in the amount of their EMG activity at any given VT. 5. During steady-state ventilatory stimulation, 2 min intervals were chosen during which the two types of chemoreceptor stimulation had caused hyperpnoeas with similar values for VT, total time per breath (TTOT) and inspiratory time divided by the total time (TI/TTOT). Comparison of EMG activities during these matched hyperpnoeas revealed that there were no differences in the activities of any of the muscles between the two forms of stimulation. We conclude that peripheral chemoreceptor stimulation causes significant and sustained recruitment of expiratory muscles even in the absence of pulmonary feedback and that both expiratory and inspiratory muscles are recruited to the same extent during peripheral chemoreceptor stimulation as they are during an identical hyperpnoea caused by central chemoreceptor stimulation.

Almitrine↗
PubMed1992

Load compensation and respiratory muscle function during sleep.

The sleeping state places unique demands on the ventilatory control system. The sleep-induced increase in airway resistance, the loss of consciousness, and the need to maintain the sleeping state without frequent arousals require the presence of complex compensatory mechanisms. The increase in upper airway resistance during sleep represents the major effect of sleep on ventilatory control. This occurs because of a loss of muscle activity, which narrows the airway and also makes it more susceptible to collapse in response to the intraluminal pressure generated by other inspiratory muscles. The magnitude and timing of the drive to upper airway vs. other inspiratory pump muscles determine the level of resistance and can lead to inspiratory flow limitation and complete upper airway occlusion. The fall in ventilation with this mechanical load is not prevented, as it is in the awake state, because of the absence of immediate compensatory responses during sleep. However, during sleep, compensatory mechanisms are activated that tend to return ventilation toward control levels if the load is maintained. Upper airway protective reflexes, intrinsic properties of the chest wall, muscle length-compensating reflexes, and most importantly chemoresponsiveness of both upper airway and inspiratory pump muscles are all present during sleep to minimize the adverse effect of loading on ventilation. In non-rapid-eye-movement sleep, the high mechanical impedance combined with incomplete load compensation causes an increase in arterial PCO2 and augmented respiratory muscle activity. Phasic rapid-eye-movement sleep, however, interferes further with effective load compensation, primarily by its selective inhibitory effects on the phasic activation of postural muscles of the chest wall. The level and pattern of ventilation during sleep in health and disease states represent a compromise toward the ideal goal, which is to achieve maximum load compensation and meet the demand for chemical homeostasis while maintaining sleep state.

Animals↗
PubMed1992

Vagal contributions to respiratory muscle activity during eupnea in the awake dog.

We examined the effects of reversible vagal cooling on respiratory muscle activities in awake chronically instrumented tracheotomized dogs. We specifically analyzed electromyographic (EMG) activity and its ventilatory correlates, end-expiratory lung volume (EELV) and diaphragmatic resting length via sonomicrometry. Elimination of phasic and tonic mechanoreceptor activity by vagal cooling doubled the EMG activity of the costal, crural, and parasternal muscles, with activation occurring sooner relative to the onset of inspiratory flow. Diaphragmatic postinspiration inspiratory activity in the intact dog coincided with a brief mechanical shortening of the diaphragm during early expiration; vagal blockade removed both the electrical activity and the mechanical shortening. Vagal blockade also doubled the EMG activity of a rib cage expiratory muscle, the triangularis sterni, but reduced that of an abdominal expiratory muscle, the transversus abdominis. Within-breath electrical activity of both muscles occurred sooner relative to the onset of expiratory flow during vagal blockade. Vagal cooling was also associated with a 12% increase in EELV and a 5% decrease in end-expiratory resting length of the diaphragm. We conclude that vagal input significantly modulates inspiratory and expiratory muscle activities, which help regulate EELV efficiently and optimize diaphragmatic length during eupneic breathing in the awake dog.

Afferent Pathways↗
PubMed1992

Vagal modulation of respiratory muscle activity in awake dogs during exercise and hypercapnia.

Using chronically instrumented awake tracheotomized dogs, we examined the contributions of vagal feedback to respiratory muscle activities, both electrical and mechanical, during normoxic hypercapnia (inspired CO2 fraction = 0.03, 0.04, 0.05, and 0.06) and during mild treadmill exercise (3, 4.3, and 6.4 km/h). Cooling exteriorized vagal loops eliminated both phasic and tonic mechanoreceptor input during either of these hyperpneas. At a given chemical or locomotor stimulus, vagal cooling caused a further increase in costal, crural, parasternal, and rib cage expiratory (triangularis sterni) muscles. No further change in abdominal expiratory muscle activity occurred secondary to vagal cooling during these hyperpneas. However, removal of mechanoreceptor input during hypercapnia was not associated with consistent changes in end-expiratory lung volume, as measured by the He-N2 rebreathe technique. We conclude that during these hyperpneas 1) vagal input is not essential for augmentation of expiratory muscle activity and 2) decrements in abdominal expiratory muscle activity may be offset by increments in rib cage expiratory muscle activity and contribute to the regulation of end-expiratory lung volume.

Afferent Pathways↗
PubMed1992

Oxygen cost of exercise hyperpnea: measurement.

To quantitate the O2 cost of maximal exercise hyperpnea, we required eight healthy adult subjects to mimic, at rest, the important mechanical components of submaximal and maximal exercise hyperpnea. Expired minute ventilation (VE), transpulmonary and transdiaphragmatic (Pdi) pressures, and end-expiratory lung volume (EELV) were measured during exercise at 70 and 100% of maximal O2 uptake. At rest, subjects were given visual feedback of their exercise transpulmonary pressure-tidal volume loop (WV), breathing frequency, and EELV, which they mimicked repeatedly for 5 min per trial over several trials, while hypocapnia was prevented. The change in total body O2 uptake (VO2) was measured and presumed to represent the O2 cost of the hyperpnea. In 61 mimicking trials with VE of 115-167 l/min and WV of 124-544 J/min, VE, WV, duty cycle of the breath, and expiratory gastric pressure (Pga) integrated with respect to time (integral of Pga.dt/min) were not different from those observed during maximum exercise. integral of Pdi.dt/min was 14% less and EELV was 6% greater during maximum exercise than during mimicking. The O2 cost measurements within a subject were reproducible over 3-12 trials (coefficient of variation +/- 10% range 5-16%). The O2 costs of hyperpnea correlated highly and positively with VE and WV and less, but significantly, with integral of Pdi.dt and integral of Pga.dt. The O2 cost of VE rose out of proportion to the increasing hyperpnea, so that between 70 and 100% of maximal VO2 delta VO2/delta VE increased 40-60% (1.8 +/- 0.2 to 2.9 +/- 0.1 ml O2/l VE) as VE doubled.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Oxygen cost of exercise hyperpnea: implications for performance.

We addressed two questions concerned with the metabolic cost and performance of respiratory muscles in healthy young subjects during exercise: 1) does exercise hyperpnea ever attain a "critical useful level"? and 2) is the work of breathing (WV) at maximum O2 uptake (VO2max) fatiguing to the respiratory muscles? During progressive exercise to maximum, we measured tidal expiratory flow-volume and transpulmonary pressure- (Ptp) volume loops. At rest, subjects mimicked their maximum and moderate exercise Ptp-volume loops, and we measured the O2 cost of the hyperpnea (VO2RM) and the length of time subjects could maintain reproduction of their maximum exercise loop. At maximum exercise, the O2 cost of ventilation (VE) averaged 10 +/- 0.7% of the VO2max. In subjects who used most of their maximum reserve for expiratory flow and for inspiratory muscle pressure development during maximum exercise, the VO2RM required 13-15% of VO2max. The O2 cost of increasing VE from one work rate to the next rose from 8% of the increase in total body VO2 (VO2T) during moderate exercise to 39 +/- 10% in the transition from heavy to maximum exercise; but in only one case of extreme hyperventilation, combined with a plateauing of the VO2T, did the increase in VO2RM equal the increase in VO2T. All subjects were able to voluntarily mimic maximum exercise WV for 3-10 times longer than the duration of the maximum exercise. We conclude that the O2 cost of exercise hyperpnea is a significant fraction of the total VO2max but is not sufficient to cause a critical level of "useful" hyperpnea to be achieved in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise↗
PubMed1992

Mechanical constraints on exercise hyperpnea in endurance athletes.

We determined how close highly trained athletes [n = 8; maximal oxygen consumption (VO2max) = 73 +/- 1 ml.kg-1.min-1] came to their mechanical limits for generating expiratory airflow and inspiratory pleural pressure during maximal short-term exercise. Mechanical limits to expiratory flow were assessed at rest by measuring, over a range of lung volumes, the pleural pressures beyond which no further increases in flow rate are observed (Pmaxe). The capacity to generate inspiratory pressure (Pcapi) was also measured at rest over a range of lung volumes and flow rates. During progressive exercise, tidal pleural pressure-volume loops were measured and plotted relative to Pmaxe and Pcapi at the measured end-expiratory lung volume. During maximal exercise, expiratory flow limitation was reached over 27-76% of tidal volume, peak tidal inspiratory pressure reached an average of 89% of Pcapi, and end-inspiratory lung volume averaged 86% of total lung capacity. Mechanical limits to ventilation (VE) were generally reached coincident with the achievement of VO2max; the greater the ventilatory response, the greater was the degree of mechanical limitation. Mean arterial blood gases measured during maximal exercise showed a moderate hyperventilation (arterial PCO2 = 35.8 Torr, alveolar PO2 = 110 Torr), a widened alveolar-to-arterial gas pressure difference (32 Torr), and variable degrees of hypoxemia (arterial PO2 = 78 Torr, range 65-83 Torr). Increasing the stimulus to breathe during maximal exercise by inducing either hypercapnia (end-tidal PCO2 = 65 Torr) or hypoxemia (saturation = 75%) failed to increase VE, inspiratory pressure, or expiratory pressure. We conclude that during maximal exercise, highly trained individuals often reach the mechanical limits of the lung and respiratory muscle for producing alveolar ventilation. This level of ventilation is achieved at a considerable metabolic cost but with a mechanically optimal pattern of breathing and respiratory muscle recruitment and without sacrifice of a significant alveolar hyperventilation.

Adult↗
PubMed1992

Determinants of poststimulus potentiation in humans during NREM sleep.

To test whether active hyperventilation activates the "afterdischarge" mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.

Carbon Dioxide↗
PubMed1992

Demand vs. capacity in the healthy pulmonary system.

This review examines the lung and chest wall adaptation to exercise in health in persons of widely varying degrees of fitness. First we examine the regulation of breathing and gas exchange in the sedentary young adult who shows a near perfect regulation of alveolar gases, ventilation to perfusion distribution, diffusion equilibrium in the lung during all levels of exercise. This individual's respiratory muscles are also ideally recruited both tonically and phasically so as to meet multi-faceted postural, locomotory and respiratory demands. The topic of plasticity in the pulmonary system is discussed with specific reference to the effects of physical training and athleticism. The key point made here is that both homeostasis of gas transport and mechanical efficiency, with which the pulmonary system meets the demands of muscular exercise will depend upon the ability to maintain a significant margin between demand vs. structural capacity. Pulmonary diffusion capacity and at least some aspects of respiratory muscle function seem to be "overbuilt" in the young untrained adult. This margin of safety no longer prevails as the athlete becomes fitter. The cause is to be found in the relative lack of adaptability of the lung and chest wall to the training stimulus. Examples of demand coming very close or exceeding the capacity of the pulmonary system include the highly trained young endurance athlete and the aged athlete. Examples of "failure" or near failure in the pulmonary system's response to exercise include: a) exercise induced arterial hypoxemia via diffusion limitation; b) diaphragmatic fatigue in endurance exercise; c) expiratory flow limitation at VO2max.; d) achieving the capacity of inspiratory muscles for pressure generation at VO2max. and e) oxygen cost of breathing which is in excess of 15% of VO2max. in those athletes who experience the most mechanical limitation.

Adaptation, Physiological↗
PubMed1991

Characterization of the opa (class 5) gene family of Neisseria meningitidis.

Class 5 outer membrane proteins of Neisseria meningitidis show both phase- and antigenic variation of expression. The proteins are encoded by a family of opa genes that share a conserved framework interspersed with three variable regions, designated the semivariable (SV) region and hypervariable regions 1 (HV1) and 2 (HV2). In this study, we determined the number and DNA sequence of all of the opa genes of meningococcal strain FAM18, to assess the structural and antigenic variability in the family of proteins made by one strain. Pulsed field electrophoresis and Southern blotting showed that there are four opa genes in the FAM18 chromosome, and that they are not tightly clustered. DNA sequence analysis of the four cloned genes showed a modest degree of diversity in the SV region and more extensive differences in the HV1 and HV2 regions. There were four versions of HV1 and three versions of HV2 among the four genes. Each of the FAM18 opa loci contained a gene with a unique combination of SV, HV1, and HV2 sequences. We used lambda gt11 cloning and synthetic peptides to demonstrate that HV2 sequences completely encode the epitopes for two monoclonal antibodies specific for different class 5 proteins of FAM18.

Amino Acid Sequence↗
PubMed1991

Physical map of the chromosome of Neisseria gonorrhoeae FA1090 with locations of genetic markers, including opa and pil genes.

A physical map of the chromosome of Neisseria gonorrhoeae FA1090 has been constructed. Digestion of strain FA1090 DNA with NheI, SpeI, BglII, or PacI resulted in a limited number of fragments that were resolved by contour-clamped homogeneous electric field electrophoresis. The estimated genome size was 2,219 kb. To construct the map, probes corresponding to single-copy chromosomal sequences were used in Southern blots of digested DNA separated on pulsed-field gels, to determine how the fragments from different digests overlapped. Some of the probes represented identified gonococcal genes, whereas others were anonymous cloned fragments of strain FA1090 DNA. By using this approach, a macrorestriction map of the strain FA1090 chromosome was assembled, and the locations of various genetic markers on the map were determined. Once the map was completed, the repeated gene families encoding Opa and pilin proteins were mapped. The 11 opa loci of strain FA1090 were distributed over approximately 60% of the chromosome. The pil loci were more clustered and were located in two regions separated by approximately one-fourth of the chromosome.

Bacterial Outer Membrane Proteins↗
PubMed1991

Effect of sleep-induced increases in upper airway resistance on respiratory muscle activity.

To investigate the response of inspiratory and expiratory muscles to naturally occurring inspiratory resistive loads in the absence of conscious control, five male "snorers" were studied during non-rapid-eye-movement (NREM) sleep with and without continuous positive airway pressure (CPAP). Diaphragm (EMGdi) and scalene (EMGsc) electromyographic activity were monitored with surface electrodes and abdominal EMG activity (EMGab) with wire electrodes. Subjects were studied in the following conditions: 1) awake, 2) stage 2 sleep, 3) stage 3/4 sleep, 4) CPAP during stage 3/4 sleep, 5) CPAP plus end-tidal CO2 pressure (PETCO2) isocapnic to stage 2 sleep, and 6) CPAP plus PETCO2 isocapnic to stage 3/4 sleep. Inspired pulmonary resistance (RL) at peak flow rate and PETCO2 increased in all stages of sleep. Activity of EMGdi, EMGsc, and EMGab increased significantly in stage 3/4 sleep. CPAP reduced RL at peak flow, increased tidal volume and expired ventilation, and reduced PETCO2. EMGdi and EMGsc were reduced, and EMGab was silenced. During CPAP, with CO2 added to make PETCO2 isocapnic to stage 3/4 sleep, EMGsc and EMGab increased, but EMGdi was augmented in only one-half of the trials. EMG activity in this condition, however, was only 75% (EMGsc) and 43% (EMGab) of the activity observed during eupneic breathing in stage 3/4 sleep when PETCO2 was equal but RL was much higher. We conclude that during NREM sleep 1) inspiratory and expiratory muscles respond to internal inspiratory resistive loads and the associated dynamic airway narrowing and turbulent flow developed throughout inspiration, 2) some of the augmentation of respiratory muscle activity is also due to the hypercapnia that accompanies loading, and 3) the abdominal muscles are the most sensitive to load and CO2 and the diaphragm is the least sensitive.

Airway Resistance↗
PubMed1991

Ventilatory afterdischarge in the awake goat.

Ventilatory afterdischarge (VAD) has been defined as a persistent gradually diminishing elevation of ventilatory activity that occurs after withdrawal of a variety of respiratory stimuli. The phenomenon has been well documented in the anesthetized cat, piglet, and lamb in response to electrical stimulation of the carotid sinus nerve. We sought to determine whether VAD could be demonstrated in the standing awake goat (n = 7) by use of an extracorporeal circuit to provide square-wave physiological stimulation of the carotid chemoreceptor (carotid body PO2 40 Torr). After 5 min of isolated carotid body stimulation, the mean time constants for diminishing inspired minute ventilation, tidal volume, and respiratory frequency were 27.7, 34.5, and 25.5 s, respectively. These results indicate that VAD does exist in the awake goat model. A critical factor for the demonstration of VAD is the maintenance of systemic arterial PCO2 (isocapnia) during the period of increased ventilatory activity. If arterial PCO2 is allowed to decrease even slightly during the hyperventilation, the magnitude and duration of VAD are greatly attenuated.

Animals↗
PubMed1991

Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population.

In 29 older (69 +/- 1 yr), physically active subjects (VO2max = 44 +/- 2 ml.kg-1.min-1), we determined the effect of an age-related decline in elastic lung recoil (i.e., Vmax50 = 65% of 30-yr-old adults) on the ventilatory response to progressive exercise. More specifically, we assessed if expiratory airflow limits were achieved and how this may modulate the regulation of end-expiratory lung volume (EELV). We found that with only mild to moderate (50 to 75% VO2max) exercise, the mean EELV was reduced 0.38 +/- 0.07 L, and that expiratory flow limitation was present over 25 +/- 4% of the VT. In 11 subjects during this intensity of exercise, EELV was within their closing capacity. As exercise intensity progressed, VT plateaued at 58 +/- 2% of the vital capacity, and increased expiratory air flow rates were achieved by significantly increasing the EELV back to near resting levels, thereby moving a portion of the expiratory tidal flow-volume envelope away from the constraints of the effort independent portion of the maximal flow-volume curve. During heavy exercise, end-inspiratory lung volume (EILV) approached 90% of TLC. To achieve greater expiratory flow with maximal exercise, EELV remained similar to the previous intensity, and a significantly greater portion of the tidal expiratory flow-volume envelope (greater than 40% of the VT) became flow-limited. Despite this significant expiratory limitation, a rise in EELV, and an EILV approaching TLC, TI/Ttot remained constant throughout exercise, and the ventilatory response for the metabolic demand (VA/VCO2) was appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Mechanical constraints on exercise hyperpnea in a fit aging population.

We studied 12 physically fit (VO2 max = 44 ml.kg-1.min-1) older subjects (age = 63 to 77 yr) who showed the usual age-related declines in lung function (i.e., reduced maximal expiratory flow rates, vital capacity and increased functional residual capacity, closing capacity, and residual volume). We measured the optimal transpulmonary pressures for maximal expiratory airflow and the capacity of the muscles of inspiration for developing pleural pressure (taking into account the effects of lung volume and flow rate). Within these mechanical constraints to ventilation we plotted tidal pleural pressure-volume loops for mild through maximal exercise according to a measured end-expiratory lung volume (EELV). We found EELV to decrease a mean of 0.26 +/- 0.09 L and maximal effective pleural pressures to be reached in nine subjects near EELV with only light to moderate exercise intensities, whereas peak inspiratory pressure was only 45% of the capacity for pressure generation. With progressive increases in exercise intensity, EELV increased, and pleural pressures encroached to a greater extent on the maximal effective pressures; however, they remained effective in the majority of subjects. During maximal exercise EELV was 0.13 +/- 0.10 L greater than resting values, 20% of the Vt reached maximal effective pressures, and 83% of the capacity for inspiratory pressure was achieved. Three subjects significantly surpassed their maximal effective expiratory pressures, and four subjects achieved 95 to 100% of the capacity for inspiratory pressure generation. These subjects also showed no further increase in ventilation while breathing 0.02 to 0.05 FICO2 at maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Effect of hypercapnia on total pulmonary resistance during wakefulness and during NREM sleep.

We investigated the effect of different levels of hypercapnia on total pulmonary resistance (RL) in 13 subjects ranging from nonsnorers with low RL to snorers with high RL and dynamic narrowing of the upper airway during inspiration. Added CO2 was adjusted to achieve a steady-state increase in PETCO2 of +2, +4, or +6 mm Hg. RL was measured at peak inspiratory flow (RLpf), at maximal resistance within breath (RLmax), and at 10 equally spaced points within inspiration in several trials. During wakefulness, hypercapnia was associated with decreased RLmax. During steady state +6 mm Hg hypercapnia, RLmax decreased by 30% (p less than 0.01). During NREM sleep, low levels of hypercapnia did not affect RL. However, +6 mm Hg hypercapnia was associated with decreased RLmax in six of eight subjects (p = 0.07), especially in subjects with high RLmax during room air breathing. The effects of hypercapnia on RLpf paralleled its effect on RLmax. We concluded that (1) the decrease in RL during awake hypercapnia suggests an increase in upper airway dimensions and stiffness, (2) the absence of increased RL during low level NREM hypercapnia (despite the increase in inspiratory flows and collapsing pressures) also suggests an increase in upper airway dimensions and stiffness, and (3) upper airway dilating muscles appear to be recruited in a coordinated fashion with inspiratory muscles in normal humans during NREM sleep. The implications of these findings in patients with obstructive sleep apnea are not clear at this point.

Airway Resistance↗
PubMed1991

Role of airway mechanoreceptors in the inhibition of inspiration during mechanical ventilation in humans.

The purpose of this study was to demonstrate a neuromechanical inhibitory effect on respiratory muscle activity during mechanical ventilation and to determine whether upper and lower airway receptors provide this inhibitory feedback. Several protocols were completed during mechanical ventilation: (1) positive and negative pressure changes in the upper airway, (2) airway anesthesia to examine the consequences of receptor blockade on respiratory muscle activity, (3) increasing FRC with positive end-expiratory pressure to study the effect of hyperinflation or stretch on respiratory muscle activity, and (4) use of heart-lung transplant patients to determine the effects of vagal denervation on respiratory muscle activity. All subjects were mechanically hyperventilated with positive pressure until inspiratory muscle activity was undetectable and the end-tidal PCO2 decreased to less than 30 mm Hg. End-tidal PCO2 (PETCO2) was increased by either adding CO2 to the inspired gas or decreasing tidal volume (50 ml/min). The PETCO2 where a change in inspiratory muscle activity occurred was taken as the recruitment threshold (PCO2RT). Neuromechanical feedback caused significant inspiratory muscle inhibition during mechanical ventilation, as evidenced by the difference between PCO2RT and PETCO2 during spontaneous eupnea (45 +/- 4 versus 39 +/- 4 mm Hg) and a lower PCO2RT when tidal volume was reduced with a constant frequency and fraction of inspired CO2. Recruitment threshold was unchanged during positive and negative pressure ventilation, during upper and lower airway anesthesia, and in vagally denervated lung transplant patients. These findings demonstrate that neuromechanical feedback causes highly significant inhibition of inspiratory muscle activity during mechanical ventilation; upper and lower airway receptors do not appear to mediate this effect.

Adult↗