Influence of end-expiratory level and tidal volume on gravitational ventilation distribution during tidal breathing in healthy adults

Our understanding of regional filling of the lung and regional ventilation distribution is based on studies using stepwise inhalation of radiolabelled tracer gases, magnetic resonance imaging and positron emission tomography. We aimed to investigate whether these differences in ventilation distribution at different end-expiratory levels (EELs) and tidal volumes (V _Ts) held also true during tidal breathing. Electrical impedance tomography (EIT) measurements were performed in ten healthy adults in the right lateral position. Five different EELs with four different V _Ts at each EEL were tested in random order, resulting in 19 combinations. There were no measurements for the combination of the highest EEL/highest V _T. EEL and V _T were controlled by visual feedback based on airflow. The fraction of ventilation directed to different slices of the lung (VENT_RL1?VENT_RL8) and the rate of the regional filling of each slice versus the total lung were analysed. With increasing EEL but normal tidal volume, ventilation was preferentially distributed to the dependent lung and the filling of the right and left lung was more homogeneous. With increasing V _T and maintained normal EEL (FRC), ventilation was preferentially distributed to the dependent lung and regional filling became more inhomogeneous (p < 0.05). We could demonstrate that regional and temporal ventilation distribution during tidal breathing was highly influenced by EEL and V _T.     

Breathing mechanics during exercise with added dead space reflect mechanisms of ventilatory control

Small increases in external dead space (V_D) augment the exercise ventilatory response via a neural mechanism known as short-term modulation (STM). We hypothesized that breathing mechanics would differ during exercise, increased V_D and STM. Men were studied at rest and during cycle exercise (10–50 W) without (Control) and with added V_D (200–600 ml). With added V_D, V_T increased via increased end-inspiratory lung volume (EILV), with no change in end-expiratory lung volume (EELV), indicating recruitment of inspiratory muscles only. With exercise, V_T increased via both decreased EELV and increased EILV, indicating recruitment of both expiratory and inspiratory muscles. A significant interaction between the effects of exercise and V_D on mean inspiratory flow indicated that the augmented exercise ventilatory response with added V_D (i.e. STM) resulted from increased drive to the inspiratory muscles. These results reveal different patterns of respiratory muscle recruitment among experimental conditions. Hence, we conclude that fundamental differences exist in the neural control of ventilatory responses during exercise, increased V_D and STM.     

Closing volume: a reappraisal (1967–2007)

Measurement of closing volume (CV) allows detection of presence or absence of tidal airway closure, i.e. cyclic opening and closure of peripheral airways with concurrent (1) inhomogeneity of distribution of ventilation and impaired gas exchange; and (2) risk of peripheral airway injury. Tidal airway closure, which can occur when the CV exceeds the end-expiratory lung volume (EELV), is commonly observed in diseases characterised by increased CV (e.g. chronic obstructive pulmonary disease, asthma) and/or decreased EELV (e.g. obesity, chronic heart failure). Risk of tidal airway closure is enhanced by ageing. In patients with tidal airway closure (CV > EELV) there is not only impairment of pulmonary gas exchange, but also peripheral airway disease due to injury of the peripheral airways. In view of this, the causes and consequences of tidal airway closure are reviewed, and further studies are suggested. In addition, assessment of the “open volume”, as opposed to the “closing volume”, is proposed because it is easier to perform and it requires less equipment.     

The effect of lung inflation on the control of respiratory frequency in the neonate

1. We have measured the relationship between tidal volume (V_T) and the duration of inspiration (T_i) and expiration (T_e) for individual breaths (30 in each steady state).

2. Ten pre-term and ten term infants were studied during steady state while breathing 21% O₂, then 21% O₂ plus 2 and 4% CO₂.

3. In all infants, the average T_i at the various chemical drives was remarkably constant, and did not decrease as the tidal volume increased. However, at any given level of respiratory drive, there was a slightly positive correlation of V_T with T_i and T_e in 95% of the cases.

4. In four pre-term and two term infants, T_e increased with increasing respiratory drive. In these infants, therefore, instantaneous respiratory frequency (1/(T_i + T_e)) actually decreased as lung volume increased.

5. We suggest that T_i is independent of V_T within the range of volumes studied (up to 2 times the resting V_T) and that changes in instantaneous respiratory frequency (1/(T_i + T_e)) result from changes in T_e.

     

Measuring end-expiratory lung volume and pulmonary mechanics to detect early lung function impairment in rabbits

We investigated whether end-expiratory lung volume (EELV) or lung mechanical parameters are more sensitive for the detection of a compromised gas exchange during bronchoconstriction and after surfactant depletion. EELV was determined via SF(6) multiple breath wash-outs in mechanically ventilated rabbits while a positive end-expiratory pressure (PEEP) of 1, 3 or 7 cm H(2)O was maintained. Airway resistance (R(aw)) and parenchymal elastance (H) were estimated from the pulmonary input impedance measured at each PEEP level by means of forced oscillations. Measurements were repeated during i.v. methacholine (MCh) infusions and following lung injury induced by saline lavage. MCh induced marked elevations in R(aw), with no significant change in EELV or H at any PEEP. After lavage, the severity of hypoxia was reflected systematically in significant decreases in EELV at all PEEP levels (-42+/-13%, -26+/-4%, and -18+/-5% at 1, 3 and 7 cm H(2)O, respectively), whereas compromised gas exchange was not associated with consistent changes in the mechanical parameters at a PEEP of 7 cm H(2)O (20+/-9% and 14+/-9% in R(aw) and H, respectively; p=0.2). We conclude that R(aw) is the only sensitive indicator for the detection of a compromised lung function during MCh infusions, whereas the estimation of EELV is necessary to follow the progression of a lung injury when a high PEEP level is applied.     

Respiratory inductive plethysmography accuracy at varying PEEP levels and degrees of acute lung injury

Background and objective: This study was performed to assess the accuracy of respiratory inductive plethysmographic (RIP) estimated lung volume changes at varying positive end-expiratory pressures (PEEP) during different degrees of acute respiratory failure.

Methods: Measurements of inspiratory tidal volume were validated in eight piglets during constant volume ventilation at incremental and decremental PEEP levels and with increasing severity of pulmonary injury. RIP accuracy was assessed with calibration from the healthy state, from the disease state as the measurement error was assessed, and at various PEEP levels.

Results: Best results (bias 3%, precision 7%) were obtained in healthy animals. RIP accuracy decreased with progressing degrees of acute respiratory failure and was PEEP dependent, unless RIP was calibrated again. When calibration was performed in the disease state as the measurement error was assessed, bias was reduced but precision did not improve (bias – 2%, precision 9%).

Conclusions: RIP accuracy is within the accuracy range found in monitoring devices currently in clinical use. Most reliable results with RIP are obtained when measurements are preceded by calibration in pulmonary conditions that are comparable to the measurement period. When RIP calibration is not possible, fixed weighting of the RIP signals with species and subject size adequate factors is an alternative. Measurement errors should be taken into account with interpretation of small volume changes.     

Contribution of central and reflex nervous activity to the rapid increase in pulmonary ventilation at the start of muscular exercise in man

Summary To investigate the relative contributions of the central and peripheral neural drive to hyperventilation at the onset of muscular exercise, five volunteers were tested during the first ten breaths while performing both voluntary (VM) and passive (PM) ankle rotations with a frequency of 1 Hz and through an angle of 10°. Resulting breathing patterns for the two movements were compared. Hypocapnic hyperventilation, found in both PM and VM, indicated its neural origin. Respiratory changes were higher in VM than in PM. In both experimental conditions, increases in ventilation ( ) depended more on respiratory frequency (f) than on tidal volume (V _T). Moreover, increases inV _T adapted, breath-by-breath, to values lower than the initial ones, while increases inf rose progressively. Expiratory time was reduced more than inspiratory time (T _I); increases in inspiratory flow (V _T/T _I) depended to the same extent on changes in bothT _I andV _T. Increases in expiratory tidal volume were initially higher than in inspiratory tidal volume, thereby producing a reduction in functional residual capacity. Because PM respiratory changes could be considered to be of nervous reflex origin only, the identical breathing patterns in PM and VM indicated that the hyperventilation found also in VM was mainly of reflex origin. The increase in was considered to be dependent on a greater stimulus from muscle proprioreceptors.     

Lung mechanics are both dose and tidal volume dependant in LPS-induced lung injury

Endotoxin stimulus plays a significant role in various forms of acute lung injury (ALI) which may be exacerbated by mechanical ventilation. Here, we identify the temporal pathophysiologic sequence following inhaled lipopolysaccharide (LPS) and subsequently examine both LPS dose and V_T relationships. Rats received intratracheal LPS (3, 9 or 15 mg/kg) prior to mechanical ventilation (V_T = 6, 9 or 12 ml/kg) and measurement of forced impedance mechanics for up to 4 h. LPS-induced lung injury was achieved within the 15 min of LPS instillation with a 78% decrease in PaO₂ promptly followed by 30% deterioration in tissue elastance. Despite a 41% increase in total surfactant, the active disaturated phospholipid fraction decreased 3–7% with decreasing PaO₂ and tissue mechanics and with increases in total lung lavage protein (150%) and wet-to-dry lung weight ratio (10%). V_T = 12 ml/kg resulted in an additional deterioration in tissue resistance (130%) and elastance (63%). These results suggest that LPS-induced lung injury is both LPS dose and V_T sensitive, supporting a ‘two hit’ model of ALI.     

Compartmental chest wall volume changes during volitional hyperpnoea with constant tidal volume in healthy individuals

Prolonged high-intensity ventilation is associated with the development of rapid shallow breathing with decreased end-inspiratory volumes of all chest wall compartments. During respiratory muscle endurance training using normocapnic hyperpnoea, tidal volume (V_T) is normally kept constant. The aim of this study was to investigate possible changes in muscle recruitment during constant-V_T hyperpnoea, to assess potential mechanisms related to rapid shallow breathing. Ten healthy subjects performed 1 h of normocapnic hyperpnoea at 70% of maximal voluntary ventilation. Chest wall volume changes were assessed by optoelectronic plethysmography. End-inspiratory (1.08 ± 0.18 versus 0.96 ± 0.27 l, p = 0.017) and end-expiratory volumes (−0.13 ± 0.15 versus −0.31 ± 0.19 l, p = 0.007) of the pulmonary ribcage decreased significantly and lung function and respiratory muscle strength were reduced (all p < 0.05). Since with forced, constant V_T only the inspiratory rib cage muscles were unable to sustain end-inspiratory volume of their compartment, inspiratory rib cage muscles are the most likely candidate responsible for the development of rapid shallow breathing.     

A new instrument for the measurement of rib cage and abdomen circumference variation in respiration at rest and during exercise

A simple and inexpensive new extensometer for measuring changes in chest wall circumference during human respiratory movements is presented. The instrument detects the delay between ultrasound emission and reception at opposite ends of two rubber tubes encircling the rib cage and abdomen. Assuming a two degree of freedom model of the chest wall and employing an isovolume procedure for determination of volume-motion coefficients, extensometer estimation of tidal volume (V _T) from changes of rib cage and abdomen circumference was compared with spirometer measurements at rest and during exercise on a cycle ergometer (55–155 W) in six subjects and, in four of them, on a treadmill (4–12 km·h^–1). In three subjects hypercapnic hyperpnoea at rest was also studied. The slopes of the linear relationship between extensometer and spirometerV _T (litres) averaged 0.9967 (SD 0.0117) (r ² = 0.995–0.998;n = 90–143) for cycle ergometer exercise, 1.0072 (SD 0.0078) (r ² = 0.991–0.998;n = 75–93) for treadmill exercise and 0.9942 (SD 0.0188) (r ² = 0.997–0.998;n = 18–25) for hypercapnic hyperpnoea. In all instances the slope of the regression line was consistent with the model of the identity line (slope = 1). The changes in end-expiratory lung volume between respiration at rest and during exercise were determined by the extensometers, and were nearly identical (98.4% on average) to those measured with the spirometer (r ² = 0.945;n = 24). It is concluded that determination of chest wall circumference with this new instrument is suitable for quantitative measurement of ventilation and lung volume variations in humans under most physiological conditions.     

Bronchodilator effect on ventilatory,pulmonary gas exchange,and heart rate kinetics during high-intensity exercise in COPD

Respiratory mechanical abnormalities in patients with chronic obstructive pulmonary disease (COPD) may impair cardiodynamic responses and convective oxygen delivery during exercise, resulting in slower ventilatory, pulmonary gas exchange (PGE), and heart rate (HR) kinetics compared with normal. We reasoned that bronchodilators and the attendant reduction of operating lung volumes should accelerate ventilatory, PGE, and HR kinetics in the transition from rest to high-intensity exercise. Twelve clinically stable COPD patients undertook constant-work rate cycle testing at 75% of each individual’s maximum work capacity after receiving either combined nebulized bronchodilators (BD) or placebo (PL), randomly. Mean response time (MRT) and amplitude of slow component for oxygen uptake (V′O₂), carbon dioxide production (V′CO₂), ventilation (V′_E), and HR together with operating dynamic end-expiratory lung volume (EELV) were measured. Resting and exercise EELV decreased significantly by 0.38 L after BD compared with PL. After BD, V′O₂, V′CO₂, V′_E, and HR MRT accelerated (p < 0.05) by an average of 12, 22, 27, and 22 s, respectively (i.e., 15, 18, 22 and 27%, respectively). The slow component for V′O₂ declined by an average of 55 ml/min compared with PL. Speeded MRT for V′O₂ correlated with indices of reduced lung hyperinflation, such as resting EELV (r = −0.64, p = 0.025) and EELV at isotime (r = −0.77, p = 0.0032). The results confirm an important interaction between abnormal dynamic respiratory mechanics and indices of cardio-circulatory function in the rest-to-exercise transition in COPD patients.     

Transient hypoxia: Ventilatory response after vagotomy and during artificial phasic inflation

The early ventilatory response to transient hypoxia was examined in the anaesthetized rabbit. In intact spontaneously breathing animals, an increase in tidal volume (V _T) with an accompanying slight increase in inspiratory duration (T _I) and a decrease in the expiratory duration (T _E) was observed. After vagotomy, the ventilatory response was distinguished by a greater increase inV _T and a significant decrease inT _I andT _E.In another group of artificially ventilated rabbits, an increase in inspiratory volume with a simultaneous decrease in breathing frequency was found to involve a smaller reflex increase in phrenic inspiratory discharge after onset of transient hypoxia.These observations suggest that afferents from pulmonary vagal stretch receptors inhibit those from arterial chemoreceptors.     

Systemic filling pressure in the intact circulation determined with a slow inflation procedure

In eight mechanically ventilated, anaesthetized pigs weighing 10.3 ± 0.8 kg (mean ± SD) we studied the effect of the inflation time of the lung on the estimation of the mean systemic filling pressure (P _sf) from the changes in venous return and central venous pressure during inflation of the lung. For this purpose we applied slow inflation procedures (SIP) to the lung with inflation times of 2.4, 4.8, 7.2, 9.6 and 12 s at tidal volumes (V _T) of 15 and 30 ml/kg. The data were compared with the values of P _sf obtained from inspiratory pause procedures (IPPs). A linear regression between venous return and central venous pressure applied during a SIP underestimated P _sf compared with the value obtained with IPPs. An exponential fit through the values of P _sf obtained from the different SIPs predicted an inflation time of about 15 s for an estimation of P _sf that is not different from the P _sf (IPP). The advantage of the SIP method is that the P _sf can be determined much faster than with the method based on IPPs. However, due to the rather long inflation time needed, the method may be only applicable under circumstances where neurohumoral control mechanisms are suppressed as during intensive care and anaesthesia. Received: 18 July 1995/Received after revision: 22 November 1995 /Accepted: 15 December 1995     

Determinants of pulmonary perfusion measured by electrical impedance tomography

Electrical impedance tomography (EIT) is a non-invasive imaging technique for detecting blood volume changes that can visualize pulmonary perfusion. The two studies reported here tested the hypothesis that the size of the pulmonary microvascular bed, rather than stroke volume (SV), determines the EIT signal. In the first study, the impedance changes relating to the maximal pulmonary pulsatile blood volume during systole (Z_sys) were measured in ten healthy subjects, ten patients diagnosed with chronic obstructive pulmonary disease, who were considered to have a reduced pulmonary vascular bed, and ten heart failure patients with an assumed low cardiac output but with a normal lung parenchyma. Mean Z_sys (SD) in these groups was 261 (34)×10^–5, 196 (39)×10^–5 (P<0.001) and 233 (61)×10^–5 arbitrary units (AU) (P=NS), respectively. In the second study, including seven healthy volunteers, Z_sys was measured at rest and during exercise on a recumbent bicycle while SV was measured by means of magnetic resonance imaging. The Z_sys at rest was 352 (53)×10^–5 and 345 (112)×10^–5 AU during exercise (P=NS), whereas SV increased from 83 (21) to 105 (34) ml (P<0.05). The EIT signal likely reflects the size of the pulmonary microvascular bed, since neither a low cardiac output nor a change in SV of the heart appear to influence EIT.     

The effect of pulmonary stretch receptor activity on the respiratory response to ammonia-inhalation

The contribution of pulmonary stretch receptor (SR) activity to the changes in breathing pattern (f,V _T,t _I,t _E,t _I:t _E) following inhalation of ammonia vapour has been studied in rabbits at three levels of lung distension, i.e., three levels of SR activity, and during reversible SO₂-blockade of SR.The results show that the increase in breathing frequency (f) and the decrease in tidal volume (V _T) due to ammonia inhalation are almost identical for animals with and without blockade of SR, whereas the duration of inspiration and expiration (t _I,t _E) as well as their relationship (t _I:t _E) vary considerably, the variations dependeing on the level of SR activity. For a givent _I the expiration was longer in animals with SR intact than in animals with SR blocked.It is concluded that in rabbits the increased activity of SR after inhalation of ammonia counteracts significantly the predominant effects of irritant (deflation) receptor stimulation, thus rendering possible a longer expiration.     

Exercise breathing pattern during chronic altitude exposure

Summary Breathing pattern in response to maximal exercise was examined in four subjects during a 7-day acclimatisation to a simulated altitude of 4247 m (barometric pressure,PB = 59.5 kPa). Graded exercise tests to exhaustion were performed during normoxia (day 0), and on days 2 and 7 of hypoxia, respectively. Ventilation was significantly augmented in the hypoxic environment, as were both the mean inspiratory flow (V _T/T _I) and inspiratory duty cycle (T _I/T _TOT) components of it.V _I/T _I was increased due to a significant increase in tidal volume (VT) and a corresponding decrease in inspiratory time duration (TI). Throughout a range of exercise ventilation,T _I/T _TOT was increased due to an apparently greater decrease in expiratory time duration (T _E) with respect to TI. In all cases, the relation betweenV _T andT _I displayed a typical range 2 behaviour, with evidence of a range 3 occurring at very high ventilatory rates. There was essentially no difference observed in theV _T-T _I relation during exercise between the normoxic and hypoxic conditions. No significant changes were observed in the breathing pattern in response to exercise within the exposure period (from day 2 to day 7), although there was a discernible tendency to a higher stage 3 plateau by day 7 of altitude exposure.     

Inter-individual differences in breathing pattern at high levels of incremental cycling exercise in healthy subjects

Interindividual differences in the rate of changes in tidal volume (V_T) and respiratory frequency (f_R) were examined during a maximal incremental cycling exercise. The gain of the inspiratory off-switch reflex was inferred from the V_T vs. inspiratory duration (T_i) relationship. Some subjects also executed a static handgrip exercise, used as a “non-dynamic” exercise trial to study patterning of breathing.     

Medullary and carotid chemoreceptor interaction for mild stimuli

The interaction of medullary and carotid chemoreceptors during mild stimulation was investigated in 44 experiments on 6 chloralose-urethane anesthetized mongrel dogs using a donor-perfused, bilateral carotid sinus preparation. The donor dog breathed hypoxic mixtures (averageP _{a O 2} of 78 mm Hg) and the experimental animal breathed hypercapnic mixtures (averageP A _{CO 2} of 49 mm Hg) in order to separately or simultaneously stimulate both chemoreceptor areas at low levels. After 4 min, the changes of tidal volume (V_T), respiratory rate (f) and minute ventilation (V_I), as a percentage of the control value, were compared to test whether the sums of the changes for separate stimuli were the same as for simultaneous stimuli, i.e. additive chemoreceptor effects. The simultaneous stimuli had significantly (P<0.05) greater responses for V_T (19% >5%) and V_I (42%>13%), but not for f (23%=9%). Stepwise multiple regression studies of the response/control ratios on the blood gas values showed that multiplicative interaction terms accounted for more of the variance than additive terms for V_T, f and V_I and yielded equations which had overall significant slopes. We conclude that this evidence demonstrates that the two chemoreceptor effects combine synergistically at low levels of stimulation.     

Human corticotropin-releasing factor (hCRF) is a potent respiratory analeptic

Summary During intravenous corticotropin-releasing factor stimulation tests we observed a deepening of the tidal volume in 35 patients. To investigate this presumed respiratory stimulation we measured respiratory parameters in 12 healthy male volunteers in a single-blind placebo-controlled trial. The intravenous 60-s infusion of 100 µg of human corticotropin-releasing factor induced a very potent respiratory stimulation in every subject: respiratory minute volume (mean ± S.D.) increased by 81% from 6.319±0.577 to 11.464±1.264 liters per min (P<0.001), whereas there was only a slight rise in the mean respiratory rate from 12.4±3.0 to 14.7±2.7 breaths per min (P<0.001). Mean tidal volume increased from 531±105 to 809±175 ml (P<0.001). Mean end-tidal partial pressure of carbon dioxide decreased (P<0.001) from 40.3±1.2 to 33.4±1.2 mmHg, whereas mean end-tidal partial pressure of oxygen increased (P<0.001) from 93.2±5.4 to 113.5±5.4 mmHg. After 10 to 20 min both end-tidal carbon dioxide and oxygen partial pressures returned to the baseline values. The placebo had no measurable effects.We conclude that human corticotropin-releasing factor is a potent respiratory stimulant. With 100 µg the resting respiratory minute volume increases by 81%. These data point to the possible importance of the corticotropin-releasing factor as a useful adjunct in the management of patients with alveolar hypoventilation.Abbreviations hCRF human corticotropin-releasing factor - P_ETCO₂ end-tidal partial pressure of carbon dioxide (the last portion of the V_T during expiration, called end-tidal volume, contains CO₂ from the alveolar region) - P_ETO₂ end-tidal partial pressure of oxygen - minute volume - V_T respiratory tidal volume     

Electrical stimulation of arterial and central chemosensory afferents at different times in the respiratory cycle of the cat: I. Ventilatory responses

Ventilatory responses to stimulation of chemoreceptor afferents were studied in the anesthetized, spontaneously breathing cat. Short bursts of electrical stimuli were applied, at various times in the inspiratory or expiratory phase of consecutive breaths, to the carotid sinus (CSN) and aortic nerves (AN) and to the ventral medulla (VM), and effects on tidal volume (V _T), inspiratory, expiratory and cycle durationst _I,t _E,t _tot) and in ventilation (_E) were measured. The responses evoked by stimulating CSN, AN and VM were qualitatively the same, although there were quantitative differences. It was found that effects of stimulation in expiration were restricted to the expiratory phase, and vice versa for inspiration. Stimulation during both inspiration and expiration resulted in increasedV _T, by increasing end-inspiratory or decreasing end-expiratory lung volume, respectively, and also increased ventilation, _E. These effects were most marked in response to stimulation in inspiration. During both phases there was an increasing effect with increasing delay of the stimulus,t _St, from onset of inspiration or expiration, respectively. There was a continuous increase int _I, from below control to above control values, with increasingt _St during inspiration and similarly fort _E during expiration. Hence, the total respiratory cycle duration was shortened when a stimulus was applied early in either phase, and was prolonged, when it was applied late. The results show that stimulation of peripheral and of central chemoafferents exerts qualitatively similar effects on respiration. The central neuronal mechanisms generating both inspiration and expiration show the same changes in reactivity in the respiratory cycle.Supported by the Deutsche Forschungsgemeinschaft, SFB 114 Bionach