Monaldi Arch Chest Dis 2004; 61: 1, 6-13
ORIGINAL ARTICLE
P0.1 during exercise in normal subjects breathing mixtures of gas with varying densities A. Van Meerhaeghe1, R. Sergysels2 ABSTRACT: P0.1 during exercise in normal subjects breathing mixtures of gas with varying densities. A. Van Meerhaeghe, R. Sergysels. Background and Aim. The aim of the study was to reexamine the occlusion pressure measured simultaneously in the mouth (P0.1) and the oesophagus (Poes.1) during exercise in normal subjects submitted to different gas mixtures. Methods. 7 healthy men breathing random gas mixtures containing 21% oxygen with either by 79% helium (He-O2) or sulphur hexafluoride (SF6-O2) and room-air, were studied during a steady-state 90w exercise performed on a cyclo-ergometer. Ventilatory parameters were derived from the flow signal recorded by a pneumotachograph calibrated with the different gas mixtures. Three pressure transducers (mouth, eosophageal and gastric) were checked to have iso-time identical responses up to 4Hz. P0.1, Poes.1, ∆Poes (difference in oesophageal pressure between end-in-
spiratory and end-expiratory levels) and ∆Pdi (variation of transdiaphragmatic pressure between end-inspiratory and end-expiratory levels) were measured. Results. Hyperventilation associated with a similar ∆Poes/∆Pdi but a lower P0.1/∆Pdi ratio was observed in He-O2 breathing compared to SF6-O2 and air. Variable time delays between oesophageal and mouth pressures were observed during air and SF6-O2. Whatever the condition involved, no change was detected in the shape of the inspiratory pressure during the occlusion manoeuvres. Conclusions. He-O2 breathing probably induced a change in the shape of the pressure wave later on in the inspiratory phase, making P0.1 not representing the total inspiratory drive. On the contrary in air and SF6-O2 conditions, P0.1 seemed to remain a useful tool for looking at the output of the respiratory controller. Monaldi Arch Chest Dis 2004; 61: 1, 6-13.
Keywords: Exercise, normal subjects, inert gases. 1
Department of Pneumology CHU Vésale, Montigny-le- Tilleul and 2 CHU St-Pierre, Brussels, Belgium.
Correspondence: A. Van Meerhaeghe, CHU A. Vésale, 706 route de gozée, Montigny-le - Tilleul 6110, Belgium; e-mail:
[email protected]
Introduction Although widely used since 1975 as an index of the inspiratory centre output [1], the validity of the occlusion pressure (P0.1) has often been questioned. The basic problem in the measurement of the output of the respiratory controller is that we do not have any “gold standard” to assess this function. We measure something measurable (flow, volume, pressure, electromyogram) and consider it to be the output of an entity that is in fact defined by the measurement we have chosen [2]. When the estimation of the output involves P0.1 [3] a first problem is to know if the disease or the experimental procedure under study creates by themselves changes in the shape of the pressure wave. In such cases, P0.1 values may underestimate (more concave to the time axis) or overestimate (more convex to the time axis) the real changes occurring in the total inspiratory motor output. For instance, in exercising normal subjects and COPD patients, a change in the shape to a more convex one seems to occur during the occlusion manoeuvres with increasing loads [4, 5]. Beside this, a change in the shape of the pressure wave can occur later in the inspiration, leading to
the same alterations between P0.1 and the total inspiratory pressure A second concern arising when measuring P0.1 is the existence of the respiratory time constant or changes in this constant due to diseases or applied experimental procedures which can affect the measurement of P0.1 by the development of significant phase shifts between a fall of oesophageal pressure from the end-expiratory level to the beginning of inspiration defined as starting when mouth pressure falls below atmospheric pressure. If the inspiratory pressure waveform is not a straight line but keeps the same shape, the pressure must absolutely be sampled at exactly the same phase of inspiration in order to bear a similar relation to the inspiratory cycle later on and being representative of the overall inspiratory drive. Finally, at high levels of ventilatory responses, the contraction of the expiratory muscles pushes the respiratory system to a volume below the functional residual capacity and their relaxation allows negative elastic recoil to be transmitted to the pleural space and to the mouth with or without a concomitant inspiratory muscles contraction giving for P0.1 a complex value depending of relaxation and/or contraction of the respiratory pump.
P0.1 DURING EXERCISE IN NORMAL SUBJECTS BREATHING MIXTURES OF GAS WITH VARYING DENSITIES
With the object of evaluating these potential flaws when P0.1 is used as an index of the inspiratory motor output, we studied seven normal subjects during a moderate steady-state exercise while breathing room-air and inert gases with different densities in order to modify the resistive loading and the length of the time constant of the respiratory system. He-O2 (79-21%) was chosen to decrease the resistive loading and SF6-O2 (79-21%) to induce a moderate loading of the respiratory system. Methods Seven healthy men ranging from 29 to 50 years of age and with a body mass from 62 to 80 kg were studied during a steady-state moderate exercise while breathing three different gas mixtures (room-air, He-O2, SF6-O2). All subjects underwent a normal physical examination. Pulmonary function tests were within normal limits and the mean load ± SD achieved during a maximal exercise was 210 ± 12.2 w. They gave informed consent to the procedure but none of them, with the exception of one, were aware of the specific purpose of the study. The institutional review board approved the protocol. The Subjects were seated on an electrically braked bicycle ergometer (Jeager) controlled by a computer. They were breathing trough a fixed Hans-Rudolph valve (dead-space 95 ml). From the flow signal recorded by a Fleisch n°3 pneumotachograph, the following variables were derived: tidal volume (VT), respiratory frequency (Fr), ventilation (VE), inspiratory time (TI), duty cycle (TI/Ttot) and mean inspiratory flow (VT/TI). An electrical occluding valve allowed a silent short occlusion of 150 ms at end-expiratory level and the pressure developed during the first 100 ms after the onset of occlusion was measured. The resistance of the system was 0,098 kPa. l-1. s. Inhaled inert gas mixtures (He-O2 79-21%, SF6-O2 79-21%) were humidified by the passage through a bubble chamber and warmed in a neoprene bag (meteorological balloon). A manually operated valve situated immediately upstream of the occlusion valve system, allowed abrupt switches to be made among the three studied gases without the subjects awareness. Volume calibration was checked before each exercise session by using a 1-litre syringe with the different gas mixtures. The end-expiratory level was estimated by measuring the inspiratory capacity (IC) asking the subjects to inspire from rest lung volume to TLC. IC was only measured once in each condition. To avoid possible effects of anticipation, the subjects were given no warning of the impending IC manoeuvre. Two typed-balloons catheters measured oesophageal and gastric pressures. The balloons were 5 cm long with a 3.2 cm circumference sealed over one end of a polyethylene catheter. The other end of both catheters was connected to Validyne pressure transducers similar to the one measuring mouth pressure. The three transducer sys-
tems were checked to have iso-time, identical responses by applying sinusoidal pressure changes over ranges of frequencies up to 4 Hz. Occlusion pressure was also measured iso-time at the oesophageal level (Poes.1). Inspiration was considered to start when a negative deflection appeared at the mouth. Transdiaphragmatic pressure (Pdi) was calculated by subtracting oesophageal pressure from gastric pressure (Pga). Four subjects performed the occlusion test described by Baydur et al [6]. The mean P0.1/Poes.1 ratios were close to unity and values ranged from 0.94 to 1.02 for all the measurements performed. During the exercise, transpulmonary pressure (PTP) was calculated in 4 subjects from the difference between mouth and oesophageal pressures. Total lung resistance (RL) was obtained by measuring the difference in PTP at iso-volume points during inspiration and expiration [7, 8]. Dynamic compliance of the lung (Cdyn) was obtained by dividing tidal volume by the difference in oesophageal pressure between points of no flow (FRC and end-inspiration). CO2 was continuously monitored at the mouth by a rapid infrared CO2 analyser with a sampling rate of 250 ml/min. that was disregarded in our calculations. Mixtures of 5% CO2 in He-O2 and SF6O2 and room-air were measured in order to determine the influence of the inert gases on the results. SF6-O2 did not affect the CO2 analysis; on the contrary the 74% He concentration caused an underestimation in CO2 concentration by 10%. For this reason, 1.1 multiplied values of end-tidal CO2 during He-O2 breathing. The signals were continuously displayed on a multichannel strip-chart recorder at a 5 cm/s speed during the occlusion manoeuvres and at 5 or 10mm/s outside the occlusion manoeuvre. An online recording on a microprocessor was also done in order to perform further analysis. The P0.1 recordings were magnifed in order to achieve a better assessment of the pressure waves shape during the occlusions manoeuvres. Exercise session Each session consisted in a two minutes warming–up period at 50w and was then divided in five periods of time where the exercise level was set at 90 w.The last level was chosen to avoid additional effect on VE by lactic acidosis and to minimize the possible effects from more slowly developing stimuli, such as rising body temperature [9] or modification of the levels of cathecholamines [10]. Air was the inhaled gas during the first, the third and the fifth period. SF6-O2 and He-O2 were randomised as the second or the fourth period in each subject. SF6-O2 period was reduced to one minute because of mild central effects experienced by all the subjects after two minutes. The other periods had three-minute duration. Data averages were taken from the last minute of each period, except for SF6-O2 where the results 7
A. VAN MEERHAEGHE, R. SERGYSELS
are the mean of the only performed minute. No statistical significant difference for any variables was observed among the three control periods, demonstrating steady-state conditions in air breathing during the experiment. Therefore, the results of periods 1-3-5 were averaged for each subject and these values were compared to the results from the SF6-O2 and He-O2 periods. The calculations were the mean of variables measured during five breaths in each condition and in each subject. Statistical analysis Friedman two-way ANOVA was used to compare values during the three conditions. If the F test of equal means was statistically significant (null hypothesis rejected), a multiple comparison test was used (Tukey’s test) in order to compare the difference between all pairs of means. Limit of statistical significance was P< 0.05. Results Before starting exercise, FRC was estimated in each subject by measuring inspiratory capacity in the three conditions. The results were the following ones: 3.31 l ± 0.34 in He-O2, 3.35 l ± 0.31 in SF6-O2, and 3.38 l ± 0.29 in air breathing (no statistical significant difference). Oxygen Consumption, parameters of thoracopulmonary mechanics and ventilatory pattern during exercise are displayed in table 1. Despite the fact that the SF6-O2 period was shorter than the others two, no statistical differences were found in O2 consumption among the three conditions, demonstrating that the subjects conditions were the same at the time of measurements.
No change occurred in end-expiratory level as assessed by inspiratory capacity and end-expiratory oesophageal pressure. In comparison to resting conditions the end-expiratory level was lower during the steady-state exercise and the observed difference ranged from 80 ml to 160 ml. Breathing SF6-O2 increased RL by 131% compared to air condition. On the other hand, RL was diminished by 41% during He-O2 compared to air breathing. Hyperventilation with sustained hypocapnia was present in He-O2 compared to both air and SF6-O2 conditions. The increase in VE was due to an increase in VT (P
