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Muscle activity during chest wall restriction and positive pressure breathing in man
Respiration Physiology(1978) 35, 283 300 © Elsevier/North-Holland Biomedical Press
M U S C L E A C T I V I T Y D U R I N G C H E S T WALL R E S T R I C T I O N A N D P O S I T I V E P R E S S U R E B R E A T H I N G IN M A N ~
M A L C O L M G R E E N , JERE M E A D 2 and T H O M A S A. SEARS Sobell Department o["Neurophysiology Institute of Neurology, Queen Square, London WCI, United Kingdom and Department o['Physiology, Harvard School o/' Public Health, Boston, MA 02115, U.S.A.
Abstract. The effects of sustained constriction of the rib cage (RCC), constriction of the abdomen (AC)
and of breathing against a positive pressure of 10 cms of water (PPB) were studied in four normal subjects with moderate constant hypercapnia. Intercostal electrical activity (Eic) was measured by implanted wire electrodes and diaphragmatic electrical activity (Edia) by oesophageal electrodes. There was no fixed relation between Edia and VT. VT was unaltered during AC and RCC: Edia was unaltered during AC but increased during RCC. The response to PPB without constriction varied: three subjects increased end-expiratory VL with increase in Edia and inspiratory Eic. One subject initially, and one subject after training, maintained end-expiratory VL constant with no change in Edia and an increase in expiratory Eic. When PPB was applied during AC and RCC there was an increase in Edia proportional to end-expiratorylung volume. The overall response to distortion was determined by voluntary choice, but muscle electrical activity reflected chest wall configuration : when the diaphragm was shorter and at a mechanical disadvantage its electrical activity increased. This was compatible with a reflex with afferent information from diaphragm tendon organ and muscle spindle receptors. Chest wall mechanics Diaphragm Diaphragm reflexes
Intercostal muscles Patterns of breathing Respiratory mechanics
It has been shown that as the diaphragm becomes shorter and less curved, its mechanical efficiency at reducing intrapleural pressure and hence of inducing changes in lung volume, becomes less (Marshall, 1962; Pengelly, Alderson and Milic-Emili, 1971). In the course of some other experiments (Mead and Sears, unpublished observations), four subjects were exposed to positive pressures at the Accepted [br publication 2 August 1978 I This work was presented in part at the International Symposium on 'The Effects of Mechanical Loads on Breathing" at McMaster University, April 1973. 2 j. M. was supported by National Heart and Lung Institute Grant HL 14580. 283
284
M. G R E E N et al.
mouth and in all four the increased end-expiratory lung volume was associated with an increase in diaphragm electrical activity during tidal breathing. This might have been due to increased respiratory drive consequent upon an increased chemical stimulation to the respiratory centres, but another possibility was that there might be reflexes which were able to compensate for the decreased mechanical advantage of the shortened diaphragm by increasing efferent activity for the diaphragm at a given level of chemical respiratory drive. Previous workers had assumed that efferent drive to the diaphragm remained constant for a given chemical drive over a range of lung volumes (Marshall, 1962). We set out to test whether we could confirm that manoeuvres which put the respiratory system or the diaphragm at a mechanical disadvantage did indeed cause increase in diaphragm electrical activity when chemical respiratory drive was held constant, and whether we could identify the mechanical factors which correlated with increased diaphragm electrical activities. We argued that if the excursion of the rib cage was restricted, diaphragmatic shortening would be augmented and this might be associated with increased diaphragmatic electrical excitation. Conversely, if abdominal excursion was restricted, the diaphragm configuration would be maintained at a more advantageous length and hence there would be no increase in electrical excitation, and there might even be a decrease. Because mechanical interventions would be expected to influence pulmonary ventilation and thereby alter stimuli to breathing, we used a technique which minimised fluctuations in alveolar (and hence blood) gas composition as described by Eger et al. (1968). Since our electromyograph (EMG) recordings were relatively insensitive, we stimulated breathing by moderate hypercapnia.
Methods
Studies were caried out on four healthy males (table 1). They differed in their level of sophistication as respiratory subjects. J.M. was very experienced, having performed respiratory manoeuvres, including positive pressure breathing, on numerous previous occasions. M.G. and M.H. had a grasp of respiratory mechanisms, and without instruction simply believed that they should relax in TABLE 1 Physical characteristics of subjects Subject
Age (yr)
Height (cm)
Weight (kg)
TLC (liter)
VC (liter)
J.M. M.H. M.G. R.L.
50 34 29 26
188 163 175 178
86 63 65 68
9.0 6.2 6.0 7.0
6.8 4.9 4.7 5.6
R E S P I R A T O R Y M U S C L E A C T I V I T Y IN M A N 2 Liter tube
I I
Blower
285
I I
Volume
Diaphragm EMG
Intercostal EMG
Fig. 1. Diagram of experimental set-up, see text. R C C indicates arrangement for restricting rib cage excursion and A b d o C for restricting abdominal excursion. 'Blower' represents the reversed vacuum cleaner.
the face of distortions, but had not previously performed positive pressure breathing. R.L. although medically qualified was a neophyte as a respiratory subject. The experimental set up (fig. 1) consisted of a rigid metal frame in which the subject was seated, with his back against a flat board. He breathed through a mouthpiece into a long wide bore tube, 2 litres in volume. Air was added close to the mouth at a constant rate throughout all the manoeuvres (Bias flow in fig. 1). Thus the subject was able to breathe air up to this rate, but further ventilation was derived from expired air re-inhaled from the large bore tube. Hence the chemical stimulus to breathing remained independent of the levels of ventilation as described by Eger et al. (1968). The rate of flow of air was adjusted for each subject so that his breathing was slightly stimulated by hypercapnia to a level where tidal volume was 25-30~ of his vital capacity. Carbon dioxide concentration within the mouthpiece assembly was continuously analysed by a Godart Capnograph Infra-red Analyser. Flow was measured at the mouth by a Fleisch Pneumotachograph and a variable capacitance pressure transducer (Hilger and Watts Ltd., London) and
286
M. GREEN et al.
was integrated to give tidal volume. Volume was recorded on a six-channel ultraviolet recorder (Aviation Electronics Ltd., London), adjusted so that one vital capacity manoeuvre covered 10 cm of recording paper and read 1.0 on a digital voltimeter. Volumes could thus be read directly in per cent vital capacity (Newsom Davies and Sears, 1970). The diaphragm EMG was recorded with a balloon-stabilised oesphageal lead (Sears et al., 1968). The subject swallowed a gastric balloon which was pulled back until the inflated balloon rested against the cardia of the stomach, being held there by the weight of the tap at the mouth-end of the catheter. Electrical activity of the diaphragm was recorded by means of two oesphageal electrical leads 2 cm apart on the balloon catheter which picked up action potentials of the vertical crural part of the diaphragm (Agostoni and Torri, 1962; Petit, Milic-Emili and Delhez, 1960). Following the experience of Draper, Ladefoged and Whitteridge (1960) and Newsom Davis and Sears (1970) intercostal EMG activity was led from a pair of wires inserted into the 6th or 7th intercostal spaces in line with the lower part of the scapula (Taylor, 1960). This had the advantage of sampling from both the internal and external layers and this gave a less restricted view of the electrical response of the intercostal muscles than would have been the case with recording from a single layer. Recording from the parasternal region was not used because of the difficulty of avoiding movement artefact when pressing on the sternum. Intercostal activity was judged as inspiratory (external intercostal) or expiratory (internal intercostal) by its time relation to the phases of ventilation and confirmed also by voluntary activation of the muscles at the time the electrodes were introduced. The EMG was full-wave rectified, smoothed (time constant 200 msec), amplified and recorded with high frequency response galvanometers on the ultra-violet recorder. Abdominal excursion could be limited by means of a block of wood shaped to fit the abdominal contour anteriorly and held rigidly in place on an adjustable clamp fixed to the metal frame. The block could be forced inwards without impinging on the rib cage or pelvis to a previously established point where end-expiratory volume was reduced by not more than 5~o vital capacity and fixed in this position. Similarly, rib cage excursion could be limited by an adjustable board held rigidly against the sternum which severely restricted rib cage expansion but did not reduce end-expiratory volume by more that 5 ~ VC. The subject breathed for a period through the apparatus to establish satisfactory and stable levels of ventilation and electrical activity. Rib cage restriction alone was applied for ten breaths on three occasions and then abdominal constriction alone on three occasions. Following this, positive pressure breathing (PPB) was studied. Positive mouth pressures were produced at the outlet of a commercial vacuum cleaner (reversed so that it blew), and applied to the distal end of the long tube. A pressure of 10 cm of water (measured by a water manometer) was applied by turning a tap to connect in the vacuum cleaner at the onset of an inspiration and was maintained throughout the respiratory cycle for ten full breaths. The experimental procedure consisted of three periods of positive pressure breathing of ten
RESPIRATORY MUSCLE ACTIVITY IN MAN
287
breaths each, with ten breaths or more between (PPB with no restrictions). The rib cage was then restricted, and PPB again applied for three periods after which the restriction was released (PPB with RC restriction). After a further period of control breathing, abdominal compression was applied and the PPB repeated three times (PPB with abdominal constriction). Finally PPB was again applied three times with no restrictions. The experiments on JM and MG and the first experiment on RL were all completed before any analysis of the records and before we were able to recognise any of the trends or patterns in the responses. This turned out to be important when we realised the role of training in the responses to PPB. The records were analysed by taking the individual breaths and the means of the responses over ten breaths before, during and after an intervention. The EMG signals were read as the maximum activity achieved during a given inspiration or expiration. Clearly this measure of EMG signals is relatively crude as the maximum EMG may occur at different points in the tidal volume, depending on respiratory frequency, pattern of breathing and other factors. However, we felt that to relate the electrical activity to mechanical events would be no less arbitrary. Although EMG activity is comparable within a subject during an experiment, the activity is measured in arbitrary units, and the absolute levels are not necessarily comparable between experiments.
Results
The method of controlling CO_, was largely effective in maintaining a constant end-expiratory Pco_, throughout each experiment, at levels which varied between 44 and 56 mm Hg Pco: in the different subjects. End-expiratory Pco.~ altered by less than 2 mm Hg Pco~ during the course of an experiment: there was a small decrease (range 0 to - 2 mm Hg Pco~, mean -1.25 mm Hg) in those subjects where PPB caused an increase in end-expiratory volumes. In no experimental circumstance was there an increase in Pco.~. It seems likely that the falls in Pcoz we observed were due to dilution of alveolar gas with deadspace and atmospheric air when endexpiratory volume rose. The effects of rib cage and abdominal restriction alone on tidal volume and electrical activity of the diaphragm in the four subjects are shown in fig. 2, expressed relative to their levels before restriction. There was little change in tidal volume with either mode, and abdominal restriction did not significantly alter diaphragm electrical activity. Neither rib cage nor abdominal restrictions on their own shifted end-expiratory lung volume by more than 5% VC (see Methods). However, there was a considerable rise in diaphragm electrical activity when the rib cage was restricted. Intercostal activity showed no consistant changes, either in inspiration or in expiration during the restrictions. Illustrative records of the effects of the application of PPB with no restrictions on lung volume, diaphragm electrical activity and intercostal activity in two subjects
288
M. GREEN et al. 2.0
Abdolinal r e s ~
1.5 l.O 0.5
0.5
1.0
1.5
i
0.5
2.0
i
l.O
i
1.5
i
i
2.0
2.5
F. (restricted) E (control) Fig. 2. Effects of abdominal restriction (left) and rib cage restriction (right) without PPB on tidal volume and electrical activity. On the ordinate tidal volume (Vx restricted) is expressed as a fraction of the control values for each subject before restriction. On the abscissa is plotted the electrical activity (E restricted) for the diaphragm (filled-in circles for individual points, square for the means). In addition, for abdominal restriction only, is shown the electrical activity of the inspiratory intercostal muscles (triangles for individual points, circled triangle for the mean), again expressed as a fraction of the respective control value for each subject before restriction. The lines of identity are shown: points would lie on these if the increase in E was proportionately similar to the increase in Vx. Subject J . M
Edia
~ 10 S e c s
Subject R.L.
Edia
Eic
~ m~
I
~ 10 Secs
Fig. 3. Representative tracings of effects of one application of PPB on tidal volume (VT), and electrical activity of the diaphragm (Edia) and intercostal muscle (Eic) in two subjects, see text. Inspiration is upwards. Edia and Eic are in arbitrary units (see Methods).
are shown in fig. 3. One subject (JM) increased end-expiratory volume in response to PPB whilst the other (RL) maintained end-expiratory volume about constant (see below). Table 2 shows the effect of PPB on ventilation, expressed as VC/min (derived by dividing minute ventilation of a subject by his own vital capacity. All subjects showed a fall in tidal volume (Mean fall 25~) which was maintained during the pressure but returned to control levels immediately PPB was stopped. On average
R E S P I R A T O R Y M U S C L E ACTIVITY IN M A N M.H.
J.M.
289
M.H. after
instruction
1001
5°°1[. I Ins 201 0" T
C
[ I t[ I
T
PPB
It
] It
C
PPB
R.L.
M.G.
[ C
PPB
R . L . after
instruction
1001
OolI. o
Ins 201 T 0
'°o1:C
I I
I
I
t
t
PPB
IT
C
T ]l PPB
C
T
PPB
Fig. 4.' Effect of PPB on lung volume (~o Vc), electrical activity of diaphragm (Edia) and of intercostals (Eic) in the four subjects. Edia and Eic are in arbitrary units (see Methods). C are control values. Inspiratory intercostal activity (ins) is shown above the baseline and expiratory (exp) below the baseline for Eic, On the left are shown the four subjects initially. On the right are shown subjects M H and RL after instruction, see text.
there were small increases in respiratory frequency giving overall small decreases in minute ventilation. The mean effects of PPB with no restrictions in the four subjects are shown in fig. 4. Three subjects (JM, MG and MH before instruction) showed an immediate rise in end-expiratory lung volume with PPB. End-expiratory lung volume remained steady during pressure in subject JM and was identical on each occasion of PPB and on different experimental days. The rise in end-expiratory lung volume with PPB in subjects M G and MH was also marked but more variable from brath to breath and between separate days of PPB. In these three subjects the diaphragm EMG activity of each breath increased with PPB. At the same time inspiratory intercostal activity increased while in the one subject in whom it could be detected (MG) expiratory intercostal activity diminished. The fourth subject (RL) did not increase end-expiratory volume and in him the activity of the diaphragm remained constant during PPB. Furthermore, inspiratory intercostal activity diminished while expiratory intercostal activity greatly increased. Thus in general when end-expiratory volume increased during PPB (with no restrictions), inspiratory activity was increased and expiratory activity reduced and vice versa. It seemed that the apparently conflicting results in the four subjects
290
M. G R E E N et al.
might have a common explanation in the pattern of breathing adopted. We therefore 'trained' subjects MH and RL after their initial experiments were finished to react to PPB in a different way from their initial responses. Subject MH had relaxed and allowed the pressure to inflate his respiratory system along its relaxation pressure-volume characteristic. We trained him to hold FRC constant. This he achieved (fig. 4B : MH after instruction) by increased activity of intercostal muscles, which from their phasing were in all probability expiratory muscles, and a slight fall in diaphragm electrical activity. Subject RL on the other hand was instructed to allow PPB to increase his end-expiratory volume instead of resisting the changes in lung volume. He now showed (fig. 4: RL after instruction) an increase in endexpiratory volume and despite a fall in tidal volume his diaphragmatic excitation was increased during PPB. Thus whenever individuals allowed PPB (with no restrictions) to increase endexpiratory lung volume, diaphragmatic activity increased. However, no increase in activity was seen when end-expiratory volume was prevented from increasing. Similarly, expiratory intercostal activity diminished and inspiratory increased when end-expiratory lung volume rose, whereas expiratory intercostal activity increased when end-expiratory lung volume was not allowed to rise with PPB. PPB on
! It I t ~t
PPB off
'l I
t
!
!
I I
I' I
: I \k
.SO-
100
0
0
2
'
4
~ 6 Breath No.
8
]0
0
2
4
6 Breath No.
8
lO
Fig. 5. Response of diaphragm electrical activity (Edia) and tidal volume (VT) breath-by-breath to PPB: mean of three applications of PPB in each of the three subjects who initially increased end-expiratory volume with PPB. (Left). Edia and VT of each breath after initiation o f PPB at Breath 0 expressed as ~°/0of the mean response of the 10 breaths. (Right). Edia and VT following finish of PPB at Breath 0.
R E S P I R A T O R Y MUSCLE ACTIVITY IN MAN
291
The changes in tidal volume and diaphragmatic excitations in response both to the onset and the stopping of PPB occured abruptly (fig. 5). Although there is some variability, there was no significant difference when the tidal volumes of the first, second, third or tenth breaths were compared with the mean during the PPB loads or when the comparisons were made after stopping PPB. Similarly the changes in electrical activity were on average completed by the second breath (fig. 5). When PPB was applied during rib cage and abdominal restriction, the changes in electrical activity of the diaphragm and intercostal muscles were somewhat variable. Howeyer, when these were related to end-expiratory lung volume and chest wall configuration, a consistant pattern emerged and this is presented in the discussion.
Discussion
When external loads were aplied to the respiratory system there could be dramatic changes in excitation of the respiratory muscles without corresponding changes in tidal volume and minute ventilation. Thus there was no fixed relationship between electrical activity of the respiratory muscles and the VT achieved when respiratory system configuration altered. The experimental procedure was designed to hold Pco_~ constant in the face of mechanical loading. The lack of change in Pco~ was confirmed by the measurements of end-tidal (end-expiratory) Pco~. Thus chemical causes for altered electrical activity can be excluded. When we alalysed our results it became clear that an adequate explanation for them could only be made if the configuration of the chest wall was taken into consideration. In our experiments we did not measure chest wall configuration directly, but the changes can be deduced qualitatively from the reports of Goldman and Mead (1973) and Grassino et al. (1973). In this discussion, therefore, we analyse our results along these lines.
EMG R E C O R D I N G S
We assume in this discussion that the electrical activity recorded with oesophageal electrodes is a true reflection of the EMG activity of the diaphragm muscle, and that this relationship is not itself altered by changes in configuration of the diaphragm or changes in lung volume. Unfortunately this assumption has proved difficult to test directly (Mead, 1974). Electrodes inserted into the body of the diaphragm in the cat recorded electrical signals at constant phrenic stimulation which did not vary with lung volume or chest wall configurations (Grassino, Whitelaw and MilicEmili, 1976). Attempts to confirm that the same relationship held true in man were thwarted as it proved impossible to achieve supramaximal stimulation of the phrenic nerves in conscious man with safety (Mead, 1974). We can conclude that
292
M. G R E E N et al.
diaphragmatic EMG signals in cats are uninfluenced by lung volume and chest wall configuration, and that there is no evidence to the contrary in man at present. E F F E C T S OF RIB C A G E A N D A B D O M I N A L R E S T R I C T I O N
The effects of abdominal restriction without PPB on tidal volume, and electrical activity of the diaphragm and intercostal muscles were small (fig. 2). This probably reflects the tendency in normal subjects for tidal volume to be achieved by contraction of the diaphragm and increase in size of the rib cage. During eupneic breathing and moderate hypercapnia there are only small increases in abdominal diameter during inspiration (Goldman and Mead, 1973). To the extent that enlargement of the abdomen is prevented by abdominal restriction (without PPB), it would be expected that the diaphragm would be maintained throughout inspiration at a more curved shape and hence at a greater mechanical advantage, causing either an increase in tidal volume or a decrease in diaphragmatic electrical activity. Neither of these were seen, possibly due to the increased impedance to inspiration presented by the restricted and hence stiffened abdomen, or possibly because some flattening of the diaphragm occurs in lifting the rib cage. During quiet breathing tidal volume is achieved by expansion of the rib cage and descent of the diaphragm. If expansion of the rib cage is prevented, while the same tidal volume is maintained, it might be expected that the diaphragm would descend further, and thus shorten more. Indeed, Konno and Mead (1967) have shown that for a given tidal volume, if the rib cage is prevented from expanding, abdominal displacement is increased. Since, to a useful approximation, abdominal displacement reflects diaphragm length (Grassino et al., 1978), during rib cage restriction the diaphragm must shorten more than during unrestricted breathing. In our experiments restriction of the rib cage (without PBB) caused no fall in tidal volume despite the tendency .to increase the mechanical impedance of the respiratory system, and to force the diaphragm to shorten more for a given volume inspired, thereby decreasing its mechanical efficiency. Tidal volume was almost completely maintained (on average at 92~ of control levels) by a striking increase in diaphragmatic electrical activity (average increase 55~, fig. 2). E F F E C T S O F PPB
(1) Lung volume changes Studies of responses to PPB have usually implicitly assumed that it is possible to define a physiologically normal and uniform response to such respiratory insults (Agostoni, 1962; Christiansen and Haldane, 1914; Ernsting, 1966; Rahn et al., 1946). However the strictly rational response of the ordinary man to PPB would be to come off the mouthpiece ! The response of subjects instructed only to stay on the mouthpiece and not told whether to relax nor in any way to respond to the stimulus
R E S P I R A T O R Y MUSCLE ACTIVITY IN M A N
293
does not seem to have been reported. Christiansen and Haldane (1914) described an apneustic response to PPB (in informed subjects doubtless influenced at that time by knowledge of the Hering Breuer reflexes). More recent reports have uniformly described a rise in end-expiratory lung volume which more or less closely followed the relaxation pressure-volume characteristic of the respiratory system (Agostoni, 1962; Boothby and Berry, 1915 Ernsting, 1966 ; Flenley, Pengelly and Milic-Emili, 1971; Heaf and Prime, 1956; Johnson and Mead, 1963). These results may have been influenced by the concepts introduced by Rahn et al. (1946). Three subjects familiar with respiratory manoeuvres (JM, MH, MG) assumed that they should allow end-expiratory volume to increase in response to PPB. The fourth subject RL, however, had no pre-conceived ideas as to 'normal' response to PPB and was simply told that 'he would feel a pressure' when he was breathing. His response was to maintain end-expiratory volume constant in response to PPB. This proved fortuitous as it allowed us to distinguish between the effects of PPB itself and the effects of changes in configuration of the respiratory system produced by PPB as well as the importance of conscious control and training in response to this mechanical load. Both MH (who initially increased end-expiratory volume in response to PPB) and RL (who did not) were easily trained to adopt a response to PPB opposite to their initial reaction. Subsequently both stated that they had no subjective preference to either pattern of breathing. The different patterns of response adopted by our subjects do re-emphasise the importance of subject instruction in physiological experiments and the dangers of looking for, and indeed finding, predetermined 'normal' responses. (2) Tidal volumes and inspiratory./low rates PPB caused a fall in tidal volume, although in subjects MG and RL this was partially counteracted by a rise in respiratory rate (table 2). In subjects RL and MH, the decreases in tidal volume were greater when end-expiratory position increased (fig. 4) than when it was unaltered. This is compatible with the increased impedence of the respiratory system at higher lung volumes. Flenley et al. (1971) found similar changes during four breaths of PPB, although there is evidence that minute ventilation is well maintained during PPB over several minutes (Ernsting, 1966; Grassino, Lewinsohn and Tyler, 1973; Petit, Milic-Emili and Delhez, 1960). It is postulated that the central respiratory neurones achieve a given tidal volume by producing a particular inspiratory flow rate which is interrupted at end inspiration by a respiratory timing mechanism (Clarke and Von Euler, 1972). In our experiments there were only small changes in respiratory frequency, and the relative duration of inspiration and expiration (illustrated in fig. 3A and B) did not change appreciably in any of the experimenial circumstances. We conclude that there was an equivalence between tidal volume and mean inspiratory flow rate in these experiments. Furthermore, since inspiratory duration was little altered by the manoeuvres it seems reasonable to interpret the amplitude of the Edia signal as adequately reflecting the intensity of diaphragmatic stimulation.
M.H.
J.M.
R.L.
M.G.
1
V (VC/min)
27
25
I
13.1
14.8
13.3
20 22.3
26 20
25
17.3
36
3.3
4.0
3.3
5.2 4.5
6.2
28
14
20
21 12
29
VT C,o VC)
f (min - l)
VT
(% vc)
PPB
Control
I1
I1
Subject
11.0
14.2
13.4
22 22.5
19.8
f (min - J)
2.0 3.1
2.8
2.7
4.6
5.8
V (VC/min)
+ 6
-48
-20
-40
- 19
- 19
Vl ("~o)
Change
4
-16
-
+ 0.7
+ 10 + 1
+ 13
f (?Jo)
TABLE 2 Effect of PPB for 10 breaths on VT, frequency (f) and minute ventilation (V min) (Mean of 3 applications, see text)
6.7
-50 - 6
-15
-11.5 -40
(%)
t~
R E S P I R A T O R Y MUSCLE ACTIVITY IN MAN
295
(3) Electrical Activity In our experiments, the three subjects who raised lung end-expiratory volume in response to PPB, showed markedly increased diaphragm and inspiratory intercostal activity with reduced expiratory intercostal activity (when recorded). This suggests that there are substantial neural mechanisms that act to defend tidal volume (and inspiratory flow rate) under adverse circumstances. In confirmation of this, RL showed a similar increase in diaphragm activity when, after training, he allowed PPB to increase his lung end-expiratory volume. Changes which shorten the diaphragm put it on a less advantageous part of its length tension characteristic both through being shorter and by being less curved (and hence less powerful by the Laplace relationship (Marshall, 1962)). Flenley et al. (1971) argued on mechanical grounds that the fall in tidal volume they described was a simple reflection of the impaired mechanical efficiency of the diaphragm, because they assumed that neural excitation was constant during PPB. However, it now appears that this mechanical effect is much greater than they conceived since the increase in diaphragmatic excitation concomitant with a flattening of the diaphragm would tend to mask the potential reduction in tidal volume. By contrast two of our subjects (RL initially and MH after instruction) responded to PPB with little change in end-expiratory lung volume. In them the effects of the applied static pressure resisting expiration were compensated for by an increase in expiratory intercostal activity during inspiration. Our observations contrast with the findings in anaesthetised dogs and cats by Bishop (1963, 1964, 1967; Bishop and Bachofen, 1972) and anaesthetised men by Guz et al. (1964) that PPB with rise in end-expiratory volume caused diaphragmatic inhibition and expiratory excitation. It appears therefore that anaesthesia has an important role in modifying the neurological responses to PPB. When PPB was applied during rib cage and abdominal restriction, the changes in electrical activity were quantitatively rather variable. However, we postulated that diaphragm electrical activity would relate to its degree of shortening. It is at end-inspiration that the diaphragm is maximally shortened. Therefore, if diaphragmatic electrical activity did relate to its degree of shortening, there might be a relationship between end-inspiratory lung volume and electrical activity of the diaphragm. This relationship during PPB is plotted in fig. 6 for the four subjects. A line can be drawn through the points in each subject and this projects to zero electrical activity at, or close to, FRC. Figure 7 is a plot showing the same lines and in addition, the electrical activity of the diaphragm before and during PPB applied whilst either the abdomen or the rib cage were restricted. The points during abdominal restriction alone lie close to the unrestricted relationship. During PPB with abdominal restriction in subjects JM, MG and MH there appears to be about the same or slightly less increase in electrical activity of the diaphragm as without restrictions. During PPB the decreased compliance of the system therefore, seemed to be matched by the increased mechanical efficiency which the diaphragm derived from maintaining a higher degree of curvature. Subject RL showed a very much
296
M. G R E E N
Eda i"~IM~
et al.
40R~ ~)0
OL /
FRC 20
4O
6O
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0
FRC 20 ,4O 60
4.0
E
MH
oL,11 FRC 2 0
40
60
O/oVC
x :withc~ PPB X:during PPB
FIRC 20 40
60
% vc
End Impl'o~'y Lung 'vblun~
Fig. 6. Relationship between Edia (arbitrary units) and end-inspiratory lung volume C'/o VC) b e f o r e and during PPB in four subjects. "Best fit' lines drawn by eye. Each point represents mean of three applications o f 10 breaths.
JM
80
Abdo. restr n Rib restr n
+ o
-P O
,10
60
!
60
//
E dia
g
4o
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dia
Control
/
/ O
t
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40
60
/
N:IC 2 0
,0 ~
%vc
%vc
End ~r~o~o~ LungV o ~
Fig. 7. Relationship between Edia (arbitrary units) and end-inspiratory lung volume (')i, VC) b e f o r e and during PPB applied whilst either rib cage or abdomen is restricted. "Best fit' lines re-drawn f r o m fig. 6: each point represents mean of three applications o f 10 breaths.
smaller increase in end-inspiratory volume during PPB with abdominal restriction and concomitantly a slight decrease in diaphragm activity. It him, the increased mechanical advantage of the diaphragm during abdominal restriction appeared to more than match the increased load, allowing less neural drive for a given endinspiratory lung volume. During rib cage constriction alone electrical activity of the diaphragm increased at a given lung volume, as shown by small circles in fig. 7. When PPB was applied in addition (large open circles) two of the subjects (MG and MH) showed further increases in electrical activity of the diaphragm which about matched their increases in end-inspiratory lung volume. The other two subjects (JM and RL) showed relatively much larger increases in electrical activity of the diaphragm than
RESPIRATORY MUSCLE ACTIVITY IN MAN
297
predicted from the unrestricted relationships. This suggests that in them, the combination of rib cage restriction and PPB compounded each other in decreasing mechanical efficiency of the diaphragm, and this was associated with larger compensatory increases in its nervous excitation. The differences between the subjects may relate to differences in their chest wall anatomy or their central nervous system sensitivities.
CONTROL OF RESPIRATORY MUSCLE
We have evidence that there is a fine control of patterns of respiratory muscle activity. In particular, increased excitation of the diaphragm tends to compensate in situations where the diaphragm's mechanical efficiency is impaired at a given chemical stimulus. We now analyse the mechanisms which might co-ordinate these patterns of respiratory muscle activity. One possibility is that the alterations in ventilation are achieved by chemical regulation. This seems unlikely. Rise in lung end-expiratory volume by application of suction to the chest wall of subjects breathing air causes no change in tidal volume or in alveolar Pco~ over 10 minutes (Grassino, Lewinsohn and Tyler, 1973; Rahn et al., 1946). Our experiments were designed to minimise changes in the subject's Pco, and the small changes seen when PPB caused a rise in end-expiratory lung volume were always in a direction of a lower Pco_,. Despite this, diaphragm activity always increased. Conscious control undoubtedly played a role in the breathing pattern adopted, at least with respect to end-expiratory volumes. Thus the three subjects with experience and insights into concepts such as ~relaxation' pressure-volume curves allowed pressure to drive their end-expiratory volume up, and as a result their diaphragm electrical activity, and presumably muscular activity, increased. There are, however, several reasons for thinking that detailed control of neural excitation of the respiratory muscles by a conscious mechanism alone was improbable. Firstly, the patterns of response to each distortion were reproducible within a given individual, both within an experiment and from one experimental day to another. Secondly, the responses were surprisingly consistent between subjects when related to end-expiratory lung volumes. Finally, the subjective sensation was maximal when the stimulus was applied, and diminished thereafter, whereas the neural drive remained relatively constant throughout a given stimulus (fig. 5). Thus while the mechanical factors involved in the response to PPB were broadly understood by some subjects this gave no subjective clues to the underlying neurophysiological mechanisms responsible for achieving tidal volume. In essence our results seem to suggest the existence of a reflex mechanism sensitive to mechanical efficiency of the diaphragm, adjusting the neural excitation accordingly, to achieve the required tidal volume. However, our data gave no specific information as to the pathways of the reflexes involved.
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The increase in inspiratory muscle excitation seen with increases in end-expiratory lung volume precludes an explanation based on Hering-Breuer inflation reflexes (Widdicombe, 1964). Head's paradoxical reflex (1889), that is inspiratory excitation resulting from rapid lung inflation (if indeed applicable with the vagi intact), could perhaps be implicated when PPB is applied, but could not account for the response during ribcage restriction nor for the maintained excitation throughout restriction or PPB. A wholly spinal reflex has been described for the lower intercostal muscles in cats, in which there is increased phrenic excitation when the rib-cage is stretched (Decima, Von Euler and Thoden, 1969) and this reflex can be stimulated by contractions of the diaphragm itself (Decima and Von Euler, 1969). A reflex arising from the upper rib cage mediated via the brain stem and affecting phrenic motor neurone excitability has been described by Remmers and Tsiaras (1973). The relevance of these reflexes to our results is difficult to assess, as the experimental situations were very different and the mechanisms of the rib cage are complex. However, as described they would not explain our results, as there was increased electrical activity of the diaphragm both when the size of the rib cage increased during PPB and when it was restricted during rib cage restriction : these two manoeuvres in all probability have opposite effects on intercostal stretch receptors. It is possible that intercostal joint receptors may play a part in detecting the position of the rib cage, and hence in part lung volume. However, little is known of their action and their relevance remains conjectural (Godwin-Austin, 1969). Alternatively the pattern of neural activity might be regulated by reflexes from receptors in the diaphragm itself, with the afferent pathway via the phrenic nerve. In contrast to the intercostal muscles where muscle spindles predominate over tendon organs (2.9: 1), in the diaphragm tendon organs predominate over muscle spindles (0.8 : 1) (Corda, Von Euler and Lennerstrand, 1965). Recent work in other sites have suggested that Golgi tendon organs do act in voluntary movements to maintain constant tension in the face of changes in muscle length, velocity or fatigue (Houk and Henneman, 1967). Nevertheless, tension receptors alone would not fully explain our findings as a given tension achieved by the diaphragm will have different implications for lung volume at different configurations. It seems likely, therefore, that the afferent information for such a reflex would depend on a complex interaction of tendon organ and muscle spindle information, analogous to the interaction which occurs in control of limb muscles (Houk and Henneman, 1967). A reflex based on" diaphragm receptors would detect situations in which the diaphragm did not achieve sufficient tension at a given configuration and would provide compensating reflex excitations. Presumably both afferent and efferent paths would be in the phrenic nerves. Such reflex control of the diaphragm seems physiologically logical and would be closely analogous to similar mechanisms in skeletal muscles. Natural changes in internal loading of the respiratory system occur frequently. For example, change from supine to upright posture involves downward displacement of lung and diaphragm. Weight-lifting and carrying, climbing, standing
RESPIRATORY MUSCLE ACTIVITY IN MAN
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and running are all acts which involve chest wall or abdominal muscles in nonrespiratory distortion. Our experiments may have thrown some light on the response of the system to this type of distortion. Thus, PPB may cause a similar shift in diaphragm mechanics to the change from supine to upright posture. Restriction of abdomen or rib cage may be analagous to situations where their musculature is fixed by being involved in a non-respiratory muscle activity. There appear to be some conscious options in response to changes in load as to broad type of breathing pattern adopted. However, within these patterns there seems to be control of respiratory muscle activation. In the case of the diaphragm this control acts by a compensating increased neural excitation when the diaphragm is put at a decreased mechanical advantage. The mechanism of this is likely to be reflex.
References Agostoni, E. (1962). Diaphragm activity and thoracoabdominal mechanics during positive pressure breathing. J. Appl. Physiol. 17: 215-220. Agostoni, E. and G. Torri (1962). Diaphragm contraction as a limiting factor to maximum expiration. J. Appl. Physiol. 17: 427-428. Bishop, B. (1963). Abdominal muscle and diaphragm activities and cavity pressures in pressure breathing. J. Appl. Physiol. 18:37 42. Bishop, B. (1964). Reflex control of abdominal muscles during positive pressure breathing. J. Appl. Physiol. 19: 224-232. Bishop, B. (1967). Diaphragm and abdominal muscle responses to elevated airway pressures in the cat. J. Appl. Physiol. 22:959 965. Bishop, B. and H. Bachofen (1972). Vagal control of ventilation and respiratory muscles during elevated pressures in the cat. J. Appl. Physiol. 32:103-112. Boothby, W. M. and F.B. Berry (1915). Distension of the lungs: its effect on the respiration in man and in normal and vagotomised dogs. Am. J. Physiol. 37: 433451. Christiansen, J. and J. S. Haldane (1914). The influence of distension of the lungs on human respiration. J. Physiol. (London) 48:272 277. Clark, F.J. and C. Von Euler (1972). On the regulation of depth and rate of breathing. J. Physiol. (London) 222:267 285. Corda, M., C. von Euler and G. Lennerstrand (1965). Proprioceptive innervation of the diaphragm. J. Physiol. (London) 178:161 177. Decima, E.E. and C. von Euler (1969). Excitability of phrenic motoneurones to afferent input from lower intercostal nerves in the spinal cat. A cta Physiol. Scand. 75: 580-591. Decima, E.E., C. von Euler and U. Thoden (1969). Intercostal to phrenic reflexes in the spinal cat. Acta Physiol. Scand. 75:568 579. Draper, M.H., P. Ladefoget and D. Whitteridge (1960). Expiratory pressures and air flow during speech. Brt. Med. J. 1837 1843. Eger, E.R., R.H. Kellogg, A.H. Mines, M. Lima-Ostos, C.G. Morrill and D.W. Kent (1968). Influence of CO~_ on ventilatory acclimatisation to altitude. J. Appl. Physiol. 24: 607-615. Ernsting, J. (1966). Some effects of raised intra-pulmonary pressure in man. (The Advisory Group for Aerospace Research and Development of the North Atlantic Treaty Organisation). Maidenhead, Technivision Ltd. Flenley, D.C., L.D. Pengelly and J. Milic-Emili (1971). Immediate effects of positive pressure breathing on the ventilatory response to CO 2. J. Appl. Physiol. 30 : 7 11.
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Godwin-Austin, R.B. (1969). The mechanoreceptors of the costo-vertebral joints. J. Physiol. (London) 202:737 753. Goldman, M.D. and J. Mead (1973). Mechanical interaction between the diaphragm and rib cage. J. Appl. Physiol. 35:197 204. Grassino, A. E., G. E. Lewinsohn and J. M. Tyler (1973). Effects of hyperinflation of the thorax on the mechanics of breathing. J. Appl. Physiol. 35 : 335-342. Grassino, A.E., W.A. Whitelaw and J. Milic-Emili (1976). Influence of lung volume and electrode position on electro-myography of the diaphragm. J. Appl. Physiol. 40: 971-975. Grassino, A.~ M.D. Goldman, J. Mead and T.A. Sears (1978). Mechanics of the human diaphragm during voluntary contraction: statics. J. Appl. Physiol. 44: 82%839. Guz, A., M. Noble, D. Trenchard, H.L. Cochrane and A.R. Makey (1964). Studies on the vagus nerve in man : Their role in respiratory and circulatory control. Clin. Sci. 27 : 293 304. Head, H. (18893. On the regulation of respiration. J. Physiol. (London) 10:1 70. Heat', P. J. D. and F.J. Prime (19563. The compliance of the thorax in normal human subjects. Clin. Sci. 15: 319-327. Houk, J. and E. Henneman (1967). Responses of Golgi tendon organs to active contractions of the soleus muscle of the cat. J. Neurophysiol. 30: 466481. Johnson, L.F. and J. Mead (1963). Volum~pressure relationships during pressure breathing and voluntary relaxation. J. Appl. Physiol. 18: 505-508. Konno, K. and J. Mead (19673. Measurement of the separate volume changes of rib cage and abdomen during breathing. J. Appl. Physiol. 22:407 422. Marshall, R. (1962). Relationships between stimulus and work of breathing at different lung volumes. J. Appl. Physiol. 17:917 921. Mead, J. (1974). In: Loaded Breathing, edited by L. D. Pengelly, A.S. Rebuck and E. J. M. Campbell. Don Mills, Ontario, Longman Canada Ltd., pp. 206 207. Newsom Davis, J. and T.A. Sears (1970). The proprioceptive reflex control of the intercostal muscles during their voluntary activation. J. Physiol. (London) 209: 711-738. Pengelly, L.D., A.M. Alderson and J. Milic-Emili (1971). Mechanics of the diaphragm. J. Appl. Physiol. 30:797 805. Petit, J.M., J. Milic-Emili and L. Delhez (1960). Role of the diaphragm in breathing in conscious normal man: an electromyographic study. J. Appl. Physiol. 15:1101-1106. Rahn, H., A.B. Otis, L.,E. Chadwick and W.O. Fenn (1946). The pressure volume diagram of the thorax and lung. Am. J. Physiol. 146:161 178. Remmers, J.E. and W.G. Tsiaras (19733. Effect of lateral cervical cord lesions on the respiratory rhythm of anaesthetised, decerebrate cats after vagotomy. J. Physiol. (London) 233: 63-74. Sears, T. A., J. Mead, D. Leith, R. Kellogg, R. Knudson and M.D. Goldman (19683. The role of the diaphragm in stabilising ventilation. Proc. Int. Un. Physiol. Sci. 7: 394. Taylor, A. (19603. The contribution of the intercostal muscles to the effort of respiration in man. J. Physiol. (London) 151:390 402. Widdicombe, J.G. (1%4). Respiratory reflexes. In: Handbook of Physiology, Section 3, Respiration, Vol. 1, edited by W. O. Fenn and H. Rahn. Washington, Am. Physiol. Soc., pp. 585-630.
M U S C L E A C T I V I T Y D U R I N G C H E S T WALL R E S T R I C T I O N A N D P O S I T I V E P R E S S U R E B R E A T H I N G IN M A N ~
M A L C O L M G R E E N , JERE M E A D 2 and T H O M A S A. SEARS Sobell Department o["Neurophysiology Institute of Neurology, Queen Square, London WCI, United Kingdom and Department o['Physiology, Harvard School o/' Public Health, Boston, MA 02115, U.S.A.
Abstract. The effects of sustained constriction of the rib cage (RCC), constriction of the abdomen (AC)
and of breathing against a positive pressure of 10 cms of water (PPB) were studied in four normal subjects with moderate constant hypercapnia. Intercostal electrical activity (Eic) was measured by implanted wire electrodes and diaphragmatic electrical activity (Edia) by oesophageal electrodes. There was no fixed relation between Edia and VT. VT was unaltered during AC and RCC: Edia was unaltered during AC but increased during RCC. The response to PPB without constriction varied: three subjects increased end-expiratory VL with increase in Edia and inspiratory Eic. One subject initially, and one subject after training, maintained end-expiratory VL constant with no change in Edia and an increase in expiratory Eic. When PPB was applied during AC and RCC there was an increase in Edia proportional to end-expiratorylung volume. The overall response to distortion was determined by voluntary choice, but muscle electrical activity reflected chest wall configuration : when the diaphragm was shorter and at a mechanical disadvantage its electrical activity increased. This was compatible with a reflex with afferent information from diaphragm tendon organ and muscle spindle receptors. Chest wall mechanics Diaphragm Diaphragm reflexes
Intercostal muscles Patterns of breathing Respiratory mechanics
It has been shown that as the diaphragm becomes shorter and less curved, its mechanical efficiency at reducing intrapleural pressure and hence of inducing changes in lung volume, becomes less (Marshall, 1962; Pengelly, Alderson and Milic-Emili, 1971). In the course of some other experiments (Mead and Sears, unpublished observations), four subjects were exposed to positive pressures at the Accepted [br publication 2 August 1978 I This work was presented in part at the International Symposium on 'The Effects of Mechanical Loads on Breathing" at McMaster University, April 1973. 2 j. M. was supported by National Heart and Lung Institute Grant HL 14580. 283
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mouth and in all four the increased end-expiratory lung volume was associated with an increase in diaphragm electrical activity during tidal breathing. This might have been due to increased respiratory drive consequent upon an increased chemical stimulation to the respiratory centres, but another possibility was that there might be reflexes which were able to compensate for the decreased mechanical advantage of the shortened diaphragm by increasing efferent activity for the diaphragm at a given level of chemical respiratory drive. Previous workers had assumed that efferent drive to the diaphragm remained constant for a given chemical drive over a range of lung volumes (Marshall, 1962). We set out to test whether we could confirm that manoeuvres which put the respiratory system or the diaphragm at a mechanical disadvantage did indeed cause increase in diaphragm electrical activity when chemical respiratory drive was held constant, and whether we could identify the mechanical factors which correlated with increased diaphragm electrical activities. We argued that if the excursion of the rib cage was restricted, diaphragmatic shortening would be augmented and this might be associated with increased diaphragmatic electrical excitation. Conversely, if abdominal excursion was restricted, the diaphragm configuration would be maintained at a more advantageous length and hence there would be no increase in electrical excitation, and there might even be a decrease. Because mechanical interventions would be expected to influence pulmonary ventilation and thereby alter stimuli to breathing, we used a technique which minimised fluctuations in alveolar (and hence blood) gas composition as described by Eger et al. (1968). Since our electromyograph (EMG) recordings were relatively insensitive, we stimulated breathing by moderate hypercapnia.
Methods
Studies were caried out on four healthy males (table 1). They differed in their level of sophistication as respiratory subjects. J.M. was very experienced, having performed respiratory manoeuvres, including positive pressure breathing, on numerous previous occasions. M.G. and M.H. had a grasp of respiratory mechanisms, and without instruction simply believed that they should relax in TABLE 1 Physical characteristics of subjects Subject
Age (yr)
Height (cm)
Weight (kg)
TLC (liter)
VC (liter)
J.M. M.H. M.G. R.L.
50 34 29 26
188 163 175 178
86 63 65 68
9.0 6.2 6.0 7.0
6.8 4.9 4.7 5.6
R E S P I R A T O R Y M U S C L E A C T I V I T Y IN M A N 2 Liter tube
I I
Blower
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I I
Volume
Diaphragm EMG
Intercostal EMG
Fig. 1. Diagram of experimental set-up, see text. R C C indicates arrangement for restricting rib cage excursion and A b d o C for restricting abdominal excursion. 'Blower' represents the reversed vacuum cleaner.
the face of distortions, but had not previously performed positive pressure breathing. R.L. although medically qualified was a neophyte as a respiratory subject. The experimental set up (fig. 1) consisted of a rigid metal frame in which the subject was seated, with his back against a flat board. He breathed through a mouthpiece into a long wide bore tube, 2 litres in volume. Air was added close to the mouth at a constant rate throughout all the manoeuvres (Bias flow in fig. 1). Thus the subject was able to breathe air up to this rate, but further ventilation was derived from expired air re-inhaled from the large bore tube. Hence the chemical stimulus to breathing remained independent of the levels of ventilation as described by Eger et al. (1968). The rate of flow of air was adjusted for each subject so that his breathing was slightly stimulated by hypercapnia to a level where tidal volume was 25-30~ of his vital capacity. Carbon dioxide concentration within the mouthpiece assembly was continuously analysed by a Godart Capnograph Infra-red Analyser. Flow was measured at the mouth by a Fleisch Pneumotachograph and a variable capacitance pressure transducer (Hilger and Watts Ltd., London) and
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was integrated to give tidal volume. Volume was recorded on a six-channel ultraviolet recorder (Aviation Electronics Ltd., London), adjusted so that one vital capacity manoeuvre covered 10 cm of recording paper and read 1.0 on a digital voltimeter. Volumes could thus be read directly in per cent vital capacity (Newsom Davies and Sears, 1970). The diaphragm EMG was recorded with a balloon-stabilised oesphageal lead (Sears et al., 1968). The subject swallowed a gastric balloon which was pulled back until the inflated balloon rested against the cardia of the stomach, being held there by the weight of the tap at the mouth-end of the catheter. Electrical activity of the diaphragm was recorded by means of two oesphageal electrical leads 2 cm apart on the balloon catheter which picked up action potentials of the vertical crural part of the diaphragm (Agostoni and Torri, 1962; Petit, Milic-Emili and Delhez, 1960). Following the experience of Draper, Ladefoged and Whitteridge (1960) and Newsom Davis and Sears (1970) intercostal EMG activity was led from a pair of wires inserted into the 6th or 7th intercostal spaces in line with the lower part of the scapula (Taylor, 1960). This had the advantage of sampling from both the internal and external layers and this gave a less restricted view of the electrical response of the intercostal muscles than would have been the case with recording from a single layer. Recording from the parasternal region was not used because of the difficulty of avoiding movement artefact when pressing on the sternum. Intercostal activity was judged as inspiratory (external intercostal) or expiratory (internal intercostal) by its time relation to the phases of ventilation and confirmed also by voluntary activation of the muscles at the time the electrodes were introduced. The EMG was full-wave rectified, smoothed (time constant 200 msec), amplified and recorded with high frequency response galvanometers on the ultra-violet recorder. Abdominal excursion could be limited by means of a block of wood shaped to fit the abdominal contour anteriorly and held rigidly in place on an adjustable clamp fixed to the metal frame. The block could be forced inwards without impinging on the rib cage or pelvis to a previously established point where end-expiratory volume was reduced by not more than 5~o vital capacity and fixed in this position. Similarly, rib cage excursion could be limited by an adjustable board held rigidly against the sternum which severely restricted rib cage expansion but did not reduce end-expiratory volume by more that 5 ~ VC. The subject breathed for a period through the apparatus to establish satisfactory and stable levels of ventilation and electrical activity. Rib cage restriction alone was applied for ten breaths on three occasions and then abdominal constriction alone on three occasions. Following this, positive pressure breathing (PPB) was studied. Positive mouth pressures were produced at the outlet of a commercial vacuum cleaner (reversed so that it blew), and applied to the distal end of the long tube. A pressure of 10 cm of water (measured by a water manometer) was applied by turning a tap to connect in the vacuum cleaner at the onset of an inspiration and was maintained throughout the respiratory cycle for ten full breaths. The experimental procedure consisted of three periods of positive pressure breathing of ten
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breaths each, with ten breaths or more between (PPB with no restrictions). The rib cage was then restricted, and PPB again applied for three periods after which the restriction was released (PPB with RC restriction). After a further period of control breathing, abdominal compression was applied and the PPB repeated three times (PPB with abdominal constriction). Finally PPB was again applied three times with no restrictions. The experiments on JM and MG and the first experiment on RL were all completed before any analysis of the records and before we were able to recognise any of the trends or patterns in the responses. This turned out to be important when we realised the role of training in the responses to PPB. The records were analysed by taking the individual breaths and the means of the responses over ten breaths before, during and after an intervention. The EMG signals were read as the maximum activity achieved during a given inspiration or expiration. Clearly this measure of EMG signals is relatively crude as the maximum EMG may occur at different points in the tidal volume, depending on respiratory frequency, pattern of breathing and other factors. However, we felt that to relate the electrical activity to mechanical events would be no less arbitrary. Although EMG activity is comparable within a subject during an experiment, the activity is measured in arbitrary units, and the absolute levels are not necessarily comparable between experiments.
Results
The method of controlling CO_, was largely effective in maintaining a constant end-expiratory Pco_, throughout each experiment, at levels which varied between 44 and 56 mm Hg Pco: in the different subjects. End-expiratory Pco.~ altered by less than 2 mm Hg Pco~ during the course of an experiment: there was a small decrease (range 0 to - 2 mm Hg Pco~, mean -1.25 mm Hg) in those subjects where PPB caused an increase in end-expiratory volumes. In no experimental circumstance was there an increase in Pco.~. It seems likely that the falls in Pcoz we observed were due to dilution of alveolar gas with deadspace and atmospheric air when endexpiratory volume rose. The effects of rib cage and abdominal restriction alone on tidal volume and electrical activity of the diaphragm in the four subjects are shown in fig. 2, expressed relative to their levels before restriction. There was little change in tidal volume with either mode, and abdominal restriction did not significantly alter diaphragm electrical activity. Neither rib cage nor abdominal restrictions on their own shifted end-expiratory lung volume by more than 5% VC (see Methods). However, there was a considerable rise in diaphragm electrical activity when the rib cage was restricted. Intercostal activity showed no consistant changes, either in inspiration or in expiration during the restrictions. Illustrative records of the effects of the application of PPB with no restrictions on lung volume, diaphragm electrical activity and intercostal activity in two subjects
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Abdolinal r e s ~
1.5 l.O 0.5
0.5
1.0
1.5
i
0.5
2.0
i
l.O
i
1.5
i
i
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F. (restricted) E (control) Fig. 2. Effects of abdominal restriction (left) and rib cage restriction (right) without PPB on tidal volume and electrical activity. On the ordinate tidal volume (Vx restricted) is expressed as a fraction of the control values for each subject before restriction. On the abscissa is plotted the electrical activity (E restricted) for the diaphragm (filled-in circles for individual points, square for the means). In addition, for abdominal restriction only, is shown the electrical activity of the inspiratory intercostal muscles (triangles for individual points, circled triangle for the mean), again expressed as a fraction of the respective control value for each subject before restriction. The lines of identity are shown: points would lie on these if the increase in E was proportionately similar to the increase in Vx. Subject J . M
Edia
~ 10 S e c s
Subject R.L.
Edia
Eic
~ m~
I
~ 10 Secs
Fig. 3. Representative tracings of effects of one application of PPB on tidal volume (VT), and electrical activity of the diaphragm (Edia) and intercostal muscle (Eic) in two subjects, see text. Inspiration is upwards. Edia and Eic are in arbitrary units (see Methods).
are shown in fig. 3. One subject (JM) increased end-expiratory volume in response to PPB whilst the other (RL) maintained end-expiratory volume about constant (see below). Table 2 shows the effect of PPB on ventilation, expressed as VC/min (derived by dividing minute ventilation of a subject by his own vital capacity. All subjects showed a fall in tidal volume (Mean fall 25~) which was maintained during the pressure but returned to control levels immediately PPB was stopped. On average
R E S P I R A T O R Y M U S C L E ACTIVITY IN M A N M.H.
J.M.
289
M.H. after
instruction
1001
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C
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PPB
It
] It
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R.L.
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[ C
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R . L . after
instruction
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Ins 201 T 0
'°o1:C
I I
I
I
t
t
PPB
IT
C
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C
T
PPB
Fig. 4.' Effect of PPB on lung volume (~o Vc), electrical activity of diaphragm (Edia) and of intercostals (Eic) in the four subjects. Edia and Eic are in arbitrary units (see Methods). C are control values. Inspiratory intercostal activity (ins) is shown above the baseline and expiratory (exp) below the baseline for Eic, On the left are shown the four subjects initially. On the right are shown subjects M H and RL after instruction, see text.
there were small increases in respiratory frequency giving overall small decreases in minute ventilation. The mean effects of PPB with no restrictions in the four subjects are shown in fig. 4. Three subjects (JM, MG and MH before instruction) showed an immediate rise in end-expiratory lung volume with PPB. End-expiratory lung volume remained steady during pressure in subject JM and was identical on each occasion of PPB and on different experimental days. The rise in end-expiratory lung volume with PPB in subjects M G and MH was also marked but more variable from brath to breath and between separate days of PPB. In these three subjects the diaphragm EMG activity of each breath increased with PPB. At the same time inspiratory intercostal activity increased while in the one subject in whom it could be detected (MG) expiratory intercostal activity diminished. The fourth subject (RL) did not increase end-expiratory volume and in him the activity of the diaphragm remained constant during PPB. Furthermore, inspiratory intercostal activity diminished while expiratory intercostal activity greatly increased. Thus in general when end-expiratory volume increased during PPB (with no restrictions), inspiratory activity was increased and expiratory activity reduced and vice versa. It seemed that the apparently conflicting results in the four subjects
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might have a common explanation in the pattern of breathing adopted. We therefore 'trained' subjects MH and RL after their initial experiments were finished to react to PPB in a different way from their initial responses. Subject MH had relaxed and allowed the pressure to inflate his respiratory system along its relaxation pressure-volume characteristic. We trained him to hold FRC constant. This he achieved (fig. 4B : MH after instruction) by increased activity of intercostal muscles, which from their phasing were in all probability expiratory muscles, and a slight fall in diaphragm electrical activity. Subject RL on the other hand was instructed to allow PPB to increase his end-expiratory volume instead of resisting the changes in lung volume. He now showed (fig. 4: RL after instruction) an increase in endexpiratory volume and despite a fall in tidal volume his diaphragmatic excitation was increased during PPB. Thus whenever individuals allowed PPB (with no restrictions) to increase endexpiratory lung volume, diaphragmatic activity increased. However, no increase in activity was seen when end-expiratory volume was prevented from increasing. Similarly, expiratory intercostal activity diminished and inspiratory increased when end-expiratory lung volume rose, whereas expiratory intercostal activity increased when end-expiratory lung volume was not allowed to rise with PPB. PPB on
! It I t ~t
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'l I
t
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!
I I
I' I
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.SO-
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0
0
2
'
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8
]0
0
2
4
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lO
Fig. 5. Response of diaphragm electrical activity (Edia) and tidal volume (VT) breath-by-breath to PPB: mean of three applications of PPB in each of the three subjects who initially increased end-expiratory volume with PPB. (Left). Edia and VT of each breath after initiation o f PPB at Breath 0 expressed as ~°/0of the mean response of the 10 breaths. (Right). Edia and VT following finish of PPB at Breath 0.
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The changes in tidal volume and diaphragmatic excitations in response both to the onset and the stopping of PPB occured abruptly (fig. 5). Although there is some variability, there was no significant difference when the tidal volumes of the first, second, third or tenth breaths were compared with the mean during the PPB loads or when the comparisons were made after stopping PPB. Similarly the changes in electrical activity were on average completed by the second breath (fig. 5). When PPB was applied during rib cage and abdominal restriction, the changes in electrical activity of the diaphragm and intercostal muscles were somewhat variable. Howeyer, when these were related to end-expiratory lung volume and chest wall configuration, a consistant pattern emerged and this is presented in the discussion.
Discussion
When external loads were aplied to the respiratory system there could be dramatic changes in excitation of the respiratory muscles without corresponding changes in tidal volume and minute ventilation. Thus there was no fixed relationship between electrical activity of the respiratory muscles and the VT achieved when respiratory system configuration altered. The experimental procedure was designed to hold Pco_~ constant in the face of mechanical loading. The lack of change in Pco~ was confirmed by the measurements of end-tidal (end-expiratory) Pco~. Thus chemical causes for altered electrical activity can be excluded. When we alalysed our results it became clear that an adequate explanation for them could only be made if the configuration of the chest wall was taken into consideration. In our experiments we did not measure chest wall configuration directly, but the changes can be deduced qualitatively from the reports of Goldman and Mead (1973) and Grassino et al. (1973). In this discussion, therefore, we analyse our results along these lines.
EMG R E C O R D I N G S
We assume in this discussion that the electrical activity recorded with oesophageal electrodes is a true reflection of the EMG activity of the diaphragm muscle, and that this relationship is not itself altered by changes in configuration of the diaphragm or changes in lung volume. Unfortunately this assumption has proved difficult to test directly (Mead, 1974). Electrodes inserted into the body of the diaphragm in the cat recorded electrical signals at constant phrenic stimulation which did not vary with lung volume or chest wall configurations (Grassino, Whitelaw and MilicEmili, 1976). Attempts to confirm that the same relationship held true in man were thwarted as it proved impossible to achieve supramaximal stimulation of the phrenic nerves in conscious man with safety (Mead, 1974). We can conclude that
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M. G R E E N et al.
diaphragmatic EMG signals in cats are uninfluenced by lung volume and chest wall configuration, and that there is no evidence to the contrary in man at present. E F F E C T S OF RIB C A G E A N D A B D O M I N A L R E S T R I C T I O N
The effects of abdominal restriction without PPB on tidal volume, and electrical activity of the diaphragm and intercostal muscles were small (fig. 2). This probably reflects the tendency in normal subjects for tidal volume to be achieved by contraction of the diaphragm and increase in size of the rib cage. During eupneic breathing and moderate hypercapnia there are only small increases in abdominal diameter during inspiration (Goldman and Mead, 1973). To the extent that enlargement of the abdomen is prevented by abdominal restriction (without PPB), it would be expected that the diaphragm would be maintained throughout inspiration at a more curved shape and hence at a greater mechanical advantage, causing either an increase in tidal volume or a decrease in diaphragmatic electrical activity. Neither of these were seen, possibly due to the increased impedance to inspiration presented by the restricted and hence stiffened abdomen, or possibly because some flattening of the diaphragm occurs in lifting the rib cage. During quiet breathing tidal volume is achieved by expansion of the rib cage and descent of the diaphragm. If expansion of the rib cage is prevented, while the same tidal volume is maintained, it might be expected that the diaphragm would descend further, and thus shorten more. Indeed, Konno and Mead (1967) have shown that for a given tidal volume, if the rib cage is prevented from expanding, abdominal displacement is increased. Since, to a useful approximation, abdominal displacement reflects diaphragm length (Grassino et al., 1978), during rib cage restriction the diaphragm must shorten more than during unrestricted breathing. In our experiments restriction of the rib cage (without PBB) caused no fall in tidal volume despite the tendency .to increase the mechanical impedance of the respiratory system, and to force the diaphragm to shorten more for a given volume inspired, thereby decreasing its mechanical efficiency. Tidal volume was almost completely maintained (on average at 92~ of control levels) by a striking increase in diaphragmatic electrical activity (average increase 55~, fig. 2). E F F E C T S O F PPB
(1) Lung volume changes Studies of responses to PPB have usually implicitly assumed that it is possible to define a physiologically normal and uniform response to such respiratory insults (Agostoni, 1962; Christiansen and Haldane, 1914; Ernsting, 1966; Rahn et al., 1946). However the strictly rational response of the ordinary man to PPB would be to come off the mouthpiece ! The response of subjects instructed only to stay on the mouthpiece and not told whether to relax nor in any way to respond to the stimulus
R E S P I R A T O R Y MUSCLE ACTIVITY IN M A N
293
does not seem to have been reported. Christiansen and Haldane (1914) described an apneustic response to PPB (in informed subjects doubtless influenced at that time by knowledge of the Hering Breuer reflexes). More recent reports have uniformly described a rise in end-expiratory lung volume which more or less closely followed the relaxation pressure-volume characteristic of the respiratory system (Agostoni, 1962; Boothby and Berry, 1915 Ernsting, 1966 ; Flenley, Pengelly and Milic-Emili, 1971; Heaf and Prime, 1956; Johnson and Mead, 1963). These results may have been influenced by the concepts introduced by Rahn et al. (1946). Three subjects familiar with respiratory manoeuvres (JM, MH, MG) assumed that they should allow end-expiratory volume to increase in response to PPB. The fourth subject RL, however, had no pre-conceived ideas as to 'normal' response to PPB and was simply told that 'he would feel a pressure' when he was breathing. His response was to maintain end-expiratory volume constant in response to PPB. This proved fortuitous as it allowed us to distinguish between the effects of PPB itself and the effects of changes in configuration of the respiratory system produced by PPB as well as the importance of conscious control and training in response to this mechanical load. Both MH (who initially increased end-expiratory volume in response to PPB) and RL (who did not) were easily trained to adopt a response to PPB opposite to their initial reaction. Subsequently both stated that they had no subjective preference to either pattern of breathing. The different patterns of response adopted by our subjects do re-emphasise the importance of subject instruction in physiological experiments and the dangers of looking for, and indeed finding, predetermined 'normal' responses. (2) Tidal volumes and inspiratory./low rates PPB caused a fall in tidal volume, although in subjects MG and RL this was partially counteracted by a rise in respiratory rate (table 2). In subjects RL and MH, the decreases in tidal volume were greater when end-expiratory position increased (fig. 4) than when it was unaltered. This is compatible with the increased impedence of the respiratory system at higher lung volumes. Flenley et al. (1971) found similar changes during four breaths of PPB, although there is evidence that minute ventilation is well maintained during PPB over several minutes (Ernsting, 1966; Grassino, Lewinsohn and Tyler, 1973; Petit, Milic-Emili and Delhez, 1960). It is postulated that the central respiratory neurones achieve a given tidal volume by producing a particular inspiratory flow rate which is interrupted at end inspiration by a respiratory timing mechanism (Clarke and Von Euler, 1972). In our experiments there were only small changes in respiratory frequency, and the relative duration of inspiration and expiration (illustrated in fig. 3A and B) did not change appreciably in any of the experimenial circumstances. We conclude that there was an equivalence between tidal volume and mean inspiratory flow rate in these experiments. Furthermore, since inspiratory duration was little altered by the manoeuvres it seems reasonable to interpret the amplitude of the Edia signal as adequately reflecting the intensity of diaphragmatic stimulation.
M.H.
J.M.
R.L.
M.G.
1
V (VC/min)
27
25
I
13.1
14.8
13.3
20 22.3
26 20
25
17.3
36
3.3
4.0
3.3
5.2 4.5
6.2
28
14
20
21 12
29
VT C,o VC)
f (min - l)
VT
(% vc)
PPB
Control
I1
I1
Subject
11.0
14.2
13.4
22 22.5
19.8
f (min - J)
2.0 3.1
2.8
2.7
4.6
5.8
V (VC/min)
+ 6
-48
-20
-40
- 19
- 19
Vl ("~o)
Change
4
-16
-
+ 0.7
+ 10 + 1
+ 13
f (?Jo)
TABLE 2 Effect of PPB for 10 breaths on VT, frequency (f) and minute ventilation (V min) (Mean of 3 applications, see text)
6.7
-50 - 6
-15
-11.5 -40
(%)
t~
R E S P I R A T O R Y MUSCLE ACTIVITY IN MAN
295
(3) Electrical Activity In our experiments, the three subjects who raised lung end-expiratory volume in response to PPB, showed markedly increased diaphragm and inspiratory intercostal activity with reduced expiratory intercostal activity (when recorded). This suggests that there are substantial neural mechanisms that act to defend tidal volume (and inspiratory flow rate) under adverse circumstances. In confirmation of this, RL showed a similar increase in diaphragm activity when, after training, he allowed PPB to increase his lung end-expiratory volume. Changes which shorten the diaphragm put it on a less advantageous part of its length tension characteristic both through being shorter and by being less curved (and hence less powerful by the Laplace relationship (Marshall, 1962)). Flenley et al. (1971) argued on mechanical grounds that the fall in tidal volume they described was a simple reflection of the impaired mechanical efficiency of the diaphragm, because they assumed that neural excitation was constant during PPB. However, it now appears that this mechanical effect is much greater than they conceived since the increase in diaphragmatic excitation concomitant with a flattening of the diaphragm would tend to mask the potential reduction in tidal volume. By contrast two of our subjects (RL initially and MH after instruction) responded to PPB with little change in end-expiratory lung volume. In them the effects of the applied static pressure resisting expiration were compensated for by an increase in expiratory intercostal activity during inspiration. Our observations contrast with the findings in anaesthetised dogs and cats by Bishop (1963, 1964, 1967; Bishop and Bachofen, 1972) and anaesthetised men by Guz et al. (1964) that PPB with rise in end-expiratory volume caused diaphragmatic inhibition and expiratory excitation. It appears therefore that anaesthesia has an important role in modifying the neurological responses to PPB. When PPB was applied during rib cage and abdominal restriction, the changes in electrical activity were quantitatively rather variable. However, we postulated that diaphragm electrical activity would relate to its degree of shortening. It is at end-inspiration that the diaphragm is maximally shortened. Therefore, if diaphragmatic electrical activity did relate to its degree of shortening, there might be a relationship between end-inspiratory lung volume and electrical activity of the diaphragm. This relationship during PPB is plotted in fig. 6 for the four subjects. A line can be drawn through the points in each subject and this projects to zero electrical activity at, or close to, FRC. Figure 7 is a plot showing the same lines and in addition, the electrical activity of the diaphragm before and during PPB applied whilst either the abdomen or the rib cage were restricted. The points during abdominal restriction alone lie close to the unrestricted relationship. During PPB with abdominal restriction in subjects JM, MG and MH there appears to be about the same or slightly less increase in electrical activity of the diaphragm as without restrictions. During PPB the decreased compliance of the system therefore, seemed to be matched by the increased mechanical efficiency which the diaphragm derived from maintaining a higher degree of curvature. Subject RL showed a very much
296
M. G R E E N
Eda i"~IM~
et al.
40R~ ~)0
OL /
FRC 20
4O
6O
4oIMG
0
FRC 20 ,4O 60
4.0
E
MH
oL,11 FRC 2 0
40
60
O/oVC
x :withc~ PPB X:during PPB
FIRC 20 40
60
% vc
End Impl'o~'y Lung 'vblun~
Fig. 6. Relationship between Edia (arbitrary units) and end-inspiratory lung volume C'/o VC) b e f o r e and during PPB in four subjects. "Best fit' lines drawn by eye. Each point represents mean of three applications o f 10 breaths.
JM
80
Abdo. restr n Rib restr n
+ o
-P O
,10
60
!
60
//
E dia
g
4o
© FP~2 2 0
dia
Control
/
/ O
t
40JRL
40
60
/
N:IC 2 0
,0 ~
%vc
%vc
End ~r~o~o~ LungV o ~
Fig. 7. Relationship between Edia (arbitrary units) and end-inspiratory lung volume (')i, VC) b e f o r e and during PPB applied whilst either rib cage or abdomen is restricted. "Best fit' lines re-drawn f r o m fig. 6: each point represents mean of three applications o f 10 breaths.
smaller increase in end-inspiratory volume during PPB with abdominal restriction and concomitantly a slight decrease in diaphragm activity. It him, the increased mechanical advantage of the diaphragm during abdominal restriction appeared to more than match the increased load, allowing less neural drive for a given endinspiratory lung volume. During rib cage constriction alone electrical activity of the diaphragm increased at a given lung volume, as shown by small circles in fig. 7. When PPB was applied in addition (large open circles) two of the subjects (MG and MH) showed further increases in electrical activity of the diaphragm which about matched their increases in end-inspiratory lung volume. The other two subjects (JM and RL) showed relatively much larger increases in electrical activity of the diaphragm than
RESPIRATORY MUSCLE ACTIVITY IN MAN
297
predicted from the unrestricted relationships. This suggests that in them, the combination of rib cage restriction and PPB compounded each other in decreasing mechanical efficiency of the diaphragm, and this was associated with larger compensatory increases in its nervous excitation. The differences between the subjects may relate to differences in their chest wall anatomy or their central nervous system sensitivities.
CONTROL OF RESPIRATORY MUSCLE
We have evidence that there is a fine control of patterns of respiratory muscle activity. In particular, increased excitation of the diaphragm tends to compensate in situations where the diaphragm's mechanical efficiency is impaired at a given chemical stimulus. We now analyse the mechanisms which might co-ordinate these patterns of respiratory muscle activity. One possibility is that the alterations in ventilation are achieved by chemical regulation. This seems unlikely. Rise in lung end-expiratory volume by application of suction to the chest wall of subjects breathing air causes no change in tidal volume or in alveolar Pco~ over 10 minutes (Grassino, Lewinsohn and Tyler, 1973; Rahn et al., 1946). Our experiments were designed to minimise changes in the subject's Pco, and the small changes seen when PPB caused a rise in end-expiratory lung volume were always in a direction of a lower Pco_,. Despite this, diaphragm activity always increased. Conscious control undoubtedly played a role in the breathing pattern adopted, at least with respect to end-expiratory volumes. Thus the three subjects with experience and insights into concepts such as ~relaxation' pressure-volume curves allowed pressure to drive their end-expiratory volume up, and as a result their diaphragm electrical activity, and presumably muscular activity, increased. There are, however, several reasons for thinking that detailed control of neural excitation of the respiratory muscles by a conscious mechanism alone was improbable. Firstly, the patterns of response to each distortion were reproducible within a given individual, both within an experiment and from one experimental day to another. Secondly, the responses were surprisingly consistent between subjects when related to end-expiratory lung volumes. Finally, the subjective sensation was maximal when the stimulus was applied, and diminished thereafter, whereas the neural drive remained relatively constant throughout a given stimulus (fig. 5). Thus while the mechanical factors involved in the response to PPB were broadly understood by some subjects this gave no subjective clues to the underlying neurophysiological mechanisms responsible for achieving tidal volume. In essence our results seem to suggest the existence of a reflex mechanism sensitive to mechanical efficiency of the diaphragm, adjusting the neural excitation accordingly, to achieve the required tidal volume. However, our data gave no specific information as to the pathways of the reflexes involved.
298
M. GREEN et al.
The increase in inspiratory muscle excitation seen with increases in end-expiratory lung volume precludes an explanation based on Hering-Breuer inflation reflexes (Widdicombe, 1964). Head's paradoxical reflex (1889), that is inspiratory excitation resulting from rapid lung inflation (if indeed applicable with the vagi intact), could perhaps be implicated when PPB is applied, but could not account for the response during ribcage restriction nor for the maintained excitation throughout restriction or PPB. A wholly spinal reflex has been described for the lower intercostal muscles in cats, in which there is increased phrenic excitation when the rib-cage is stretched (Decima, Von Euler and Thoden, 1969) and this reflex can be stimulated by contractions of the diaphragm itself (Decima and Von Euler, 1969). A reflex arising from the upper rib cage mediated via the brain stem and affecting phrenic motor neurone excitability has been described by Remmers and Tsiaras (1973). The relevance of these reflexes to our results is difficult to assess, as the experimental situations were very different and the mechanisms of the rib cage are complex. However, as described they would not explain our results, as there was increased electrical activity of the diaphragm both when the size of the rib cage increased during PPB and when it was restricted during rib cage restriction : these two manoeuvres in all probability have opposite effects on intercostal stretch receptors. It is possible that intercostal joint receptors may play a part in detecting the position of the rib cage, and hence in part lung volume. However, little is known of their action and their relevance remains conjectural (Godwin-Austin, 1969). Alternatively the pattern of neural activity might be regulated by reflexes from receptors in the diaphragm itself, with the afferent pathway via the phrenic nerve. In contrast to the intercostal muscles where muscle spindles predominate over tendon organs (2.9: 1), in the diaphragm tendon organs predominate over muscle spindles (0.8 : 1) (Corda, Von Euler and Lennerstrand, 1965). Recent work in other sites have suggested that Golgi tendon organs do act in voluntary movements to maintain constant tension in the face of changes in muscle length, velocity or fatigue (Houk and Henneman, 1967). Nevertheless, tension receptors alone would not fully explain our findings as a given tension achieved by the diaphragm will have different implications for lung volume at different configurations. It seems likely, therefore, that the afferent information for such a reflex would depend on a complex interaction of tendon organ and muscle spindle information, analogous to the interaction which occurs in control of limb muscles (Houk and Henneman, 1967). A reflex based on" diaphragm receptors would detect situations in which the diaphragm did not achieve sufficient tension at a given configuration and would provide compensating reflex excitations. Presumably both afferent and efferent paths would be in the phrenic nerves. Such reflex control of the diaphragm seems physiologically logical and would be closely analogous to similar mechanisms in skeletal muscles. Natural changes in internal loading of the respiratory system occur frequently. For example, change from supine to upright posture involves downward displacement of lung and diaphragm. Weight-lifting and carrying, climbing, standing
RESPIRATORY MUSCLE ACTIVITY IN MAN
299
and running are all acts which involve chest wall or abdominal muscles in nonrespiratory distortion. Our experiments may have thrown some light on the response of the system to this type of distortion. Thus, PPB may cause a similar shift in diaphragm mechanics to the change from supine to upright posture. Restriction of abdomen or rib cage may be analagous to situations where their musculature is fixed by being involved in a non-respiratory muscle activity. There appear to be some conscious options in response to changes in load as to broad type of breathing pattern adopted. However, within these patterns there seems to be control of respiratory muscle activation. In the case of the diaphragm this control acts by a compensating increased neural excitation when the diaphragm is put at a decreased mechanical advantage. The mechanism of this is likely to be reflex.
References Agostoni, E. (1962). Diaphragm activity and thoracoabdominal mechanics during positive pressure breathing. J. Appl. Physiol. 17: 215-220. Agostoni, E. and G. Torri (1962). Diaphragm contraction as a limiting factor to maximum expiration. J. Appl. Physiol. 17: 427-428. Bishop, B. (1963). Abdominal muscle and diaphragm activities and cavity pressures in pressure breathing. J. Appl. Physiol. 18:37 42. Bishop, B. (1964). Reflex control of abdominal muscles during positive pressure breathing. J. Appl. Physiol. 19: 224-232. Bishop, B. (1967). Diaphragm and abdominal muscle responses to elevated airway pressures in the cat. J. Appl. Physiol. 22:959 965. Bishop, B. and H. Bachofen (1972). Vagal control of ventilation and respiratory muscles during elevated pressures in the cat. J. Appl. Physiol. 32:103-112. Boothby, W. M. and F.B. Berry (1915). Distension of the lungs: its effect on the respiration in man and in normal and vagotomised dogs. Am. J. Physiol. 37: 433451. Christiansen, J. and J. S. Haldane (1914). The influence of distension of the lungs on human respiration. J. Physiol. (London) 48:272 277. Clark, F.J. and C. Von Euler (1972). On the regulation of depth and rate of breathing. J. Physiol. (London) 222:267 285. Corda, M., C. von Euler and G. Lennerstrand (1965). Proprioceptive innervation of the diaphragm. J. Physiol. (London) 178:161 177. Decima, E.E. and C. von Euler (1969). Excitability of phrenic motoneurones to afferent input from lower intercostal nerves in the spinal cat. A cta Physiol. Scand. 75: 580-591. Decima, E.E., C. von Euler and U. Thoden (1969). Intercostal to phrenic reflexes in the spinal cat. Acta Physiol. Scand. 75:568 579. Draper, M.H., P. Ladefoget and D. Whitteridge (1960). Expiratory pressures and air flow during speech. Brt. Med. J. 1837 1843. Eger, E.R., R.H. Kellogg, A.H. Mines, M. Lima-Ostos, C.G. Morrill and D.W. Kent (1968). Influence of CO~_ on ventilatory acclimatisation to altitude. J. Appl. Physiol. 24: 607-615. Ernsting, J. (1966). Some effects of raised intra-pulmonary pressure in man. (The Advisory Group for Aerospace Research and Development of the North Atlantic Treaty Organisation). Maidenhead, Technivision Ltd. Flenley, D.C., L.D. Pengelly and J. Milic-Emili (1971). Immediate effects of positive pressure breathing on the ventilatory response to CO 2. J. Appl. Physiol. 30 : 7 11.
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M. GREEN et al.
Godwin-Austin, R.B. (1969). The mechanoreceptors of the costo-vertebral joints. J. Physiol. (London) 202:737 753. Goldman, M.D. and J. Mead (1973). Mechanical interaction between the diaphragm and rib cage. J. Appl. Physiol. 35:197 204. Grassino, A. E., G. E. Lewinsohn and J. M. Tyler (1973). Effects of hyperinflation of the thorax on the mechanics of breathing. J. Appl. Physiol. 35 : 335-342. Grassino, A.E., W.A. Whitelaw and J. Milic-Emili (1976). Influence of lung volume and electrode position on electro-myography of the diaphragm. J. Appl. Physiol. 40: 971-975. Grassino, A.~ M.D. Goldman, J. Mead and T.A. Sears (1978). Mechanics of the human diaphragm during voluntary contraction: statics. J. Appl. Physiol. 44: 82%839. Guz, A., M. Noble, D. Trenchard, H.L. Cochrane and A.R. Makey (1964). Studies on the vagus nerve in man : Their role in respiratory and circulatory control. Clin. Sci. 27 : 293 304. Head, H. (18893. On the regulation of respiration. J. Physiol. (London) 10:1 70. Heat', P. J. D. and F.J. Prime (19563. The compliance of the thorax in normal human subjects. Clin. Sci. 15: 319-327. Houk, J. and E. Henneman (1967). Responses of Golgi tendon organs to active contractions of the soleus muscle of the cat. J. Neurophysiol. 30: 466481. Johnson, L.F. and J. Mead (1963). Volum~pressure relationships during pressure breathing and voluntary relaxation. J. Appl. Physiol. 18: 505-508. Konno, K. and J. Mead (19673. Measurement of the separate volume changes of rib cage and abdomen during breathing. J. Appl. Physiol. 22:407 422. Marshall, R. (1962). Relationships between stimulus and work of breathing at different lung volumes. J. Appl. Physiol. 17:917 921. Mead, J. (1974). In: Loaded Breathing, edited by L. D. Pengelly, A.S. Rebuck and E. J. M. Campbell. Don Mills, Ontario, Longman Canada Ltd., pp. 206 207. Newsom Davis, J. and T.A. Sears (1970). The proprioceptive reflex control of the intercostal muscles during their voluntary activation. J. Physiol. (London) 209: 711-738. Pengelly, L.D., A.M. Alderson and J. Milic-Emili (1971). Mechanics of the diaphragm. J. Appl. Physiol. 30:797 805. Petit, J.M., J. Milic-Emili and L. Delhez (1960). Role of the diaphragm in breathing in conscious normal man: an electromyographic study. J. Appl. Physiol. 15:1101-1106. Rahn, H., A.B. Otis, L.,E. Chadwick and W.O. Fenn (1946). The pressure volume diagram of the thorax and lung. Am. J. Physiol. 146:161 178. Remmers, J.E. and W.G. Tsiaras (19733. Effect of lateral cervical cord lesions on the respiratory rhythm of anaesthetised, decerebrate cats after vagotomy. J. Physiol. (London) 233: 63-74. Sears, T. A., J. Mead, D. Leith, R. Kellogg, R. Knudson and M.D. Goldman (19683. The role of the diaphragm in stabilising ventilation. Proc. Int. Un. Physiol. Sci. 7: 394. Taylor, A. (19603. The contribution of the intercostal muscles to the effort of respiration in man. J. Physiol. (London) 151:390 402. Widdicombe, J.G. (1%4). Respiratory reflexes. In: Handbook of Physiology, Section 3, Respiration, Vol. 1, edited by W. O. Fenn and H. Rahn. Washington, Am. Physiol. Soc., pp. 585-630.