Human respiratory muscles: fibre morphology REVIEW

REVIEW
Eur Aesplr J
1991, 4, 587-601
Human respiratory muscles: fibre morphology
and capillary supply
M. Mizuno
Human respiratory muscles: fibre morphology and capillary supply. M.
Mizuno.
ABSTRACT: In man the diaphragm (DIA) and abdominal muscles
comprise approximately 50% slow-twitch (ST) fibres, whereas a higher
proportion (60%) is found in intercostal muscles and the scalenes.
All respiratory muscles show an equal distribution of fast-twitch (Ffa
and b) fibres with the exception of the expiratory Intercostal muscles
which have few Ffb fibres. The inspiratory muscles have a uniformly
small fibre size, in contrast to the expiratory intercostal muscle
fibres which are large. The fibre size of the inspiratory muscles Is
maintained with ageing, whereas that of the expiratory Intercostal
muscles appears to be reduced after the age of 50 yrs. Capillary supply
Is most abundant in the expiratory muscles followed by DIA and the
inspiratory intercostal muscles. In patients with chronic obstructive
pulmonary disease (COPD) it is unknown whether a reduction in fibre
size of the thoracic respiratory muscles is caused by extreme use due to
increased ventilatory work, or by disuse due to an increased Involvement of the extrathoracic respiratory muscles. Histochemical character·
istlcs suggest that, in normal humans, the load on the inspiratory muscles
is relatively small during contractions, whereas the expiratory intercostal
muscles are exposed to severe continuous activity with a heavy load.
Eur Respir ]., 1991, 4, 587-601.
Skeletal muscles possess a large plasticity to
altered pattern of use. The same muscle adapts
differently to recruitment for either short intense or
prolonged activity with low or high force development
[1). Structural and metabolic characteristics of muscle
fibres will therefore depend on a combination of
the pattern and workload in which the muscle is
engaged.
The respiratory muscles provide the pump for ventilation. To move and/or to stabilize the rib cage the
respiratory muscles have to overcome a certain resistance to contractions. During quiet breathing inspiration
is associated with electromyographic (EMG) activity
from the diaphragm, scalenes, sternomastoid, internal
intercostal muscles (INT) of the parasternal region and
external intercostal muscles (EXT) of the posterior part
[2-6] (fig. 1). During expiration EMG activity is limited to the lateral INT. Accordingly, studies have
focused on inspiratory muscles [5, 6, 8-10] and regimes
have been provided for training inspiratory rather than
expiratory muscles [11-15].
In addition to ventilation, the respiratory muscles play
a role during coughing, talking and singing where the
expiratory muscles, e.g. the lateral INT and the
abdominal muscles, would be considered to contribute
significantly (4]. Also, the expiratory muscles dominate
the contribution of the respiratory muscles to postural
Dept of Anaesthesia, Rigshospitalet and August
Krogh Institute, University of Copenhagen, DK-2100
Copenhagen 0, Denmark.
Correspondence: M. Mizuno, Dept of Biochemistry
A, Panum Institute, University of Copenhagen,
Blegdamsvej 3C, DK-2200 Copenhagen N,
Denmark.
Keywords: Ageing; chronic obstructive pulmonary
disease; diaphragm; intercostal muscles; muscle
capillaries; muscle fibre types.
Received: March 27, 1990; accepted after revision
November 20, 1990.
Supported by the Danish Medical Research Council
(12·8198), the Danish National Association against
Pulmonary Disease, Organon, Denmark and
Simonsen & Weel's Foundation.
Poatarlor
Mid-ex llary llneMid-clavlcular line
Fig. 1. - Schematic illustration demonstrating intercostal regions
where electromyographic activity is recorded during breathing at
rest (hatched area for expiration; crossed area for inspiration). The
locations of sampling sites for external (EXT) and internal (INT)
intercostal muscles as well as for the costal diaphragm (DIA) are
marked. Q: inspiratory muscles; 0 : expiratory muscles. Adapted
from MIZUNO and SECHER [1).
588
M. MIZUNO
support during rotation of the trunk as well as during
lifting, carrying and reaching in performing a Valsalvalike manoeuvre. Furthermore, during forced expiration,
as in ventilation during intense exercise, and notably
in patients with asthma, the expiratory muscles are of
utmost importance.
The respiratory muscles may be impaired or severely
taxed in several disease and clinical states. In
patients with chronic obstructive pulmonary disease
(COPD), or with other lung disease, the ventilatory
load is increased and respiratory muscle fatigue may
develop [16]. In patients with muscle dystrophy or with
postoperative partial curarization, weakness of respiratory muscles may cause an inadequate alveolar gas
exchange [17].
In previous reviews on respiratory muscles, functional
rather than morphological aspects have been emphasized [4-6, 8-10]. In this review the histochemical
fibre morphology, capillary supply and biochemical
observations on the inspiratory and expiratory muscles
are described and compared with data from limb skeletal
muscles. Adaptive responses of respiratory muscle
morphology to inspiratory and expiratory function as
well as to ageing are discussed. In addition, the effects
of neuromuscular blocking agents on the respiratory
muscle are summarized.
Classification of skeletal muscle fibres
With the use of histochemical staining for myofibrillar
adenosine triphosphatase (ATPase) [18], two major
fibre types have been classified as type I and type II,
respectively [19]. Because a direct coupling exists
between contraction speed and ATPase activity [20],
it is more descriptive to call them slow- (ST) and fasttwitch (FT) fibres [21). Although a large proportion of
muscle fibres show a coexistence of ST and FT myosin
heavy chain isoforms [22), those fibres histochemically
classified as ST contract slower than FT fibres [23-25).
FT fibres can be further subdivided into FTa or FTb,
identified following preincubations at different pH
values [26) (fig. 2, left panels). ST fibres fatigue less
during repetitive contractions than FTb fibres, whereas
FTa fibres are able to maintain tension similar to ST
fibres (24).
ST fibres are surrounded by a slightly larger number
of capillaries (4-5) than FTa and FTb fibres (2-4)
(fig. 2, middle right panel). Accordingly, ST fibres possess high mitchondrial and low glycolytic enzyme
activity represented by, e.g. nicotinamide adenine
dinucleotide tetrazolium reductase (NADH-TR, fig. 2,
upper right panel) and alpha-glycerophosphate dehydrogenase (a-GPD, fig. 2, lower right panel), respectively. In contrast, the reverse is true for FTb fibres.
Metabolic characteristics of FTa fibres resemble those
of the ST fibres [1]. Although the metabolic profile has
been used to classify muscle fibres, the use of ATPase
staining has been most widely accepted. One of the
reasons for this is that there is not a complete coupling
between fibre classification based on histochemical
~a
FTb
ST
Fig. 2. - Photomicrograpbs of serial transverse sections from
human vastus lateralis muscle incubated for myofibrillar ATPase
activity with preincubations at different pH indicated (left panels),
for NADH-TR activity (mitochondrial enzyme, upper right panel),
for capillaries with the amylase-PAS method (middle right panel)
and for a-GPD activity (glycolytic enzyme, lower right panel). Ff:
fast-twitch; ST: slow-twitch; NADH-TR: nicotinamide adenine dinucleotide tetra~olium reductase; a-GPD: alpha-glycerophosphate
dehydrogenase; ATPase: adenosine triphosphatase; CAP: capillaries.
staining for metabolic enzymes and for myofibrillar
ATPase, in particular, among subgroups of FT fibres
(27). Furthermore, at postmortem, metabolic enzyme
activities decrease more rapidly than ATPase activity
(28, 29).
As may be expected, skeletal muscles such as
antigravity muscles comprise a larger proportion of ST
fibres when compared with muscles recruited less during daily life (30, 31). Successful endurance athletes
possess a dominance of ST fibres (and few FTb fibres)
in their leg muscles, while a high proportion of FT
fibres is found in elite sprinters [1). These findings are
probably dominated by genetic factors (32]. However,
following endurance training a conversion of myosin
heavy chain isoforms is noted towards ST fibres
[33-35]. Endurance training alters FTb fibres in the
direction of FTa fibres (36, 37) and may also partly be
responsible for the dominance of ST fibres in
endurance trained athletes. In contrast, no significant
change in fibre type proportion has been observed
following strength training (38, 39) (table 1).
Skeletal muscle adapts differently to recruitment
depending on the pattern of activity. Endurance training
causes relatively less increase in muscle mass than
strength training. Muscle hypertroph y following
INSPIRATORY AND EXPIRATORY MUSCLES
589
Table 1. - Fibre morphology and capillary supply in human skeletal muscles
Fibre type
distribution
%
Subjects
ST
Mean
fibre
area
Cap.
per
fibre
Fibre
Fibre
area per circumf.
per cap.
cap.
~m~
n
!liD~
FTa
FTb
40
32
28
4900
1.8
990
55
[7}
66
32
2
4700
2.6
710
38
(37]
48
30
22
8700
2.1
1300
[38]
[39]
5000
1.9
990
[40]
6900
3.1
820
11000
2.5
1740
1-lffi
Ref.
Vastus lateralis muscle
Untrained
Endurance
trained•
Strength
trained
Triceps branchii muscle
Untrained
Endurance
trained
Strength
trained
58..
42
44
55
49
1
51°*
38
(37]
(41]
•: data obtained from gastrocnemius muscles; ••: no sub-classification of FT fibres performed; ST: slow-twitch; FT: fast-twitch.
training is probably due to an increase in the size of
individual muscle fibres (table 1) rather than in the total
number of fibres. "Fibre-splitting" may account for
only a marginal increase in muscle volume [42), or
alternatively, represent muscle fibre damage [43).
Capillary supply in muscle fibres increases more with
endurance than strength training (table 1).
Histochemical profile of human
respiratory muscles
The diaphragm
Autopsy materials. In contrast to biopsies from limb
skeletal muscles, which have been obtained largely by
the needle technique [1, 44), samples from respiratory
muscles have most often been acquired during thoracotomy and autopsy. From postmortem studies,
where diaphragm muscle biopsies were obtained from
previously healthy individuals who had suffered a sudden accidental death, the mean relative occurrence of
ST fibres is approximately 50% [7, 45] (table 2). The
remaining proportion is evenly divided into FTa (25%)
and Ffb fibres (25%). Thus, fibre type distribution of
the diaphragm resembles the pattern existing in limb
skeletal muscles of untrained subjects (table 1).
A comparison of the size of individual muscle fibres
between the diaphragm and limb skeletal muscles is
complicated by the use of two different methods. In
order to reduce errors resulting from measurements of
obliquely sectioned fibres [53), muscle fibre size of the
diaphragm has been frequently expressed as "the least
(lesser) diameter" [47-49, 51, 52]. However,
determinations based on measurements of cross-sectional
area by planimetry are more accurate because a curvilinear relationship exists between fibre cross-sectional
area and least fibre diameter (fig. 3) [40, 50] . Furthermore, an implicit assumption of the least diameter
method is that cross-sections of muscle fibres are
circular, whereas either a pentagonal or hexagonal shape
is more accurate (fig. 2) [7, 50). Thus, the crosssectional area of muscle fibres will be constantly underestimated with the use of the least diameter.
The average fibre size of the costal diaphragm determined using the cross-sectional area is 2,200 ~-tm2 in
normal subjects [7, 45] (table 3). ST fibres (800
~-tm2) are slightly larger than both FTa (2,200 ~-tm 2) and
Ffb fibres (1,800 ~-tm 2). Thus, the size of diaphragmatic
muscle fibres is relatively small as compared with that
of limb skeletal muscles (table 1).
The mean number of capillaries per fibre determined
in the costal diaphragm is 1.9 (1.5-2.4) [7). ST
fibres are surrounded by 4--6 capillaries, whereas slightly
less (3-5) are found around FTa and Ffb fibres. These
values are similar to those reported for limb skeletal
muscles of untrained individuals. However, the calculated values for the fibre area surrounded by each
capillary are smaller in the diaphragm (table 4) than in
leg or arm muscles (table 1) [7].
The reason for taking the cross-sectional area
of muscle fibres into account when expressing
capillary supply is that this inde:x may serve as an
indicator for diffusing distance between the capillary
and muscle fibres. According to tlie Krogh concept,
capillaries in skeletal muscles are assumed to serve a
certain cylinder of tissue [55), and thereby indices
based on capillaries pet mm2 of tissue area or conversely tissue area per capillary have been used [1, 36).
Justification for these indices is the finding that the
index for capillary supply related to fibre area has
been shown to be closely linked to the oxidative potential of muscle fibres and also to aerobic work capacity
[1, 56].
M. MlZUNO
590
Table 2. - Fibre type distribution of human respiratory muscles
Expiratory
Inspiratory
Subjects
Intercostal muscles
Diaphragm
n
External
Age
Lateral%
Costal%
MIF
ST
Ffa
2-59 54
17-72 50
17-51 49
21
28
yrs
Internal
Fib
ST
Ffa
Parasternal %
Fib
ST
Ffa
Fib
24
52
61
25
27
21
12
Postmortem
4/3
3/2
8/0
46
69
26
23
62
Lateral %
ST
Ffa
62
31
14
Ref.
64
Fib
38
35
1
[46)
[45)
[7)
0
[25]
[47]
[45]
[48)
[49)
[50]
Thoracotomy
N
N
N
N
8
4/4
7
8
10
5/1
COPD
COPD
COPD
COPD
18
8
22
17-39
<60
30-72
54
47
28-67
47
55
53
53
65
57
35
43
63
37
24
21
47
47
59
55
57
53
43
47
24-77
60
47
53
60
27
14
62
38
48
47
52
53
.
64
40
36
62
38
48
47
52
53
[48)
[49)
[51)
(52)
N: Normal ventilatory capacity; COPD: chronic obstructive pulmonary disease; ST: slow-twitch; Ff: fast-twitch.
Fibre area
x1o2 1-1m2
80
60
40
20
30
40
50
60
70
80
1-1m
L.eeaer diameter
Fig. 3. - Relationship between lesser diameter and cross-sectional
area of the fibre types determined by planimetry in external and
internal intercostal muscles laterally placed. External intercostal
muscles: e: ST; 0: FTa; t.: FTb. Internal intercostal muscles: • :
ST; Q : FTa. ST: slow-twitch; FT: fast·twitch. Adapted from MIZ\JNO
et al. [SO].
Patients. The mean relative occurrence of ST (54%),
FTa (21%) and Fib fibres (21%) of the diaphragm in
patients with normal ventilatory function and with COPD
is the same as in autopr.y materials (table 2) [48, 49, 52,
57). Regional distribution of fibre types in the diaphragm
has been studied showing no difference between the
crural and costal parts [49]. However, the costal part
possesses a 15% larger diameter of muscle fibres than
the crural part, and this finding applies to patients with
normal ventilatory function as well as those with COPD
[49).
In postmortem studies of COPD patients
measurements of the total size of the diaphragm have
revealed conflicting results indicating both hypertrophy
[58, 59) and atrophy [60). Muscle atrophy has been
attributed to an impaired use of the diaphragm as seen
on radiography [61). A small muscle mass of the
diaphragm in COPD is related to low body weight of
the patients [62, 63) . Consequently, the increased
ventilatory work in COPD is not reflected by an in·
crease in muscle fibre size of the diaphragm. On the
contrary, a 16% reduction in the least diameter of
diaphragmatic muscle fibres has been found, and this
reduction in fibre size is present in both ST (15%) and
FT fibres (18%) (48, 49). The small muscle fibre size
of the diaphragm in COPD patients may indicate
over-use atrophy as observed in limb skeletal muscle of
extremely endurance-trained athletes (64). However, at
present, this aspect is debated, since values are not
available on either subgroups of FT fibres or capillary
supply in the diaphragm of COPD patients.
Furthermore, the effect of COPD on the diaphragm is
probably more complicated than disuse or over-use
atrophy, because COPD patients have generalized
muscle weakness to which d i fferent factors
contribute [16).
591
INSPIRATORY AND EXPIRATORY MUSCLES
Table 3. -
Fibre size of human respiratory muscles
Inspiratory
Subjects
Expiratory
Diaphragm
n
Intercostal muscles
Lateral%
Costal%
M/F
yrs
Internal
External
Age
ST
Ref.
Parasternal %
Ffa
Ffb
ST
Ffa
Ffb
ST
Ffa
Ffb
1960
2350
1520
2120
2790
3350
2980
2830
2600
2060
3350
1810
3000
2720
2760
2820
Lateral %
ST
Ffa
Ffb
Fibre cross-sectional area 1-1m2
Postmortem
3/2
8/0
17-72
17-51
Thoracotomy
5/1
N
28-67
2640
2320
(45]
(7]
3680 5360
2840 4560
-
[50]
Fibre diameter 1-1m
Thoracotomy
N
N
N
4/4
8
10
5/1
<60
54
47
28-67
COPD
COPD
COPD
COPD
18
8
22
17- 39
47
55
24- 77
60
62
60
59
49
48
50
47
48
47
55
45
50
54
47
47
48
40
44
45
45
57
47
46
49
56
so
41
44
49
42
40
41
44
(47]
(48]
(49]
(50]
(48]
(49]
(54]
(52]
N: normal ventilatory function; COPD: chronic obstrucitve pulmonary disease; ST: slow-twitch; Ff: fast-twitch .
Relation to ventilatory function. Although fibre type
distribution and the number of capillaries in the
diaphragm are similar to those obtained from limb
skeletal muscles of untrained individuals, the lower
diffusing distance, indicating a greater oxidative
potential, represents an adaptive response to the constant use of the diaphragm during ventilation.
A regional difference in muscle fibre size indicates
an adaptive response to different function. The costal
parts of the diaphragm have inspiratory functions not
only to lower the central aponeurosis but also to expand
the lower rib cage [65, 66]. This finding may imply
that the costal part carries relatively larger loads during
contractions. Indirect evidence is a positive correlation
between forced vital capacity (FVC) or forced expiratory volume in one second (FEV ) and muscle fibre
size of the costal diaphragm [49j. However, such a
correlation has not be established for muscle fibres of
the crural diaphragm [ 49] or for the inspiratory
intercostal muscles [50-52].
Intercostal muscles
Autopsy materials. Because of the inspiratory function
of the EXT, and the expiratory role of the lateral INT
(fig. 1), morphological characteristics of these two
muscle layers are considered to be different. Further-
more, the functional difference between the inspiratory
parasternal INT and the expiratory lateral INT may
induce similar histochemical differences. Indeed it has
been shown that fibre morphology and capillary supply
of intercostal muscles are bound to functional differences
rather than to anatomical classification as EXT or INT
[7].
The relative occurrence of ST fibres is the same for
all the investigated intercostal muscles (62%), while the
expiratory INT have more FTa fibres (35%) than the
inspiratory INT and EXT (22%) (fig. 1 and table 2)
[7, 45]. Accordingly, the expiratory INT have far fewer
Fib fibres (1 %) than the inspiratory intercostal muscles
(19%) (fig. 4). Thus, fibre type distribution of the
inspiratory intercostal muscles is similar to that of limb
skeletal muscles in non-athletes, whereas the almost
complete lack of Fib fibres in the expiratory INT makes
them resemble, and even exceed, fibre type distribution
of muscles from extremely well-trained athletes in
endurance events (table 1). Both the inspiratory and
expiratory intercostal muscles have at least 10% more
ST fibres than the diaphragm and most other skeletal
muscles [1]. The absence of FTb fibres in the expiratory INT together with a proportion of ST fibres similar
to the inspiratory INT and EXT suggests independent
control of factors governing fibre type expression
according to the two major types (ST vs FT) and the
subgroups of FT fibres (FTa vs FTb). Of note is the
M. MIZUNO
592
Table 4. - Diffusing distance between capillaries and
muscle fibres
Expiratory
Inspiratory
Diaphragm
Intercostal muscles
External
Costal
Lateral
Internal
Parasternal
Lateral
570:50
700±50
790:t80
680:t20
940:t40
Fibre area per capillary ~-tm 2
Postmortem (7)
ST
Ffa
Ffb
450:t30
520:40
540:40
630:t40
790:t80
750:t80
Thoracotomy [50)
620:t40
740:t70
890:t70
ST
Ffa
Ffb
Fibre circumference per capillary
560:40
940:tl20
~-tm
Postmortem (7)
ST
Ffa
Ffb
37±1
43:t2
45:t2
48:t2
55:t3
57:t3
43:t2
49:t3
57:t2
42:tl
47:t2
Thoracotomy (50)
ST
Ffa
Ffb
45:t2
55:t4
67±4
ST: slow-twitch; Ff: fast-twitch.
39:2
52:3
finding that the range of relative occurrence of ST
fibres is less in the intercostal muscles (55-80%) than
in vastus lateralis muscles (10-70%) [7). A narrow range
of the ST fibre proportion has been suggested to occur
as an adaptive response to an increased use of leg
muscles [67].
The mean cross-sectional area for the expiratory INT
is large (4,300 f..lm 2) as compared with the inspiratory
INT and EXT (2,900 J.tm2) (table 3). The inspiratory
intercostal muscles show no significant difference in
the cross-sectional area between sample sites (7] and
have a similar value to the diaphragm (table 3). The
larger fibre area of the expiratory INT is reflected by a
greater area for both ST (3, 700 j.tm2 ) and FTa fibres
(5,400 14m2) [7). Thus, the expiratory INT have large
muscle fibres, and FTa fibres are the largest. This result
is in contrast to the inspiratory intercostal muscles in
which a similar area is seen among the different fibre
types.
The expiratory INT have a greater number of
capillaries per fibre (2.3) than the inspiratory INT and
EXT (1.6). Accordingly, more capillaries are found
around both ST and FTa fibres (5-6) than in the
inspiratory intercostal muscles (4-5). These differences
are further emphasized by the finding that the
expiratory INT in the eighth intercostal space, which
are the most active for expiration during normal
breathing as well as non-ventilatory tasks [2, 3, 68-71 ],
show the fewest F1b fibres (0.3%) and the largest fibre
area (4,000 J.tm 2 for ST and 5,900 J.tm 2 for FTa fibres)
supplied by the highest number of capillaries (2.4
capillaries per fibre) among the investigated intercostal
muscles [7].
50 pm
Fig. 4. - Photomicrographs of serial transverse sections from the inspiratory external (left panels) and the expiratory internal intercostal
muscle (right panels) obtained from the 5th intercostal space in the mid-axillary line and incubated for myofibrillar ATPase activity with
preincubations at pH 4.6 (upper panels) and pH 4.3 (lower panels). Three fibre types are observed in the external intercostal muscles, whereas
only ST and FTa fibres are distinguished in the internal intercostal muscles. For abbreviations see legend to figure 2.
INSPIRATORY AND EXPIRATORY MUSCLES
When diffusing distance is expressed as fibre area per
capillary, the large fibres of the expiratory EXT (table
3) have the largest area per capillary and thus the longest diffusion distance among all the respiratory muscles
studied [7] (table 4). However, for a muscle containing
large fibres induced by increased use, the area per
capillary ratio may not be an appropriate index for diffusing distance. It is evident in electron-microscopic
characteristics of human limb skeletal muscles that the
predominant location of mitochondria is underneath
the sarcolemma. Furthermore, a pronounced increase in
mitochondrial volume under the surface is observed for
both ST and FT fibres following endurance training [72,
73). When the intracellular localization of mito- chondria
is considered with the use of fibre circumference per
capillary, the large fibres of the expiratory INT show a
value similar to the inspiratory INT and EXT as well as
the diaphragm [7] (table 4). Furthermore, all respiratory
muscles show the lowest value for ST fibres (37-48
14m) with slightly higher values for FTa fibres (43-55
14m) and the highest value for Frb fibres (45-67 !!ffi).
This order of diffusing distance is constant with that of
oxidative potential such as mitochondrial enzyme activities which are highest in ST, intermediate in FTa
and lowest in Frb [1). Thus, the circumference per
capillary index may be of value to describe the diffusing distance, in particular for muscles generating relatively high tension during repetitive contractions as
suggested in limb skeletal muscles [45]. In the respiratory muscles this is the case for the expiratory INT.
Patients. Results from patients with normal ventilatory
function or with COPD are consistent with the histochemical profile of intercostal muscles obtained from
autopsy of normal humans. Thus, the relative occurrence of ST fibres is the same (62%, table 2) [25, 47,
48, 50]. Some patients with COPD have a slightly lower
value for ST fibre proportion (49% ), and this applies
for both the inspiratory EXT and expiratory INT [51,
52]. The difference in relative occurrence of FTa and
FTb fibres between the inspiratory intercostal muscles
and the expiratory INT in normal subjects is represented
in patients as well [50].
A second similarity among patients and normal
subjects is the relative size of FTa fibres which are
larger in the expiratory INT than in the inspiratory
EXT, expressed as the cross-sectional area [50) (table
3). SANcHEZ et al. [48] did not observe such a difference
in muscle fibre size expressed by the least diameter.
Since a curvilinear relationship exists between the crosssectional area and the least diameter of muscle fibres
(fig. 3), the difference in fibre size between inspiratory
and expiratory intercostal muscles may have been
too small to be detected by the use of the least diameter. Like the diaphragm, however, patients with COPD
have a 15% reduction in the least diameter of FT fibres
of the expiratory INT [51, 52]. On the contrary, this
reduction is not observed in the inspiratory EXT [51).
Thirdly, when capillary supply is considered, the
highest values are observed for the expiratory INT in
patients with normal ventilatory function [50]. Thus,
593
the number of capillaries per fibre and surrounding each
fibre are 1.6 and 5 for the expiratory INT and 1.3 and
4 for the inspiratory EXT. These values for capillary
supply are 20-30% lower than values observed in normal subjects. The area index for diffusing distance is
greater in the expiratory INT than in the inspiratory
EXT, whereas a similar value for the circumference
index is observed among these two muscle groups in
patients undergoing thoracotomy (table 4). The values
for both indices are similar among normal subjects and
patients with normal ventilatory function. No data on
capillary supply in intercostal muscles are available for
COPD patients.
6
0
<)
FTb
r.
Relative
fibre type
dletrlbullon ~
Expiratory
lntercottal
lnaplratory
mute!..
Cotter
diaphragm
M. vaatua
leterelle
Fig. 5. - Schematic illustration of findings in expiratory and
inspiratory intercostal muscles, the costal diaphragm and m. vastus
lateralis of normal subjects (MIZUNO and SECHER [7]. Relative fibre
cross-sectional area and the number of capillaries are indicated.
Relative fibre type distribution; e: ST; 0: FTa;O: FTb. ST: slow·
twitch; FT: fast-twtich.
Relation to ventilatory function. A lack of FTb fibres,
muscle fibre hypertrophy and capillary proliferation in
the expiratory INT (fig. 5) indicates that these muscles
are intensively recruited with relatively large force
development during repeated contractions. One explanation for the apparent intense use of the expiratory
INT is that their relative small mass is recruited
extensively even during quiet breathing. In contrast, inspiration is shared among the diaphragm, parasternal
INT, EXT, scalene and sternomastoid muscles [2, 3, 71,
74-78]. Thus, it is likely that the inspiratory muscles
are loaded below training stress, while the expiratory
INT are overloaded routinely. This aspect on the expiratory INT is further confirmed with the observation
that a positive correlation between forced expiratory
function (FVC, FEY) or maximal ventilatory volume
(MVV) and fibre size of the expiratory INT is found in
patients, including those with COPD [48, 50-52).
In dogs sonomicrometric measurements of muscle
length during spontaneous breathing have suggested that
the lateral INT and EXT are antagonistic to rotation of
the trunk rather than to moderate ventilatory efforts [79).
594
M. MIZUNO
However, postural function alone does not explain
the distinct histochemical characteristics of the
expiratory INT, because the abundant, large and capillary rich FTa fibres are found only in humans and not
in rats [46, 80], cats [81, 82), dogs [83] or baboons
[84]. Thus, despite the correlation found between
ventilatory function and fibre size of the expiratory INT,
their apparent histochemical characteristics may reflect
an adaptive response to non-ventilatory tasks such
as vocalization and upright posture in performing
Valsalva-like manoeuvres during lifting, carrying and
reaching.
Extrathoracic muscles
The relative occurrence of ST (59%), FTa (22%) and
FTh (17%) fibres in the scalene muscles of autopsy
materials is similar to that reported for the inspiratory
intercostal muscles [45]. The proportion of ST fibres
exceeds that found in most of the skeletal muscles
including the diaphragm (tables 1 and 2). The fibre
cross-sectional area of the scalenes (1,900 ~m 2) is
smaller than that reported for the other inspiratory
muscles [45]. This difference is reflected by a smaller
cross-sectional area of FTa (1,500 ~m 2) and FTb fibres
(1,200 ~m2), whereas the ST fibres (2,300 ~m 2) have a
similar area to that of the other inspiratory muscles (table
3). Thus, ST fibres are larger than FT fibres in the
scalenes, as also found in the diaphragm.
In patients with COPD intense EMG activity is
recorded in the scalenes and hypertrophy is
visually recognized (85], suggesting that these muscles
are involved increasingly during normal breathing. The
increased work of the scaleoes in severe COPD
probably reflects the impaired function of the
diaphragm due to its lower position caused by emphysema.
The sternomastoid muscles have a smaller proportion
of ST fibres (35%) than other respiratory muscles [86].
Explanation of this finding, as well as information on
the proportion of subgroups of FT fibres is lacking. The
size of muscle fibres in patients with COPD is smaller
than in normal subjects [87).
The expiratory extrathoracic muscles, the abdominal
muscles including the rectus and transverse as well as
the external and internal oblique, have 54% ST
fibres in normal humans [86] and in patients undergoing abdominal surgery [88]. In these patients FTa
(20%) and FTb fibres (23%) are evenly distributed. The
fibre size, expressed as the mean least diameter, is
similar among the abdominal muscles and among three
fibre types (52 ~m) with the exception of FTa fibres
(45 ~m) in the transverse abdominal muscle, which are
smaller [88]. These values are within the range
determined in other respiratory muscles (table 3).
As noticed for the scalene muscles, patients with severe
COPD use the abdominal muscles extensively
during breathing [89, 90]. However, the fibre size of
abdominal muscles in COPD patients has not been
reported.
Relative occurrence
of ST fibres %
100
80
60
40
20
0
~~~~~·-r-r~~~~~--·
·
20
24-37
1-4 1-3 7-24
..___.
Weeks
Months
~
60
Age yrs
I
Unborns
40
Infants
Fig. 6. -The relative occurrence of ST fibres determined in expiratory internal (lNT), inspiratory external intercostal muscles (EXT)
and the costal diaphragm (DIA) in relation to age. •· Q, eg from
KEENS et al. (91); e, 0, ®from MIZUNO and SECKER (7) and MIZUNO
et al. [50]; ! from SANcKEz et al. [48, 49] and~ from LlEBERMAN
et al. [57]. The values from autopsy materials and patients with
normal ventilatory capacity are plotted as mean±sD.• .6: INT; Q
0 6: EXT; eg ® 4 ~: DIA; ST: slow-twitch.
e
Mean fibre
croea-aectlonal area,
:~e102 14 m2
60
40
20
+
+
+
r
2o
+
~
40
60
Age yra
Fig. 7. - Mean fibre cross-sectional area of expiratory internal
(INT), inspiratory external intercostal mus~les (EXT) and the costal
diaphragm (DIA) in relation to age. The values are pooled data
from M1ZUNO and S.ECKER [7] and MIZUNO et al. (50], and expressed
as mean±sn. The number of observations is 6 for 24 yrs. 5 for 47
yrs and 3 for 65 yrs. Among INT the value for 65 yrs is significantly
lower than those for the other two groups (•p<0.05). e: INT; 0:
EXT; ®: DIA.
Histochemical changes with ageing
In the diaphragm and inspiratory as well as in expiratory intercostal muscles, fibre type differentiation is
completed by the age of two years [91, 92). Thereafter,
595
INSPIRATORY AND EXPIRATORY MUSCLES
Table 5. - Enzyme activities of human respiratory muscles
Subjects
0
MIF
Lactate
dehydrogeoase
Muscles Phosphorylase Hexokinase
Age
yrs
Succinic
dehydrogenase
Citrate
synthase
3-hydroxyacyl- Ref.
coenzyme A
dehydrogenase
Normal ventilatory function
10
5/1
9
5!1
9
50
28-67
53
28-67
53
DIA
EXT
EXT
INT
INT
42
44
6.7:0.6
8.1 (6.1-9.7)
6.1 (5.6-6.6)
(21-60) 7.8 (6.8-8.5)
6.1 (5.6-6.6)
1060:110
(26-52)
1160 (90Q-1500)
1160 (1000-1400)
34:3
29 (22-40)
30 (26-33)
26 (21- 33)
26 (22-31)
59:3
[102]
29 (20- 38) [50]
41 (35-48) (103]
26 (20- 35) (50]
35 (30-42) (103)
32:3
50:5
Chronic obstructive pulmonary disease
11
22
11
22
11
8
24-77
52
24-77
52
DIA
EXT
EXT
INT
INT
4.8:t0.6
630:70
39:5
6.7
(6.0-7.3)
980 (80Q-1100)
38 (33-47)
37:4
6.9
(6.2-8.0)
970 (70Q-1200)
34 (28-39)
(102]
(51]
54 (45- 67) (103]
(51]
47 (41- 55) (103]
DIA: costal diaphragm; EXT: external intercostal muscles; INT: internal intercostal muscles. Enzyme activities are expressed
as j.lmol·min·1·g·1 dry weight of protein determined at 25°C. Values are means:tSEM or with a range in parenthesis.
Table 6. - Substrata concentrations of human respiratory muscles
Subjects
n
Age
yrs
MIF
Muscles
ATP
PCr
Glycogen
Lactate
Ref.
Normal ventilatory function
4/8
511
48-78
28-67
EXT
EXT
INT
13:1
48:t2
191:9
6:t2
277 (158-362) 20 (11-33)
380 (221-575) 18 (9-26)
(54]
[108]
(108)
204:30
250:t16
310:t25
255
302
315
(54]
[51]
(51]
[52]
[52]
[52]
Chronic obstructive pulmonary disease
10/2
22
46-75
24-77
15-40 60
EXT
EXT
INT
EXT
INT
DIA
10:2
19:1
19:t1
19
19
20
46:5
70:t3
69:t3
65
63
55
12:2
lO:tl
10:t2
10
10
10
Substrate concentrations are expressed as ~-tmol·g·' dry weight. Values are means:seM
or with a range in parenthesis. EXT: external intercostal muscles; INT: internal
intercostal muscles; DIA: diaphragm; ATJ>: adenosine triphosphate; PCr: phosphocreatine.
the relative occurrence of ST fibres remains constant
(fig. 6), as has been observed in limb skeletal muscles
[93-96). A lower proportion of ST fibres. in the diaphragm than in intercostal muscles appears to exist at
all ages (fig. 6).
The diaphragmatic muscle mass is maintained from
early youth (19 yrs) to old age (91 yrs) [62). Accordingly, the fibre cross-sectional area of inspiratory
muscles remains fa irly constant from the 20th to 65th
year (fig. 7). In contrast, the expiratory INT appears to
be approximately 20% smaller in fibre cross-sectional
area after the age of fifty years due to a reduction of
both ST and Ff fibre areas. Muscle mass of the thigh
decreases (30%) more than the fibre cross-sectional area
(15%) after the age of fifty years, suggesting that muscle
atrophy with age reflects· not only a decrease in fibre
cross-sectional area but also in the number of muscle
fibres [97] .
A functional equivalent to the reduced muscle mass
in the thigh is a similar reduction in both static
strength and dynamic power (97]. However, training
maintains or even increases the work performance in
elderly individuals [98, 99]. In the respiratory muscles,
the reduced fibre cross-sectional area observed in the
M. MIZUNO
596
expiratory INT may explain the reduction in FEV1 and
MVV after the age of 35 yrs [100, 101). Conversely,
the constant fibre size of inspiratory muscles with
ageing is an indication of maintained use of these muscles. As previously mentioned, the large fibre size of
expiratory INT is considered to be an adaptation to
non-ventilatory rather than to ventilatory function so
that their reduced size with age may reflect a more
sedentary life style.
Enzyme activities and substrate contents
Mitochondrial and glycolytic enzyme activities
Quantitative biochemical de terminations of substrate
contents and enzyme activities are other expressions of
altered degree of use. Mitochondrial enzyme activities
represented by e.g. citrate synthase (CS) and 3hydroxyacyl-coenzyme A dehydrogenase (HAD) are
within a range of values reported for skeletal muscles in
the extremities of non-athletes [1) (table 5). The differences noted between the histochemical characteristics
of the expiratory INT and the inspiratory muscles is not
reflected in the reported mitochondrial enzyme
activities. In contrast to histochemical characteristics,
mitochondrial enzyme activities adapt at an early
stage of training or inactivity [104-107]. Thus, the fact
that most biochemical data are obtained from patients
admitted for surgery and not from normal individuals
may have influenced the results due to reduced physical
activity of patients during hospitalization. Additional
evidence for this assumption is the finding that when
biopsies have been obtained from patients with COPD,
the mitochondrial enzyme activities in both inspiratory
and expiratory intercostal muscles are higher than in
other skeletal muscles [103).
In patients with normal ventilatory function,
HAD activity is slightly higher in the costal diaphragm
(102) than in both the EXT and expiratory INT. CS
activity as well as glycolytic enzyme activities,
represented as hexokinase (HK) and lactate dehydrogenase (LDH), are similar among these muscles (table 5)
[50, 78, 102]. In COPD patients both HK and LDH
activity in the costal diaphragm are lower than in
intercostal muscles, while CS and HAD activities are
similar [102].
In both inspiratory EXT and expiratory INT, CS and
HAD activity are higher in patients with moderate COPD
than in patients with normal ventilatory function [103).
However, in patients with severe COPD, a similar
mitochondrial enzyme activity exists for both the
inspiratory EXT and expiratory INT [51].
Glycogen and lactate
In the diaphragm and intercostal muscles the average
glycogen content is 190-380 ~mol·g· dry weight
and lactate varies from 7 to 20 ~-tmol·g·1 dry weight
(table 6). The values observed in respiratory muscles
1
are within a range reported for limb skeletal muscles.
The wide range of values partly reflects the circumstances under which the muscle biopsies were obtained.
In normal subjects relatively high muscle lactate
concentrations of 20 J.tmol·g·' dry weight are seen only
after intense exercise [109). Such values observed in
patients may be associated 'with metabolic acidosis due
to muscle hypoperfusion during surgery. More likely
the high concentration of lactate in intercostal muscles
is caused by the use of a depolarizing muscle relaxant,
such as suxamethonium for tracheal intubation, leading
to muscle fibrillations which result in lactate accumulation (17).
Independent of ventilatory function of the patients,
the inspiratory intercostal muscles have 20% less
glycogen content than the expiratory INT and the diaphragm in surgical biopsies (table 6). However, when
biopsies were taken during spontaneous breathing, and
thus without the use of muscle relaxants, the inspiratory
and expiratory intercostal muscles have similar glycogen contents [54). The ventilatory problems of
patients with COPD appear to be reflected by a high
lactate concentration in the inspiratory intercostal
muscles [54].
Phosphagen
Mean values of adenosine triphosphate (ATP) concentration in the diaphragm and intercostal muscles range
between 10 and 20 J,Amol·g·1 dry weight (table 6). The
concentration of phosphocreatine (PCr) ranges from 60
to 70 J,Amol·g· 1 dry weight. These values are similar to
those reported for limb skeletal muscles [1). A slightly
lower PCr content (47 J.tmol·g·1 dry weight) has been
reported in intercostal muscles obtained during spontaneous breathing. This value may have resulted from
biopsies being taken from working muscles as compared with others obtained from relaxed muscles during
surgery.
Effect of muscle relaxants
It is a classical observation in animals that muscle
relaxants affect respiratory muscles less than other
skeletal muscles [110). This difference in effects among
skeletal muscles exists in man and holds for both
depolarizing and non-depolarizing neuromuscular
blocking agents [111, 112]. Thus, a popular test for
post-operative patients is to evaluate the ability for lifting
the head in order to ensure that the strength of the
respiratory muscles is restored after the use of
neuromuscular blocking agents (113),
In human [114, 115) as well as animal skeletal muscles [110, 116) it has been demonstrated that the nondepolarizing muscle relaxant tubocurarine affects ST
fibres to a greater extent than FT fibres after a single
dose which produce partial neuromuscular blockade. The
larger proportion of ST fibres exists in intercostal and
scalene muscles (approximately 65%) as compared with
597
INSPIRATORY AND EXPIRATORY MUSCLES
the diaphragm (approximately 50%). This difference may
partly explain the g reater effects of non-depolarizing
neuromuscular blocking agents on the scalenes and
intercostal muscles as compared with the diaphragm
(117). The fact that EMG activity in the diaphragm
increases after the administration of Pavulon suggests
that more unblocked diaphragmatic fibres are recruited
when the other inspiratory muscles are blocked [117).
In intercostal muscles a substantial decrease in intramuscular glycogen and accumulation of muscle lactate
takes place following the administration of the depolarizing agent suxamethonium for tracheal intubation.
Under this circumstance a marked glycogen depletion
occurs particularly in FTb fibres [17]. More FTb
fibres are present in the inspiratory intercostal
muscles than in the expiratory INT. As noted previously, this finding may explain the lower glycogen
content in the inspiratory than the expiratory intercostal
muscles among patients undergoing surgery, whereas
no difference is noted in normal subjects. Thus, muscle
fasciculations induced by the use of depolarizing agents
appear to affect in particular the FTb fibres.
On a broader comparison between different muscles,
the histochemical classification of ST and FT fibres does
not explain a difference in effects between nondepolarizing and depolarizing neuromuscular blocking
agents. Moreover, the diaphragm is less affected by nondepolarizing agents than other skeletal muscles [111),
which cannot be explained by the relative proportion of
ST fibres alone. Therefore, unknown differences must
exist at the neuromuscular junction between muscles or
between muscle fibre types. This difference appears to
be independent of the relative proportion of ST fibres.
The heterogeneity of fibre types in the respiratory
muscles, however, gives rise to some clinical considerations for postoperative patients. The head-lift test
depends mainly on the strength of the sternomastoid
muscle, which possesses only 35% ST fibres. Thus, the
ability to perform head-lift may be less affected by
non-depolarizing agents than the respiratory muscles.
Furthermore, with the combined use of depolarizing and
non-depolarizing neuromuscular blocking agents during
surgery, postoperative ventilatory function may be
impaired for two reasons: 1) persistent neuromuscular
blockade of particularly ST fibres; and 2) weakness
caused by the development of fatigue in glycogen
depleted FT fibres.
Conclusion
Histochemical profiles indicate that the expiratory
intercostal muscles have adapted to heavy and continuous activity in man. Because no similar characteristics
reflecting training effects are observed in the inspiratory muscles, the inspiratory work load seems to be
insufficient to elicit such an adaptation.
With ageing the expiratory (but not inspiratory) intercostal muscles appear to show atrophy, indicating that
the larger fibre size of the expiratory intercostal muscles
is adapted to non-ventilatory rather than to ventilatory
function despite a correlation with the results of standard ventilatory functional tests. The demands on the
expiratory intercostal muscles for vocalization and for
performing Valsalva-like manoeuvres during lifting and
reaching may cause this adaptation. The atrophy of these
muscle fibres with age may simply reflect an increasingly sedentary life style.
In patients with only moderate COPD, increased
mitochondrial enzyme activities exist in both the
inspiratory and expiratory intercostal muscles. In
patients with severe COPD the activity of these enzymes
decreases, and a reduction in muscle fibre size occurs,
particularly in the diaphragm and the expiratory intercostal muscles. Thus, the increased work of breathing
in these patients seems to be accomplished by intense
involvement of extrathoracic muscles, even during
quiet breathing.
Following the use of the depolarizing neuromuscular
agent suxamethonium, a selective depletion of muscle
glycogen occurs in fast-twitch (particularly FTb) fibres.
Thus, the glycogen content of the expiratory muscles,
which possess the fewest FTb fibres, appears to be
greater than that of the inspiratory intercostal muscles
in surgical patients. The lowest proportion of slow-twitch
fibres in the diaphragm may account for the minimal
effect of non-depolarizing neuromuscular agents on
respiratory muscles. This characteristic does not, however, explain the similar effect of depolarizing
neuromuscular blocking agents. Thus, differences in
muscle morphology alone do not provide an adequate
explanation for the different sensitivity to neuromuscular
blocking agents which exists between thoracic and
extrathoracic respiratory muscles as well as between
the respiratory muscles and limb skeletal muscles.
Acknowledgements: The author wishes to express
gratitude to Dr N.H. Secher, Department of
Anaesthesia, Rigshospitalet, University of
Copenhagen, for stimulating constructive criticism.
References
1. Saltin B, Gollnick PD. - Skeletal muscle adaptability.
Significance for metabolism and performance. In: Handbook
of physiology. Section 10: Skeletal muscle. L.D. Peachey,
R.H. Adrian eds, Am Physiol Soc, Bethesda, 1983 pp.
555-631.
2. Taylor A. - The contribution of the intercostal muscles
to the effort of respiration in man. J Physio/ (Lond), 1960, 151,
39~02.
3. Tokizane T, Kawamata K, Tokizane H. Electromyographic studies on the human respiratory muscles. Studies on the activity pattern of neuromuscular units.
Jap J Physio/, 1951-1952, 2, 232-247.
4. Campbell EJM, Agostoni E, Newson Davis J. -In: The
Respiratory Muscles. Mechanics and Neural Control. LloydLuke, London, 1970.
5. De Troyer A, Loring SH. - Action of the respiratory
muscles. In: Handbook of physiology, section 3: The
respiratory system, vol. III, part 2. A.P. Fishman ed., Am
Physiol Soc, Bethesda, 1986, pp. 443-461.
6. Loring SH, De Troyer A. - Actions of respiratory
598
M. MIZUNO
muscles. In: The thorax. Part A. C. Roussos, P.T. Macklem
eds, Marcel Dekker Inc, New York, 1985, pp. 327-349.
7. Mizuno M, Secher NH.- Histochemical characteristics
of human expiratory and inspiratory muscles. J Appl Pllysiot
1989, 67, 592-598.
8. Derenne J-PH, Macklem PT, Roussos C. - The
respiratory muscles. Mechanics, control and pathophysiology.
Am Rev Respir Dis, 1978, 118, 119-133, 373-390,
581--601.
9. Edwards RHT, Faulkner JA. - Structure and function
of respiratory muscles. In: The thorax. Part A. C. Roussos,
P.T. Macklem eds, Marcel Dekker Inc., New York, 1985, pp.
297-326.
10. Roussos C, Macklem PT. - The respiratory muscles. N
Engl J Med, 1982, 23, 786-797.
11. Delhez L, Bottin R, Thomon A, Vierset J. - Modifications du diagramme-pression-volume maximum de l'appareil
thoracopulmonaire apr~s entrainement des muscles
respiratoires par des exercises statiques. Arch lnt Physiol
Biochem, 1966, 74, 335-336.
12. Leith DE, Bradley M. - Ventilatory muscle strength
and endurance training. J Appl Physiol, 1976, 41, 508-516.
13. Belman MJ, Sieck GC. - The ventilatory muscles.
Fatigue, endurance and training. Chest, 1982, 6, 761-766.
14. Flenley DC.- Inspiratory muscle training. Eur J Respir
Dis, 1985, 67, 153-158.
15. Pardy RL, Leith D. - Ventilatory muscle training. In:
The thorax. Part B. C. Roussos, P.T. Macklem eds, Marcel
Dekker Inc, New York, 1985, pp. 1353-1371.
16. Decramer M. - Effects of hyperinflation on the
respiratory muscles. Eur Respir J, 1989, 2, 299-302.
17. Secher NH, Mizuno M, Saltin B. - Adaptation of
skeletal muscles to training. Bull Eur Physiopathol Respir,
1984, 20, 453-457.
18. Padykula HA, Herman E. - The specificity of the
histochemical method for adenosine triphosphatase. J
Histocllem Cytochem, 1955, 107-195.
19. Engel WK.- The essentiality of histo- and cytochemical
studies of skeletal muscle in the investigation of neuromuscular disease. Neurology (Minneapolis) , 1962, 12,
778-794.
20. B6r6ny M.- ATPase activity of myosin correlated with
speed of muscle shortening. J Gen Physiol, 1967, 50 (part 2),
197-218.
21. Saltin B, Henriksson J, Nygaard E, Andersen P, Jansson
E. - Fiber types and metabolic potentials of skeletal muscles
in sedentary man and endurance runners. Ann A N A cad Sci,
1977, 301, 3-29.
22. Biral D, Betto R, Danieli-Betto D, Salviati G. - Myosin
heavy chain composition of single fibres from normal human
muscle. Biochem J, 1988, 250, 307-308.
23. Buchthal F, Schmalbruch H. - Contraction times and
fibre types in intact human muscle. Acta Physiol Scand, 1970,
79, 435-452.
24. Garnett RAF, O'Donovan MJ, Stephens JA, Taylor AMotor unit organization of human medial gastrocnemius. J
Physiol (Lond), 1979, 33-43.
25. Hanson J. - Effects of repetitive stimulation on
membrane potentials and twitch in human and rat intercostal
muscle fibres. Acta Physiol Scand, 1974, 92, 238-248.
26. Brooke MH, Kaiser KK. - Three "myosin adenosine
triphosphatase" systems. The nature of their pH !ability and
sulfhydryl dependence. J Histochem Cytochem, 1970, 18,
670-672.
27. Sj!ifgaard G, Houston ME, Nygaard E, Saltin B. Sub-grouping of fast twitch fibres in skeletal muscles of man:
A critical appraisal. Histochemistry, 1978, 58, 79-87.
28. Eriksson P-0, Eriksson A, Ringqvist M, Thomell L-E.The reliability of histochemical fibre typing of human
necropsy muscles. Histochemistry, 1980, 65, 193-205.
29. Maxwell LC, Kuehl TJ, Robotham JL, McCarter RJM. Temporal changes after death in primate diaphragm muscle
oxidative enzyme activity. Am Rev Respir Dis, 1984, 130,
1147-1151.
30. Monster A W, Chan HC, O'Connor D. - Activity
patterns of human skeletal muscles: relation to muscle fiber
type composition. Science, 1978, 200, 314-317.
31. Warmolts JR, Engel WK. - Open-biopsy electromyography. I. Correlation of motor unit behavior with histochemical muscle fiber type in human limb muscle. Arch Neurol,
1972, 27, 512-517.
32. Komi PV, Vitasalo JHT, Havu M, Thorstensson A. Skeletal muscle fibres and muscle enzyme activities in
monozygous and dizygous twins of both sexes. Acta Physiol
Scand, 1977, 100, 385-392.
33. Baumann H, Jliggi M, Soland F, Howald H, Schaub MC.
- Exercise training induced transitions of myosin isoform
subunits within histochemically typed human muscle
fibres. Pjlugers Arch, 1987, 409, 349-360.
34. Billeter R, Weber H, Lutz H, Howald H, Eppenberger
HM, Jenny E.- Myosin types in human skeletal muscle fibers.
Histochemistry, 1980, 65, 249-259.
35. Schantz P, Dhoot GK. - Coexistence of slow and fast
isoforms of contractile and regulatory proteins in human
skeletal muscle fibres induced by endurance training. Acta
Physiol Scand, 1987, 131, 147-154.
36. Andersen P, Henriksson J. - Capillary supply of the
quadriceps femoris muscle of man. Adaptive response to
exercise. J Physiol (Lond), 1977, 270, 677--690.
37. Mizuno M, Juel C, Bro-Rasmussen T, Mygind E, Schibye
B, Rasmussen B, Saltin B. - Limb skeletal muscle
adaptation in athletes following training at altitude. J Appl
Physiol, 1990, 68, 496-502.
38. Costil DL, Coyle EF, Fink WF, Lesmes GR, Witzmann
FA. - Adaptations in skeletal muscle following strength
training. J Appl Physiol: Respirat Environ Exercise Physiol,
1979, 46, 96-99.
39. Tesch PA, Thorsson A, Kaiser P. - Muscle capillary
supply and fiber type characteristics in weight and power
lifters. J Appl Physiol, 1984, 56, 35-38.
40. Sj!ifgaard G. - Capillary supply and cross-sectional area
of slow and fast twitch muscle fibres in man. Histochemistry,
1982, 76, 547-555.
41. Schantz P. - Capillary supply in heavy-resistance
trained non-postural human skeletal muscle. Acta Physiol
Scand, 193, 117, 153-155.
42. Appell H-J, Forsberg S, Hollmann W. - Satellite cell
activation in human skeletal muscle after training: evidence
for muscle fiber neoformation. lnt J Sports Med, 1988, 9,
297-299.
43. Gollnick PD, Timson BF, Moore RL, Riedy M. Muscular enlargement and number of fibers in skeletal
muscles of rats. J Appl Physiol: Respirat Environ Exercise
Physiol, 1981, 50, 936-943.
44. BergstrOm 1. - Muscle electrolytes in man. Determined
by neutron activation analysis on needle biopsy specimens. A
study on normal subjects, kidney patients, and patients with
chronic diarrhoea. Scand J Clin Lab lnvest, 1962, 14 (Suppl.)
68.
45. McKenzie DK, Gandevia SC, Shorey CD. - A histochemical study of human inspiratory muscles. (Abstract). In:
Proc lnt Un Physiol, vol XV, Sydney, 1983 p. 351.
46. Keens TG, Chen V, Pate! P, O'Brien P, Levison H,
Ianuzzo CD. - Cellular adaptations of the ventilatory
INSPIRATORY AND EXPIRATORY MUSCLES
muscles to a chronic increased respiratory load. J Appl Physiol,
1978, 44, 905-908.
47. Stern LZ, Payne CM, Gruener R, Anderson RM,
Hannapel LK. - Intercostal muscle biopsy in human
neuromuscular disease. Histochemical and electron microscopic studies. J Neurol Neurosurg Psychiat, 1975, 38,
900-910.
48. SAnchez J, Derenne JP, Debesse B, Riquet M, Monod H.
- Typology of the respiratory muscles in normal men and in
patients with moderate chronic respiratory diseases. Bull Eur
Physiopathol Respir, 1982, 18, 901-914.
49. S~nchez J, Medrano G, Debesse B, Riquet M, Derenne
JP. - Muscle fibre types in costal and crural diaphragm in
normal men and in patients with moderate chronic respiratory disease. Bull Eur Physiopathol Respir, 1985, 21, 351-
356.
50. Mizuno M, Secher NH, Saltin B. - Fibre types, capillary
supply and enzyme activities in human intercostal muscles.
Clin Physiol, 1985, 5, 121-135.
51. Campbell JA, Hughes RL, Sahgal V, Frederiksen J,
Shields TW. - Alterations in intercostal muscle morphology
and biochemistry in patients with obstructive lung disease.
Am Rev Respir Dis, 1980, 122, 679-686.
52. Hughes RL, Katz H, Sabgal V, Campbell JA, Hartz R,
Shields W . - Fiber size and energy metabolites in five
separate muscles from patients with chronic obstructive lung
disease. Respiration, 1983, 44, 321-328.
53. Dubolwitz V, Brooke MH. - In: Muscle biopsy: a
modern approach. W.B. Saunders Company, London, 1973.
54. Gertz I, Hedenstierna G, Hellers G, Wahren J.- Muscle
metabolism in patients with chronic obstructive lung disease
and acute respiratory failure. Clin Sci Mol Med, 1977, 52,
395-403.
55. Krogh A. - The number and distribution of capillaries
in muscles with calculations of the oxygen pressure head
necessary for supplying the tissue. J Physiol (Lond), 191819, 52, 409-415.
56. Saltin B, Rowell LB. - Functional adaptations to
physical activity and inactivity. Fed Proc, 1980, 39,
1506-1513.
57. Lieberman DA, Faulkner JA, Craig Jr AB, Maxwell LC.
- Performance and histochemical composition of guinea
pig and human diaphragm. J Appl Physiol, 1973, 34,
233-237.
58. Ishikawa S, Hayes JA. - Functional morphometry of
the diaphragm in patients with chronic obstructive lung
disease. Am Rev Respir Dis, 1973, 108, 135-138.
59. Scott KWM, Hoy J. - The cross-sectional area of
diaphragmatic muscle fiber in emphysema, measured by an
automated image analysis system. J Pathol, 1976, 120,
121-128.
60. Steele RH, Heard BE. - Size of the diaphragm in chronic
bronchitis. Thorax, 1973, 28, 55-60.
61. Barach AL. - Restoration of diaphragmatic function
and breathing exercise in pulmonary emphysema. NY State J
Med, 1956, 56, 3319-3332.
62. Arora NS, Rochester DF. - Effect of body weight and
muscularity on human diaphragm muscle mass, thickness,
and area. J Appl Physiol: Respirat Environ Exercise Physiol,
1982, 52, 64-70.
63. Arora NS, Rochester DF.- COPD and human diaphragm
muscle dimension. Chest, 1987, 91, 719-724.
64. Jansson E, Kaijser L. - Muscle adaptation to extreme
endurance training in man. Acta Physiol Scand, 1977, 100,
315-324.
65. De Troyer A, Sampson MG, Sigrist S, Macklem PT. Action of costal and crural parts of the diaphragm on the rib
599
cage in dog. J Appl Physiol: Respirat Environ Exercise
Physiol, 1982, 53, 30-39.
66. Stewart MB, Hanson RE, De Troyer A, Macklem PT. Radiology of the diaphragm as two muscles. Invest Radio/,
1983, 18, 155-159.
67. Terrados N, Melichna J, Sylv~n C, Jansson E, Kaijser L.
- Effects of training at simulated altitude on performance
and muscle metabolic capacity in competitive road cyclists.
Eur J Appl Physiol, 1988, 57, 203-209.
68. Draper MH, Ladefoged P, Whitteridge D.- Respiratory
muscles in speech. J Speech Hearing Res, 1959, 2,
16-27.
69. Munro RR, Adams C. - Electromyography of the
intercostal muscles in connected speech. Electromyography,
1971, 11, 365-378.
70. Munro RR, Adams C. - The patterns of internal
intercostal muscle activity used by some non-native speakers
of English. Electromyogr Clin Neuropltysiol, 1973, 13, 271288.
71. Murphy AJ, Koepke GH, Smith EM, Dickinson DG. Sequence of action of the diaphragm and intercostal muscles
during respiration. II. Expiration. Arch Phys Med Rehabil,
1959, 40, 337-342.
72. Hoppeler H, Howald H, Conley K, Lindstedt S, Claassen
H, Vock P, Weibel ER. - Endurance training in humans.
Aerobic capacity and structure of skeletal muscle. J Appl
Physiol, 1985, 59, 320-327.
73. Howald H, Hoppeler H, Claassen H, Mathieu 0, Straub
R. - Influences of endurance training on the ultrastructural
composition of different muscle fiber types in humans.
Pflugers Arch, 1985, 403, 369-376.
74. De Troyer A, Estenne M. - Coordination between rib
cage muscles and diaphragm during quiet breathing in
humans. J Appl Physiol: Respirat Environ Exercise Physiol,
1984, 57, 899-906.
75. De Troyer A, Sampson MG. - Activation of the
parasternal intercostals during breathing efforts in human
subjects. J Appl Physiol: Respirat Environ Exercise Physiol,
1982, 52, 524-529.
76. Koepke GH, Smith EM, Murphy AJ, Dickinson DG. Sequence of action of the diaphragm and intercostal muscles
during respiration. I. Inspiration. Arch Phys Med Rehabi/1958,
39, 426-430.
77. Raper AJ, Thompson Jr WT, Shapiro W, Patterson Jr
JL. - Scalene and sternomastoid muscle function. J Appl
Physiol, 1966, 21, 497-502.
78. Sampson MG, De Troyer A. - Role of intercostal muscles in the rib cage distortions produced by inspiratory loads.
J Appl Physiol: Respirat Environ Exercise Physiol, 1982, 52,
517-523.
79. Decramer M, Kelly S, De Troyer A. - Respiratory
and postural changes in intercostal muscle length in supine
dogs. J Appl Physiol, 1986, 60, 1686-1691.
80. Schraufnagel DE, Roussos CH, Macklem P, Wang N-S.
- The geometry of the microvascular bed of the diaphragm.
Comparison to intercostals and triceps. Microvasc Res, 1983,
26, 291-306.
81. Nishiyama A. - Histochemical studies on the red, white
and intermediate muscle fibers of some skeletal muscles. I.
Succinic dehydrogenase activity and physiological function
of intercostal muscle fibers. Acta Med Okayama, 1965, 19,
177-189.
82. Nishiyama A. - Histochemical studies on the red, white
and intermediate muscle fibers of some skeletal muscles. 11.
Histochemical demonstration of oxidative enzymes, phosphorylase and glycogen in respiratory muscle fibers. Acta Med
Okayama, 1966, 20, 137-146.
600
M. MIZUNO
83. Reid MB, Ericson GC, Feldman HA, Johnson Jr RL. Fiber types and fiber diameters in canine respiratory
muscles. J Appl Physiol, 1987, 62, 1705-1712.
84. Maxwell LC, McCarter RJM, Kuehl TJ, Robotham JL.
- Development of histochemical and functional properties of
baboon respiratory muscles. J Appl Physiol: Respirat Environ
Exercise Physiol, 1983, 54, 551-561.
85. Thompson Jr WT, Patterson Jr JL, Shapiro W . Observations on the scalene respiratory muscles. Arch Inter
Med, 1964, 113, 856-865.
86. Johnson MA, Polgar J, Weightman D, Appleton D. Data on the distribution of fibre types in thirty six
human muscles. An autopsy study. J Neurol Sci, 1973, 18,
111-129.
87. Arora NS, Rochester DF.- Effect of chronic obstructive
pulmonary disease on sternocleidomastoid muscle. (Abstract).
Am Rev Respir Dis, 1982, 125, 252.
88. Haggmark T, Thorstensson A. - Fibre types in human
abdominal muscles. Acta Physiol Scand, 1979, 107,
319-325.
89. Delgado HR, Braun SR, Skatrud JB, Reddan WG,
Pegelow DF. - Chest wall and abdominal motion during
exercise in patients with chronic obstructive pulmonary
disease. Am Rev Respir Dis, 1982, 126, 200-205.
90. Sharp JT. - The chest wall and respiratory muscles in
airflow. In: The thorax. Part B. C. Roussos, P.T. Macklem
eds, Marcel Dekker Inc, New York, 1985 pp. 1155- 1202.
91. Keens TG, Bryan AC, Levison H, Ianuzzo CD. Developmental pattern of muscle fiber types in human
ventilatory muscles. J Appl Physiol: Respirat Environ Exercise Physiol, 1978, 44, 909-913.
92. Keens TG, Ianuzzo CD. - Development of fatigueresistant muscle fibers in human ventilatory muscles. Am Rev
Respir Dis, 119 (part 2), 1979, 139-141.
93. Aniansson A, Grimby G, Nygaard E, Saltin B. -Muscle
f iber composition and fiber area in various age groups.
(Abstract). Muscle Nerve, 1980, 3, 271-272.
94. Colling-Saltin A-S. - Enzyme histochemistry on
skeletal muscle of the human fetus. J Neurol Sci, 1978, 39,
169-185.
95. Colling-Saltin A-S. - Skeletal muscle development in
the human fetus and during childhood. In: Children and
Exercise. IX. K. Berg, B. Eriksson eds, University Park Press,
Baltimore, 1980, pp. 193-207.
96. Grimby G, Aniansson A, Zetterberg C, Saltin B. Is there a change in relative muscle fibre composition
with age? Clin Physiol, 1984, 4, 189-194.
97. Grimby G, Saltin B. - The ageing muscle. Clin Physiol,
1983, 3, 209-218.
98. Aniansson A, Gustafsson E. - Physical training in
elderly men with specific reference to quadriceps muscle
strength and morphology. Clin Physiol, 1981, 1, 87-98.
99. Larsson L. - Physical training effects on muscle
morphology in sedentary males at different ages. Med Sci
Sports Exerc, 1982, 14, 203-206.
100. Berglund E, Birath G, Bjure J, Grimby G, Kjellmer I,
Sandqvist L, Soerholm B. - Spirometric studies in normal
subjects. I. Forced expirograms in subjects between 7 and 70
years of age. Acta Med Scand, 1963, 173, 185-192.
101. Birath G, Kjellmer I, Sandqvist L. - Spirometric
studies in normal subjects. II. VentiJatory capacity testing in
adults. Acta Med Scand, 1963, 173, 193-198.
102. Sanchez J, Bastien C, Medrano G, Riquet M, Derenne
JP. - Metabolic enzymatic activities in the diaphragm of
normal men and patients with moderate chronic obstructive
pulmonary disease. Bull Eur Physiopathol Respir, 1984, 20,
535-540.
103. Sanchez L, Brunei A, Medrano G, Debesse B, Derenne
JP. - Metabolic enzymatic activities in the intercostal and
serratus and in the latissimus dorsi of middle-aged normal
men and patients with moderate obstructive pulmonary
disease. Eur Respir J, 1988, 1, 376-383.
104. Bangsbo J, Mizuno M. - Morphological and metabolic
alterations in soccer players with detraining and retraining
and their relation to performance. In: Science and Football.
T. Reilly, T. Lees, K. Davids, W.J. Murphy eds, E. & F.N.
Spon, New York, 1988, pp. 114-124.
105. Coyle EF, Martin III WH, Sinacore DR, Joyner MJ,
Hagberg JM, Holloszy JO. - Time course of loss of
adaptations after stopping prolonged intense endurance training. J Appl Physiol: Respirat Environ Exercise Physio/, 1984,
57, 1857-1864.
106. Henriksson J, Reitman JS.- Time course of changes in
human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with
physical activity and inactivity. Acta Physiol Scand, 1977, 99,
91-97.
107. Richter EA, Kiens B, Mizuno M, Strange S. - Insulin
action in human thighs after one-legged immobilization. J Appl
Physiol, 1989, 67, 19-23.
108. Mizuno M, Secher NH, Saltin B. -Biochemical findings
in external and internal intercostal muscles in man. Acta
Physiol Scand, 1984, 121, 12A.
109. Bangsbo J, Gollnick PD, Graham TE, Juel C, Kiens B,
Mizuno M, Saltin B. - Anaerobic energy production and
0 2 deficit-debt relationship during exhaustive exercise in
humans. J Physiol (Lond), 1990, 422, 539-559.
110. Paton WDM, Zaimis EJ. -The action of D-tubocurarine
and of decamethonium on respiratory and other muscles in
the cat. J Physiol (Lond), 112, 311-331.
111. Johansen SH, Jl'!rgensen M, Molbech S. - Effect of
tubocurarine on respiratory and nonrespiratory muscle power
in man. J Appl Physiol, 1964, 19, 990-994.
112. Jl'!rgensen M, Molbech S, Johansen SH. - Effect of
decamethonium on head lift, hand grip and respiratory
muscle power in man. J Appl Physiol, 1966, 21, 509-512.
113. Dam WH, Guldmann N. - Inadequate postanesthetic
ventilation. Anesthesiology, 1961, 22, 699-707.
114. Leonard B, Mitchell JH, Mizuno M, Rube N, Saltin B,
Secher NH. -Partial neuromuscular blockade and cardiovascular responses to static exercise in man. J Physiol (Lond),
1985, 359, 365-379.
115. Secher NH, Rube N, Secher 0.- Effects of tubocurarine
on human soleus and gastrocnemius muscles. Acta Anaesth
Scand, 1982, 26, 231-234.
116. Jewell PA, Zaimis EJ. - A differentiation between
red and white muscle in the cat based on response to neuromuscular blocking agents. J Physiol (Lond), 1954, 417-428.
117. De Troyer A, Bastenier J, Delhez L. - Function of
respiratory muscles during partial curarization in humans. J
Appl Physiol: Respirat Environ Exercise Physiol, 1980, 49,
1049-1056.
Muscles respiratoires humains: morphologie des fibres et
apport cqpillaire. M. Mizuno. .
RESUME: Chez l'homme, le dtaphragme (DIA) et les muscles abdominaux comportent approximativement 50% de fibres areaction lente, alors qu'une proportion superieure (60%)
est decelee dans les muscles intercostaux et les scal~nes. Tous
les muscles respiratoires ont une distribution egale de fibres
a reaction rapide (FTa et b) a !'exception des muscles
intercostaux expiratoires, qui n'ont que peu de fibres FTb.
INSPIRATORY AND EXPIRATORY MUSCLES
Les muscles inspiratoires ont des fibres d'une taille
uniform6ment petite, A !'oppose des muscles intercostaux
expiratoires dont les fibres sont plus grandes. La dimension
des fibres des muscles inspiratoires se maintient au cours du
vieillissement, alors que celle des muscles intercostaux
expiratoires semble diminuer apres l'age de 50 ans. L'apport
capillaire est plus abondant dans les muscles expiratoires,
suivis par le diaphragme et les muscles inspiratoires
intercostaux. Chez les patients atteints de
bronchopneumopathies chroniques obstructives, on ignore si
601
une reduction de la taille des fibres des muscles respiratoires
thoraciques est causee par leur surutilisation due au travail
ventilatoire accru ou par une mauvaise utilisation due a une
implication accrue des muscles respiratoires extra-thoraciques.
les caracteristiques histochimiques suggerent que, chez les
sujets humains normaux, la charge des muscles inspiratoires
est relativement faible au cours des contractions, alors que
les muscles intercostaux expiratoires sont exposes a une
activite continue marquee avec un charge importante.
Eur Respir J., 1991, 4, 587-601.