62 P
Medical Research Society
e r r o r i n the-measurement of e f f e c t i v e pulmonary
blood flow (Qc) t h a t t h i s may produce h a s been
i n v e s t i g a t e d by u s i n g a t e s t g a s c o n t a i n i n g two
i n s o l u b l e g a s e s of widely d i f f e r e n t molecular
weights: argon (mol.wt:40) and sulphur hexaf l u o r i d e (SF6;mol.wt:146).
The composition of
t h e t e s t g a s used was: argon:12%, SF6:8%,
Freon 22:5%, oxygen:45%, n i t r o q e n 30%.
We conclude t h a t whole smoke b u t n o t gas
phase a l t e r s t h e P-V loops of i s o l a t e d l u n g s .
This a g r e e s w i t h t h e i n v i t r o s u r f a c t a n t
o b s e r v a t i o n s and we s u s p e c t t h a t t h e tobacco
' t a r ' i n t e r a c t s with the s u r f a c t a n t i n 'vivo'.
S i x p a t i e n t s w e r e s t u d i e d a t l e a s t t h r e e hours
a f t e r c a r d i a c s u r g e r y while v e n t i l a t e d by a
Siemens s e r v o v e n t i l a t o r . A l l s u b j e c t s had
normal lung f u n c t i o n tests p r e - o p e r a t i v e l y . For
each s u b j e c t f o u r estimates of a c c e s s i b l e lung
volume (VA) and 6, were made u s i n g argon or SF6
as t h e r e f e r e n c e gas. The range of v a l u e s
i n v e s t i g a t e d f o r 6, w a s 2.2 f 0.1 - 4.9 f 0.4
L/min (mean f ED): The mean v a l u e s c a l c u l a t e d
u s i n g argon w e r e : Qc = 3.2 L/min; VA = 1.40L
and u s i n g SF6: 6, = 3 . 1 L/min; VA = 1.39L.
Analysis by p a i r e d t t e s t r e v e a l e d no s i g n i f i c a n t
d i f f e r e n c e between t h e s e v a l u e s f o r Qc and VA.
171 ESTIMATED DAILY WATER LOSS DURING MOUTH
W e conclude t h a t t h e t h e o r e t i c a l e r r o r a r i s i n g
from t h e d i f f e r e n t d i f f u s i v i t i e s of argon and
Freon 2 2 i s n o t of p r a c t i c a l s i g n i f i c a n c e i n t h e
d e t e r m i n a t i o n of oc by t h e r e b r e a t h i n a method i n
v e n t i l a t e d p a t i e n t s w i t h normal lungs.
170 TOBACCO SWXI?, AND THE PRESSURE-VOLUME
CHARACTERISTICS OF THE ISOLATED LUNG
N e i l Cracknell, C o l i n Hardy, T i m Higenbottam.
Depts of R e s p i r a t o r y Physiology, Addenbrooke's
H o s p i t a l , Cambridge.
With tobacco smoke exposure i n i t i a l
p a t h o l o g i c a l changes a r e t o be found i n p e r i p h e r a l a i r s p a c e s (Niewoehner e t a l . N Eng J
1974, 291:755-758).
I t h a s a l s o been shown
t h a t wholesmoke, b u t not gas phase, a l t e r s t h e
s u r f a c e p r o p e r t i e s of pulmonary s u r f a c t a n t i n
v i t r o (Davis B e t a l , Thorax 1984, No 9 : p702).
W
e have q u e s t i o n e d whether tobacco smoke i n t e r a c t s w i t h s u r f a c t a n t i n vivo and t o study i t s
e f f e c t s i n t h e absence of v a g a l r e f l e x e s wehave
used i s o l a t e d r a t s lungs t o a s s e s s changes i n
t h e pressure-volume (P-V) c h a r a c t e r i s t i c s of
t h e lungs a f t e r smoke exposure.
A t o t a l of 19 CFHB r a t s were a n a e s t h e t i z e d
and s a c r i f i c e d by exsanguination.
The t r a c h e a
was cannulated, then clamped. The h e a r t and
lungs were e x c i s e d and suspended v i a t h e c a n n u l a
i n a c o n s t a n t temperature (37OC) and humidity
chamber. The t r a c h e a l p r e s s u r e was monitored
a s t h e lungs were slowly (10 ml/min) i n f l a t e d
and d e f l a t e d u s i n g a mechanically d r i v e n s y r i n g e ,
p r e s s u r e w a s p l o t t e d a g a i n s t time. AFter a rei n f l a t i o n cycle a control inflation-deflation
loop was performed. E i t h e r whole smoke o r gas
phase ( f i l t e r e d through a Cambridge f i l t e r ) o r
a i r (sham) was used t o i n f l a t e t h e lungs.
F u r t h e r P-V loops were performed.
Comparison
Whole smoke
Gas phase
Limb
infl
defl
infl
infl
df
1,8
1,8
1,8
1,8
F
.I3
12.9
.025
.29
Signif
NS
P(O.01
NS
NS
The whole smoke d e f l a t i o n limb was s i g n i f i c a n t l y
different
.
BREATHING
N e i l C r a c k n e l l , Karen Harmes and
Tim Higenbottam
R e s p i r a t o r y Physiology Department, Addenbrooke's
H o s p i t a l , Cambridge.
We have developed a method f o r t h e measurement
of e x p i r e d a i r water c o n t e n t u s i n g a f a s t responding Dew p o i n t a n a l y s e r (Michelle Laborat o r i e s , Cambridge).
There remains u n c e r t a i n t y
as t n t h e t o t a l r e s p i r a t o r y l o s s o f water a t
rest o v e r a 24 hour period. Nine s i t t i n g
v o l u n t e e r s ( 6 men, 3 women) q u i e t b b r e a t h e d
through a low r e s i s t a n c e 2 way valve.
Inc o r p o r a t e d i n t h e valve were 2 f a s t responding
thermocouples t o s e p a r a t e l y r e c o r d i n s p i r e d and
e x p i r e d air t e m p e r a t u r e s , at 0.5 cm from t h e
mouth. The e x p i r e d a i r was sampled 1 cm from
t h e mouth and e x p i r e d t i d a l valume was recorded
u s i n g a h e a t e d and i n t e g r a t e d pneumotachograph.
A f t e r a 5 minute s t a b i l i s i n g p e r i o d c a l c u l a t i o n
for R e s p i r a t o r y h e a t exchange (RHE) (Chandler
Deal e t a1 J Appl P h y s i o l 1979:49;476) and water
loss were made over a f u r t h e r 5 minute6,extrap o l a t i o n t o 24 h o u r s was made.
The mean d a i l y water l o s s was i n men(N=6)
329.99 (SD=122.4g) and women (N=3) 115.33
(SD=29g) with a n a r e r a g e t i d a l vblume of f o r
men 0.751 ( . gsl=OO.12)for women 0.3 ( s ~ d . 1 8 ) .
The ME i n 24 hours w a s i n men 253.6 k c a l
(SD=96.5) and women N = 3 88.1 (SD=23.9).
These
r e s u l t s r e p r e s e n t a c o n s e r v a t i v e estimate as
e x e r c i s e c a u s e s i n c r e a s e d v e n t i l a t i o n and
~
e t a l , C l i n S c i 1985
g r e a t e r w a t e r . 1 0 ~ (Hay
69 ( s u p p l 1 2 ) , b u t exclude t h e water Eonserv a t i o n due t o t h e nose as y e t n o t s t u d i e d .
172
AN EMG STUDY OF TRIANGULARIS STERN1 USE
I N MAN
J.J. GILMARTIN, V. N I N A N E , C. LEMERRE,
M. ESTENNE AND A. DE TROYER.
R e s p i r a t o r y Research U n i t , Erasme
H o s p i t a l , B r u s s e l s , Belgium
Recent work h a s shown i n v a r i a b l e c o n t r a c t i o n
of t h e T r i a n g u l a r i s S t e r n i (TS) d u r i n g q u i e t
e x p i r a t i o n i n t h e dog (De Troyer and Ninane,
Fed. Proc. 44 : 1003, 1985). but t h e use of
t h i s m u s c l e i n man h a s n o t been d e f i n e d .
Gle have recorded t h e EMG a c t i v i t y of TS i n
8 normal s u b j e c t s ( 5 t r a i n e d , 3 n a i v e ) with a
needle e l e c t r o d e i n e i t h e r t h e 4 t h . or 5 t h .
i n t e r c o s t a l space. The s u b j e c t s were s t u d i e d
63 P
Medical Research Society
supine and sitting during quiet breathing,
slow voluntary expiration from FRC, expulsive
manoeuvres,static manoeuvres (neck flexion,
trunk rotation) and phonation. There was no
TS activity during quiet breathing in the
naive subjects, but 3 of the 5 trained
subjects when breathing on a mouthpiece
occasionnally showed a small amount of phasic
expiratory EMG activity. Voluntary expiration
from FRC (even during attempts to expire with
the abdomen alone) invariably elicited a
large amount of TS activity in all subjects.
TS was also invariably recruited during
phonation as well as expulsive and static
manoeuvres. The results were similar in the
sitting and supine posture.
We conclude that, in normal subjects, TS is
not active during quiet unencumbered breathing
but is always recruited during active
expiration below FRC and static manoeuvres.
Supported by FRSM Belgium, Erasme Foundation
and Boehringer-Ingelheim, Int.
173
TAE EFFECT OF P R O " J N R
AND DIAZEPAM ON
RRSPIRATORY CONTROL I N BREATfILESS PATIENTS
A.L.JONES
AND I.R.CAMERON
Department of Medicine, St Thomas' Hospital
Medical School (ITMT)S), London SE1 7EH
Promethazine (Pz) and niazepam (Dz) have been
reported to relieve dyspnoea in patients with
chronic lung disease (Mitchell-Heggs et a1
Q.J.M. 1980 193 9; Woodcock et a1 R.M.J. 1981
287 343). W e a v e previously reported the
effects of these drugs on normal respiratory
control (Jones and Cameron, Clin Sci 1"85 69
6p) and have now investigated their effects on
respiratory control in 9 patients with chronic
airflow limitation who were breathless at rest.
None were hypercapnic. Subiects entered a
douhle hlind, placeho controlled, crossover
study of two weeks treatment with Pz (3.5mg om
and S h g on) and nz 15mg om and l h g on).
These are lower than the doses used hv
Woodcock et al, which our patients were unahle
to tole rat^. Tn the afternoon at the end of
each treatment period we tested:1. Hypercapnic responsiveness. (Read method)
2 . Six minute walking distance (6MD)
3. Progressive unsteady state exercise test
4. Breath holding time (BHT)
5.
Visual analogue scales of dyspnoea WAS)
6 . The effect of mental concentration on the
pattern of ventilation
Compared with placeho, Dz treatment caused an
increase from 37.6 5 1.7 to 41.9 2 1.7 mmHg i n
restjng PCO2 (pt0.005) and a prolongation of
RHT from 18.56 ? 1.83s to 27.00 5 1.8% (mean 5
SEM).
Following Dz, the ventilatory response
to raised CO2 was reduced from 1 . 1 7 5 0.22 to
0.74 + 0.22 (p<n.Ol), the reduction heing
accompanied by a decline in VAS of dysonoea at
the end of the test (p<0.05). 6MD was also
reduced from 491.4 2 '31.0 to 476.6 2 '31.0
(p<0.01) by Dz. Pz ha4 no significant
ventilatory effects. Patients were more drowsy
o n hoth drugs than on placebo but were not less
hreathless at rest. I n contrast to findings in
normals, respiratory pattern changed little in
response to mental concentration
.
We conclude that although Dz is a respiratory
depressant, neither this nor Pz has reduced
dyspnoea or improved exercise performance in
our patients. Both drugs had unpleasant slde
effects in addition to drowsiness.
DEPRESSED MUSCLE PROTEIN SYNTHESIS IS THE
PREDOMINANT MECHANISM OF MUSCLE WASTING IN
EMPHYSEMA
174
W.L. MORRISON, J.N.A. GIBSON, R.N. JOHNSTON,
R.A. CLARK AND M.J. RENNIE
Departments ofPhysiology and Respiratory
Medicine, The University, Dundee
Severe emphqsema is commonly associated with
loss of lean body mass and muscle wasting. We
have investigated the mechanism of this wasting
in 8 men with emphysema, with a mean body weight
of 49.3 f 4.8 kg compared to an 'ideal' body
weight of 67.7 f 3.7 kg. From measurements of
leg blood flow, and amino acid concentrations in
femoral venous and arterialised hand vein blood,
the exchanges across leg tissue of tyrosine and
3-methylhistidine were calculated as specific
indicators of net protein balance and
myofibrillar protein breakdown respectively
1984, Metabolism 33:250-256).
(Rennie
The results were compared to those obtained in 8
normal men.
Tyrosine efflux was significantly greater in
the emphysematous patients compared to the
normal controls (5.17 versus 3.38 Pmo1/100 g
leg/min, p
0.01) indicating a state of net
negative protein balance. 3-methylhistidine
efflux was not elevated above the normal level
indicating that muscle protein breakdown was not
increased.
These results suggest that the predominant
mechanism of muscle wasting in emphysema is a
fall in muscle protein synthesis. Thus emphysema
is another condition of chronic muscle wasting,
1985,
like thyrotoxicosis (Morrison
Scott. Med. J., 30:194-195), cancer cachexia and
muscular dystrophy (Rennie & Harrison, 1984,
Lancet, i:323-325), characterised by decreased
muscle protein turnover.
-.,
u.,
Support from the Wellcome Trust, the White Top
Foundation, Dundee, and the Mason Medical
Research Foundation is gratefully acknowledged.
THE EFFECT OF ACUTE BILATERAL DIAPHRAGM
PARALYSIS ON BREATHING IN AWAKE AND ASLEEP DOGS
175
J.R.STRAOLING, L.KOZAR, J.OARK, T.KIRBY,
S.ANDREY A N 0 E.A.PHILLIPSON.
Departments of Medicine and Surgery, University
of Toronto, Ontario, CANADA
The effect of acute bilateral diaphragm paralysis (BOP) on ventilation has not been studied
in unanaesthetised o r sleeping animals. It has
been suggested that the severe hypoxaemia during
rapid-eye-movement sleep (REMS) in patients with
respiratory failure from BOP (compared to normal
subjects) is due to the REMS inhibition o f inter
costal and accessory muscles of respiration.
63 P
Medical Research Society
supine and sitting during quiet breathing,
slow voluntary expiration from FRC, expulsive
manoeuvres,static manoeuvres (neck flexion,
trunk rotation) and phonation. There was no
TS activity during quiet breathing in the
naive subjects, but 3 of the 5 trained
subjects when breathing on a mouthpiece
occasionnally showed a small amount of phasic
expiratory EMG activity. Voluntary expiration
from FRC (even during attempts to expire with
the abdomen alone) invariably elicited a
large amount of TS activity in all subjects.
TS was also invariably recruited during
phonation as well as expulsive and static
manoeuvres. The results were similar in the
sitting and supine posture.
We conclude that, in normal subjects, TS is
not active during quiet unencumbered breathing
but is always recruited during active
expiration below FRC and static manoeuvres.
Supported by FRSM Belgium, Erasme Foundation
and Boehringer-Ingelheim, Int.
173
TAE EFFECT OF P R O " J N R
AND DIAZEPAM ON
RRSPIRATORY CONTROL I N BREATfILESS PATIENTS
A.L.JONES
AND I.R.CAMERON
Department of Medicine, St Thomas' Hospital
Medical School (ITMT)S), London SE1 7EH
Promethazine (Pz) and niazepam (Dz) have been
reported to relieve dyspnoea in patients with
chronic lung disease (Mitchell-Heggs et a1
Q.J.M. 1980 193 9; Woodcock et a1 R.M.J. 1981
287 343). W e a v e previously reported the
effects of these drugs on normal respiratory
control (Jones and Cameron, Clin Sci 1"85 69
6p) and have now investigated their effects on
respiratory control in 9 patients with chronic
airflow limitation who were breathless at rest.
None were hypercapnic. Subiects entered a
douhle hlind, placeho controlled, crossover
study of two weeks treatment with Pz (3.5mg om
and S h g on) and nz 15mg om and l h g on).
These are lower than the doses used hv
Woodcock et al, which our patients were unahle
to tole rat^. Tn the afternoon at the end of
each treatment period we tested:1. Hypercapnic responsiveness. (Read method)
2 . Six minute walking distance (6MD)
3. Progressive unsteady state exercise test
4. Breath holding time (BHT)
5.
Visual analogue scales of dyspnoea WAS)
6 . The effect of mental concentration on the
pattern of ventilation
Compared with placeho, Dz treatment caused an
increase from 37.6 5 1.7 to 41.9 2 1.7 mmHg i n
restjng PCO2 (pt0.005) and a prolongation of
RHT from 18.56 ? 1.83s to 27.00 5 1.8% (mean 5
SEM).
Following Dz, the ventilatory response
to raised CO2 was reduced from 1 . 1 7 5 0.22 to
0.74 + 0.22 (p<n.Ol), the reduction heing
accompanied by a decline in VAS of dysonoea at
the end of the test (p<0.05). 6MD was also
reduced from 491.4 2 '31.0 to 476.6 2 '31.0
(p<0.01) by Dz. Pz ha4 no significant
ventilatory effects. Patients were more drowsy
o n hoth drugs than on placebo but were not less
hreathless at rest. I n contrast to findings in
normals, respiratory pattern changed little in
response to mental concentration
.
We conclude that although Dz is a respiratory
depressant, neither this nor Pz has reduced
dyspnoea or improved exercise performance in
our patients. Both drugs had unpleasant slde
effects in addition to drowsiness.
DEPRESSED MUSCLE PROTEIN SYNTHESIS IS THE
PREDOMINANT MECHANISM OF MUSCLE WASTING IN
EMPHYSEMA
174
W.L. MORRISON, J.N.A. GIBSON, R.N. JOHNSTON,
R.A. CLARK AND M.J. RENNIE
Departments ofPhysiology and Respiratory
Medicine, The University, Dundee
Severe emphqsema is commonly associated with
loss of lean body mass and muscle wasting. We
have investigated the mechanism of this wasting
in 8 men with emphysema, with a mean body weight
of 49.3 f 4.8 kg compared to an 'ideal' body
weight of 67.7 f 3.7 kg. From measurements of
leg blood flow, and amino acid concentrations in
femoral venous and arterialised hand vein blood,
the exchanges across leg tissue of tyrosine and
3-methylhistidine were calculated as specific
indicators of net protein balance and
myofibrillar protein breakdown respectively
1984, Metabolism 33:250-256).
(Rennie
The results were compared to those obtained in 8
normal men.
Tyrosine efflux was significantly greater in
the emphysematous patients compared to the
normal controls (5.17 versus 3.38 Pmo1/100 g
leg/min, p
0.01) indicating a state of net
negative protein balance. 3-methylhistidine
efflux was not elevated above the normal level
indicating that muscle protein breakdown was not
increased.
These results suggest that the predominant
mechanism of muscle wasting in emphysema is a
fall in muscle protein synthesis. Thus emphysema
is another condition of chronic muscle wasting,
1985,
like thyrotoxicosis (Morrison
Scott. Med. J., 30:194-195), cancer cachexia and
muscular dystrophy (Rennie & Harrison, 1984,
Lancet, i:323-325), characterised by decreased
muscle protein turnover.
-.,
u.,
Support from the Wellcome Trust, the White Top
Foundation, Dundee, and the Mason Medical
Research Foundation is gratefully acknowledged.
THE EFFECT OF ACUTE BILATERAL DIAPHRAGM
PARALYSIS ON BREATHING IN AWAKE AND ASLEEP DOGS
175
J.R.STRAOLING, L.KOZAR, J.OARK, T.KIRBY,
S.ANDREY A N 0 E.A.PHILLIPSON.
Departments of Medicine and Surgery, University
of Toronto, Ontario, CANADA
The effect of acute bilateral diaphragm paralysis (BOP) on ventilation has not been studied
in unanaesthetised o r sleeping animals. It has
been suggested that the severe hypoxaemia during
rapid-eye-movement sleep (REMS) in patients with
respiratory failure from BOP (compared to normal
subjects) is due to the REMS inhibition o f inter
costal and accessory muscles of respiration.