The Functional and Molecular Nature of Lung

21P
Medical Research Society
These r e s u l t s provide f u r t h e r evidence
t h a t impaired performance o f the i n s p i r a t o r y muscles c o n t r i b u t e s t o c h r o n i c
ventilatory failure i n p a t i e n t s w i t h
severe CAFO.
( S u p p o r t e d by a
Trust)
78
grant from t h e Wellcome
MEASUREMENT OF SERIES DEAD SPACE
K. HORSFIELD, G. CUMMING, J.D.
C.L.
RICHARDSON AND
BOWES
The Midhurst Medical Research I n s t i t u t e ,
Midhurat, West Suaaex
Dept. of Engineering and Applied Sciences,
University of Suaaex, Brighton
The main aim of t h i s study is t o compare t h e
method of Cumrning and Guyatt of measuring dead
a p a c e ( C l i n . Sci.. 6 2 : 541) w i t h t h a t of
Fowler (Am. J. Physiol., 154: 405). Cumming
and Guyatt u t i l i s e d the plot of volume of gas
e x p i r e d a g a i n s t volume of n i t r o g e n expired
from the single breath nitrogen t e s t . Taking
t h e s e c t i o n of curve corresponding t o phase
111, and using polynomial r e g r e s s i o n . t h e
curve was extended u n t i l i t cut the abscissa.
The i n t e r c e p t waa defined as the dead space.
Using a mathematical model of a lung with
asymmetrical alveolar ducts, the single breath
n i t r o g e n t e s t was s i m u l a t e d . The concept of
Fowler's method was extended from t h e crude
drawing of a s t r a i g h t l i n e on phase 111 t o
curve f i t t i n g with various order polynomials.
This was done on t h e p a r t of t h e curve l y i n g
between 500 and 1250 m l expired volume, and
waa repeated s t a r t i n g a t 6 0 0 , 700 and 800 m l
expired volume.
It waa found t h a t an n t h
order polynomial regression in Fowler's method
gave a dead space very close to that obtained
u s i n g an ( n + l ) t h o r d e r r e g r e s s i o n i n Cumming
and Guyatt's method. This was because t h e
p l o t i n Cumming and Guyatt's method is the
i n t e g r a l of the plot i n Fowler's method. The
v a l u e of dead space obtained in both methods
depended on the order. The beat polynomial
f i t was chosen by examining the relationship
between o r d e r and r o o t mean s q u a r e r e s i d u a l .
Phase 111 was b e s t r e p r e s e n t e d i n most caaea
by a 2nd o r d e r polynomial in Fowler's method
and a 3rd o r d e r polynomial i n Cumming and
Guyatt's method. An advantage of the Cumming
and Guyatt method is t h a t i t i s l e s s prone t o
i n a c c u r a c i e s , aa t h e p l o t used h a s l e s s
e x p e r i m e n t a l s c a t t e r , and a l s o i t does not
involve the calculation of areas.
77
THE JRJNCTIONAL AND MOLECULAR NATURE OF LUNG
d l ANTITRYPSIN
R. A. 'SMCXLEY AND S. C.
AFR)RD
The General Hospital, Steelhouse Lane,
Birmingham
The balance between proteolytic enzymes and
t h e i r i n h i b i t o r s i n t h e lung i s thought t o be an
important determinant of t h e development of
emphyaema and several workers have shown a
decrease i n t h e i n h i b i t o r y function of lung& AT
of smokers although t h e cause remains u n c e r t J n .
The only d i r e c t study has shownotlAT p u r i f i e d
from smokers lung lavage had undergone oxidation
thereby accounting f o r a reduction i n i n h i b i t o r y
function (Carp e t al, Proo. l a t l Aoad Soi, 1982,
2041). However,d AT can a l s o be inactivated by p a r t i a l p r o t e o b s i e or oomplexing with
enzymes and t h e detection of these forms maJr be
affected by p u r i f i c a t i o n procedures. We have
developed a method f o r identifying the moleoular
form of lung l a v e g a d AT without'purifioation
and compared t h e r e s u l t s with t h e i n h i b i t o r y
funotion i n 27 subjects (17 with i r r e v e r s i b l e
airflow Obstruction). Lung lavage f l u i d s are
aubjeoted t o SDS polyacrylamide g e l electrophore s i s ( t o separate t h e proteins by s i z e ) and t h e
proteins t r a n s f e r r e d onto a n i t r o c e l l u l o s e membrane. Thed AT bands are i d e n t i f i e d by psroxidase l a b e l l e a s p e c i f i c antiserum incubated with
3 amino 9 e t h y l cwbaeole t o produce a brown
colour. T h i s technique regularly i d e n t i f i e d
varyi
proportions o f d AT i n i t s native (m w t
54,oOOT p a r t i a l l y proteolysed (49,000) and c o w
.plexed (80,000)forms i n t h e lavage samples.
Those showing t h e presence of n a t i v e d AT inhibi t e d more porcine pancreatic e l a e t a s e ahan those
where the native form was not eean or t h e proteolyaed form predominated (p<O.O1) but no d i f f e r
encs w a s found between subjects with and without
airflow obstruction. The r e s u l t s demonstrate
t h a t lungoclAT e x i s t s i n several molecular forms
which maJr be associated with a l o s e of i t s
i n h i b i t o r y function. The lack of differences
between normal subjects and those with airflow
obstruction auggests the developuent of
emphysema i s not dependant upon a reduction i n
$AT i n h i b i t o r y capacity alone.
141
70
ADRELWLINE sEcRErIoN INRING EXE~ZCISE
N. DALToi,
CLARK, PA. 'IUSELAND.
J.B.WARlUi,
C.T.
'RIRNdR,
&pts.
Respiratory Medicine
Chemistry.
Guy's Hospital, London S E l 9RT.
&
'1.J.H.
Clinical
I n s i x normal s u b j e c t s during graduated
treadmill exercise, we have shown t n a t there is
no s i g n i f i c a n t rise i n venous p h m a adrenaline
levels during mild or Werate exercise. &ring
severe exercise plasma adrenaline rises from
approximately
0.3
to
1.9
ml/l
(Warren &
Dalton, Clin Sci 1983;64:475-479).
During a second study, adrenaline was infused
intravenously i n s i x resting subjects a t a rate
of 0.025 ug/kg/min.
'ibis elevated the basal
adrenaline level in venous plasma, drawn from
t h e opposite forearm, f r a n 0.28 (tO.04) ml/l
t o 0.92 (+0.16), 1.16 (M.20) and 1.28 (M.19)
ml/l a t 3 , s and 7 min a f t e r the s t a r t of t h e
infusion. ( a l l mean +SEYJ
.
In a t h i r d study t h i s ajrenaline infusion was
repeated in the same subjects 7 min a f t e r the
onset of moderate exercise a t a constant r a t e
(59-103 UJ on a s t a t i c exercise bicycle). J u s t
before the start of the infusion,
plasma