Medical Research Society
36 P
100 ABOLITION OF DROGINDUCED
BRONCEOCONSTRICTION BY EXERCISE AND
EYF'ERVENTILATION
S FREEDMAN, R LANE, M GILLETT and A GUZ
Dept o f Medicine, Charing Cross & Westminster
Medical School, Fulham Palace Road, London, W6
We measured total pulmonary resistance at
rest, during exercise and during voluntary
hyperventilation in 6 normal young males, using
oesophageal balloons with the technique o f Mead
& Whittenberger (J Appl Physiol 1953;5;779-796).
Prior to each test pulmonary resistance was
increased by inhalation of an aerosol of
methacholine, raising specific resistance by
150-570%. Subjects performed 2 tests on 2
separate occasions. F o r the first test they
exercised on a bicycle ergometer with workload
increasing over the first 3 min to a level
sufficient to achieve approximately 85%
predicted maximum heart rate. They then
maintained this level for a further 10 min. The
tidal volume signal was recorded on an FM tape
recorder. On the second occasion, 5 of the
subjects repeated the above protocol but instead
of exercising they voluntarily copied their
previous exercise ventilation pattern by
following the replayed tidal volume signal on an
oscilloscope screen. Isocapnia was maintained
by administration of COz at the mouth as
necessary.
In all subjects, both exercise (EX) and
hyperventilation (HV) produced falls in specific
pulmonary resistance (SRP) which began
immediately, and within 2 min approached or
reached baseline values.
act partly directly and partly by reflex
actions.
The surgical procedure o f combined
heart lung transplantation involves the loss Of
the autonomic nervous supply to the lungs and we
have studied the effect of this on bronchial
responsiveness.
Five combined heart-lung
transplant patients (HLT) and four heart
transplant patients (HT) were studied 3-11
months postoperatively.
All patients were
receiving immunosuppressive treatment with
cyclosporin and azathioprine. Each subject was
studied on two consecutive days. On day 1 the
provocative dose of methacholine
(PD35M)
necessary to cause a 35% fall in specific
airways conductance was measured as previously
&
Snashall.
Clin
Sci
described(Chung
1984;66;665-673). On day 2 the responsiveness
to histamine was determined in a similar manner
(PD35H).
The geometric mean PD35 values (micromoles) _t.
lGSD were:
PD 5M
1.67
HLT
4.22 2 1.82
7.35 2 4.80
8.05 z 4.23
HT
;!??",
The HT patients had normal responsiveness to
both methacholine and histamine. However there
was a significant increase in the responsiveness
to methacholine in the HLT patients (PD35M, vs
PDyjH p<O.Ol).
This increased responsiveness to methacholine
may be due to denervation hypersensitivity of
Histamine
the bronchial smooth muscle.
responsiveness appears unaffected by pulmonary
denervation.
................................................
SRP Mean (SD)
2 min
5 min
10 min
EX 21.3(4.5) 13.2(3.0) 11.8(3.5)6.5( 1.2)8.4 (2.5)
HV 23.1 (4.6) 12.0( 1.9) 11.1 ( 1.8)9.1(4.7 )7.1(3.1)
0
1 min
Prior inhalation of Edrophonium (10mg) failed
to stabilise the methacholine-induced
bronchoconstriction. Bronchoconstriction
produced by Histamine inhalation was similarly
abolished by exercise.
These results suggest that the mechanical
effects of deep breaths are more important than
humoral factors in the bronchodilatation
occurring during exercise.
101
MCREASED BRONCHIAL RESPONSIVENESS TO
METHACEIOLINE BUT NOT EISTAMINE IN COMBINED
HEART-LUNG TRANSPLANT RECIPIENTS
MK GILLETT, R HEATON, NR BANNER, MH YACOUB, A
GUZ
Dept of Medicine, Charing Cross Hospital, London
and Cardiothoracic Unit, Harefield Hospital,
Middlesex
The responsiveness of the bronchi to inhaled
methacholine aerosol has been shown to correlate
closely with the responsiveness to inhaled
histamine aerosol in normal and asthmatic
subjects (Juniper.et a1 Thorax 1978;33;705-710).
Methacholine acts directly on the bronchial
smooth muscle whereas histamine is thought to
102
INCREBSED CO2 SENSITIVITY FOLLOWING AIRUAY
ANBESTKESIA I N LARYNGECTOMISED MAN
R.D. HAMILTON, A.J. WINNING, A. PERRY, A.D.
CHEESMAN and A. GUZ
Departments of Medicine and ENT, Charing Cross
and Westminster Medical School, London, W6 8RF
We have previously demonstrated that airway
anaesthesia increases the ventilatory response
to COz in normal man primarily by enhancing the
rise in respiratory frequency (Cross et al.
Clin.Sci. 1976,2,439). In the cat, stimulation
of the larynx with 5 or 10% COz produces a
decrease in minute ventilation by decreasing
respiratory frequency (Boushey & Richardson. J.
Physiol. 1973;=;181).
We therefore wished to
test whether the effect of airway anaesthesia
was due simply to the removal of an inhibitory
laryngeal effect.
Seven fit male subjects (age 59-77 years),
with permanent tracheal stomas following surgery
for laryngeal carcinoma, performed a normoxic
C02 rebreathe following inhalation of control
(0.9% saline) and local anaesthetic (5%
bupivacaine) aerosols. During COz rebreathing
subjects recorded their sensation of
breathlessness every 30 sec using a visual
analogue scale (VAS). The cough reflex, tested
by mechanical stimulation below the main carina
with a polythene catheter, was abolished by
bupivacaine aerosol in 6 subjects.
In 6 subjects following inhalation of
bupivacaine aerosol the VE/PETC02 slope was
increased (all 7 subjects: saline 2.3920.59;
Medical Research Society
bupivacaine 4.0621.87 1 min-l mmHg-1; P<0.02)
while the intercept with the C02 axis was
unchanged (saline 37.127.1; bupivacaine 38.227.2
mmHg; P>0.5). In 5 subjects the fR/PETCO2 slope
was increased while in the other 2 it fell (all
7 subjects: saline 0.41+0.27; bupivacaine
0.9220.70 min-l mmHg-1;-0.1>P>0.05). In the 6
subjects who reported breathlessness, its onset
occurred at a lower VE after bupivacaine (saline
35.9213.8; bupivacaine 20.2210.1 1 min-1;
P<0.02) and the VAS scores at matched maximum
ventilations were increased (saline 49.5534.8;
bupivacaine 66.9228.6 ma; P-0.01).
Since the exaggerated ventilatory response to
C02 after bupivacaine aerosol is not removed by
the removal of the larynx, we conclude that this
effect must be mediated by receptors lower in
the respiratory tract.
103 THE EFFECT
OF VOLUNTARY ISOCAPNIC BYPERVENTILATION ON B ~ T A L E S S N E S SDURING EXERCISE IN
NORU4I.S
R. LANE, A . COCKCROFT AND A. GUZ
Dept of Medicine, Charing Cross and Westminster
Medical School, Fulham Palace Road, London W6
~ R F
In respiratory patients we have shown that
breathlessness is diminished or absent during
voluntary isocapnic hyperventilation, in
contrast to ventilation at the same level
stimulated by C02. When a C02 stimulus is added
during voluntary hyperventilation,
breathlessness is much greater. (Adams et al,
Clin. Sci. 3:663-72). We have now studied
voluntary hyperventilation and the more
'physiological'ventilatory stimulus of exercise,
in 6 normals (29). Subjects exercised on a
bicycle ergometer, with measurements of
ventilation (VE) and breathlessness indicated on
a visual analogue scale (VAS) every 30s. During
2 of the tests the tidal volume signal was
recorded and later replayed onto an oscilloscope
during 2 further tests when the subjects were
asked to copy these breathing patterns. Two
levels of workload were used: high ( 6 1 at 150Wd,
lOOWg) and low (61 at lOOWd: 65Wy). Each subject
performed 5 exercises: A-high workload; B-low
workload copying VE of A; C-low workload only;
?-high workload repeat; E-high workload copying
VE of D. During B and E , GO2 was added to
maintain isocapnia. Mean VE and VAS score during
the exercise were calculated for each subject.
These values were compared for the 6 subjects
between tests, using paired-t analysis.
E
A
B
C
D
64.8 68.7
61.2
40.2
Mean ~E(SD) 61.0
(Lain-')
(18.5) (17.4) (10.0) (18.5) (21.1)
NS p<0.002
NS
29.0
25.7 \L
10.5
8.2
Mean VAS(SD) 32.7
(ma)
(15.8) (7.2) (12.9) (20.1) (22.9)
p<0.02
NS
Ns
Thus, when voluntarily copying a higher VE,
breathlessness was not greater than that expected at the low workload (AvB and BvC) but voluntary copying in itself did not reduce breathlessness (DvE). We conclude that-breathlessnessis
not related to the level of VE itself but to the
stimulation of VE produced by exercise. This
supports our previous results with hypercapnia.
37 P
EFFECTS OF COLD EXPOSURE ON ACUTE
RESPONSES OF SINGLE-BREATH TRANSFER FACTOR
(TLco) IN NORMALS AND RAYNAUDS
104
A. ROZKOVEC,
A.H. KENDRICK,
P. INGLIS,
M. CASEBOW AND P. HICKLING
Cardiac and Respiratory Departments, Bristol
Royal Infirmary and Plymouth General Hospital
There is indirect evidence of cold induced
changes in pulmonary vascular resistance in
Raynauds. The influence of cold stimuli was
studied in 4 groups of 8 patients: 1) primary
Raynauds, 2 ) secondary Raynauds due to rheumatoid arthritis, 3) secondary Raynauds due to
other causes and 4) normals. The effects of
nifedipine were studied in groups 1-3.
TLco
and spirometry were measured before and at 9
and 1 2 minutes during leg immersion at 17.C.
Groups 1-3 were randomized to 2 weeks of
placebo and 2 weeks of nifedipine 20mg bd in a
double-blind cross-over design, and tested at
the end of each period. Single-breath pulmonary
blood flow (Qc) was estimated simultaneously
with TLco in groups 1 and 4. Blood Pressure
(BP) and heart rate (fc) were measured in group
4. The mean(SD)Tlco results (as %predicted)
were:Group Drug
Pre
Immersion
Immersion
9min
12min
1
108.5
102.8*
102.2*
(9.7)
(11.3)
(9.4)
+
107.8
103.8
103.7
(7.4)
(8.2)
(9.2)
2
106.1
104.8
105.9
(25.9)
(26.4)
(25.9)
4102.9
102.9
102.0
(26.8)
(28.3)
(27.3)
96.9*
101.4
3
102.5
(13.1)
(10.4)
(11.9)
100.8*
101.4*
+
106.5
(10.6)
(10.3)
(9.5)
4
105.5
103.1
103.4
(17.1)
(17.7)
(16.9)
* sig. dif. from pre-immersion at p<0.05
.............................................
The changes in TLco were not accounted for by
changes in alveolar volume. Qc, BP and fc did
not alter. These findings are consistant with
cold induced pulmonary pre-capillary vasoconstriction occuring independent of significant
systemic changes. Nifedipine did not influence
TLco o r spirometry.
105 VARIATION IN STROKE
VOLUME IN ATRIAL
FIBRILLATION
D.J. ROBSON AND J. FLAXMAN
Cardiac
Department,
Greenwich
Hospital, London, SElOPHE, England.
District
This study was designed to determine the
factors responsible f o r the variation in
stroke volume in atrial fibrillation.
Methods Simultaneous M-mode echocardiography
and continuous wave Doppler aortic velocity
recordings were made in 19 patients including
7 with mitral stenosis 7 with dilated
cardiomyopathy and 5 with normal left
-