Download Effect of Oral N-Acetylcysteine on Tracheal Hypersecretion in the Rat

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Medical Research Society Communications
92 THE INFLUENCE OF NON-SPECIFIC AIRWAY
REACTIVITY ON THE IMMEDIATE BRONCHWONSTRICTOR
RESPONSE TO EXERCISE AND ANTIGEN IN ASTHMA
HOWARTH P.H.,
SIHRA B.S. and HOLGATE S.T.
Southampton General Hospita1,Southampton SO9 4Xy
Six atopic asthmatic subjects (4M,2F) with
a mean age of 29.3 years ( range 21-38 years)
underwent treadmill exercise bronchial challenge
on 3 separate occasions. On each occasion the
treadmill speed and the duration of exercise
were constant while the inspired air conditions
randomly differed, such that the subjects
exercised while inhaling air at (a) room
temperature, room humidity (b) body temperature
fully saturated (c) sub-freezing temperature
and dry. With all t!!e challenges, ventilation
rate,inspired and expired air temperature and
inspired air humidity were recorded and the
respiratory heat exchange (RAE) calculated.
Airway calibre was recorded.as the forced
expiratory volume in 1 second (FEvl), both
before and up to 30 minutes after challenge. The
same subjects subsequently underwent bronchial
provocation on seperate days with methacholine
(MI and antigen (Ag) to define the provocative
concentration of M and Ag required to produce
a 20% fall in FEVl (PC20!.
A linear relationshlp was found for
exercise with each individual between the RHE
and the maximum fall in FEVl on each occasion
(r=0.97
0.02 (+ SEM)) A close correlation
existed between the RHE required to produce a
20% fall in FEVl ( P D Z ~
RHE) and the PCz0M
(r=0.96) for the group. This relationship was
not found between the PCzO Ag and the PC20 M
(r=0.14).
These results indicate that non-specific
airway reactivity is an important determinant
of exercise-induced asthma, and that the
mechanism of exercise- and antigen-induced
bronchoconstriction differs.
.
93
OF ORAL N-ACETYLCYSTEINE ON
TRACI-EAL HYPERSECRETION I N 2HE RAT
~~
D.F.RCGERS, N.C.
AND P.K. JEFFERY
21179 Pathology, kdiothoracic Institute,
London, SW3 6HP
?he present study investigates whether or
m t oral N-acetylcysteine
(NAC) inhibits
hypersecretion of rrmcus i n an a n h l model of
bronchitis.
14 m l e specific pthogen-free
rats were nade bronchitic by e x ~ ~ s u rto
e the
mbacco mke (TS) of 25 cigarettes, daily for
14 days. 10 were similarly ~ s e but
d were
also given NAC as 1%
of their drinking water:
the daily dose con-d
was a b x t 1000 ng/kg
body weight. 19 rats, not exposed t o Ts served
as controls. 7 rats weregivenuralNACsnd
m t exposed,
A t the end of expsure each r a t
was anaesthetised a d an i n situ tracheal
sement isolated, c a r t d a t e d and continuxlsly
perfused for 30 minute periods over5 hcurs
with physiological saline. Ihe 10 samples of
saline, containing tracheal secretions, were
collected and d y s e d for fucose (as a
specific
marker
of rmcus-glycopmteins) ,
h e m e and protein.
In 38 rats, before
collecticn pericds 5 and 8 tk s a l i m was
replaced by an acute administration of TS
(diluted 1:3 w i t h air) or air. Following
eqilibration, the man basal concentrations
(ug/sample + SEM) with (+I or withcut (-1 NAC
were:
control
'bronchitic'
-
+
-
+
fuc.
3(1)
7(3)
24(6)*
7(3)*
hex.
41(8)
97(27)
lOl(26)
69(25)
prot. 1082(385)1405(476) 2000(520) 2055(599)
*
T k man value for h o s e i s significantly
higher in bronchitic than i n control rats (p<
0.01); -Mr NAC m p l e t e l y inhibited the
bronchitic response.
Only the f i r s t acute administration of E
significantly increased the mean concentration
of k m s e above basal levels and then only in
control r a t s (p<0.05). NAC inhibited the
acute effect. Acute administration of a i r had
no statistically significant effect.
Thus, Ts for 2 weeks produces airway
hypersecretion
snd N X cunpletely inhibits
both the 'chronic' and acute responses.
94
L U X Sclrll OBSEWATIOIIS 011 THE MKCEAIUsII OF
HtpOxhgLIu I11 ACUTB WlDB
m L I S 4
G.H. BURTON, W.A.
SEED, AND P. VERNON
Departments of Medicine and Nuclear Medicine,
Charing Cross Hospital, Fulham, London W6 8RF
Although arterial hypoxaemia is found in a high
proportion of patients with uncomplicated acute
pulmonary embolism, the mechanism remains
unclear. Since cardiac output does not fall in
minor pulmonary embolism, regions of lung
uninvolved in the embolism receive an increased
blood flow, and if ventilation is not redistributed or increased appropriately, such regions of
relative underventilation would be a potential
cause of hypoxaemia. We have examined this
possibility, using an automated computer analysis
of ventilation-perfusion lungscans to quantitate
the distribution of ventilation and perfusion and
their relationship.
Normal ranges were established for the distribution of ventilation, perfusion, and their
matching down the vertical axis of each lung in
55 non-smoking human volunteers. Data was then
collected retrospectively from scans performed
acutely in 11 patients with a firm clinical
diagnosis of minor pulmonary embolism, uncomplicated by pre-existing cardiopulmonary disease,
and with a normal chest x-ray, in whom arterial
blood-gas analysis had been performed within 24
hours of the scan.
In each case the analysis showed the presence of
areas of lung, remote from those involved in the
pulmonary embolism, which had a pathological
disturbance of ventilation-perfusion matching
with relative underventilation. The extent of
this disturbance showed a significant inverse
correlation with arterial PO (r = -0.68,
2
~(0.05). When the extent of the mismatching was
calculated in terms of relative blood flow and
alveolar VentilationCobtained from the scan data,
corrected via the arterial blood-gas tensions),
the correlation was improved (r = -0.61, p<O.Ol).