Medical Research Society
than was leupeptin. These and other specific
enterokinase inhibitors may eventually permit,.
some effective chemotherapeutic preve'ntion of
lethal acute necrotising pancreatitis.
146TIGHTLY BOUND METABOLITES OF THE PURINE
NUCLEOTIDE CYCLE IN MUSCLE FROM DYSTROPHIC MICE
G.
LUTAYA, L.M. RODRIGUES AND J.R. GRIFFITHS
Department of Biochemistry, St George's Hospital
Medical School, London SW17
The purine nucleotide cycle (PNC)
AMP
+ H20
IMP
:
+ NH3
ASPARTATE + GTP
DP + pi
ADE~SUCCINATE
(AMPS)
is known to be disturbed in the murine muscular
dystrophy (Senada & Yamaguchi, 1979, Biochim.
Biophys.Res.Commun. 90, 453-459; Fitt, P.S. &
Parliament, M.B., 1982, Biosci.Rep. 2, 177-183).
We have found that its three purine metabolites
are tightly bound to proteins from dystzophic
muscle.
The posterior thigh muscles of 4 normal (C57B1)
and 5 dystrophic (C57B1/6Jdy 2Jdy 25) mice were
freeze clamped and the soluble nucleotides
removed by exhaustive washing (10 times) with
50% ethanol. The washed pellet was then
extracted with 10% trichloroacetic acid/20%
methanol to release tightly bound nucleotides
which were measured by HPLC (Shuttlewood &
Griffiths, 1982, Clin.Sci. 62, 113-115).
The bound ATP and ADP in dystrophic muscles was
not significantly different from that in normal
muscle (where they are known to be attached to
myosin and actin respectively) (P=0.44 and 0.14
respectively) but the dystrophic muscle was
unusual in that it contained significant amounts
of tightly bound AMP ( 4 of the 5 specimens), IMP
(3/5) and AMPS (4/5). Only one,of the four
normal specimens contained bound IMP and A M P S .
It seems likely that this abnormality is
associated with the disordered PNC function in
dystrophic muscle, but whether it is cause or
effect is unclear.
1 4 7 LIMITING-SYMPTOMS IN CBRONIC HEART FAILURE
ARE DEPENDENT ON RATE OF INCREASE OF WORK LOAD
AND INDFPWENT OF FIAFMODYNAMICS
R. CANEPLANSON, C. REID, S. GIBBS, E. PARIS,
M. STEVENS, E. &oGEfls AND P.A. WOLELWILSON.
National Heart Hospital, London, England.
Treadmill exercise is conmonly used to assess
exercise capacity and the effects of vasodilator
therapy in patients with heart failure. But we
have observed that in patients with chkonic heart
failure the limiting symptom and the duration of
exercise appeared to be determined by the protocol used.
In order to test this hnothesis 6 trained
patients with stable chronic heart failure (NYFIA
class 3) underwent symptom limited treadmill
exercise using 3 different protocols; a "slow"
51 P
test 0.51.0 METS and 6 minlstage); a "fast"
test [l min/stage); and a "sudden" test (straight
into the maximum workload achieved in the "slow"
test). The order of the "fast" and "sudden"
tests was randomised.
The mean duration of treadmill exercise was
39.e5.9 min (mean f S M ) f o r the "slow" test,
7.720.9 min f o r the "fast" test (p<O.Ol) and
6.0i1.9 min f o r the "sudden" test (p<O.Ol).
in the "slow"
Peak stage achieved was 5.&0.8
test and 7.720.9 in the "fast" test. In the
"slow" test 5/6 were stopped by fatigue, but in
the "fast" and "sudden" tests 5/6 were stopped by
dyspnoea. Peak heart rate (142?7, 141f8 and
1483 b.p.m. f o r "slow", "fast" and "sudden" respectively), systolic BF' (148f11, 12&11 and 1523
19 mmEg), left ventricular filling pressure (33.7
26.2, 40.7i5.6 and 31.2~4.8 mmHg) and blood lactate (1.9820.18, 2.4120.42 and 2.1920.38 mMol.l-')
were similar f o r each protocol (p>0.3).
In patients with chronic heart failure limiting
symptoms are determined by the rate of increase
of workload and are independent of exercise haemodynamics. The duration of exercise is greatly
increased by a gradual "warm up'* period.
These findings should be taken into account
when designing or choosing protocols to evaluate
exercise capacity or the effects of therapy in
patients with chronic heart failure.
148CAN THE DISADVANTAGES OF POSITIVE INOTROPIC STIMULATION BE OFFSET BY CONCOMITANT
VENODILATATION IN ACUTE LEFT VENTRICULAR (LV)
FAILURE FOLLOWING MYOCARDIAL INFARCTION (MI)?
G.I.C. NELSON, S.P. VERMA, M. HUSSAIN, J.
CLARKE, B. SILKE AND S.H. TAYLOR
University Dept. of Cardiovascular Studies and
Dept. of Medical Cardiology, General Infirmary,
Leeds, UK
The role of beta-adrenoceptor agonists and digitalis glycosides in acute LV failure following
MI remains controversial. Some of their limitations may in theory be countered by concomitant
venodilatation. Accordingly a randomised
between group study of dobutamine (200-800mcg/kg/hr) and digoxin (10 mcg/kg over 1 hour)
alone and in combination with isosorbide dinitrate (50-200mcg/kg/hr) was undertaken in 20
males (36-63 yrs) with pulmonary oedema (LV
filling pressure 2OmmHg) 11-22 hr after acute
MI without hypotension (SBP>llOmmHg). Haemodynamic measurements (intravascular pressures,
thermaldilution cardiac output) were made
before (1 hour: control) and every 30 minutes
for 1X hrs after either dobutamine or digoxin,
and repeated every 30 min for a further 1% hrs,
during concomitant ISDN infusion. Dobutamine
increases systolic arterial pressure ( + IllmmHg,
pC0.01) due to increases in heart rate ( + 12
beat/min, p 0.01) and CO (+0.9 l/min/m2, p<
0.01). Systemic vascular resistance fell.
Digoxin, in contrast, increased systolic and
diastolic blood pressure (WO.01) without
change in h e y t rate. Cardiac output increased
(+0.2 l/min/m ) and hence calculated resistance
was unchanged. Neither drug reduced LV filling
pressure (LVFP). ISDN, in both groups, reduced
LVFP (-BmmHg, pc0.01) and systemic vascular
resistance without change in HR or CO with the
result that the mean systemic arterial pressure
fell (-lOmmHg, ~0.01).