Medical Research Society
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men. In the plasma, for the first 6 h, the rapid disappearance of lipid soluble radioactivity was resolved
graphically into two exponential functions. Water
soluble radioactivity in the plasma reached a peak
about 2 h and remained near this level for at least
24 h.
Radioactivity rapidly appealed in the urine, peak
excretion occurring 2-5 h after administration. In 3
days 19-26% of the administered dose was excreted
in the urine while 34-38% was recovered from the
6. BLOOD KETONE-BODY LEVELS DURING faeces. Biliary excretion of labelled metabolites was
EXERCISE BY PATIENTS W m H ACROME- shown to occur in patients in whom duodenal intubaGALY
tion was being carried out or in patients with T-tube
R. H. JOHNSON,
M. J. RENNIE
and M. H. C. WEBSTER drainage of the common bile duct.
Most of the radioactivity in urine and bile was
University Department of Neurology, Institute of
Neurological Sciences, Southern General Hospital, present as water soluble metabolites which could be
Glasgow, and University Department of Surgery, rendered lipid soluble by acid or B-glucuronidase
hydrolysis. Subsequent thin layer chromatography of
Royal Infirmary, Glasgow
Plasma free fatty acids rise during exercise and blood this lipid from the urine at the time of peak excretion
ketone-body levels rise afterwards in normal subjects. revealed the presence of a major radioactive metabolite
Growth hormone, a known lipolytic agent, also rises which was more polar than vitamin K1 plactone and
during exercise and falls afterwards (Hunter, Fonseka which could be extracted with 5% sodium bicarbonate.
This acidic metabolite was also detected in bile, but
& Passmore, 1965, Science, 150, 1051). Athletes show
smaller increases in free fatty acids and ketone bodies only small amounts were present in the faeces.
Ultraviolet spectroscopic studies carried out on a
than non-athletes (Johnson, Walton, Krebs &
Williamson, 1969, Lancet, ii, 452) but show a greater similarly isolated acidic metabolite from urine after
and more prolonged elevation of growth hormone the intravenous injection of 10 mg unlabelled vitamin
(Sutton, Young, Lazenu, Hickie & Makarylis, 1968, K1showed the spectral characteristics of a 2,3 disubLancet, ii, 1304). Despite an inability to raise growth stituted 1,4 naphthoquinone.
These studies are an extension of previous work on
hormone, patients with hypopituitarism show increases in levels of free fatty acids and ketone bodies the absorption and excretion of an oral dose of
during and after exercise and, therefore, these changes tritium labelled vitamin K1 in man (Shearer, Barkhan
are not solely dependent upon growth hormone & Webster, 1970, British Journal of Haematology, 18,
(Johnson, Rennie, Walton & Webster, 1971, Clinical 297).
Science, 40, 127). An opportunity to extend the
investigation of the effects of growth hormone during 8. GRAVITY-DEPENDENT PERIPHERAL AIRexercise is provided by the study of acromegalic WAY CLOSURE IN LEFT HEART FAILURE
subjects who secrete an excess of growth hormone. J. V. COLLINS,T. J. H. CLARK,S. MCHARDY-YOUNG,
and J. TURNER
We have, therefore, investigated five patients and J. CRAWLEY
eight controls during and after bicycle ergometer Departments of Respiratory Function and Medicine,
exercise for 30 min at 450 kpm/min. In both groups the Guy's Hospital, and M.R.C. Isotope Department,
levels of lactate, pyruvate, glycerol and free fatty acids Northwich Park
rose. In the acromegalic subjects ketone bodies rose
rapidly during exerciseto a peak at 15 min and fell away Closing volume (CV)is defined as that lung volume
above residual volume (RV) at which gravitythereafter. Postexercise ketosis was almost absent.
The results show unusual ketone body metabolism dependent peripheral airway closure begins. The
during exercise by acromegalics which may indicate technique for measurement of closing volume inan initial lipolytic phase followed by a depression of volves the injection of a marker gas at the beginning
of slow maximal inspiration (less than 0.5 I/s) from
fat metabolism.
residual volume followed by full expiration a t a
7. STUDIES I N MAN WITH TRlTlATED VITA- similar rate, to residual volume. The concentration of
the marker gas is monitored throughout expiration
MIN K1 ADMINISTERED INTRAVENOUSLY
M. J. SHEARER,C. MALLINSON, G. R. WEBSTER
and at the mouth and is related to the change in lung
volume measured with a spirometer. We have meaP. BARKHAN
sured closing volume using a 2 ml bolus of 133Xenon
Departments of Haematology, Physiology and Chemi- in fifty-two normal subjects, forty patients with left
cal Pathology, Guy's Hospital and Medical School
heart failure and five patients with bronchial asthma.
(Introduced by H. Keen)
Measurements have been made in both erect and
The fate of tritium labelled vitamin K1after intra- supine positions and following the inspiration of
venous injection has been studied in three normal bronchodilator aerosols. In normal subjects we have
were obtained. Not all those with an impaired
stimulation test had a raised serum level, the elevation
of serum TSH being more indicative of a later stage
of thyroid failure.
In the assessment of subclinical thyoid disease,
combined thyroid antibody and serum TSH measurements appear to be of value particularly in conditions
in which involvement of the thyroid gland may not
immediately be apparent.
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Medical Research Society
found that closing volume increases with age in a
linear relationship and is unaffected by bronchodilators. Our preliminary results showed that a
satisfactory alveolar plateau and terminal increase in
133Xenonconcentration could be achieved in cardiac
patients. Closing volume is increased above the value
predicted for age in patients with left heart failure and
some of these patients, without reversible airways
obstruction, have shown a reduction in closing
volume following sympathomimetic bronchodilators.
A positive correlation was found between closing
volume and residual volume but increase in closing
volume was poorly correlated with dyspnoea index
and left heart pressures. From our preliminary results
we suggest that patients with heart disease may have
abnormal airway narrowing and that in some cases
this may reflect increased bronchomotor tone.
In asthmatic patients the traces produced are difficult to interpret but in some cases following bronchodilator aerosols a change has occurred towards a
more normal pattern. Our experience suggests that the
133Xenontechnique may be a useful method for examining airway closure in patients with heart disease.
lamella net of elastin and collagen in the media. In
addition, the decrease of the area ratio, with the
consequent partial standing wave of pressure in the
aorta, enhances the oscillatory stress components in
the wall at and above the junction. If these localized
regions of stress can no longer be distributed uniformly by the damaged interlamella net it would explain
the focal nature of atheromatous plaques and their
distribution above the junction.
In man, the area ratio of the aortic bifurcation has
been measured from aortagrams of Caucasian subjects with ages between 0 and 50 years exhibiting no
radiological or clinical signs of atherosclerosis. It is
found that the area ratio in infancy is 1.11 (close to
the expected matched value) and decreases linearly to
a value of -0.75 for subjects within the age range of
41-50 years. No significant sex difference was found.
10. LEFT VENTRICULAR WALL MOVEMENT
MEASURED BY REFLECTED ULTRASOUND
C. S. SMITHEN
and E. SOWTON
C. F. P. WHARTON,
Cardiac Department, Guy's Hospital
Movement of the posterior wall of the left ventricle
9. IS ATHEROMA A SECONDARY PHENO- was assessed using an ultrasound technique in eleven
normal subjects at rest and immediately following
MENON ?
R. G. GOSLING,
D. L. NEWMAN
and N. L. BOWDEN maximal erect exercise. Maximum posterior wall
Department of Physics, Guy's Hospital Medical School velocity was measured as the initial slope of the wall
movement from end-diastole t o end-systole, and
(Introduced by H. Keen)
posterior wall excursion was measured as the distance
An increase in aortic distensibility is observed in between the end-diastolic and end-systolic positions.
cockerels fed an atherogenic crushed egg diet. The Posterior wall velocity increased from a mean of
abnormal distensibility is correlated with the severity 37 mmjs at rest to 96 mm/s after exercise (P<O.Ol),
of the atherosclerotic lesion using an atherosclerotic and post-wall excursion increased from 4.00 mm at
index I ranging from 1 to 100. It is found that in- rest to 6.8 mm after exercise (P<0.01). The effect of
creased distensibility occurs very early in athero- heart rate alone on posterior wall movement was
genesis and reaches a maximum value around index evaluated using the technique of atrial pacing. Invalues of -40. For index values > 60 the distensi- creasing the heart rate in six patients resulted in a
bility decreases to below the normal value due to reduction in both posterior wall velocity and excurincreasing calcification and fibrosis.
sion. At identical heart rates in four patients there
The increase in aortic distensibility in early athero- was a significant increase in both posterior-wall
genesis causes a decrease in the area ratio' of the velocity and excursion during exercise compared to
aortic junction which remains as the vessel hardens. atrial pacing. Posterior wall velocity and excursion
For an equibifurcation the area ratio giving minimum were potentiated following ectopic beats and were
reflection of the pressure pulse is shown theoretically depressed after propranolol injection.
to be -1.15. Normal cockerels have aortic junction
It is suggested that changes in posterior wall movearea ratios close to this value-1.1 6&0.06 for fourteen ment reflect alterations in left ventricular function
birds-whilst eighteen diet cockerels had an average independent of heart rate, and that these changes can
area ratio of 0.86-10.06. This would be expected to be measured by reflected ultrasound.
lead to the reflection of the pressure pulse increasing
from 2% for the matched junction to 25% for the 11. THE USE OF SYSTOLIC TIME INTERVALS
diet birds, resulting in a partial standing wave of AS AN ASSESSMENT OF LEFT VENTRICULAR
pressure in the aorta with an antinode at the junction. FUNCTION IN ACUTE MYOCARDIAL INComparison of the aortic elastic moduli/pressure FARCTION
characteristics, measured in situ, for normal and diet
E. D. BENNETT,
C. S. SMITHEN
and G. E. SOWTON
cockerels suggests that an essential factor in early
Institute
of
Cardiology,
London,
W.l
atherogenesis is the partial breakdown of the interThe
systolic
time
intervals
obtained
from the arterial
* Area ratio of any vessel junction = Sum of crosssectional areas of branch vessels divided by the pressure trace, the electrocardiogram and the phonocardiogram have been shown to be useful indicators
cross-sectional area of the parent vessel.
-