Download The Cell Membrane and the Cardiostimulant Effect of Adrenaline

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pulmonary venous pressure on pulmonary vein
flow have also been studied.
left ventricular filling pressure, provided the assessment is made within 36 h of the acute infarction.
16. THE VALUE OF LEFT ATRIAL VECTORCARDIOGRAPHY I N THE ASSESSMENT O F
LEFT VENTRICULAR FUNCTION FOLLOWING ACUTE MYOCARDIAL INFARCTION
17. A STUDY OF RIGHT VENTRICULAR
FUNCTION USING INDICES OF CONTRACTILITY DERIVED FROM PRESSURE MEASUREMENTS
P. FINNEGAN
and M. V. FORBES
University of Birmingham, Department of Medicine,
Queen Elizabeth Hospital, Birmingham
The analysis of myocardial muscle mechanics in
terms of the Hill analogue model led to the observation that the maximal velocity of the contractile
elements (Vmax)was independent of loading (Sonnenblick, 1962, American Journal of Physiology, 202,
931). The later application of these concepts in patient
studies was based on ventricular volume and pressure
measurements (Hugenholtz, Ellison, Urschel, Mirsky
& Sonnenblick, 1970, Circulation, 41,191). A number
of investigators claimed that V,,, in the intact
ventricle was also unaffected by loading and was
therefore a valid index of contractility (Wolk, Keefe,
Bing, Finkelstein & Levine, 1971, Journal of Clinical
Zntestigation, 50, 1276; Mason, Spann & Zelis, 1970,
American Journal of Cardiology, 26,248).
In the present studies of right ventricular function in
twenty-three patients, pressure-velocity curves were
derived using the formula (dp/dt)/KPand the indices
of contractility (Vmaxand V,,,,,)
were calculated. The
pressure-velocity curves were variable in shape and
curves with single, linear descending slopes were
observed in only seven patients. The other patients
had pressure-velocity curves which were either
biphasic or hyperbolic in form.
The effects of a number of physiological variables
were examined and it was demonstrated that Vmax
and V,,, were not independent of the loading conditions of the ventricle. An impaired response of maximum dp/dt to inotropic stimulation was observed in
patients with right ventricular failure.
J. R. MUIR,G. J. WILLIAMS
and G. DAVIES
Department of Cardiology, University Hospital of
Wales, Heath Park, Cardiff
It is now established that, in the absence of lungdisease or long-standing pulmonary venous hypertension, the pulmonary arterial diastolic pressure
reflects left ventricular end diastolic pressure. The
measurement of pulmonary diastolic pressure by a
flow guided catheter technique has, therefore, been
widely used in the early detection of left ventricular
failure following acute myocardial infarction. However, a non-invasive method for the measurement of
left ventricular end diastolic pressure would have
obvious advantages in this situation.
The pulmonary arterial diastolic pressure, a timed
vectorcardiogram and a standard twelve lead electrocardiogram were recorded simultaneously in thirtytwo previously well patients following an acute
myocardial infarction. The recordings were made
as soon as possible after the patients were free of pain
(2-18 h after admission). A pulmonary arterial
diastolic pressure of 15 mmHg was taken as the upper
limit of normal. If the pressure was raised, the recordings were repeated twice daily until the pressure was
within the normal range. Time vectorcardiograms were
also obtained from sixty ‘normal’ hospitalized individuals.
There was a close correlation between the initial
left atrial electrical activity calculated from the timed
vectorcardiogram and the pulmonary arterial diastolic pressure (correlation coefficient = 0.85 ; P c
0.001). The correlation of ‘P terminal force’ calculated from V1 of the standard ECG with the pulmonary arterial diastolic pressure did not reach
significance. The vector results at the initial investigation enabled the patients to be separated into three
groups corresponding to the pulmonary diastolic
pressure: (a) normal (< 15 mmHg), (b) mildly
elevated (16-20 mmHg), (c) severely elevated (2130 mmHg). The value for the atrial electrical activity
for the sixty ‘normal’ individuals all fell within the
range for normal pressure.
However, the subsequent vectorcardiographic
values obtained on reinvestigation of those patients
with initially high pressures were poorly correlated
with subsequent pressure measurements, in that left
atrial electrical activity returned more slowly to normal
than did the pressure.
These findings indicate that analysis of the left
atrial trace obtained from the timed vectorcardiogram
at high gain is a valuable non-invasive indicator of
18.THE CELL MEMBRANE AND THE CARDIOSTIMULANT EFFECT O F ADRENALINE
WINFREDG. NAYLER
Cardiothoracic Institute, 2 Beaumont Street, London,
w.1
Excitation-contraction coupling in heart muscle cells
depends upon an inwards displacement of Ca2+
from the extra to the intracellular phase. Drugs which
increase the peak tension developed during contraction, e.g. adrenaline, may act by increasing the
amount of Caz+ which is displaced inwards in response to the arrival of the depolarizing signal. Recent
studies in our laboratories have shown that adrenaline
interacts with the cell membrane of cardiac muscle
cells, thereby increasing its capacity to accumulate
Ca2+. Possibly some of the Ca2+ which is displaced
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inwards during the processes associated with excitation-contraction coupling is derived from superficially-located sites within or close to the cell membrane. The hypothesis that the cardiostimulant effect
of adrenaline results from a cell-membrane located
action is supported by the finding that its positive
inotropic effect is abolished by processes which
render the cell membrane freely permeable to Ca2+.
19. RELATIONSHIP BETWEEN CARBOHYDRATE AND FAT METABOLISM IN THE
NORMAL AND DIABETIC DOG HEART IN
vzvo
S. P. ALLISON
GeneraZ Hospital, Nottingham NGI 6HA
Randle and his colleagues have described the relationship between glucose and fatty acid metabolism,
the so-called glucose fatty acid cycle, whereby fatty
acid oxidation inhibits glycolysis at the level of PFK
and pyruvate dehydrogenase. This concept has
derived from in uitro work and until recently had not
been confirmed in vivo. Experiments were therefore
carried out on anaesthetized beagle dogs weighing
8-10 kg. The coronary sinus was catheterized under
radiological control and simultaneous arterial and
coronary sinus blood samples were taken throughout
all experiments. The elevation of free fatty acid levels
from infusion of intralipid and Heparin inhibited
glucose lactate and pyruvate lactate by the dog heart.
The inhibition of lactate and pyruvate uptake was
reversed by sodium dichloroacetate, a substance
which activates pyruvate dehydrogenase. Similar
data was obtained on dogs rendered diabetic with
Alloxan. The significance of these results will be
discussed.
20. WATER VAPOUR EXCHANGE WITHIN THE
LUNG
G. CUMMING
Midhurst Medical Research Institute, Midhurst, Sussex
Expired air contains more water vapour than inspired
air, though the water content of the latter may vary
within very wide limits. How far expired gas represents
alveolar gas remains a matter for discussion in respect
of oxygen and carbon dioxide, but there is much
evidence t o suggest that expired gas is in no way
representative of alveolar gas in respect of its water
vapour content.
There is a tacit assumption that the water vapour
tension within alveoli is the vapour tension of lung
water at body temperature. Since lung water contains
solutes this tension will be somewhat less than the
value for distilled water, but only by about 0.5 torr
so that at 37°C body temperature the expected tension
would be 46.5 torr.
Measurements made of expired water vapour
tension indicate values of less than 40 torr, equivalent
to a temperature of 33°C at full saturation. Direct
measurements of temperature confirm this value.
In the present study water vapour tension was
measured directly with a Quadropole mass spectrometer (20th Century Electronics 4806) at a mass/
charge ratio of 18.
Twenty-two normal subjects were studied, their
mean end tidal water vapour tension being 37.9 torr
(male subjects, 38.6+ 3-3 torr (s.D.); female subjects
37.1 & 3.3 torr). At the end of a vital capacity this
increased to 39.7 torr (males, 40.4_+2.8 torr; females
38.7 & 2.8 torr), and did not alter when preceded by a
10 s breath-hold.
Inspired water vapour tension was then increased
to about 80 torr when the end tidal tension rose from
45.4 torr in the first breath to 4 7 7 torr in the third
breath. A vital capacity in the first breath yielded a
value of 48.7 torr not increasing with repetition.
Thirdly, the ambient air was warmed to 80°C and
the end tidal and end expiratory tensions measured.
These did not differ significantly from those breathing
ambient air at 23°C.
The explanation of these observations is thought
to be as follows: during inspiration of water vapour
at a tension of about 10 torr, water vapour is added
so that in the alveoli it has a tension around 47 torr.
Water evaporates from the fluid lining the bronchial
tree and requires the latent heat of change of state and
also the heat required to raise the inspirate to body
temperature. The mucosal surface of the bronchi is
thereby cooled and a gradient of temperature then
exists down the airways from ambient in the mouth
to core temperature in the alveoli. The anatomical
site of this gradient i s undefined.
On expiration the gas saturated at core temperature
is cooled by the mucosal surface which is itself warmed
by latent heat of condensation and by temperature
difference.
Thus the airways retain both heat and water vapour
during ventilation. During breathing of air heated to
80°C the subjective sensation is of coolness, because
of the large heat transfer resulting from latent heat of
evaporation.
The flux of water vapour occurring at an undefined
part of the airways and of the order of 35 torr has
important consequences for the measurement of other
gases during the course of an expiration.
21. THE EFFECT OF VARIATION IN ALPHA 1ANTITRYPSIN PHENOTYPE UPON THE INCIDENCE OF RESPIRATORY ILLNESS I N A
WORKING POPULATION
R. B. COLE,N. C. NEVINand G. BLUNDELL
Departments of Medicine and Medical Statistics,
Queen’s University of Belfast, and Department of
Clinical Chemistry, Belfast City Hospital
An increased liability to chronic obstructive lung
disease occurs in the few individuals who have
inherited severe alpha I-antitrypsin (alpha 1-AT)