In recent years, significant conceptual advances have helped to
formulate a broad scheme of the mechanisms which regulate ventricular function.
Likewise, methodological advances now enable a wide range of haemodynamic
measurements to be made in human subjects, with reasonable precision and
relative ease. It has thus become possible to relate changes in several
haemodynamic variables recorded simultaneously.
Although it is still not feasible to estimate the functional competence
of the left ventricle (or the heart as a whole) in absolute terns, the
qualitative changes can now be assessed with greater confidence.
The studies reported here were designed to investigate the changes
in left ventricular performance in man during dynamic exercise and following
the administration of two pharmacological agents used in clinical practice.
The two pharmacological agents, morphine and propranolol, were
selected for different reasons.
Morphine was chosen in order to determine the circulatory effects that
may be attributable to the drug and thereby provide, if possible, a rational
basis for its use in the treatment of acute left ventricular failure. The
therapeutic efficacy of morphine in this disorder is widely acknowledged, but
to date no attempts, other than the one reported here, seem to have been made,
(or at least none reported) to delineate the precise mode of action of this
drug in the treatment of acute left ventricular failure. A detailed investigation
was, therefore, designed to study the haemodynamic changes, with particular
reference to left ventricular function, following an intravenous injection of
morphine in therapeutic amounts. The report on this study forms the subject
matter of Chapter IV.
The other pharmacological agent used was propranolol, which is an
adrenergic JS-receptor blocking agent. It is generally agreed that the
sympathetic nervous system (and the adrenal medulla) dominates in the
regulation of the cardiovascular response during dynamic exercise. Since the
sympathetic influence (both chronotropic and inotropic) on the heart is
mediated through ^-receptors (Ahlquist, 1948), it was felt that with the
help of propranolol it should be possible to assess the importance of the
sympatho-adrenal system in the regulation of cardiac performance during
dynamic exercise. A study was, therefore, designed to investigate the
haemodynamic changes during supine leg exercise before and after ^-adrenergic
block with propranolol. The report on this investigation is presented in
Chapter V.
An assessment of the changes in left ventricular performance rg
supine leg exercise, which has been used as the standard physiological
stimulus, was also undertaken in the course of the study reported in Chapter V.
In Chapter I a summary of the present concepts (and some controversies)
regarding the regulation cf left ventricular performance is presented. Also
Included in this chapter is additional information relevant to the understanding
of left ventricular function and the methods that may be used to assess this.
A detailed critique of the methods used is given in Chapter II.
Since it was not feasible to measure either end-diastolic fibre length
or end-diastolic pressure in the left ventricle, the mean pulmonary wedge
pressure has been used as an indirect estimate of left ventricular end-diastolic
pressure and hence end-diastolic fibre length. It was felt necessary to
determine the confidence with which the mean pulmonary wedge pressure could be
used as an estimate of left ventricular end-diastolic pressure. To this end,
therefore, another study was designed and the report on this is presented in
Chapter III.
A brief comment on the statistical methods used is given in the appendix.
Since this thesis is being presented In two volumes, it was thought
best, for ease of reference, to Include all the tables and references in the
companion volume
