Effect of some physiological factors and pharmacological agents on left ventricular function in man
Sapru, R. P.
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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.