THE CONTROL OF VENTRICULAR FUNCTION IN MAN*

Since William Harvey's discovery of the prime function of the heart as a pump, clinicians and physiologists have marvelled at the extraordinary ability of this organ to adjust its performance almost instantaneously to meet the rapidly changing requirements of the peripheral tissues. Probably no other aspect of cardiovascular research has received as much effort and attention as the attempts to gain an understanding of the systems that control the heart's ability to propel blood through the circulatory system. During the past century, this problem has been investigated at many levels; from isolated extracts of contractile proteins, to isolated atrial and papillary muscle preparations, to isolated hearts and heart-lung preparations, and anesthetized open-chest dogs, as well as closed-chest, unanxsthetized dogs. Among the most significant contributions to these investigations were those that came from the laboratories of Professors Frank (1895) and Starling (1918). These investigators extended to the heart the earlier observations of Fick (1882), Kries (1892), and Blix (1895) who had already established for skeletal muscle that the length and tension of the muscle at the time of stimulation determined the magnitude of its contractile response. The immediate impact of this work, as presented by Starling in his Linacre lecture (1918), requires little emphasis at this time. However, during the past 15 years some investigators have challenged the importance, indeed even the applicability, of the Frank-Starling principle in the regulation of cardiac performance in intact man. Until quite recently the techniques available to the clinical investigator have not permitted a definitive answer to the important question of the control of ventricular function in man, and prevailing opinions have of necessity been based primarily upon extrapolations from animal experiments, as well as on indirect measurements in patients. During the past few years, however, the refinement of methods that permit a detailed study of the circulation in man has made possible a direct attack on this fundamental question. It is the objective of this presentation to review the results of a series of experiments directed towards elucidating the role of two basic mechanisms of cardiac adjustment; (1) the Frank-Starling principle, i.e. the dependence of the mechanical activity of the heart on the ventricular end-diastolic volume and pressure, and (2) the adrenergic nervous system, changes in the activity of which alter the humoral environment of the heart muscle and thereby permit variations in ventricular performance at any given level of end-diastolic volume or pressures. These investigations were begun by asking a simple question: "How does changing the length of a segment of human myocardium affect its contractile activity? " It was possible to obtain an answer by sewing a specially modified Walton-Brodie strain gauge arch to the right ventricle of 10 patients and to the left ventricle of 1 patient, at the time of cardiac operation. This instrument permits the controlled alteration of the length of the myocardial segment to which it is attached, as well as measurement of the tension exerted by this segment of myocardium throughout the cardiac cycle. In all