Certain aspects of the role of catecholamines in circulatory regulation.

W E WERE welcomed to this Symposium by Dr. Raab as a group of what he referred to as “catecholaminiacs.” I presume he meant by this that we communally share a vigorous enthusiasm for the belief that the continued study of these substances will unroof helpful areas of knowledge. One might even venture to say that we are composed of two wings: the “good catecholaminiacs” and the “evil catecholaminiacs.” The “good’wing holds that the physiologic activity of these substances is an essential ingredient of a fully competent organism and that, occasionally, when the circulation of the organism deteriorates markedly, the catecholamines are called upon to perform such a Herculean task that the very intensity of their action may unwittingly produce a harmful result. On the other hand, the protagonists of the “evil” camp hold that we would, in general, fare better without these widely enthusiastic chemical mediators and that much of the circulatory svmptomatology and disease we encounter are attributable to their influence. Not without some reservations, I belong in the former camp. The purpose of this presentation is to introduce recent evidence concerning the importance of catecholamines in certain aspects of circulatory regulation. More specifically, the data my colleagues and I have gathered relate to the regulation of the contraction of the ventricle and the external work produced by it. In the following discussion it will be assumed that the reader accepts the view that the stimulation of sympathetic nerves produces the local elaboration of catecholamines, presumably norepinephrine, in the effector organ and that the hemodynamic phenomena observed as the result of such stimulation are attributable to its action. REGULATION OF VENTRICULAR CONTRACTION The basic influence determining the force of contraction of muscle is its length prior to contraction. This accounts for the shape of the curve relating filling pressure to the external work produced by the ventricle of the isolated heart. Such a curve, termed a ventricular function curve,’ is another way of expressing the basic Frank-Starling relationship.233 A matter of primary concern is the manner in which the central nervous system can alter the position of this curve. Figure 1 shows a schematic resume of the possible effects that autonomic nerve stimulation can have on ventricular function. The experimental data on which these curves are based has been presented elsewhere.4-8 Ejects of Autonomic Nerve Stimulation: When the stellate ganglion (to which the rami have been cut) is stimulated, the ventricle will produce a greatly augmented stroke work from any given mean atria1 pressure and also from any given left ventricular end diastolic pressure (Fig. 1A). When the distal cut end of either vagus nerve is stimulated, the ventricle will produce appreciably less work from any given mean left atria1 pressure. The contractility of the ventricle itself is, however, apparently unmodified by vagal stimulation since, from any given end diastolic pressure, the ventricle will still produce as much external work (Fig. 1B). These findings on vagal stimulation are in accord with the inability of histologists to demonstrate vagal innervation in the ventricular myocardium. Relation Between Ventricular Pressure and Changes in Myocardial Fiber Length as a Result of Either Sympathetic or Thgal .verve Stimulation: To study this question a low mass, low inertia instrument