The circulatory effects of blocking the beta adrenergic receptors with Nethalide were studied in 10 patients with hypertrophic subaortic stenosis and in five postoperative subjects undergoing right heart catheterization. In the resting state, the heart rate and the rate of pressure development in the right ventricle diminished slightly, but cardiac index was not altered by the administration of Nethalide. These observations suggest that tonic sympathetic activity is not of major importance in basal subjects in the supine position. Nethalide attenuated the increase in heart rate and right ventricular dp/dt associated with exercise, and abolished the response of these two variables to the administration of isoproterenol. In the patients with hypertrophic subaortic stenosis Nethalide had little effect on the severity of the obstruction at rest, but reduced the intensification of the obstruction produced by exercise or isoproterenol. The possible clinical benefits of blocking the beta adrenergic receptors in these patients were discussed.

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It is generally agreed that an increase in cardiac output is one of the primary circulatory adjustments that occurs during exercise. However, the nature of the alterations in the activity of the myocardium that permit this augmentation of output and the relative importance in the response to exercise of the various factors known to affect the performance of the heart and its contractile state has not been defined. It has been shown that the contractile state of cardiac muscle may be characterized by the force-velocity relation (1-3). The applicability of this concept to isolated human heart muscle has recently been demonstrated (4), and a technique has been described by which the force-velocity relation of the myocardium of intact human subjects can be evaluated (5), thus allowing determination of the effect of a variety of interventions on the contractile state of the heart. The purpose of the present investigation was to apply this technique in studying the effects of exercise on the force-velocity relations of the human heart, to define the relative roles of the changes in heart rate and of sympathetic activity that occur during exercise on the force-velocity relation, and to delineate the role of changes in ventricular end-diastolic size in the response of the heart to exercise. MethodsTwelve studies were carried out in eleven patients ranging in age from 24 to 55 years (average = 44 years). All had undergone cardiac operations consisting of the closure of an atrial septal defect in six patients, closure of a ventricular septal defect in two, aortic valve re-* Submitted for publication April 22, 1965; accepted September 16, 1965. t Address requests for reprints to Dr. Edmund H. Sonnenblick, Cardiology Branch, National Heart Institute, Bethesda, Md. 20014. placement with a Starr-Edwards prosthesis in one, and mitral valvulotomy in two patients. At the time of cardiac operation small silver-tantalum markers were sutured to the right ventricle in seven patients, the left ventricle in two patients, and to the surface of both ventricles in two patients, as described in detail previously (6). Hemodynamic studies carried out 1 to 14 months postoperatively are summarized in Table I. The resting cardiac output was normal in all patients (> 2.50 L per minute per m2), as was the right atrial pressure, although the right ventricular end-diastolic pressure was slightly elevated in one patient (C.D.). The right ventricular systolic pressure was also slightly elevated in four patients (C.D., I.D., M.W., and S.C.).The techniques for determining ventricular end-diastolic dimensions and the force-velocity relation have been described in detail elsewhere (5). At the time of postoperative catheterization, cineradiograms were exposed at 30 frames per second while intraventricular pressures were recorded simultaneously at a paper speed of 100 mm per second. A mechanical marker, activated by the R wave of the electrocardiogram and recorded on the cineradiogram, permitted precise temporal correlation of ventricular dimension...

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