The hemodynamic determinants of myocardial oxygen utilization were ascertained in the isolated, metabolically supported, nonfailing canine heart. The primary determinant was found to be the total tension developed by the myocardium as indicated by the area beneath the systolic pressure curve (Tension-Time Index). The significance of these findings for the understanding of the low efficiency of the failing heart and the consequently increased importance of Laplace's law are discussed.

The effects of both direct and reflexly induced increases in sympathetic activity on the blood flow to an extremity at rest and during muscular activity have been studied. When the O 2 uptake of an extremity is increased during muscular activity, its vascular resistance falls sharply with a small increase in O 2 uptake and thereafter declines only slightly. The responsiveness of a vascular bed to adrenergic stimulation diminishes sharply with a small increase in O 2 uptake and thereafter diminishes only slightly. The role of the carotid sinus as a sense organ which helps to regulate blood flow to the various tissues of the organism in accordance with their varying metabolic requirements rather than one which acts only as a receptor that helps to safeguard flow to the vital organs has been discussed.

The effect of increasing the activity of the ventricle on its contractility was investigated. Several beats after the ventricle increases the amount of tension it develops per unit of time, it exhibits an increased contractility as shown by the increase in work and the more rapid development of pressure from a given end-diastolic pressure or fiber length. This has been termed homeometric autoregulation in contradistinction to the Frank-Starling or heterometric type of autoregulation. It was found that changes in coronary flow are not essential to the exhibition of this phenomenon. Possible mechanisms and the physiologic significance of the findings are discussed.

The independent influences of stroke volume, heart rate, aortic pressure, hypothermia, sympathoniiiuetic amines, metered mitral and aortic valvular regurgitation, and alterations in myocardial contractility on the duration and mean rate of ventricular ejection and filling were studied. These observations were made in a metabolically supported, isolated heart preparation with performance characteristics comparable to the nouisolated heart. I T HAS long been recognized that the duration of mechanical ventricular systole is inconstant and is modified by a variety of hemodynamic, physical and humoral influences. It is generally held that mechanical systole is abbreviated by tachycardia 1 " 3 and the administration of sympathomimetic amines, 8 ' 4 and prolonged by an increase in stroke volume 1 ' 8i 4 and by hypothermia. 5 " 7 The effects of an increase in aortic pressure have been inconstant. s> 4> 8 However, in previous studies on the duration of ventricular ejection, the effect of independently altering each pertinent variable while holding the others constant has not been accomplished. The objectives of this investigation were to ascertain the effect on the duration and mean rate of left ventricular ejection of the independent alteration of stroke volume, heart rate, aortic pressure, temperature, cardioactive sympathomimetic amines, and mitral and aortic valvular regurgitation. METHODThe isolated supported heart preparation, the performance characteristics and stability of which have been described in detail elsewhere," was employed. This preparation consists of an isolated dog heart from which all coronary venous blood flows into the venous system of an intact, anesthetized dog which in turn continuously replaces biochemically normal arterial blood into the reservoir of the isolated heart system. The independent augmentation of stroke volume while heart rate WJIH held constant by right atrial stimulation was From the laboratory of Cardiovascular Physiology, achieved by increasing left atrial inflow and adjusting the aortic resistance so as to keep mean aortic pressure constant. Similarly, the independent effect of changes in aortic pressure while maintaining stroke volume and heart rate constant was studied by appropi-iate adjustment of left atrial inflow and of the aortic resistance. The effects of heart rate changes were observed by varying the atrial stimulation rate while maintaining mean aortic pressure and cardiac output constant. The effects of hypothermia were studied by cooling the blood in the reservoir of the isolated, supported heart system while maintaining mean aortic pressure, cardiac output and heart rate constant.The duration of left ventricular ejection was measured from aortic pressure pulses obtained through a catheter in the aortic arch with a Statham P-23D strain gage and generally recorded at 100 mm./sec. paper speeds on a direct-writing oscillograph. Speeds of 50 mm./sec. were occasionally used. The interval between the onset of the rise in aortic pressure and the incisura was taken as the...

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