The clinical, hemodynamic and angiographic features of four male patients with isolated congenital aortic regurgitation are described. In none was the regurgitation of major degree and in each instance left heart catheterization showed that there was no systolic gradient across the aortic valve. The presence of aortic regurgitation was substantiated by means of retrograde aortography or indicator-dilution curves. These patients appear to be the first in whom the diagnosis of isolated congential aortic regurgitation has been firmly established during life.

Transseptal left heart catheterizations were carried out in 18 patients without apparent evidence of organic cardiovascular disease. These studies have permitted delineation of the pressures that exist in the left side of the heart in normal subjects studied in a basal physiologic state.

The relationship between left ventricular end-diastolic pressure and circumference was studied in 27 open-chest dogs, utilizing a mercury-resistance gage to measure left ventricular end-diastolic circumference. In 6 experiments aortic pressure, cardiac output and heart rate were varied independently. Tachycardia above a rate critical for each heart elevated left ventricular eud-diastolic pressure for any given end-diastolic circumference. Hypothermia at a constant heart rate had a similar effect. The altered left ventricular end-diastolic pressure-end-diastolic circumference relationships resulting from tachycardia and hypothermia are believed to be related to the incomplete ventricular relaxation which occurs as the duration of diastole is encroached upon. Acute, spontaneous heart failure was accompanied by an augmented left ventricular end-diastolic circumference for any given end-diastolic pressure, an effect which may be considered to reflect an increase in myocardial extensibility. The relationship between left ventricular end-diastolic pressure and end-diastolic circumference was not modified either by changes of aortic pressure or of cardiac output. There was no constant relationship between the left ventricular end-diastolic circumference and the tension-time index. Indeed, it was possible to manipulate aortic pressure and cardiac output so that these 2 parameters moved in opposite directions. These observations are not consonant with the view that myocardial oxygen consumption is primarily dependent on end-diastolic fiber length.

The hemodynamic functions of the left atrium were studied in 26 patients with disturbances of left ventricular function and in 16 subjects without any abnormalities of the cardiovascular system. Attention was directed to the effect of atrial systole on the relationship between mean left atrial pressure (MLAP) and left ventricular end-diastolic pressure (LVEDP). This relationship was considered to be a meaningful one in view of the importance of the LVEDP in determining the characteristics of ventricular contraction, and of the MLAP in determining the symptoms of left heart failure. In the subjects with normal cardiovascular systems, LVEDP-MLAP averaged 0.2 mm. Hg, but this value averaged 9.0 mm. Hg in patients with left ventricular disease, in whom left atrial contraction elevated LVEDP while permitting MLAP to remain at a significantly lower level. The magnitude of the pressure difference between LVEDP and MLAP was found to be dependent on the characteristics of atrial contraction; the height of the "a" wave appeared to be related to the atrial pressure prior to the onset of atrial contraction. The elevation of atrial pressure produced by atrial systole was found to vary directly with the time interval between the onset and the peak of the "a" wave and to vary inversely with the time interval between the peak of the "a" wave and the onset of ventricular contraction. Evidence was presented that in intact human subjects the characteristics of left atrial and left ventricular contraction are functions of the pressures in these chambers prior to the onset of their contraction, thus lending further support to the concept that Starling's law is operative in the human heart.

Changes in systemic vascular volume, in venous return, and in the distensibility of the venous system were studied in an experimental canine preparation. The use of an extracorporeal circulation permitted complete exclusion of the heart and lungs and allowed continuous measurement of alterations of intravascular blood volume and of venous return to the oxygenator. Brief occlusion of the venous outflow line permitted the inscription of venous pressure-volume curves. Hypotension in the isolated carotid sinuses, the administration of catecholamines or of acetylcholine resulted in venoconstriction, evidenced by a decrease in vascular volume, an increase in venous return, and flattening of the venous occlusiou curves. Conversely, carotid sinus hypertension or the administration of trimethaphan produced venodilatation, a decline in venous return, and an increase in vascular volume. The significance of these observations in the regulation of cardiac output is discussed.

The presence of baroreceptors in the walls of the cardiac chambers and the pulmonary vascular bed is now well established, and their function in the reflex control of the circulation has been the subject of a number of investigations (1-11). Action potentials have been recorded from afferent fibers originating in the heart and lungs (1, 2), and elevation of pressures within the ventricular chambers (3-9) and pulmonary vascular bed (4, 10, 11) has resulted in bradycardia (3-10), a decline in systemic arterial pressure (4-9, 11), and either apnea (5, 10) or hyperpnea (4, 11). In a previous report from this laboratory, evidence was presented that the carotid baroreceptors reflexly influence total venous return and systemic vascular volume (12). The present investigations were undertaken to determine whether or not these hemodynamic parameters are also modified by activation of intracardiac baroreceptors. Studies to localize these receptors within the heart were also carried out.