1. In anesthetized open-chested dogs, relations of electrically paced heart rate to cardiac output and to other related variables were studied before and after changing one of the following four parameters: cardiac sympathetic activity, cardiac vagal activity, venous return and arterial resistance.
2. When heart rate was elevated from 40 to 60/min in control experiments, cardiac output kept increasing until the rate reached approximately 110/min, remained almost constant between 110 and 200/min, and decreased above 200/min.
3. At every pacing rate a marked augmentation of cardiac output and stroke volume occurred with curtailed ejection time following stimulation of the left stellate ganglion. The faster the rate, the more prominent augmentation was observed. Cardiac output thus maintained the maximum level even at rates beyond 200/min. The marked augmentation of peak flow velocity seemed to be responsible for the increased stroke volume.
4. Vagal stimulation usually caused, exclusively over a high heart rate range (usually beyond 180/min), a slight but definite fall in cardiac output and stroke volume with decreased peak flow velocity and unchanged ejection time. Since the ventricular contractility was found unaffected, the observed fall was ascribed to the inhibitory vagal action on the atrium.
5. An increase in cardiac output and stroke volume was observed at every pacing rate following infusion of dextran saline solution. Ejection time and peak flow velocity were both increased by infusion.
6. Cardiac output and stroke volume were always decreased by compression of the descending aorta. The decrease was marked at high heart rates and associated with diminished peak flow velocity and prolonged ejection time.