Doppler measurements of the velocity and acceleration of ascending aortic blood flow have been used as indexes of left ventricular (LV) contractility. Conflicting data exist, however, on the influence of LV loading conditions on these measurements. Therefore, simultaneous LV micromanometer pressure measurements, 2-dimensional echocardiography and continuous-wave Doppler studies were performed before and after preload or afterload manipulation in 16 patients with coronary artery disease. Nitroprusside (n = 9) was administered in combination with saline to maintain preload and achieve a 10 to 20% reduction in mean aortic pressure. Saline (n = 7) was administered (850 +/- 240 ml) to increase LV end-diastolic pressure 25 to 50%. All measurements were obtained during atrial pacing at a heart rate 10 to 15 beats/min above resting sinus rate. The administration of nitroprusside plus saline decreased LV end-systolic wall stress (94 +/- 27 to 67 +/- 14 g/cm2 X 10(3), p = 0.011) without changing LV end-diastolic pressure and end-diastolic dimension. Peak velocity (0.8 +/- 0.2 to 0.9 +/- 0.3, p = 0.044), velocity time integral (11 +/- 4 to 13 +/- 5 cm, p = 0.049) and mean acceleration (12 +/- 4 to 17 +/- 7 m/s2, p = 0.0014) increased significantly. The administration of saline alone significantly increased LV end-diastolic pressure (10 +/- 4 to 22 +/- 4 mm Hg, p = 0.0006), LV end-diastolic dimension (4.8 +/- 0.5 to 5.1 +/- 0.5 cm, p = 0.0001), peak velocity (0.9 +/- 0.3 to 1.0 +/- 0.4 m/s, p = 0.008), velocity-time integral (14 +/- 5 to 18 +/- 7 cm, p = 0.005), and mean acceleration (14 +/- 6 to 17 +/- 7 m/s2, p = 0.041). Thus, even a modest change in either preload or afterload altered peak velocity, the velocity time integral and mean acceleration. These data have important clinical implications regarding the application of Doppler aortic flow indexes in the assessment of LV function.