INFLUENCE OF SYMPATHETIC-STIMULATION AND PARASYMPATHETIC WITHDRAWAL ON DOPPLER ECHOCARDIOGRAPHIC LEFT-VENTRICULAR DIASTOLIC FILLING VELOCITIES IN YOUNG NORMAL SUBJECTS

To determine the effects of parasympathetic withdrawal or sympathetic stimulation on Doppler echocardiographic measures of left ventricular diastolic filling, we studied 10 young normal subjects aged 21 to 29 years during separate infusions of atropine (0.8 mg followed by 0.4 mg every 10 minutes until heart rate > 110 beats/min or a total dose of 2 mg was attained) and epinephrine (10, 25 and 50 ng/kg/min for 12 minutes each). At the highest atropine dose, heart rate increased from 60 +/- 9 to 105 +/- 8 beats/min (mean +/- standard deviation), the diastolic filling period decreased by 61% (573 +/- 141 to 222 +/- 34 ms), the peak early (E) filling decreased 23% (77 +/- 12 to 61 +/- 11 cm/s), the peak atrial (A) filling increased 103% (40 +/- 6 to 81 +/- 17 cm/s), and the E/A ratio decreased by 60% (2.0 +/- 0.5 to 0.8 +/- 0.3) (all p < 0.001). These alterations were not correlated to changes in systolic function, preload, blood pressure or plasma catecholamines, all of which were unchanged. However, atropine-induced changes in diastolic filling period were highly correlated to changes in E peak (r = 0.64, p < 0.01), A peak (r = -0.95, p < 0.001) and the E/A ratio (r = 0.93, p < 0.001). The effects of atropine on the E/A ratio were normalized by dividing the E/A ratio by the diastolic filling period (E/A/diastolic filling period). At the highest epinephrine dose, plasma epinephrine increased from 94 +/- 59 to 879 +/- 310 ng/liter, the heart rate increased by 26% (58 +/- 8 to 73 +/- 7 beats/min), the diastolic filling period decreased by 22% (596 +/- 144 to 464 +/- 127 ms), peak E increased 43%, peak A increased by 30% (40 +/- 6 to 52 +/- 9 cm/s) (all p < 0.01), the E/A ratio increased 15% (2.0 +/- 0.5 to 2.3 +/- 0.6, p = 0.13), and the E/A/diastolic filling period increased by 43% (3.5 +/- 0.6 to 5.0 +/- 1.3, p < 0.01). Increases in epinephrine levels directly correlated to increases in E peak (r = 0.74, p < 0.001), A peak (r = 0.58, p < 0.01) and the E/A/diastolic filling period (r = 0.59, p < 0.01). It is concluded that parasympathetic withdrawal reduces E and increases A filling velocities and reduces the E/A ratio. These changes are closely related to changes in diastolic filling period and heart rate. In contrast, epinephrine at physiological levels increases E, A and the E/A/diastolic filling period. These findings document the importance of controlling for these factors if Doppler filling velocities are used to study diastolic function.