Differential effects of parasympathetic blockade and parasympathetic withdrawal on heart rate variability

Low heart rate variability (HRV) has been shown to have important prognostic significance in multiple settings. Although this is believed to reflect reduced parasympathetic tone, the physiology of reduced parasympathetic tone has not been elucidated.

To evaluate whether parasympathetic withdrawal and partial parasympathetic blockade result in similar changes in HRV, 27 normal volunteers underwent complete beta-adrenergic blockade and then were given (1) graded doses of nitroprusside to achieve baroreflex-mediated parasympathetic withdrawal and (2) low-dose atropine (0.01 mg/kg) to achieve partial parasympathetic blockade. Five-minute ECG recordings were obtained for HRV analysis. In 19 subjects, paired 5-minute recordings from each condition were available with mean RR intervals that differed by < 50 msec (low-dose atropine: 869 +/- 96 msec and nitroprusside 875 +/- 99 msec). The root mean square of the successive RR interval differences was lower following low-dose atropine than following parasympathetic withdrawal with nitroprusside (16 +/- 11 msec vs 22 +/- 15 msec; P < 0.02). During parasympathetic withdrawal, the low-frequency (LF) power was 0.917 +/- 0.602 bpm2 and the high-frequency (HF) power was 0.501 +/- 0.521 bpm2. During partial parasympathetic blockade, the LF and HF powers were significantly lower (0.443 +/- 0.474 bpm2, P < 0.005; and 0.198 +/- 0.207 bpm2, P < 0.02).

These data confirm that HRV reflects the character of parasympathetic modulation of the heart rate rather than parasympathetic tone per se. Furthermore, this study identifies two distinct physiologic explanations for the finding of low HRV, namely, diminished vagal discharge and resistance of cardiac muscarinic receptors to vagal discharge. Further delineation of the relationships between parasympathetic tone and HRV will allow for better understanding of the pathophysiologic derangements associated with low HRV.