Effect of Graded Increases in Parasympathetic Tone on Heart Rate Variability

INTRODUCTION: Time-and frequency-domain measurements of heart rate variability have been used as indices of parasympathetic tone. However, studies of the effect of parasympathetic stimulation on these indices in humans have yielded conflicting results. METHODS AND RESULTS: This study evaluated the effects of parasympathetic stimulation on heart rate variability. Twelve normal subjects (7 males, 5 females; age 24.8 +/- 3.4 years) were evaluated in the Clinical Research Center. Five-minute ECG recordings were obtained at baseline and during graded phenylephrine infusions (0.3 and 0.6 micrograms/kg per min). Recordings were made during spontaneous respiration and when breathing was timed with a metronome at 15 cycles/min. Heart rate variability analysis was performed using standard time- and frequency-domain parameters. Graded phenylephrine infusion resulted in a progressive increase in blood pressure and RR interval but no consistent changes in heart rate variability for the group. The results during normal versus metronome breathing were similar. Stepwise linear regression analysis revealed that the phenylephrine-induced changes in heart rate variability were inversely correlated with the baseline heart rate variability and not related to the baseline RR interval or the phenylephrine-induced change in RR interval. CONCLUSION: These findings suggest that the respiratory variation in "parasympathetic effect" typically observed at the sinus node can be either increased or decreased by parasympathetic stimulation, depending on the initial level of parasympathetic tone and the intensity of stimulation. This resolves the previously conflicting data. Thus, evaluation of parasympathetic tone using heart rate variability techniques should be cautiously undertaken.