Mathematical Treatment of Autonomic Oscillations

Montano et al 1 measured RR interval and muscle sympathetic nerve activity (MSNA) autoregressive spectral power before and after small-and large-dose atropine and drew inferences regarding human central autonomic mechanisms.I have several questions for the authors, as well as comments.Your finding that low-dose atropine does not alter lowfrequency RR-interval spectral power (Table 2) is at variance with results published by Ikuta et al, 2 which document significant increases.Your observation also is at variance with one of your principal conclusions (Abstract), that low-dose atropine decreases low-frequency RR-interval spectral power.In the absence of changes of measured low-frequency RR-interval spectral power, the reduction of normalized low-frequency RRinterval spectral power that you report simply signifies that low-dose atropine increases respiratory sinus arrhythmia.3 You report that low-dose atropine does not alter MSNA.This confirms an observation we made earlier.4 You report also that high-dose atropine reduces muscle sympathetic nerve burst frequency, expressed as bursts/100 heart beats and bursts/min.Our study 4 also showed that large-dose atropine significantly reduces sympathetic activity expressed as bursts/100 heart beats.However, contrary to your observations, we found that largedose atropine does not significantly alter sympathetic activity expressed as bursts/min.This finding was supported by a related observation that large-dose atropine does not alter antecubital vein plasma norepinephrine concentrations (which correlate well with MSNA).5 Can you explain the disparity between your results and ours?You present only "normalized" MSNA; therefore, it is impossible to determine whether measured MSNA frequency or amplitude spectral power changed in high or low ranges or both.I am aware of substantial uncertainty regarding what high-and low-frequency MSNA oscillations signify individually.My sense is that when you divide one by the other (and thereby "normalize" them), you enter largely uncharted territory.The notion that a change of this quotient documents central parasympathetic modulation of sympathetic oscillations is provocative.However, high-dose atropine is a complex intervention that profoundly alters autonomic function; there may be several alternative explanations for your results.