The cumulative plot of power spectral analysis of heart rate variability assesses the kinetics of action of cholinergic drugs in rats

A new approach to assess autonomic nervous system (ANS) activity and its response to drug action is presented. The authors' approach is based on using a cumulative plot of data obtained by power spectral analysis (PSA) of heart rate variability (HRV), in defined frequency bands, during short time epochs in rats. The substantial temporal variability in power evolving from the constant balancing nature of the ANS activity is minimized by this approach and produces a measurable index of ANS activity vs. time. The cumulative plot emphasizes the temporal response pattern of different components of the ANS and thereby facilitates the investigation of the kinetics of action of drugs affecting the ANS. The authors used this method to measure the activity of cholinergic drugs in freely moving Sabra rats. The pharmacodynamic (PD) data obtained by this method was combined with the drug concentration versus time (PK) profile to enable PK/PD modeling of the kinetics of the parasympathetic effect.