Power spectral analysis of heart rate variability in rats as a quantitative tool in the PK-PD analysis of the parasympatholytic activity of atropine.
OBJECTIVE
To utilize power spectral analysis (PSA) of heart rate variability (HRV) as a pharmacodynamic (PD) measure of atropine parasympathetic effect, and to model the kinetics of action.


METHODS
Heart rate data was collected following atropine administration to rats and was analyzed off-line for high frequency peaks by PSA of HRV as a measure of parasympathetic tone. A temporal cumulative approach (TCA) detected transient changes in parasympathetic activity. The pharmacokinetics (PK) was analyzed and linked to both direct and indirect PK-PD models.


RESULTS
TCA enabled a quantitative measure of atropine parasympathetic activity. A simultaneous fit of the indirect PK-PD model to the experimental data of all three atropine doses successfully captured the experimental data.


CONCLUSIONS
TCA can be used as a quantitative measure of parasympathetic tone. Our work has established a preclinical model to investigate the kinetics of drug action on the autonomic nervous system.
Perlstein
I
I
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Israel.
Stepensky
D
D
Sapoznikov
D
D
Hoffman
A
A
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002406:Catheterization, Peripheral; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D010276:Parasympatholytics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D012815:Signal Processing, Computer-Assisted; D013686:Telemetry
D010276:Parasympatholytics; D001285:Atropine