PURPOSE: 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.
PURPOSE: 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.
Authors: G G Berntson; J T Bigger; D L Eckberg; P Grossman; P G Kaufmann; M Malik; H N Nagaraja; S W Porges; J P Saul; P H Stone; M W van der Molen Journal: Psychophysiology Date: 1997-11 Impact factor: 4.016
Authors: H Scheinin; A Helminen; S Huhtala; P Grönroos; J A Bosch; T Kuusela; J Kanto; T Kaila Journal: Ther Drug Monit Date: 1999-04 Impact factor: 3.681
Authors: L Ström; F Dalin; M Domberg; C Stenlund; U Bondesson; M Hedeland; P-L Toutain; C Ekstrand Journal: BMC Vet Res Date: 2021-04-07 Impact factor: 2.741