Cardiovascular Variability After Clonidine Challenge: Assessment of Dose-Dependent Temporal Effects by Means of Spectral Analysis

Effects of four intravenous (i.v.) doses (0.25, 0.5, 1, and 2 μg/kg) of the α2-adrenoceptor agonist clonidine (CLO) were studied in 7 normotensive male volunteers in a placebo-controlled double-blind randomized design to evaluate the role of α2-adrenoceptors in spontaneous short-term cardiovascular fluctuations. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP; Finapres device), stroke volume (SV) and total peripheral resistance (TPR) were monitored for 1 h after infusion of CLO while the subjects rested in a semirecumbent position. For HR, SBP, and DBP, power spectra and variation coefficients were calculated for consecutive time segments of 2.5 min. Power density was assessed for three frequency bandslow (LFB, 0.02–0.06 Hz), mid (MFB, 0.07–0.14 Hz), and high (HFB, 0.15–0.40 Hz). Per time-segment, baroreflex sensitivity (BRS) was estimated as the gain (or modulus) in MFB between systolic pressure values and R-R interval times. Decreases in mean levels of SBP and DBP were observed within 15 min after infusion of ≥0.5 μg/kg CLO. HR first showed a slight increase 15 min after infusion of 0.5, 1, and 2 μg/kg CLO, but decreased subsequently as in all doses, including placebo. SV and TPR decreased after a dose of 2 μg/kg CLO. LFB and MFB power of HR were reduced after 2 μg/kg CLO, but only during the first 30 min after infusion; during this period, respiratory depth was also diminished, indicating that these effects may reflect a reduction in sympathetic outflow as well as a reduction in vagal outflow. Respiratory frequency did not change after CLO, nor did BRS. DBP MFB power was reduced after 2 μg/kg CLO during the entire postinfusion period, probably as a reflection of reduced sympathetic outflow. SBP HFB power was significantly increased after ≥0.5 μg/kg CLO, but only after 30 min of infusion, which could be a consequence of alterations in both vagal outflow and mechanical respiratory properties. Thus, in a dose range of 0.25–2 μg/kg CLO, significant effects were detected for SBP, DBP, and HR after ≥0.5 μg/kg, whereas spontaneous short-term fluctuations of HR and DBP were influenced only after a dose of 2 μg/kg. The effects were slight but could be detected within a postinfusion period of 1 h. Our data show that sequential spectral analysis of spontaneous hemodynamic fluctuations can be used to unravel time-dependent dynamics of sympathetic and vagal components in short-term cardiovascular control.