Cardiovascular Variability After Clonidine Challenge

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Abstract
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 bands: low (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.

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