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 mug/kg) of the alpha2-adrenoceptor agonist clonidine (CLO) were studied in 7 n ormotensive male volunteers in a placebo-controlled double-blind rando mized design to evaluate the role Of alpha2-adrenoceptors in spontaneo us short-term cardiovascular fluctuations. Heart rate (HR), systolic a nd diastolic blood pressure (SBP, DBP; Finapres device), stroke volume (SV) and total peripheral resistance (TPR) were monitored for 1 h aft er infusion of CLO while the subjects rested in a semirecumbent positi on. For HR, SBP, and DBP, power spectra and variation coefficients wer e calculated for consecutive time segments of 2.5 min. Power density w as assessed for three frequency bands: low (LFB, 0.02-0.06 Hz), mid (M FB, 0.07-0.14 Hz), and high (HFB, 0.15-0.40 Hz). Per time-segment, bar oreflex sensitivity (BRS) was estimated as the gain (or modulus) in MF B between systolic pressure values and R-R interval times. Decreases i n mean levels of SBP and DBP were observed within 15 min after infusio n of greater-than-or-equal-to 0.5 mug/kg CLO. HR first showed a slight increase 15 min after infusion of 0.5, 1, and 2 mug/kg CLO, but decre ased subsequently as in all doses, including placebo. SV and TPR decre ased after a dose of 2 mug/kg CLO. LFB and MFB power of HR were reduce d after 2 mug/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 ch ange after CLO, nor did BRS. DBP MFB power was reduced after 2 mug/kg CLO during the entire postinfusion period, probably as a reflection of reduced sympathetic outflow. SBP HFB power was significantly increase d after greater-than-or-equal-to 0.5 mug/kg CLO, but only after 30 min of infusion, which could be a consequence of alterations in both vaga l outflow and mechanical respiratory properties. Thus, in a dose range of 0.25-2 mug/kg CLO, significant effects were detected for SBP, DBP, and HR after greater-than-or-equal-to 0.5 mug/kg, whereas spontaneous short-term fluctuations of HR and DBP were influenced only after a do se of 2 mug/kg. The effects were slight but could be detected within a postinfusion period of 1 h. Our data show that sequential spectral an alysis of spontaneous hemodynamic fluctuations can be used to unravel time-dependent dynamics of sympathetic and vagal components in short-t erm cardiovascular control.