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 micrograms/kg) of the alpha 2-adrenoceptor agonist clonidine (CLO) were studied in 7 normotensive male volunteers in a placebo-controlled double-blind randomized design to evaluate the role of alpha 2-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 > or = 0.5 micrograms/kg CLO. HR first showed a slight increase 15 min after infusion of 0.5, 1, and 2 micrograms/kg CLO, but decreased subsequently as in all doses, including placebo. SV and TPR decreased after a dose of 2 micrograms/kg CLO. LFB and MFB power of HR were reduced after 2 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Tulen
J H
JH
Department of Psychiatry, University Hospital Rotterdam Dijkzigt, The Netherlands.
Smeets
F M
FM
Man in 't Veld
A J
AJ
van Steenis
H G
HG
van de Wetering
B J
BJ
Moleman
P
P
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003000:Clonidine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D012119:Respiration / Q000187:drug effects; D013057:Spectrum Analysis; D013997:Time Factors
D003000:Clonidine