Document Detail


Hemodynamic effects of clonidine in two contrasting models of autonomic failure: multiple system atrophy and pure autonomic failure.
MedLine Citation:
PMID:  16404729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We assessed the effects of clonidine on blood pressure (BP) and heart rate (HR) in multiple system atrophy (MSA), where the autonomic nervous system lesion site is preganglionic, and in pure autonomic failure (PAF), where it is postganglionic. In normal subjects, intravenous infusion of the selective alpha2-adrenoceptor agonist clonidine reduces BP and plasma noradrenaline (NA) levels by means of central alpha2-adrenoceptor action, as well as inducing growth hormone (GH) release. Clonidine-induced GH release is impaired in MSA but spared in PAF. However, the hemodynamic effects of clonidine have not been studied extensively in these disorders. We examined intravenous clonidine test results (performed in our autonomic laboratories using the London Autonomic Units protocol) in 58 patients: 39 with probable MSA and 19 with PAF. Systolic BP (SBP), diastolic BP (DBP), HR, and NA levels were measured supine at baseline and for up to 60 minutes after clonidine. Clonidine resulted in a significant BP fall in MSA patients, which occurred earlier (within 15 minutes of clonidine) and to a greater extent than seen in PAF patients. MSA and PAF patients showed reduction in HR after clonidine administration, although this finding was significantly greater in MSA than in PAF patients. NA levels decreased significantly after clonidine administration in both groups. Although basal NA levels were lower in PAF than in MSA patients, there was no difference in NA reduction relative to baseline between groups. MSA patients showed significant negative correlation between basal NA levels and BP response to clonidine. Clonidine infusion reduces BP and HR in both MSA and PAF groups but to a greater extent in MSA patients. The greater vasodepressor action of clonidine in MSA patients suggests that there is partial preservation of brainstem sympathetic outflow pathways in MSA and may reflect its action at sites in the brainstem and spinal cord that were in part functionally preserved in MSA. Despite similar degrees of NA reduction after clonidine administration, the vasodepressor effect of clonidine was attenuated in PAF compared with MSA patients. This attenuation in PAF patients may reflect greater peripheral alpha2-adrenoceptor denervation supersensitivity due to the postganglionic lesion site. These BP differences, thus, may reflect the underlying lesion site in MSA and PAF, and the hemodynamic data after clonidine infusion may help differentiate these conditions.
Authors:
Tim M Young; Masato Asahina; Laura Watson; Christopher J Mathias
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Movement disorders : official journal of the Movement Disorder Society     Volume:  21     ISSN:  0885-3185     ISO Abbreviation:  Mov. Disord.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-11     Completed Date:  2006-10-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8610688     Medline TA:  Mov Disord     Country:  United States    
Other Details:
Languages:  eng     Pagination:  609-15     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2006 Movement Disorder Society.
Affiliation:
Neurovascular Medicine Unit, Faculty of Medicine, Imperial College London at St. Mary's Hospital, London, United Kingdom. tim.young@imperial.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Agonists / administration & dosage*
Autonomic Nervous System Diseases / blood,  drug therapy,  physiopathology*
Blood Pressure / drug effects
Case-Control Studies
Clonidine / administration & dosage*
Heart Rate / drug effects
Hemodynamics / drug effects*
Humans
Multiple System Atrophy / blood,  drug therapy,  physiopathology*
Norepinephrine / blood
Retrospective Studies
Statistics, Nonparametric
Time Factors
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 4205-90-7/Clonidine; 51-41-2/Norepinephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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