Document Detail


Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats.
MedLine Citation:
PMID:  19304949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP). CTB-SAP rats, compared with control and CTB rats, had reduced cardiac sympathetic tonus and reduced heart rate responses to graded exercise and graded doses of SNP. Furthermore, the number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)) was reduced in CTB-SAP rats. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing resting, exercise, and reflex sympathetic activity. Additional studies are required to further characterize the physiological responses to this procedure as well as determine if this new approach is safe and efficacious for the treatment of conditions associated with excess sympathetic activity (e.g., autonomic dysreflexia, hypertension, heart failure, and ventricular arrhythmias).
Authors:
Heidi L Lujan; Gurunanthan Palani; Ying Chen; Jean D Peduzzi; Stephen E Dicarlo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-20
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  296     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-04     Completed Date:  2009-06-19     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1305-11     Citation Subset:  IM    
Affiliation:
Department of Physiology, Wayne State Univ. School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Fibers / drug effects*,  metabolism,  pathology
Animals
Axonal Transport
Blood Pressure / drug effects
Cholera Toxin / administration & dosage,  metabolism,  pharmacology*
Dose-Response Relationship, Drug
Heart / innervation*
Heart Rate / drug effects
Injections
Male
Nitroprusside / pharmacology
Physical Exertion*
Rats
Rats, Sprague-Dawley
Reflex / drug effects*
Ribosome Inactivating Proteins, Type 1 / administration & dosage,  metabolism,  pharmacology*
Stellate Ganglion / drug effects*,  metabolism,  pathology
Sympathectomy, Chemical*
Time Factors
Grant Support
ID/Acronym/Agency:
HL-88615/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Ribosome Inactivating Proteins, Type 1; 0/cholera toxin B-saporin conjugate; 15078-28-1/Nitroprusside; 9012-63-9/Cholera Toxin
Comments/Corrections

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


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