Document Detail

Targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced sustained ventricular tachycardia in conscious rats.
MedLine Citation:
PMID:  20173045     Owner:  NLM     Status:  MEDLINE    
The Cardiac Arrhythmia Suppression Trial demonstrated that antiarrhythmic drugs not only fail to prevent sudden cardiac death, but actually increase overall mortality. These findings have been confirmed in additional trials. The "proarrhythmic" effects of most currently available antiarrhythmic drugs makes it essential that we investigate novel strategies for the prevention of sudden cardiac death. Targeted ablation of cardiac sympathetic neurons may become a therapeutic option by reducing sympathetic activity. Thus cholera toxin B subunit (CTB) conjugated to saporin (a ribosomal inactivating protein that binds to and inactivates ribosomes; CTB-SAP) was injected into both stellate ganglia to test the hypothesis that targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced, sustained ventricular tachycardia in conscious rats. Rats were randomly divided into three groups: 1) control (no injection); 2) bilateral stellate ganglia injection of CTB; and 3) bilateral stellate ganglia injection of CTB-SAP. CTB-SAP rats had a reduced susceptibility to ischemia-induced, sustained ventricular tachycardia. Associated with the reduced susceptibility to ventricular arrhythmias were a reduced number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)), as well as a reduced left ventricular norepinephrine content and sympathetic innervation density. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing the susceptibility to ventricular arrhythmias.
Heidi L Lujan; Gurunanthan Palani; Lijie Zhang; Stephen E DiCarlo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-02-19
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  298     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-05     Completed Date:  2010-05-18     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1330-9     Citation Subset:  IM    
Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA.
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MeSH Terms
Autonomic Fibers, Preganglionic / drug effects,  physiology
Autonomic Pathways / cytology,  physiology
Blood Pressure / physiology
Cholera Toxin / pharmacology
Electric Stimulation
Heart / innervation*
Heart Rate / physiology
Myocardial Infarction / pathology
Myocardial Ischemia / physiopathology*
Neurons / physiology*
Norepinephrine / metabolism
Rats, Sprague-Dawley
Ribosome Inactivating Proteins, Type 1 / pharmacology
Spinal Cord / cytology
Stellate Ganglion / cytology,  physiology
Sympathetic Nervous System / cytology,  physiology*
Tachycardia, Ventricular / physiopathology*
Grant Support
Reg. No./Substance:
0/Ribosome Inactivating Proteins, Type 1; 51-41-2/Norepinephrine; 9012-63-9/Cholera Toxin; EC

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