title: Targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced sustained ventricular tachycardia in conscious rats.
abstract: 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.
authors.affiliation: Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA. sdicarlo@med.wayne.edu
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Lujan
authors.forename: Gurunanthan
authors.initials: G
authors.lastname: Palani
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhang
authors.forename: Stephen E
authors.initials: SE
authors.lastname: DiCarlo
mesh_terms: D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects / Q000502:physiology; D017776:Autonomic Pathways / Q000166:cytology / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D013116:Spinal Cord / Q000166:cytology; D013233:Stellate Ganglion / Q000166:cytology / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D017180:Tachycardia, Ventricular / Q000503:physiopathology*
chemical_list: D054789:Ribosome Inactivating Proteins, Type 1; D002772:Cholera Toxin; D000076985:Saporins; D009638:Norepinephrine