Intrathecal clonidine reduces the incidence of ischemia-provoked ventricular arrhythmias in a canine postinfarction heart failure model

Ziad F. Issa, Michael R. Ujhelyi, Keith R. Hildebrand, Xiaohong Zhou, Josh Rosenberger, William J. Groh, John M. Miller, Douglas P. Zipes

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: Intrathecal clonidine (ITC) is used clinically to manage neuropathic pain but frequently causes hypotension and bradycardia due to centrally mediated sympatholytic effects. Objectives: The purpose of this study was to evaluate the cardiac electrophysiologic effects of thoracic ITC and its effects on ischemia-provoked ventricular arrhythmias. Methods: Twelve mongrel dogs with healed myocardial infarctions and heart failure were evaluated. ITC was delivered locally via catheter to the T2-T4 spinal segments and was dosed to reduce heart rate (HR) by >20% to 25%. Electrophysiologic testing was performed before and after ITC. Transient (4-minute) myocardial ischemia was induced via left circumflex coronary artery occlusion on two separate occasions to provoke ventricular arrhythmias (ventricular tachycardia [VT]/ ventricular fibrillation [VF]). Ischemic episodes were separated by 1 to 2 days, and dogs were randomly assigned to receive ITC or intrathecal saline flush (control) prior to the first or the second ischemic episode. Results: ITC produced significant decrease in HR (31%) and increases in PR interval (22%), Wenckebach cycle length (122%), and atrial and ventricular effective refractory periods (19% and 9%, respectively) but had no significant effect on systemic blood pressure. The occurrence of VT/VF was reduced from 9 of 12 to 3 of 12 dogs when ITC was administered prior to transient myocardial ischemia (P = .04). ITC also blunted ischemia-induced HR increase by 74%. Conclusion: ITC reduced ischemia-induced VT/VF in a canine model of healed myocardial infarction with superimposed heart failure and acute ischemia. Results from electrophysiologic testing were consistent with a clonidine-induced reduction in cardiac sympathetic activity from the spinal cord. These data suggest that ITC administration may be a novel approach to treating ventricular arrhythmias.

Original languageEnglish (US)
Pages (from-to)1122-1127
Number of pages6
JournalHeart Rhythm
Volume2
Issue number10
DOIs
StatePublished - Oct 1 2005

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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