Panoramic imaging reveals basic mechanisms of induction and termination of ventricular tachycardia in rabbit heart with chronic infarction: implications for low-voltage cardioversion

Heart Rhythm. 2009 Jan;6(1):87-97. doi: 10.1016/j.hrthm.2008.09.019. Epub 2008 Sep 23.

Abstract

Background: Sudden cardiac death due to arrhythmia in the settings of chronic myocardial infarction (MI) is an important clinical problem. Arrhythmic risk post-MI continues indefinitely even if heart failure and acute ischemia are not present due to the anatomic substrate of the scar and border zone (BZ) tissue.

Objective: The purpose of this study was to determine mechanisms of arrhythmia initiation and termination in a rabbit model of chronic MI.

Methods: Ligation of the lateral division of the left circumflex artery was performed 72 +/- 29 days before acute experiments (n = 11). Flecainide (2.13 +/- 0.64 microM) was administered to promote sustained arrhythmias, which were induced with burst pacing or a multiple shock protocol (four pulses, 140-200 ms coupling interval).

Results: Panoramic optical mapping with blebbistatin (5 microM) revealed monomorphic ventricular tachycardia (VT) maintained by a single mother rotor (cycle length [CL] = 174.7 +/- 38.4 ms) as the primary mechanism of arrhythmia. Mother rotors were anchored to the scar or BZ for 16 of the 19 rotor locations recorded. Cardioversion thresholds (CVTs) were determined at various phases throughout the VT CL from external shock electrodes. CVTs were found to be phase dependent, and the maximum versus minimum CVT was 7.8 +/- 1.9 vs. 4.1 +/- 1.6 V/cm, respectively (P = .005). Antitachycardia pacing was found to be effective in only 2.7% of cases in this model.

Conclusions: These results indicate that scar and BZ tissue heterogeneity provide the substrate for VT by attracting and stabilizing rotors. Additionally, a significant reduction in CVT may be achieved by appropriately timed shocks in which the shock-induced virtual electrode polarization interacts with the rotor to destabilize VT.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chronic Disease
  • Diagnostic Imaging / methods*
  • Disease Models, Animal
  • Electric Countershock / methods*
  • Female
  • Heart Rate / physiology*
  • Heterocyclic Compounds, 4 or More Rings
  • Imaging, Three-Dimensional / methods*
  • Male
  • Myocardial Infarction / complications*
  • Rabbits
  • Tachycardia, Ventricular / diagnosis*
  • Tachycardia, Ventricular / etiology
  • Tachycardia, Ventricular / therapy

Substances

  • Heterocyclic Compounds, 4 or More Rings
  • blebbistatin