Effects of central sympathetic activation on repolarization-dispersion during short-term myocardial ischemia in anesthetized rats

Life Sci. 2016 Jan 1:144:170-7. doi: 10.1016/j.lfs.2015.12.019. Epub 2015 Dec 8.

Abstract

Aims: Sympathetic activation during myocardial ischemia enhances arrhythmogenesis, but the underlying pathophysiologic mechanisms remain unclear. We investigated the central sympathetic effects on ventricular repolarization during the early-period post-coronary artery occlusion.

Main methods: We studied 12 Wistar rats (254±2 g) for 30 min following left coronary artery ligation, with (n=6) or without (n=6) pretreatment with the central sympatholytic agent clonidine. Mapping of left and right ventricular epicardial electrograms was performed with a 32-electrode array. As an index of sympathetic activation, heart rate variability in the frequency domain was calculated. Heart rate and repolarization duration were measured with a custom-made recording and analysis software, followed by calculation of intra- and inter-ventricular dispersion of repolarization.

Key findings: Heart rate and heart rate variability indicated lower sympathetic activation in clonidine-treated rats during ischemia. Repolarization duration in the left ventricle prolonged after clonidine at baseline, independently of heart rate, but no differences were present 30 min post-ligation. Dispersion of repolarization in the right ventricle remained stable during ischemia, whereas it increased in the left ventricle, equally in both groups. A similar trend was observed for inter-ventricular dispersion, without differences between groups.

Significance: In addition to intra-ventricular repolarization-dispersion, anterior-wall myocardial ischemia may also increase inter-ventricular repolarization-dispersion. Progressive central sympathetic activation occurs during myocardial ischemia, but it does not affect intra- or inter-ventricular dispersion of ventricular repolarization during the early phase. Further research is warranted on the potential effects during subsequent time-periods.

Keywords: Central sympathetic activation; Myocardial ischemia; Repolarization-dispersion; Ventricular repolarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia
  • Animals
  • Clonidine / pharmacology
  • Electrocardiography / drug effects
  • Heart Rate / drug effects
  • Ligation
  • Male
  • Myocardial Ischemia / physiopathology*
  • Rats
  • Rats, Wistar
  • Sympathetic Nervous System / physiopathology*
  • Sympatholytics / pharmacology
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Right / drug effects

Substances

  • Sympatholytics
  • Clonidine