Left ventricular extracellular matrix remodeling in dogs with right ventricular apical pacing

Jih Min Lin, Ling Ping Lai, Chih Sheng Lin, Nai Kuan Chou, Chih Yuan Chiu, Jiunn Lee Lin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Left Ventricular Remodeling in Pacing Dogs. Introduction: Right ventricle (RV) apical pacing is associated with increased incidence of heart failure due to left ventricle (LV) desynchronization. We aim to investigate extracellular matrix (ECM) remodeling of the LV in dogs with atria-sensed RV apical pacing. Methods and Results: Dogs with pacemakers underwent AV nodal ablation. After 12 weeks of atria-sensed obligatory RV pacing, LVs were separated into septum and lateral wall for analysis. Zymographic activity, including matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-3, collagen transcript expression, and histology were examined in opposite portions of the LV to identify possible ECM remodeling changes by RV apical pacing. Compared with sham-operated dogs, increased interstitial fibrosis and fragmentation of myofibrils was found in the LV lateral wall in the pacing group. Collagen type II mRNA showed a significant 2-fold increase in the LV lateral wall in the pacing group. Although collagen type I mRNA was increased, the difference was not significant. Zymography demonstrated MMP-9 activity was enhanced in both the LV lateral wall and septum in the pacing group, but MMP-2 activity was enhanced in the LV lateral wall. Immunfluorescence stain confirmed the activation of MMP-2 and MMP-9 in the LV lateral wall in the pacing group. Protein expression of TIMP-1 and TIMP-3 showed regional differences in the pacing group and both proteins were increased in the LV lateral wall. Conclusion: LV dyssynchrony by RV apical pacing elicits heterogeneous ECM remodeling in the LV. These findings assist in the elucidation of the pathophysiology of LV desynchronization. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1142-1149)

Original languageEnglish
Pages (from-to)1142-1149
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume21
Issue number10
DOIs
Publication statusPublished - Oct 1 2010
Externally publishedYes

Keywords

  • dyssynchrony
  • heart failure
  • matrix metalloproteinase
  • remodeling
  • ventricular pacing

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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