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


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. Immunofluorescence 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.


CONCLUSIONS
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.
Lin
Jih-Min
JM
Department of Internal Medicine, Keelung Hospital, Department of Health, Executive Yuan, Keelung,Taiwan.
Lai
Ling-Ping
LP
Lin
Chih-Sheng
CS
Chou
Nai-Kuan
NK
Chiu
Chih-Yuan
CY
Lin
Jiunn-Lee
JL
D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004285:Dogs; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000502:physiology*; D016278:Ventricular Function, Right / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
D016326:Extracellular Matrix Proteins