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Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix

Rupak Mukherjee1, Juozas A Zavadzkas, William T Rivers

  • 1Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. mukherr@musc.edu

American Journal of Physiology. Heart and Circulatory Physiology
|May 18, 2010
PubMed

Insights

Aberrant electrical activation in the heart increases matrix metalloproteinase (MMP) activity, contributing to myocardial remodeling. This occurs even after restoring normal heart rhythm and mechanical function.

Area of Science:

  • Cardiology
  • Cardiac Electrophysiology
  • Biochemistry

Background:

  • Increased matrix metalloproteinases (MMPs) are linked to adverse left ventricular (LV) remodeling in cardiac diseases.
  • The specific impact of regionally contained aberrant electrical activation on interstitial MMP activation was previously unknown.

Purpose of the Study:

  • To investigate whether regionally contained aberrant electrical activation of the LV, leading to dyskinesia, alters interstitial MMP activation.
  • To determine if electrical conduction disturbances alone can induce MMP activation independent of mechanical dysfunction.

Main Methods:

  • Pigs underwent controlled electrical pacing to induce normal atrioventricular activation, followed by regional LV activation, and then restoration of normal pacing.
  • Regional LV shortening was measured using piezoelectric crystals.
  • Interstitial MMP activity was assessed via microdialysis using a fluorogenic substrate at paced and remote LV sites.

Main Results:

  • During aberrant electrical stimulation, interstitial MMP activity significantly increased at the paced LV site compared to a remote site.
  • Following restoration of normal pacing, regional shortening normalized, but MMP activity remained elevated at the previously paced site.
  • These findings indicate a direct link between electrical disturbances and MMP activation.

Conclusions:

  • Disturbances in cardiac electrical conduction can acutely increase regional in vivo MMP activation.
  • This MMP activation persists even after mechanical function is restored, suggesting a role in myocardial remodeling.
  • Aberrant electrical activation is an independent contributor to adverse cardiac remodeling.

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