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

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.