Altering ventricular activation remodels gap junction distribution in canine heart

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Molecular Cardiology

Background:

• Prolonged abnormal heart activation can alter myocardial conduction and repolarization.
• Gap junction remodeling is a known factor in reentrant arrhythmias.
• The study investigated if altered ventricular activation patterns induce gap junction remodeling.

Purpose of the Study:

• To determine if altering ventricular activation patterns causes gap junction remodeling.
• To investigate the impact of pacing on myocardial conduction and repolarization.
• To examine connexin expression and distribution following prolonged ventricular pacing.

Main Methods:

• Ventricular pacing in dogs (n=12) for 21 days.
• Measurement of QRS duration and intraventricular conduction.
• Analysis of transmural left ventricular samples for connexin43 expression and distribution.

Main Results:

• Pacing induced persistent T wave changes (cardiac memory).
• Ventricular pacing prolonged QRS duration and slowed intraventricular conduction.
• Reduced epimyocardial connexin43 expression and disrupted its distribution were observed near the pacing site.

Conclusions:

• Abnormal ventricular activation causes spatially distinct gap junction remodeling.
• This remodeling is associated with altered repolarization patterns.
• The findings suggest a mechanism facilitating reentrant arrhythmogenesis.