Cardiac activation-repolarization patterns and ion channel expression mapping in intact isolated normal human hearts

Area of Science:

• Cardiology
• Electrophysiology
• Molecular Biology

Background:

• The precise repolarization pattern of the human heart remains incompletely understood.
• Existing knowledge gaps hinder a comprehensive understanding of cardiac electrical function.

Purpose of the Study:

• To conduct a detailed multisite analysis of cardiac activation-repolarization dynamics.
• To investigate mRNA expression patterns of ion channel subunits in isolated human hearts.

Main Methods:

• Utilized Langendorff-perfused human hearts (n=3) with autologous blood.
• Acquired 92 unipolar electrograms from transmural needles during right atrial pacing.
• Measured local activation/repolarization times and activation-recovery intervals (ARI); quantified ion channel subunit mRNA levels via qPCR.

Main Results:

• Observed diverse repolarization gradients across all axes, lacking midmural late repolarization.
• Identified a negative epicardial activation-repolarization relationship, contrasting with a positive whole-heart relationship.
• Found significant variability in mRNA levels (40%-80%) and Kv7.1 protein compared to ARI variability (7%-17%); regional mRNA patterns were consistent, unlike ARI profiles.

Conclusions:

• Human heart repolarization gradients span all axes, without midmural late repolarization.
• Areas activated last do not exhibit the earliest repolarization, challenging prior assumptions.
• Gradients in single ion channel subunit mRNA expression and ARIs are not correlated.