Interregional electro-mechanical heterogeneity in the rabbit myocardium

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Biophysics

Background:

• Electrical heterogeneity is a known contributor to cardiac arrhythmias.
• Understanding physiological heterogeneity is crucial for studying arrhythmic disorders.
• Rabbits are a relevant animal model for cardiac research.

Purpose of the Study:

• To investigate regional electro-mechanical heterogeneities in the healthy rabbit heart.
• To characterize differences in contraction and action potentials between the apex and base of the left ventricle.
• To explore the molecular basis of these regional differences.

Main Methods:

• Phase-contrast magnetic resonance imaging (MRI) in vivo to assess cardiac wall motion.
• Novel data-processing algorithm to calculate regional contraction profiles.
• Patch clamp recordings for action potential duration (APD) measurements.
• Western blot analysis for cardiac ion channel and calcium handling protein expression.
• In silico modeling of cardiac electrophysiology.

Main Results:

• Left ventricular (LV) apex demonstrated earlier and longer contraction compared to the LV base.
• LV apex exhibited longer action potentials (AP) than the LV base, septum, and right ventricle.
• Lower expression of key proteins (Cav1.2, KvLQT1, Kv1.4, NCX, Phospholamban) was observed in the LV apex versus the base.
• In silico model successfully replicated observed apico-basal differences in contraction and AP duration.

Conclusions:

• Physiological apico-basal electro-mechanical heterogeneity is present in the healthy rabbit heart.
• A distinct electro-mechanical gradient exists, with the apex showing longer APD and contraction duration.
• This apical mechanical dominance is associated with regionally heterogeneous protein expression and likely optimizes cardiac pumping efficiency.