Dyssynchronous calcium removal in heart failure-induced atrial remodeling

Area of Science:

• Cardiology
• Cell Physiology
• Biophysics

Background:

• Heart failure (HF) alters cardiac cell function.
• Calcium (Ca) handling is crucial for heart rhythm.
• Atrial myocytes in HF models exhibit impaired Ca removal.

Purpose of the Study:

• Investigate if spatial and temporal dyssynchrony of Ca removal, alongside increased Na/Ca exchange (NCX) activity, promotes arrhythmias in HF atrial myocytes.
• Determine the role of NCX in proarrhythmic Ca release in HF.

Main Methods:

• Used a rabbit left ventricular heart failure (HF) model.
• Measured Ca transient (CaT) decay kinetics in subsarcolemmal (SS) and central (CT) regions of atrial myocytes using confocal microscopy and Fluo-4.
• Quantified Ca removal dyssynchrony using the CV TAU metric.
• Assessed the impact of NCX inhibition on Ca waves and arrhythmias.

Main Results:

• HF atrial myocytes displayed accelerated but dyssynchronous Ca removal.
• Increased NCX activity in HF cells correlated with more spontaneous and arrhythmogenic Ca waves.
• NCX inhibition improved Ca removal synchrony (normalized CV TAU) and reduced Ca wave incidence in HF cells.

Conclusions:

• Accelerated and dyssynchronous diastolic Ca removal in HF atrial myocytes, driven by altered sarcoplasmic reticulum Ca-ATPase (SERCA) and NCX activity, increases arrhythmia susceptibility.
• NCX plays a significant role in mediating proarrhythmic Ca release and arrhythmias in HF atrial cells.