Relation between cellular repolarization characteristics and critical mass for human ventricular fibrillation

Area of Science:

• Cardiology
• Electrophysiology
• Cardiac Pathophysiology

Background:

• The critical mass for inducing ventricular fibrillation (VF) in human hearts remains unclear.
• Electrical determinants influencing VF susceptibility in diseased cardiac tissue require further investigation.

Purpose of the Study:

• To evaluate the relationship between repolarization characteristics and the critical mass for VF in diseased human cardiac tissues.
• To determine how altering action potential duration (APD) and APD restitution affects VF induction.

Main Methods:

• Studied eight explanted human ventricles, some perfused with Tyrode's solution.
• Determined APD restitution curves using an S1-S2 method and induced VF via programmed stimulation.
• Administered cromakalim, an ATP-sensitive potassium channel opener, to assess its effect on VF induction and repolarization.

Main Results:

• At baseline, VF could not be induced in any tissue, with mean APD90 of 227±49 ms and APD restitution slope of 0.22±0.08.
• In tissues treated with cromakalim, VF was consistently induced after significant shortening of APD90 (243±32 ms to 55±18 ms) and increase in APD restitution slope (0.24±0.11 to 1.43±0.10).
• The average weight of non-treated perfused heart samples where VF could not be induced was 111±23 g.

Conclusions:

• The critical mass for VF in diseased human hearts in vitro is greater than 111g.
• Shortening APD and increasing the slope of the APD restitution curve can reduce the critical mass for VF.
• These findings highlight the role of repolarization dynamics in VF susceptibility and provide insights into potential therapeutic targets.