The Kinetics of Intracellular Calcium and Arrhythmogenesis in Ischemia/Reperfusion: A Calcium-Centric Mechanism of Arrhythmia
El-Sherif N., Bub G., Lakireddy V.
Ischemia/reperfusion is associated with elevated intracellular calcium and alteration in calcium kinetics. There are several lines of evidence to suggest that alteration of sarcoplasmic reticulum function and calcium kinetics will alter membrane voltage and play a significant role in the genesis of cardiac arrhythmias in the setting of ischemia/reperfusion. The correlation between altered calcium kinetics and arrhythmogenesis has been investigated in a Langendorff-perfused guinea pig heart preparation utilizing simultaneous recordings of membrane voltage and intracellular calcium transient. At least three possible electrophysiological mechanisms by which altered calcium kinetics can result in arrhythmias can be cited: (i) Calcium alternans resulting in membrane voltage alternans, that is, action potential duration alternans and increased dispersion of repolarization; (ii) focal arrhythmias triggered by early afterdepolarizations, or delayed afterdepolarizations; (ii) uncoupling of calcium/membrane voltage which may play a crucial role in wave break and the initiation and maintenance of ventricular tachyarrhythmias. © 2009 Blackwell Publishing Ltd.