Modifying L-type calcium current to prevent ventricular fibrillation

Ventricular fibrillation (VF) is characterized by multiple reentrant waves promoted by both dynamical instabilities and anatomical heterogeneities. Decreasing dynamic wave instability by flattening action potential duration restitution (APDR) slope with drugs which block the L-type calcium current, such as verapamil and D600, has been shown to convert VF to VT. However, the doses required also severely depress contractility. We hypothesized that blocking Ca-induced inactivation of the L-type Ca current, while maintaining a normal APD, will flatten APDR slope without severely depressing the intracellular Ca transient and contractility.