Intramural gradients of intracellular Ca2+ (Cai2+) Cai2+ handling, Cai2+ oscillations, and Cai2+ transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Cai2+ handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Cai2+ handling contribute to LDVF, we measured membrane voltage ( Vm) and Cai2+ during pacing and LDVF in six perfused canine hearts using five eight-fiber optrodes. Measurements were grouped into epicardial, midwall, and endocardial layers. We found that during pacing at 350-ms cycle length, CaT duration was slightly longer (by ≃10%) in endocardial layers than in epicardial layers, whereas action potential duration (APD) exhibited no difference. Rapid pacing at 150-ms cycle length caused alternans in both APD (APD-ALT) and CaT amplitude (CaA-ALT) without significant transmural differences. For 93% of optrode recordings, CaA-ALT was transmurally concordant, whereas APD-ALT was either concordant (36%) or discordant (54%), suggesting that APD-ALT was not caused by CaA-ALT. During LDVF, Vm and Cai2+ progressively desynchronized when not every action potential was followed by a CaT. Such desynchronization developed faster in the epicardium than in the other layers. In addition, CaT duration strongly increased (by ∼240% at 5 min of LDVF), whereas APD shortened (by ∼17%). CaT rises always followed Vm upstrokes during pacing and LDVF. In conclusion, the fact that Vm upstrokes always preceded CaTs indicates that spontaneous Cai2+ oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong Vm-Cai2+ desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Cai2+ handling and may potentially contribute to LDVF maintenance.
Familial idiopathic ventricular fibrillation characterized by increased dispersion of ventricular repolarization and steep restitution of the action potential duration
