Abstract 2734: Simultaneous Transmural Measurements of Vm and Cai2+ During Rapid Pacing and Long-Duration Ventricular Fibrillation in Canine Hearts
Introduction: It was hypothesized that spontaneous oscillations of intracellular calcium (Cai2+) and Cai2+transient (CaT) alternans play a key role in initiation and maintenance of ventricular fibrillation (VF). We tested this hypothesis using simultaneous transmural optical recordings of Vm and Cai2+ during rapid pacing and VF.
Methods: Experiments were performed in Langendorff-perfused canine hearts (n = 6). Vm and Cai2+ were measured using 5 bundles of optical fibers (optrodes) inserted in anterior left ventricular wall along the apex-base direction with ~1 cm spacing. Each optrode contained 8 fibers with tips spaced 2 mm apart. Recordings were made during sinus rhythm (SR), rapid pacing, perfused VF and 5 min of no-perfusion long-duration VF (LDVF). Measurements were grouped into 4 layers: epicardium (Epi), sub-epicardium (Sub-Epi), midwall (Mid) and sub-endocardium (Sub-Endo).
Results: CaT rises always followed Vm upstrokes during SR (cycle length, CL = 494±47 ms), rapid pacing (CL = 150 ms) or VF. CaT duration (CaD) was ~18% longer on Sub-Endo than Epi during SR but not rapid pacing. Alternans of APD (APD-Alt) or CaT amplitude (CaA-Alt) were negligible during SR. At CL = 150 ms, APD-Alt and Ca-Alt were observed in all tissue layers without significant transmural gradients (p > 0.05). For the majority of optrodes (93%), CaA-Alt were transmurally concordant. In these cases, APD-Alt were either transmurally concordant or discordant (36% and 54%, respectively). Both CaA-Alt and APD-Alt increased during early VF more prominently in Epi (by 59±6% and 25±9%, respectively) than in Sub-Endo layers (by 37±11% and 18±9%, p < 0.05) with no apex-base gradients. With progression of LDVF, APs and CaTs became increasingly irregular with many APs not followed by CaTs. CaT became increasingly long: at 5 min of LDVF, CaD increased by ~220% in comparison to the early VF whereas APD decreased by ~15%.
Conclusions: The fact that Vm upstrokes always preceded CaT indicates that Cai2+ oscillations were not responsible for VF maintenance. Coexistence of transmurally concordant Ca-Alt and discordant APD-Alt during rapid pacing suggests that APD-Alt were not caused by Ca-Alt. The development of very long Cai2+ transients indicates strongly impaired Cai2+ handling during LDVF.