Fig. 9.
Role of SCR as a trigger of bradycardia-dependent ectopic beats. A: pacing protocol consisting of 2 cycles of BHR to SHR with 5-min intervals to achieve steady state followed by treatment with K201 and another cycle to examine the effects of RyR2 stabilization. Gray arrows (below trace) indicate the timing of changes in HR from BHR to SHR, and two black arrows (1st two arrows above trace) indicate changes from SHR to BHR. B and D: premature ectopic beats were reproducible during the 2 episodes of bradycardia at 3 min and 13 min of the experiment. C and E: termination of ectopic beats was consistently observed during the episode of BHR, shown here at 8- and 18-min time points. F: after pretreatment with K201 (1 μM), bradycardia-dependent ectopic beats were suppressed. G: APs and CaT measured from the RVB of a heart that developed ectopic activity during SHR (n = 5 out of 15 hearts). The paced beats are labeled with a black arrow and the spontaneous ectopic beats by gray arrows. H: activation maps of paced (left) and ectopic (right) beats. Paced beats were initiated at the stimulating electrode (left), and the first ectopic beat was initiated at site a on the map. Note the origins of the paced and ectopic beats and the collision of the ectopic and paced wavefronts. I: upstrokes of CaT and APs shown at fast sweep speeds to determine their relative kinetics. At the origin of the ectopic beat (site a), Cai preceded Vm (top traces), but farther from the origin of the ectopic wavefront (site b), Vm preceded Cai (bottom traces). During paced beats, Vm preceded Cai, as previously reported. During ectopic beats, Vm followed Cai with a variable delay ranging from 2–12 ms; however, the shift in the Cai to Vm dynamics was unmistakable.