Figure 2.
Excessive APD prolongation and frequent arrhythmias (PVCs and VT) in the presence of IL-18 in murine SCD hearts. (A) Representative AP traces under IL-18 (2 ng/mL) in both CTR and SCD hearts after IL-18 perfusion over 1 hour. Frequent PVCs and VT were developed from APD prolongation in SCD (n = 6 of 6) hearts compared with CTR (n = 0 of 6) hearts. (B) APDs were prolonged by IL-18 in both CTR (P = .004) and SCD hearts (P = .003) but were greater in SCD hearts (right panel, ΔAPD = 14.9 ± 7.2 ms in CTR vs 37.6 ± 16.6 ms in SCD; P = .009) (n = 5 mice per group). *P < .05, Error bars represent standard error. Median values displayed with whiskers using the Tukey method. (C) Representative PVC and VT traces induced by IL-18 in SCD hearts. (D) Activation maps of PVCs (marked in panel C) showed focal activations originating from the RV (concentric pattern of c, d, and e beats) that propagated and formed reentry. (E) IL-18 (5 ng/mL) prolongs APD (black) for a substantially longer time than CaD (red; from 75.0 ± 10.1 ms vs 87.1 ± 3.77 ms to 143.9 ± 16.2 ms vs 95.8 ± 3.4 ms; P < .01; n = 4 hearts). (F) Voltage precedes Ca2+ during PVC upstroke. Top: Sample traces of Vm (black) and Ca2+ (red) of PVC; bottom: corresponding activation maps of sinus rhythm (beat 1 [b1]) and PVC (b2). Right: Vm (black) precedes Ca2+ (red) during the upstroke of PVC. Spontaneous Ca2+ release preceding Vm upstrokes was not seen from n = 13 of 13 episodes of VTs recorded (see additional examples in supplemental Figure 3).