Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility

Figures

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  Figure 1. Effect of IL-17 infusion, IL-17 neutralizer infusion alone, and baseline on intracellular calcium transient. The maximum Ca2+ transient (F/F0) was decreased after IL-17 infusion compared with baseline (A,B). Cai decay (tau value) was prolonged in the IL-17 group than that in the baseline and IL-17 neutralizer groups (C). *P < 0.05; ***P < 0.001. Cai, intracellular calcium.

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  Figure 2. Effect of IL-17 on spatial heterogeneity of APD and CaiTD in the baseline and IL-17 neutralizer groups. APD80 and CaiTD80 (A,B). SD of APD80 and SD of CaiTD80 (C,D). CV (E) in the LV during different PCLs. *P < 0.05; **P < 0.01; ***P < 0.001; +P < 0.05; ++P < 0.01; +++P < 0.001. APD, action potential duration; CaiTD, calcium transient duration; APD80, action potential duration at repolarizations of 80%; CaiTD80, calcium transient duration at repolarizations of 80%; CV, conduction velocity; PCL, pacing cycle length; LV, left ventricle.

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  Figure 3. Effects of PCL on APD and CaiTD alternans. (A) The green and red tracings indicated the Cai and Vm signals, respectively. L, long; S, short. (B) APD and Cai alternans. (C) SDA of APD and Cai. (D) Incidence of positive and negative coupling of Cai-Vm alternans. (E) PCL threshold of positive and negative coupling of Cai-Vm alternans. *P < 0.05; **P < 0.01; ***P < 0.001. Vm, voltage-driven membrane; SDA, spatially discordant alternans, and other abbreviations as in Figures 1, 2.

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  Figure 4. Effects of IL-17 on the maximum slope of APD restitutions and inducibility of ventricular arrhythmia (VA). (A–D) Maximum slope of APD restitutions. (E) IL-17 on VT/VF threshold PCL. (F) Inducibility of VA. *P < 0.05; ***P < 0.001. DI, diastolic interval; VA, ventricular arrhythmia; VT/VF, ventricular tachycardia/ventricular fibrillation and other abbreviations as in Figure 2.

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  Figure 5. Effects of IL-17 on the DF and wavebreaks of VF in ventricles. (A) p-ECG recordings of pacing-induced sustained VF episodes in the baseline, IL-17, and IL-17 neutralizer groups in a normal ventricle. (B) Effects of IL-17 on DF of VF in normal ventricles. (C) Effects of IL-17 on the number of PSs. **P < 0.01; ***P < 0.001. DF, dominant frequency; VF, ventricular fibrillation; PSs, Phase singularities.

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  Figure 6. Expressions of various ion channels target in left ventricular. Relative quantities of mRNA levels by semiquantitative RT-PCR were shown among the 3 groups. (A) Shows RT-PCR gels for Nav1.5, Kir2.1, KvLQT1, NCX, Cav1.2, SERCA2a, PLB, and RyR. (B) Demonstrates the relative mRNA expression quantity. Each value represents the mean ± SD of 3 or more repeat experiments. *P < 0.05; **P < 0.01; ***P < 0.001. KvLQT1, subunit of IKs; Nav1.5, α1-subunit of Na channel; Cav1.2, subunit of ICaL; NCX, sodium-calcium exchanger; Kir2.1, subunit of IK1; RyR, ryanodine receptor Ca2+ release channel; PLB, phospholamban; SERCA2a, sarcoplasmic reticulum Ca2+-ATPase; mRNA, messenger ribonucleic acid; RT-PCR, reverse transcription polymerase chain reaction.

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  Figure 7. Proposed pathway of IL-17 effects on ventricular arrhythmia (VA). ICaL, L-type calcium current; INCX, Na+-Ca2+ exchanger current; and other abbreviations as in Figures 2, 3, 6.