Effects and mechanisms of dexmedetomidine preconditioning on isoproterenol-induced ventricular arrhythmias

Figures

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  Fig. 1. Protocol. (in vivo, in vivo experiment; ex vivo, ex vivo experiment; PES, programmed electrical stimulation; NS, saline; DEX, dexmedetomidine; ISO, isoprenaline).

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  Fig. 2. DEX preconditioning reduces the incidence of ventricular arrhythmias induced by isoprenaline-mimicking stress in mice. (A) Typical surface of the body of the heart of a mouse after the administration of DEX and ISO. (B) Statistical comparison of heart rate at different times in the two groups of mice (n = 23). (C) A typical ECG example of ventricular arrhythmias induced after ISO treatment in conjunction with rapid pacing at the in vivo level, as well as the inhibitory effect of DEX reconditioning on these ventricular arrhythmias. (D) Statistical comparison of the incidence of ventricular arrhythmias in both groups of mice in vivo (n = 23). (E) Ex vivo heart models were constructed for the perfusion of isolated Langendorff mouse hearts. Ventricular arrhythmia was induced by rapid pacing after acute stress treatment with ISO in the Con group, but sinus rhythm was restored in the DEX group. Typical ECG examples. (F) Statistical comparison of the incidence of ventricular arrhythmias in the two groups of mice at the isolation level (n = 10). (*P < 0.05, **P < 0.01, ***P < 0.001; PCL, pacing cycle length.).

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  Fig. 3. Effect of DEX on APD. (A) Mouse Langendorff perfused heart. Schematic representation of the rapid pacing region and the optically labeled region. (B) Examples of representative heatmaps of APD80 in two groups of mice paced with ventricular electrical stimulation (pacing cycle length (PCL) 100 ms). (C) Action potential waveform and schematic of the APD measurement method. (D) Statistical plots of the APD50 at different time points in the two groups of mice. (E) APD80. (F) Heterogeneity in APD80. (n = 10; *P < 0.05, **P < 0.01, ***P < 0.001).

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  Fig. 4. Effect of DEX on CaTD. (A) Mouse Langendorff perfused heart. Schematic representation of the rapid pacing region and the optically labeled region. (B) Examples of representative heatmaps of CaTD80 in two groups of mice paced with ventricular electrical stimulation (pacing cycle length (PCL) 100 ms). (C) Calcium transient waveform and schematic of the calcium transient duration measurement method. (D, E, F, G, H) Statistical plots of CaTD50, CaTD80, CaTD80 heterogeneity, and TTP100 and TTP50 at different time points in the two groups of mice. (n = 10. *P < 0.05, **P < 0.01, ***P < 0.001).

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  Fig. 5. DEX alleviates calcium transient alternation. (A) Representative heatmaps of calcium transient alternations at various time points in the two groups induced by a gradual decrease in the length of the pacing cycle through electrical stimulation, along with the corresponding waveforms of calcium transient alterations in the labeled regions on the heatmaps. (B) Calculation of the calcium transient alternans ratio. (C) Statistical plots of the mean values of the calcium transient alternation ratio for both groups at different pacing frequencies at different time points. (n = 10. *P < 0.05, **P < 0.01, ***P < 0.001, DEX + ISO vs. NS + ISO).

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  Fig. 6. Effects of DEX on spatially discordant calcium transient alternans. (A) Representative heatmap spatially concordant alternans (SCA) and the corresponding calcium transient alternans waveforms for the regions labeled in the heatmap. (B) Spatially discordant alternans (SDA). (C) Statistical results for the incidence of spatially discordant alternans. (n = 10).

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  Fig. 7. DEX slows the myocardial conduction velocity. (A) Mouse Langendorff perfused heart. Schematic representation of the rapid pacing region and the optically labeled region. (B) Examples of representative heatmaps of conduction velocity in two groups of mice paced with ventricular electrical stimulation (pacing cycle length (PCL) 100 ms). (C) Statistical comparison of the conduction velocity at different time points in the two groups of mice. (D) Conduction velocity heterogeneity. (n = 10. *P < 0.05, **P < 0.01, ***P < 0.001).