By using electrical mapping (Figure 2D), we found that doxorubicin slowed down the conduction velocity by 2.2 folds (Figure 2E), increased the dispersion index by 3.6 folds (Figure 2F) and prolonged the activation time of LA by 2.3 folds (Figure 2G) at week 4, which were reversed by dexrazoxane (Figure 2E-G). Moreover, dexrazoxane treatment reduced vulnerability to AF in doxorubicin-injected mice (Figure 2H), as measured by the AF inducibility (Figure 2I) and total duration of AF (Figure 2J).

(D). Averaged active time (E), conduction velocities (F) and dispersion index (G) from vehicle-or doxorubicin-injected mice, with or without dexrazoxane treatment at week 4 is presented. Vulnerability to AF was assessed using an intracardiac catheter placed into the right atrium. Representative intracardiac bipolar electrograms showing induction of AF from vehicle-or doxorubicin-injected mice with or without dexrazoxane treatment at week 4 (H). AF inducibility and total duration time were recorded and presented in (I) and (J). DOX: doxorubicin; DEX: dexrazoxane. Statistical analysis was performed by two-way ANOVA. For panel C: ***P<0.001 vs vehicle; †††P<0.001 DOX vs DOX+DEX. *P<0.05; ***P<0.001; ****P<0.0001. n=6-17/group.

Antioxidants & Redox Signaling

https://doi.org/10.1089/ars.2021.0002