Combination of doxorubicin liposomes with left atrial appendage radiofrequency catheter ablation to reduce post-ablation recovery of electrical conduction

Abstract

Aims

To determine whether use of radiofrequency catheter ablation (RFCA) combined with intravenously administered liposomal doxorubicin (L-DOX) facilitates a reduction in the recovery of post-ablation electrical conduction.

Methods

Circumferential ablation was performed on the epicardial surface of the left atrial appendage (LAA) in New Zealand White rabbits, and L-DOX was then administered intravenously. Fluorescence spectrophotometry was used to assess reagent bio-distribution, while Western blots and immunohistochemistry were used to assess the localization of the apoptotic markers Bcl-2, Bax, and cleaved CASP3 in the LAA. Liver, kidney, and cardiac functions were also measured to evaluate the safety of this approach.

Results

At 1 week and 1 month after RFCA, a pacing electrocardiogram could not be detected in most of the rabbits that had received the combined RFCA and L-DOX therapy. L-DOX began to target the LAA on the second day after RFCA. L-DOX treatment increased the apoptosis of cardiomyocytes in the regions peripheral to the necrotic area induced by RFCA. Doxorubicin had some effect on liver and kidney function, but these effects were reversible and did not affect survival.

Conclusion

The present results provide evidence that L-DOX treatment can reduce the recovery of electrical conduction after RFCA therapy owing to L-DOX-induced apoptosis of cardiomyocytes in the ablated area and the proximal transition zone of the LAA.

Keywords:

• doxorubicin
• liposome
• radiofrequency catheter ablation
• atrial fibrillation
• recovered electrical conduction

Acknowledgments

We would like to thank the Science and Technology Commission of Shanghai Municipality and the National Natural Science Foundation of China for supporting this study. This work was supported by grants from the Science and Technology Commission of Shanghai Municipality (16140901400 and 18140903500) and the National Natural Science Foundation of China (81870245).

Disclosure

The authors report no conflicts of interest in this work.