International Journal of Nanomedicine (Dec 2018)
Combination of doxorubicin liposomes with left atrial appendage radiofrequency catheter ablation to reduce post-ablation recovery of electrical conduction
Abstract
Ying Zhuge,1,* Huan-Er Ni,1,* Yu-Jie Wang,2 Mu-Ye He,2 Jun-Shan Wang,3 Feng Gao,2,4 Fang Wang1 1Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200800, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People’s Republic of China; 3Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, People’s Republic of China; 4Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, People’s Republic of China *These authors contributed equally to this work 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
