Ion cocktail therapy for myocardial infarction by synergistic regulation of both structural and electrical remodeling

The ion cocktail, consisting of silicate, strontium and copper could attenuate both electrical and structural remodeling after myocardial infarction in rat and Bama minipigs. The therapeutic effect of ion cocktail on myocardial infarction may account for that different ions in the cocktail have different functions to regulate cellular behaviors.

Abstract:

Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an “ion cocktail therapy” is proposed to simultaneously reverse cardiac structural and electrical remodeling post-MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post-MI by ameliorating infarct size, promoting angiogenesis in both peri-infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.

Author list:

Yumei Que†, Jiaxin Shi†, Zhaowenbin Zhang†, Lu Sun, Hairu Li, Xionghai Qin, Zhen Zeng, Xiao Yang, Yanxin Chen, Chong Liu, Chang Liu, Shijie Sun, Qishu Jin, Yanxin Zhang, Xin Li, Ming Lei, Chen Yang*, Hai Tian*, Jiawei Tian*, Jiang Chang*

How to cite:

Y. Que, J. Shi, Z. Zhang, L. Sun, H. Li, X. Qin, Z. Zeng, X. Yang, Y. Chen, C. Liu, C. Liu, S. Sun, Q. Jin, Y. Zhang, X. Li, M. Lei, C. Yang, H. Tian, J. Tian, J. Chang, Exploration 2023, 20230067.
https://doi.org/10.1002/EXP.20230067