標題: | Paradoxical Effects of Sodium-Calcium Exchanger Inhibition on Torsade de Pointes and Early Afterdepolarization in a Heart Failure Rabbit Model |
作者: | Chang, Po-Cheng Lu, Yu-Ying Lee, Hui-Ling Lin, Shien-Fong Chu, Yen Wen, Ming-Shien Chou, Chung-Chuan 分子醫學與生物工程研究所 Institute of Molecular Medicine and Bioengineering |
關鍵字: | heart failure;sodium-calcium exchangers;torsade de pointes;early afterdepolarizations |
公開日期: | 1-八月-2018 |
摘要: | Calcium homeostasis plays an important role in development of early afterdepolarizations (EADs) and torsade de pointes (TdP). The role of sodium-calcium exchanger (NCX) inhibition in genesis of secondary Ca2+ rise and EAD-TdP is still debated. Dual voltage and intracellular Ca2+ optical mapping were conducted in 6 control and 9 failing rabbit hearts. After baseline electrophysiological and optical mapping studies, E4031 was given to simulate long QT syndrome. ORM-10103 was then administrated to examine the electrophysiological effects on EAD-TdP development. E4031 enhanced secondary Ca2+ rise, EADs development, and TdP inducibility in both control and failing hearts. The results showed that ORM-10103 reduced premature ventricular beats but was unable to suppress the inducibility of TdP or EADs. The electrophysiological effects of ORM-10103 included prolongation of action potential duration (APD) and increased APD heterogeneity in failing hearts. ORM-10103 had a neutral effect on the amplitude of secondary Ca-1 rise in control and heart failure groups. In this model, most EADs generated from long-short APD junction area. In conclusion, highly selective NCX inhibition with ORM-10103 reduced premature ventricular beat burden but was unable to suppress secondary Ca2+ rise, EADs development, or inducibility of TdP. The possible electrophysiological mechanisms include APD prolongation and increased APD heterogeneity. |
URI: | http://dx.doi.org/10.1097/FJC.0000000000000598 http://hdl.handle.net/11536/148253 |
ISSN: | 0160-2446 |
DOI: | 10.1097/FJC.0000000000000598 |
期刊: | JOURNAL OF CARDIOVASCULAR PHARMACOLOGY |
Volume: | 72 |
起始頁: | 97 |
結束頁: | 105 |
顯示於類別: | 期刊論文 |