Cariporide (HOE642) attenuates lactic acidosis induced pulmonary vein arrhythmogenesis

Ameya R. Udyavar, Yao Chang Chen, Chen Chuan Cheng, Satoshi Higa, Yi J. Chen, Shih A. Chen

研究成果: 雜誌貢獻文章

6 引文 斯高帕斯(Scopus)

摘要

Aims: Lactic acidosis causes atrial fibrillation (AF), and pulmonary veins (PVs) are the most important focus for the generation of AF. Cariporide (HOE642), a Na+/H+ blocker, can prevent atrial tachycardia-induced electrical remodeling. The purpose of this study was to investigate whether cariporide can prevent lactic acidosis-induced PV arrhythmogenesis. Main methods: Conventional microelectrodes were used to record the action potentials (APs) before and after the administration of lactic acid (10 and 20 mM) in the absence and presence of cariporide (10 μM) pretreatment in isolated rabbit PV and atrial tissue preparations. Key findings: Lactic acidosis of 10 mM (pH 7.0 ± 0.1) and 20 mM (pH 6.7 ± 0.1) reduced PV (n = 6) spontaneous rates from 2.5 ± 0.3 to 1.6 ± 0.4 (by 36 ± 1%) and 1.1 ± 0.4 Hz (by 56 ± 2%), respectively, but lactic acidosis (10 and 20 mM) induced 12 episodes (3.9 ± 0.2 Hz) and 23 episodes (4.0 ± 0.3 Hz) of non-sustained burst firings in 4 PV specimens. Lactic acidosis (10 and 20 mM) decreased the AP amplitude (APA) and velocity of depolarization (Vmax), but increased the resting membrane potential (RMP), AP duration, and strength-response interval (SRI) in the PV and atrium. In the presence of cariporide (10 μM), lactic acidosis (10 and 20 mM) only reduced PV spontaneous rates from 2.4 ± 0.2 to 1.8 ± 0.4 (by 25 ± 1%) and 1.6 ± 0.4 Hz (by 33 ± 1%), respectively, and prevented lactic acidosis-induced PV burst firings. Cariporide also reduced the effects of lactic acidosis on the RMP, AP duration, APA, Vmax, and SRI. Significance: Lactic acidosis has significant arrhythmogenic effects on PVs, which may be attenuated by Na+/H+ blockers.

原文英語
頁(從 - 到)19-25
頁數7
期刊Life Sciences
85
發行號1-2
DOIs
出版狀態已發佈 - 七月 1 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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