Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure
Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure
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DOI：
10.1161/hc4601.099402
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发表时间：
2001-11-20
期刊：
影响因子：
37.8
通讯作者：
Nattel, S
中科院分区：
文献类型：
--
作者：
Li, DS;Shinagawa, K;Nattel, S
Background-Atrial structural remodeling creates a substrate for atrial fibrillation (AF), but the underlying signal transduction mechanisms are unknown. This study assessed the effects of ACE inhibition on arrhythmogenic atrial remodeling and associated mitogen-activated protein kinase (MAPK) changes in a dog model of congestive heart failure (CHF).Methods and Results-Dogs were subjected to various durations of ventricular tachypacing (VTP, 220 to 240 bpm) in the presence or absence of oral enalapril 2 mg (.) kg(-1) (.) d(-1). VTP for 5 weeks induced CBF, local atrial conduction slowing, and interstitial fibrosis and prolonged atrial burst pacing-induced AF. Atrial angiotensin H concentrations and MAPK expression were increased by tachypacing, with substantial changes in phosphorylated forms of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38-kinase. Enalapril significantly reduced tachypacing-induced changes in atrial angiotensin II concentrations and ERK expression. Enalapril also attenuated the effects of CHF on atrial conduction (conduction heterogeneity index reduced from 3.1 +/-0.4 to 1.9 +/-0.2 ms/mm, P
