Heart Rate Reduction by Ivabradine Reduces Diastolic Dysfunction and Cardiac Fibrosis
Heart Rate Reduction by Ivabradine Reduces Diastolic Dysfunction and Cardiac Fibrosis
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DOI：
10.1159/000322905
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发表时间：
2010-01-01
期刊：
影响因子：
1.9
通讯作者：
Tardif, Jean-Claude
中科院分区：
文献类型：
--
作者：
Busseuil, David;Shi, Yanfen;Tardif, Jean-Claude
目的：确定伊瓦布雷定（IVA）降低心率（HR）是否可以预防与血脂异常相关的心功能障碍，IVA是一种选择性的起搏器I-f电流抑制剂。方法：新西兰大白兔分别饲喂标准饲粮、0.5%高胆固醇饲粮（CD）或0.5%高胆固醇饲粮加IVA (17 mg/kg/d) 12周。超声心动图观察左室HR、左室收缩功能、左室舒张功能及左室局部心肌功能指数（MPI）。组织学分析包括心脏间质纤维化和I型胶原纤维。用免疫分析法测定血浆血管紧张素II和醛固酮水平。结果：IVA降低HR约11%。IVA改善MPI和减轻左室舒张功能障碍（DD） （IVA组92%轻度和8%中度DD，而CD组54%轻度和46%中度DD）。IVA还减少了心房纤维化（p = 0.027）、心室纤维化（p = 0.0002）和心室I型胶原蛋白（p = 0.0042）。IVA降低血浆血管紧张素II水平（p = 0.042），血管紧张素II和醛固酮水平与HR相关（p = 0.038和0.008）。结论：IVA选择性降低HR可减少高胆固醇血症家兔的DD和心脏纤维化。这些有益的IVA效果支持测试舒张性心力衰竭患者的纯HR降低。巴塞尔S. Karger股份有限公司版权所有
Objectives: To determine if heart rate (HR) reduction with ivabradine (IVA), a selective inhibitor of the pacemaker I-f current, prevents cardiac dysfunction associated with dyslipidemia. Methods: New Zealand White rabbits received either a standard diet, a 0.5% cholesterol-enriched diet only (CD), or a 0.5% CD with IVA (17 mg/kg/day) for 12 weeks. HR, left ventricular (LV) systolic function, diastolic function and LV regional myocardial performance index (MPI) were studied using echocardiography. Histological analysis included cardiac interstitial fibrosis and collagen type I fibers. Plasma levels of angiotensin II and aldosterone were quantified by immunoassays. Results: IVA reduced HR by approximately 11%. IVA improved MPI and attenuated LV diastolic dysfunction (DD) (92% mild and 8% moderate DD with IVA vs. 54% mild and 46% moderate DD in CD group). IVA also reduced atrial fibrosis (p = 0.027), ventricular fibrosis (p = 0.0002) and ventricular collagen type I (p = 0.0042). IVA decreased plasma angio tensin II levels (p = 0.042), and both angiotensin II and aldosterone levels were correlated with HR (p = 0.038 and 0.008). Conclusion: Selective HR reduction with IVA reduces DD and cardiac fibrosis in hypercholesterolemic rabbits. These beneficial effects of IVA support testing pure HR reduction in patients with diastolic heart failure. Copyright (C) 2011 S. Karger AG, Basel