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Reseach for action and efficacy of β-blocker for myocardial disease in dog.

β受体阻滞剂治疗犬心肌病的作用和疗效研究。

基本信息

批准号：
13660315
负责人：
YAMANE Yoshihisa
金额：
$ 1.92万
依托单位：
Tokyo University of Agriculture and Technology, Faculty of Agriculture
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Chronic β-blocker therapy has been demonstrated the salutary effects on mortality in patients with congestive heart failure (CHF) in recent clinical trials. Almost all these trials showed that β-blockers improve predominantly left ventricular (LV) systolic perfomance in patients with systolic heart failure such as dilated cardiomyopathy. In contrast to these well-recognized salutaiy effects of β-blockers on LV systolic heart failure, imformation about the effect on diastolic heart failure (DHF) is limited.In the present study, Dahl salt-sensitive rats were used as a pressure-overload cardiac hypertrophy and failure model. Dahl salt-sensitive rate fed high-salt diet from 7 weeks of age were randomized 1) untreated (DHF group ; n=20), 2) treated with β-blocker metoprolol from 7 weeks of age (DHF+7wkMP group ; n=22), 3) from 17 weeks of age (DHF+ 17wkMP group ; n=8). Compared with the rats fed low-salt diet, DHF group showed an elevation in blood pressure and progressive LV hypertrophy an … More d fibrosis, and exhibited over heart failure at about 20 weeks of age. The development of heart failure in DHF group was associated with the progression of diastolic filling abnormalities with normal LV fractional shortening, which resembled clinically observed DHF. LV hypertrophy and fibrosis were strikingly attenuated in DHF+7wkMP group compared with DHF group without change of blood pressure. In DHF+17wkMP group, the prevention of LV hypertrophy were limited, but myocardial fibrosis and the diastolic filling abnormalities were attenuated nearly the same degree as in DHF+ 7wkMP group. Survivals at 21weeks of age were 25.0%, 75.0%, and 86.4% in DHF, DHF+17wkMP, and DHF+7wkMP groups, respectively.Teatment with metoprolol prevented not only the early development of pressure-overload hypertrophy, butalso the transition from compensatory hypertrophy to DHF and improved the survival in rat model of DHF, and. These results suggests that β-blocker leads to beneficial effects for DHF in hypertensive patients by improving LV diastolic dysfunction which is predominantly associated with LV fibrosis. Less

在最近的临床试验中，慢性β受体阻滞剂治疗已被证明对充血性心力衰竭（CHF）患者的死亡率有有益的影响。几乎所有这些试验都表明β受体阻滞剂主要改善收缩期心力衰竭（如扩张型心肌病）患者的左心室收缩功能。与这些公认的β受体阻滞剂对左室收缩期心力衰竭的有益作用相反，有关其对舒张期心力衰竭（DHF）影响的信息有限。本研究采用Dahl盐敏感大鼠作为压力过载心肌肥厚和心力衰竭模型。从7周龄开始饲喂高盐饲粮的Dahl盐敏感率随机分为：1)未处理（DHF组，n=20）； 2) 7周龄开始给予β受体阻滞剂美托洛尔（DHF+7wkMP组，n=22）； 3) 17周龄开始（DHF+ 17wkMP组，n=8）。与低盐组相比，DHF组大鼠在20周龄时血压升高，左室进行性肥大，肝纤维化加重，心力衰竭加重。DHF组心力衰竭的发生与左室舒张充盈异常进展相关，左室分数缩短正常，与临床观察DHF相似。与血压无变化的DHF组相比，DHF+7wkMP组左室肥大和纤维化明显减轻。DHF+17wkMP组对左室肥厚的预防作用有限，但心肌纤维化和舒张充盈异常的减轻程度与DHF+ 7wkMP组几乎相同。DHF组、DHF+17wkMP组和DHF+7wkMP组21周龄存活率分别为25.0%、75.0%和86.4%。美托洛尔治疗不仅可以阻止压力过载性肥厚的早期发展，还可以阻止代偿性肥厚向DHF的过渡，提高DHF模型大鼠的存活率。这些结果表明β受体阻滞剂通过改善左室舒张功能障碍（主要与左室纤维化相关）对高血压患者的DHF产生有益作用。少