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

在最近的临床试验中，慢性β阻滞剂治疗已经证明了对充血性心力衰竭患者死亡率的有益影响。几乎所有这些试验都表明，β阻滞剂主要改善了扩张型心肌病等收缩期心衰患者的左心室(LV)收缩功能。与这些公认的β阻滞剂对左心室收缩期心衰的改善作用相比，关于其对舒张性心力衰竭的影响的信息有限。在本研究中，Dahl盐敏感大鼠被用作压力超负荷心肌肥大和衰竭模型。将7周龄开始饲喂高盐饮食的Dahl盐敏感率动物随机分为3组：1)未处理组(DHF组，n=20)；2)7周龄开始应用β阻滞剂美托洛尔(DHF+7wkMP组；n=22)；与低盐饮食组大鼠相比，DHF组大鼠血压升高，进行性左室肥厚和…增加更多的肝纤维化，并在大约20周龄时表现出心力衰竭。DHF组心力衰竭的发展与舒张期充盈异常的进展有关，其左心室短轴缩短率与临床观察到的DHF相似。与DHF组相比，DHF+7wkMP组大鼠左室肥厚和纤维化程度明显减轻，而血压无明显变化。DHF+17wkMP组对心肌肥厚的预防作用有限，但对心肌纤维化和舒张期充盈异常的减轻程度与DHF+7wkMP组相当。DHF组、DHF+17wkMP组、DHF+7wkMP组21周龄存活率分别为25.0%、75.0%、86.4%。美托洛尔治疗不仅可阻止DHF大鼠早期发生压力超负荷性肥厚，而且可阻止代偿性肥厚向DHF的转变，提高DHF模型大鼠的存活率。这些结果表明，β阻滞剂通过改善与左室纤维化有关的左室舒张功能障碍，对高血压患者的扩张性心衰有良好的治疗作用。较少

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