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

近年来的临床研究表明，β受体阻滞剂长期治疗对充血性心力衰竭（CHF）患者的死亡率有明显的降低作用。几乎所有这些试验都表明，β受体阻滞剂主要改善收缩性心力衰竭（如扩张型心肌病）患者的左心室（LV）收缩功能。β-受体阻滞剂对收缩性心力衰竭的治疗作用已被广泛认可，但对舒张性心力衰竭（DHF）的治疗作用的研究却很少。Dahl盐敏感组从7周龄开始喂食高盐饲料，随机分为1）未治疗组（DHF组; n=20），2）β受体阻滞剂美托洛尔治疗组（DHF+7 wkMP组; n=22），3）17周龄起治疗组（DHF+17 wkMP组; n=8）。与低盐饮食组相比，DHF组大鼠血压升高，左室肥厚进行性加重， 关于我们 d纤维化，并在约20周龄时表现出心力衰竭。DHF组心力衰竭的发生与舒张期充盈异常的进展相关，LV缩短分数正常，这与临床观察到的DHF相似。DHF+7 wkMP组左室肥厚和纤维化程度明显低于DHF组（P < 0. 05）。DHF+17 wkMP组对左室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+7 wkMP组相近。DHF组、DHF+17 wkMP组和DHF+7 wkMP组21周龄存活率分别为25.0%、75.0%和86.4%，美托洛尔治疗不仅能防止DHF大鼠早期压力超负荷性肥大的发生，而且能防止代偿性肥大向DHF的转化，提高DHF大鼠的存活率。这些结果表明，β受体阻滞剂通过改善主要与LV纤维化相关的LV舒张功能障碍，对高血压患者的DHF产生有益作用。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