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

Research Project

Project/Area Number	13660315
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Applied veterinary science
Research Institution	Tokyo University of Agriculture and Technology, Faculty of Agriculture
Principal Investigator	YAMANE Yoshihisa Faculty of Agriculture, Professor, 農学部, 教授 (50262225)
Co-Investigator(Kenkyū-buntansha)	NOIISIHKI Yasuharu Yokohama City University School of Medicine, First Deparment of Surgery, Lecturer, 医学部, 講師 (60033263) MACHIDA Noboru Faculty of Agriculture, Associate Professor, 農学部, 助教授 (20219364) IWASAKI Toshiro Faculty of Agnculture, Professor, 農学部, 教授 (50262754) TAKASHIMA Kazuaki Animal Clinical Research Foundation, Research Section, Head a Chief, 主任研究員
Project Period (FY)	2001 – 2002
Project Status	Completed (Fiscal Year 2002)
Budget Amount *help	¥3,000,000 (Direct Cost: ¥3,000,000) Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000) Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords	dog / myocardial fibrosis / β-blocker / pressure-road / volume-road / systolic function / diastolic function / ラット / 心筋病変 / 拡張型心筋症 / 心不全
Research Abstract	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