当前位置： SCI文献检索 > JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY期刊下所有文献 > Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction.

Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction.

Abstract：

OBJECTIVES:We investigated the effects of short-term tezosentan treatment on cardiac function, pulmonary edema and long-term evolution of heart failure (HF) in a rat model of myocardial infarction (MI). BACKGROUND:Endothelin (ET) may play a major role in the progression from MI to HF. Tezosentan is a new dual ET(A)/ET(B) receptor antagonist. METHODS:Rats were subjected to coronary artery ligation and were treated with either vehicle or tezosentan (10 mg/kg IV bolus) at 1 h and 24 h after MI. Cardiac hemodynamics and lung weight were measured at 48 h after MI. Survival was assessed over a five-month period. RESULTS:At 48 h after ligation, vehicle-treated rats developed HF, as evidenced by a marked increase in left ventricular end-diastolic pressure (LVEDP), reduction in dP/dt(max) and mean arterial pressure (MAP), and development of pulmonary edema. Tezosentan treatment attenuated the increase in LVEDP and in lung weight and slightly reduced MAP without affecting dP/dt(max). Infarct size was not modified by tezosentan. Despite the fact that treatment with tezosentan was stopped after 24 h, the initial tezosentan administration significantly reduced cardiac hypertrophy (22%) and decreased mortality by 51% at five months (50% survival vs. 19% survival in vehicle-treated rats, p < 0.001). CONCLUSIONS:Tezosentan administered during the first day after MI in rats, in addition to improving acutely hemodynamic conditions, markedly increases long-term survival. This increase is associated with a decrease of pulmonary edema and prevention of cardiac hypertrophy. Tezosentan could be a safe and useful therapeutic agent in the prevention and treatment of ischemic HF.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Clozel M,Qiu C,Qiu CS,Hess P,Clozel JP

doi

10.1016/s0735-1097(01)01692-8

subject

Has Abstract

pub_date

2002-01-02 00:00:00

pages

142-7

issue

1

eissn

0735-1097

issn

1558-3597

pii

S0735109701016928

journal_volume

39

pub_type

杂志文章

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