Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction.
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.[1]References
- Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction. Clozel, M., Qiu, C., Qiu, C.S., Hess, P., Clozel, J.P. J. Am. Coll. Cardiol. (2002) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg