Significance of timing of angiotensin AT1 receptor blockade in rats with myocardial infarction-induced heart failure

Objective: Blockade of angiotensin AT(1) receptors has been shown to preven t cardiac remodeling and improve left ventricular function and survival aft er myocardial infarction (MI). However, the timing of initiation of treatme nt has not been fully elucidated Therefore, the purpose of the present stud y was to compare the effects of very early (30 min after MI), early (3 and 24 h after MI) and delayed (7 days after MI) treatments with the angiotensi n AT(1) receptor antagonist fonsartan (HR 720) on cardiac morphological and hemodynamic parameters in a rat model of MI-induced heart failure and to e stablish the therapeutic window for the start of treatment. Methods: Male W istar rats underwent coronary ligation and were randomized fonsartan (HR720 ) treatment starting 30 min, 3 h, 24 h and 7 days after MI or no treatment. Treatment was continued up to 6 weeks post MI. Results: Fonsartan (HR720) treatment attenuated cardiac hypertrophy when treatment started 30 min or l ater after MI, Limited infarct size when treatment initiated 3 and 24 h aft er MI, decreased left ventricular end-diastolic pressure when treatment sta rted 3 h to 7 days after MI, and improved dP/dt(max) when treatment commenc ed 24 h and 7 days after MI compared to untreated infarct group. Conclusion : Our results show that angiotensin AT(1) receptor blockade with fonsartan (HR720) produced the best cardioprotective effects when treatment was start ed 3 to 24 h after MI although a start of treatment 7 days following MI sti ll could improve functional parameters. These results suggest an optimal ti me window for the start of treatment with angiotensin AT(1) receptor antago nists seems to be between 3 and 24 h post MI. (C) 2001 Elsevier Science B.V . All rights reserved.