Effects of the early administration of losartan on the functional and morphological aspects of postmyocardial infarction ventricular remodeling in rabbits

Abstract

Background The effects of losartan (Los) on ventricular remodeling (VR) remain controversial. The objective was to determine whether early administration of Los to rabbits with myocardial infarction (MI) modifies VR. Methods New Zealand rabbits underwent left coronary artery ligation. Four groups were analyzed: Sham (G 1; n=13), MI (G 2; n=13), Sham+Los (G 3; n=13), and MI+Los (G 4; n=13). Los (12.5 mg/kg/day) was administered from 3 h post-MI and during 35 days. At the end of the protocol, the hearts were isolated and perfused to determine pressure–volume curves (P/V). Hearts were weighed, cut, and stained with picrosirius red. The heart weight (HW)/body weight (BW) ratio was determined. Infarct size (IS;%), septum (SeT, mm) and scar thickness (ST, mm), myocyte area (μm 2), and width (μm) were measured. Results ( X±S.E.M.) Los shifted the diastolic left ventricular (LV) P/V relationship to the right in sham and MI ( P<.05 vs. sham), with no changes in the systolic relation. IS was G 2=25.38±5.31 and G 4=21.85±4.13 (NS); HW/BW was 0.34±0.01, 0.35±0.02, 0.29±0.02 ( P<.05 vs. G 1 and G 2), and 0.32±0.02 in G 1, G 2, G 3, and G 4, respectively. Scar collagen concentration (%) was lower in G 4 ( P<.05 vs. G 2). SeT was lower in G 3 and G 4 ( P<.05 vs. G 2). The width and area of the septum myocytes increased in the untreated infarct, and Los suppressed that increase. Conclusion The early administration of Los unfavorably modified post-MI VR, increasing ventricular dilation, reducing scar collagen concentration and thickness, and inhibiting myocytes width and area increase. The dilation observed in sham animals' hearts suggests that infarct was not the main factor in the dilation of the cavity.