González Germán E, Palleiro Jimena, Monroy Silvina, Pérez Susana, Rodríguez Manuel, Masucci Alejandro, Gelpi Ricardo J, Morales Celina
Instituto de Fisiopatología Cardiovascular, Departamento de Patología, Facultad de Medicina, Universidad de Buenos Aires, Uriburu 950, Piso 2, Buenos Aires C1114AAD, Argentina; National Council of Scientific and Technical Research (CONICET), Argentina.
Cardiovasc Pathol. 2005 Mar-Apr;14(2):88-95. doi: 10.1016/j.carpath.2004.12.003.
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.
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 (microm(2)), and width (mum) 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.
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.
氯沙坦（Los）对心室重构（VR）的影响仍存在争议。目的是确定对心肌梗死（MI）家兔早期给予Los是否会改变VR。
新西兰家兔行左冠状动脉结扎术。分析四组：假手术组（G(1)；n = 13）、MI组（G(2)；n = 13）、假手术+Los组（G(3)；n = 13）和MI+Los组（G(4)；n = 13）。自MI后3小时起至35天期间给予Los（12.5 mg/kg/天）。在实验方案结束时，分离心脏并进行灌注以测定压力-容积曲线（P/V）。称量心脏重量，切开并进行天狼星红染色。测定心脏重量（HW）/体重（BW）比值。测量梗死面积（IS；%）、室间隔（SeT，mm）和瘢痕厚度（ST，mm）、心肌细胞面积（μm²）和宽度（μm）。结果（X±标准误）：Los使假手术组和MI组舒张期左心室（LV）的P/V关系右移（与假手术组相比，P <.05），收缩期关系无变化。IS在G(2)组为25.38±5.31，在G(4)组为21.85±4.13（无显著性差异）；HW/BW在G(1)组、G(2)组、G(3)组和G(4)组分别为0.34±0.01、0.35±0.02、0.29±0.02（与G(1)组和G(2)组相比，P <.05）和0.32±0.02。G(4)组瘢痕胶原浓度（%）较低（与G(2)组相比，P <.05）。G(3)组和G(4)组的SeT较低（与G(2)组相比，P <.05）。未治疗的梗死灶中室间隔心肌细胞的宽度和面积增加，而Los抑制了这种增加。
早期给予Los对MI后的VR产生不利影响，增加心室扩张，降低瘢痕胶原浓度和厚度，并抑制心肌细胞宽度和面积增加。在假手术动物心脏中观察到的扩张表明梗死不是腔扩张的主要因素。
