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


CONCLUSIONS
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.
González
Germán E
GE
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.
Palleiro
Jimena
J
Monroy
Silvina
S
Pérez
Susana
S
Rodríguez
Manuel
M
Masucci
Alejandro
A
Gelpi
Ricardo J
RJ
Morales
Celina
C
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008026:Ligation; D019808:Losartan / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan