title: Comparison of the effects of losartan, enalapril and their combination in the prevention of left ventricular remodeling after acute myocardial infarction in the rat.
abstract: OBJECTIVE
  To compare the effects of losartan, enalapril and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in the rat.
  
  
  METHODS
  AMI model was induced in female SD rats by ligating left coronary artery. Forty-eight hours after the procedure, 83 surviving rats were randomized into one of the following 4 groups : 1) AMI control group (n = 19), 2) losartan group (n = 22, 3 mg x kg(-1) x d(-1)), 3) enalapril group (n = 20, 1 mg x kg(-1) x d(-1)), 4) losartan-enalapril combinative group (n = 22, 3 and 1 mg x kg(-1) x d(-1) respectively). 5) Sham-operated group (n = 10) and 6) normal rats group (n = 10) were selected randomly to serve as non-infarction controls. Losartan and enalapril were delivered by direct gastric gavage. After 4 weeks of medical therapy, hemodynamic studies were performed in each group, then the rat hearts were fixed with 10% formalin and pathologic analysis on them was performed. Complete experimental data was obtained in 56 rats, comprising 1) AMI controls (n = 11), 2) losartan group (n = 10), 3) enalapril group (n = 10), 4) the combination of losartan and enalapril group (n = 11), 5) sham-operated group (n = 6) and 6) normal controls (n = 8).
  
  
  RESULTS
  There were no significant differences among the 4 AMI groups in MI size (41.7% to approximately 43.4%, all P > 0.05). Compared with sham group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), long and short axis length (L and D), as well as LV absolute and relative weight (LVAW and LVRW) in AMI group were all significantly increased (P < 0.05 to approximately 0.001); whereas the maximum left ventricular pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were significantly reduced (all P < 0.001), indicating LVRM occurred and LV systolic and diastolic function impaired after AMI. Compared with AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased (P < 0.05 to approximately 0.001); while +/- dp/dt/LVSP were significantly enhanced in all 3 treatment groups (P < 0.05 to approximately 0.001) except -dp/dt/LVSP in losartan group (P > 0.05). There were no significant differences in the above indices among the 3 treatment groups (all P > 0.05).
  
  
  CONCLUSIONS
  Both losartan and enalapril can prevent from LVRM after AMI in the rat and improve LV function with equivalent effects. There seems no additive effect when the 2 drugs are used in combination.
authors.affiliation: Division of Coronary Heart Disease, Cardiovascular Institute and Fu Wai Hospital, CAMS & PUMC, Beijing 100037.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuejin
authors.forename: Zhang
authors.initials: Z
authors.lastname: Pei
authors.forename: Ruan
authors.initials: R
authors.lastname: Yingmao
authors.forename: Song
authors.initials: S
authors.lastname: Laifeng
authors.forename: Xu
authors.initials: X
authors.lastname: Xinglin
authors.forename: Li
authors.initials: L
authors.lastname: Yongli
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yanwen
authors.forename: Tian
authors.initials: T
authors.lastname: Yi
authors.forename: Xu
authors.initials: X
authors.lastname: Yishu
authors.forename: Chen
authors.initials: C
authors.lastname: Zaijia
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D019808:Losartan / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D004656:Enalapril; D019808:Losartan