Comparison of three doses of enalapril in preventing left ventricular remodeling after acute myocardial infarction in the rat.
OBJECTIVE
To compare the effects of high, middle and low doses of enalapril in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats, especially evaluating the efficacy of low dose enalapril.


METHODS
AMI was induced by ligating the left coronary artery in 149 female SD rats. 48 hours after the procedure, the 97 surviving rats were randomized to one of the following four groups: (1) AMI controls (n = 24), (2) high-dose (10 mg x kg(-1) x d(-1), n = 25), (3) middle-dose (1 mg x kg(-1) x d(-1), n = 23), and (4) low-dose (0.1 mg x kg(-1) x d(-1), n = 25) enalapril groups. In addition, sham-operated (n = 13) and normal rats (n = 10) were randomly selected to serve as non-infarction controls. Enalapril was delivered by direct gastric gavage. After 4 weeks of therapy, hemodynamic studies were performed, then the rat hearts were fixed with 10% formalin and pathology analysis was performed. Exclusive of the dead rats and those with MI size < 35% or > 55%, complete experimental data were obtained from 67 rats, which were comprised of (1) AMI controls (n = 13), (2) high-dose enalapril (n = 13), (3) middle-dose enalapril (n = 12), (4) low-dose enalapril (n = 12), (5) sham-operated (n = 8) and (6) normal (n = 9) groups.


RESULTS
There were no significant differences among the four AMI groups in infarction size (all P > 0.05). Compared with the sham-operated group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), absolute and relative weight (LVAW, LVRW) in AMI group were all significantly increased (all P < 0.001), while maximum LV pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were all significantly reduced in the AMI control group (P < 0.01 - 0.001), indicating LVRM occurred and LV systolic and diastolic functions were impaired. Compared with the AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased in the three enalapril groups (control P < 0.001), with the reduction of LVEDP, LVV and LVAW being more significant in high-dose than in low-dose enalapril groups (all P < 0.05), and the +/- dp/dt/LVSP were significantly increased only in the high and middle-dose enalapril groups (P < 0.01).


CONCLUSIONS
High, middle and low doses of enalapril were all effective in preventing LVRM after AMI in the rat, with low dose enalapril being effective and high dose superior. As for LV functional improvement, only high and middle-dose enalapril were effective.
Yang
Yuejin
Y
Division of Coronary Heart Disease, Cardiovascular Institute & Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100037, China. pzhmd@sina.com
Zhang
Pei
P
Song
Laifeng
L
Ruan
Yingmao
Y
Xu
Xinlin
X
Li
Yongli
Y
Zhou
Yanwen
Y
Tian
Yi
Y
Xu
Yishu
Y
Chen
Zaijia
Z
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril