[Comparison of doxycycline, losartan, and their combination in the prevention of post-infarction remodeling in rats].
OBJECTIVE
To compare the effects of doxycycline, losartan, and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats.


METHODS
Twenty-four hours after the induction of AMI, the 254 survival rats were randomly assigned to the following groups and received drug treatment: (1) AMI controls (n=64), (2) doxycycline (30 mg x kg(-1) x d(-1), n = 63), (3) losartan (10 mg x kg(-1) x d(-1), n = 62), and (4) combination doxycycline and losartan (30 and 10 mg x kg(-1) x d(-1) respectively, n = 65) treatment groups. Also, sham operated rats (n = 30) were selected randomly. Each group was further divided into three subgroups of 1, 2, and 4 weeks of treatment. After the completion of treatment, hemodynamic studies were performed. Then, the heart of rat was fixed and analyzed pathologically.


RESULTS
Exclusive of the dead rats and the hearts with the myocardial infarction size < 35% or > 50%, complete experimental data were obtained in 157 rats. Besides sham operated rats, there was no significant difference in myocardial infarction sizes among the 12 subgroups of AMI control and drug treatment groups (P> 0.05). Compared with sham operated rats, left ventricular end diastolic pressure (LVEDP) and left ventricular absolute weight and relative weight (LVAW and LVRW) were significantly increased in 1, 2, and 4 week subgroups of AMI controls (P < 0.05, P < 0.01, and P < 0.001, respectively), with LVEDP elevated more significantly in 4 week than in 1 and 2 week subgroups (P < 0.01); whereas the maximum rising and dropping rate of left ventricular pressure (+/-dp/dt) and its corrected value by left ventricular systolic pressure (+/-dp/dt/LVSP) were all significantly decreased only at 4 week subgroup of AMI controls (P < 0.001). Compared with AMI controls group, LVEDP was significantly decreased in all 1, 2, and 4 week subgroups of the three treatment groups (P < 0.05, P < 0.01, and P < 0.001, respectively); LVAW and LVRW were significantly decreased in 2 and 4 week subgroups of losartan and combination groups (P < 0.05, P < 0.01, P < 0.001, respectively), and in only 4 week subgroup in doxycycline (P < 0.05, P < 0.01, and P < 0.001, respectively); whereas the maximum dropping rate of left ventricular pressure and the corrected value of left ventricular pressure rising and dropping rate were significantly increased only in 4 week subgroups of all three treatment groups (P < 0.05, P < 0.01, respectively). There is no significant difference in all indices above among the three treatment groups at all three time points (P > 0.05).


CONCLUSIONS
It is indicated that doxycycline can prevent left ventricular remodeling and improve its systolic and diastolic function after AMI in rats, with the equivalent effect to that of losartan. There seems no additive effect when the two drugs are used in combination.
Yang
Yue-Jin
YJ
Department of Coronary Heart Disease, Fuwai Hospital, CAMS and PUMC, Beijing 100037, China. YYJ@fuwaihospital.org
Zhang
Pei
P
Ruan
Ying-Mao
YM
Chen
Xi
X
Zhou
Yan-Wen
YW
Tian
Yi
Y
Gao
Run-Lin
RL
Chen
Zai-Jia
ZJ
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D019808:Losartan / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan; D004318:Doxycycline