| Comparison of the effects of doxycycline, losartan and their combination in the prevention of left ventricular remodeling after actue myocardial infarction Purpose: The aims of this experiment were (1) to assess the effectiveness of matrix metalloproteinase (MMP) inhibitor doxycycline in preventing left ventricular (LV) remodeling after acute myocardial infarction (AMI) in the rat. and (2) to evaluate the comparative effects of doxycycline, losartan and their combination in the prevention of cardiac remodelingMethods: Of 461 female SD rats, 431 had their left coronary ligated to induce AMI. Twenty-four hours after AMI, the 254 surviving rats were randomly assigned to one of the following groups (1) AMI controls (n=64), (2) doxycycline (30mg· kg-1 · d-1) (n=63) ,(3) losartan ( 10mg· kg-1·d-1 ) (n=62) , (4) concomitant doxycycline (30mg·kg(-1)·d-1) and losartan (10mg·kg-1·d-1) (n=65)groups. The other 30 rats was sham-operated to serve as noninfarction control group. Then each of the 5 groups of rats was further divided into three subgroups according to the difference of treatment periods of 1 week ,2 weeks and 4 weeks. Losartan and doxycycline were delivered by direct gastric gavage. Hemodynamic studies were performed in each group of rat after the completion of treatment periods. The heart was excized after the completion of hemodynamic studies. Perpendicular to the long axis of the heart and at its middle point ,a 2-3mm cross-section was cut and fixed in 10% formalin for pathological examination. The hearts with the MI size<35% or >50% were excluded except those of sham-operated.Results: Complete experimental variables were obtained in 157 rats. Among them, 53 were treated for one week and 52 for both two weeks and four weeks. The number of rat treated for 1 week in each experiment group are: (1) sham-operated controls (n=10), (2)AMI controls (n=10), (3) doxycycline (n=11), (4) losartan (n=11),and (5)concomitant doxycycline and losartan (n=11). The number of rats treated for two...
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