Comparison Of The Effects Of Telmisartan, Spironolactone And Their Combination In The Prevention Of Left Ventricular Remodeling After Acute Myocardial Infarction

Comparison of the effects of telmisartan, spironolactone and their combination in the prevention of left ventricular remodeling after acute myocardial infarction Objectives: The aims of this experiment were (1) to compare the effects of selective angiotensin II type 1 receptor blocker (ARB) telmisartan , aldosterone blockade (AB) spironolactone and combination of them on the prevention of left ventricular (LV) remodeling after acute myocardial infarction (AMI) in the rats . and (2) to investigate the effect of them on the levels of angiotensin II (Ang II ),aldosterone (Ald) and tumor necrosis factor-alpha (TNF- @ ) in plasma and non-infarcted zone (NIZ) in myocardial infarction rats.Methods: Of 160 male SD rats, 148 had their left coronary ligated to induce AMI. Twenty-four hours after AMI, the 72 surviving rats were randomly assigned to one of the following groups (1) AMI controls (n=18),(2) telmisartan (10 mg kg-1d-1) (n=18),(3) spironolactone (20mg kg-1d-1) (n=18),(4) concomitant telmisartan (10mg kg-1d-1) and spironolactone ( 20 mg kg-1d-1 ) (n=18) groups. The other 12 rats were sham-operated to serve as noninfarction control group. Telmisartan and spironolactone were administered to rats after MI by direct gastric gavage once a day. At 6 weeks after MI, hemodynamics, cardiac function by Doppler echocardiography, the levels of Ang II ,Ald and TNF- a in plasma and non-infarcted myocardial zone by radioimmunoassay were assessed in each group of rat. The heart was excided 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<20% or >35% were excluded except those of sham-operated.The protein concentration of cardiac homogenate was determined according to the method of Bradford.Results: Complete experimental variables were obtained in 40 rats.The number of rat treated for 6 weeks in each experiment group are: (1) sham-operated controls(n=9),(2)AMI controls (n=8), (3) telmisartan (n=9), (4) spironolactone (n=7), (5) concomitant telmisartan and spironolactone (n=7).The mean MI size of each group was 25%-28%.There was no significant difference in MI size among all groups when compared.Compared with sham-operated rats, left ventricular end diastolic pressures (LVEDP) were all significantly elevated in AMI controls and spironolactone treatment group (9.8 2.8mmHg vs 5.2 2.0mmHg, P<0.001, and 8.6 1.8mmHg vs 5.2 2.0mmHg, P <0.01) . Compared with AMI controls, LVEDPs were all significantly reduced in telmisartan treatment group and two drugs combination treatment group (6.1 2.2 mmHg, 5.6 2.7 mmHg vs 9.8 2.8 mmHg respectively, all P<0.01) .Additionally.there was no significant difference in LVEDP between telmisartan and two drugs combination treatment group.Compared with sham-operated rats,LV absolute weight (LVAW) and relative weight (LVRW),right ventricular relative weight (RVRW), interventricular septal (IVS) thickness, LV cross-section in-perimeter (LVSPM) and collagen volume fraction (CVF) in the NIZ were all significantly increased in AMI controls (732 18mg vs676 36mg, P<0.01; 2.3 0.17mg/gvs 1.96 0.11 mg/g, P<0.001; 0.5 0.06mg/gvs0.42 0.04mg/g, P< 0.01; 1.8 0.21mmvs 1.56 0.16mm,P<0.01; 11.6 1.7mm vs9.2 1.2mm, P<0.05; 4.81 0.38% vs 1.84 0.26%, P<0.001 ) . Compared with AMI controls,all indicators as stated above in the spironolactone treatment group,did not change significantly (P>0.05), except that CVFs in the NIZ were significantly reduced (2.87 0.26% vs 4.81 0.38%, P<0.001).while all indicators as stated above in the telmisartan and two drugs combination treatment group were significantly reduced (LVAW:684 52mg 683 46 mgvs732 18 mg respectively, all P<0.05; LVRW: 1.97 0.1mg/g 1.96 0.18 mg/g vs 2.3 0.17mg/g respectively, P<0.001; RVRW: 0.43 0.05mg 0.41 0.1 mg/g vs 0.5 0.06 mg/g respectively, P<0.05 -0.01; IVS thickness: 1.6 0.17mm 1.58 0.14mmvs 1.8 0.21mm respectively, all P<0.05; LVSPM: 10.1 1.3mm 10.1 1.1 mm vs 1...