缬沙坦对心力衰竭心肌细胞收缩功能和钙瞬变的影响

Effect of valsartan on cardiacmyocytes contraction function and calcium transient in heart failure rats

目的:探讨缬沙坦对心力衰竭(HF)大鼠心肌细胞收缩功能和钙瞬变的作用。方法:结扎大鼠冠状动脉左前降支8周后,复制充血性HF模型,随机分为2组,即缬沙坦治疗组与HF对照组,分别用缬沙坦和安慰剂治疗,另设假手术组。治疗12周后,用急性酶解法获得单个大鼠心室肌细胞,用共聚焦显微镜测定单个细胞的收缩功能和钙瞬变。结果:①HF对照组左室舒张末压(LVEDP)明显大于假手术组(P<0.01),左室最大收缩压(LVSP)血压和左室内压的最大上升/下降速率(±dp/dtmax)明显小于假手术组(P<0.05、P<0.05和P<0.01);而缬沙坦治疗组LVSP和±dp/dtmax明显高于HF对照组(P<0.05和P<0.01),LVEDP明显小于HF对照组(P<0.01)。②HF对照组的心肌细胞表面积和最大舒张长度均大于假手术组(P<0.01),缩短分数明显低于假手术组(P<0.05),经缬沙坦治疗后均有明显改善(P<0.01)。③HF对照组心肌细胞的钙瞬变明显低于假手术组(P<0.01),舒张末期钙浓度明显升高(P<0.05),钙浓度下降时间明显减慢(P<0.01),经缬沙坦治疗后均明显改善(P<0.01)。结论:缬沙坦治疗能明显改善充血性HF的心肌细胞收缩功能,可能与改善HF心肌细胞钙调控异常有关。

Objective：To determine the effects of valsartan on calcium transient and contraction function in isolated ventricular myocytes of congestive heart failure （CHF） rats. Method： Eight weeks after coronary ligation, The rats with heart failure were confirmed by measuring the hemodynamic parameters and divided randomly into the group treated with valsartan （CHF-T, 20 mg/kg） and placebo （CHF-C）. Sham-operated group rats served as negative controls （PS）. Twelve weeks later, 6 rats were selected randomly for the study of ion channel. Single ventricular myocytes of rats were isolated by enzymatic dissociation. Single cardiac myocyte contractile function and calcium transient were measured simultaneously with confocal imaging technique. Result： ①In the hemodynamic variables, HR were not significantly different in three groups. Compared CHF-C with PS group, LVEDP increased（ P 〈0.01）, BP, LVSP and ± dp/dtmax decreased （ P 〈0.05, P 〈0.05 and P 〈0.01）. Compared CHF-T group with CHF group, LVEDP decreased（ P 〈0.01）, LVSP and ±dp/dtmax increased （ P 〈0.01） ; ② Compared CHF-C group with PS group myocyte areas, diastolic cell length increased significantly （ P 〈0.01） and fractional cell shortening decreased significantly （ P 〈0.05）. Compared CHF-C group with PS group ,the amplitude of [Ca^2＋ ]i transients decreased significantly （ P 〈0.05）, End-diastolic [Ca^2＋ ] i and Time to 50% decline in [Ca^2＋ ]i increased significantly（ P 〈0.01）. Treatment with valsartan showed that those parameters were significantly improved. Conclusion： Administration of valsartan was effective in preventing from cardiac function deterioration and improving cardiac myocytes contractile function, it may be relative to calcium regulation.