咪达普利对陈旧性心肌梗死代偿区心肌T型钙电流的作用

应用咪达普利(Imi)对家兔陈旧性心肌梗死(OMI)模型进行干预,探讨其对OMI心室肌细胞T型钙电流(ICaT)的影响。选择健康家兔按体重随机分为OMI、假手术组与Imi组。OMI组:采用冠状动脉前降支结扎法制备OMI模型;假手术组:手术与OMI组同,只是不结扎冠状动脉,同样喂养8周;Imi处理组:对OMI家兔口服Imi0.625mg·kg-1·d-1连续8周进行干预。取心脏分离左室游离壁代偿区三层心肌细胞,全细胞膜片钳技术记录ICaT。结果显示,家兔OMI代偿区心肌细胞发生心肌肥厚,细胞膜ICaT密度较假手术组明显增加,当刺激电位为-30mV时,其电流密度从0.35±0.02pA/pF增至2.36±0.12pA/pF(P<0.01)。Imi组代偿区心肌细胞膜ICaT密度降至0.83±0.11pA/pF。ICaT的激活曲线左移,激活曲线斜率增加。Imi组二者改变均减小。但3组心肌细胞ICaT的失活曲线和失活后恢复曲线基本不变。结论:OMI家兔代偿区发生心肌肥厚,ICaT明显增加,Imi可以逆转家兔OMI代偿区心肌肥厚,降低ICaT的电流密度。

Effect of Imidapril on T-type Calcium Current of Noninfarcted Ventricular Myocytes in Old Myocardial Infarction

This article investigated the effect of imidapril on T-type calcium current of noninfarcted ventricular myocytes in rabbit models of old myocardial infarction (OMI). Rabbits with left coronary artery liation were prepared and allowed to recover for 8 weeks, and considered as the old myocardial infarction group (OMI group). For another group, three days after surgery, rabbits were received oral administration of imidapril (0.625 mg·kg -1·d -1) for 8 weeks, and considered as the imidapril-treated group (Imi group). Animals underwent an identical surgical procedure without coronary ligation served as the sham-operated group (sham group). Calcium current was recorded with whole-cell patch clamp. Results:I_ Ca-T densities increased more markedly in noninfarcted ventricular myocytes in OMI heart than those of sham heart (P<0.01). The average current density in OMI cells was 2.36±0.12 pA/pF,only 0.35±0.02 pA/pF in sham cells. After treatment of imidapril, I_ Ca-T densities deceased to 0.83±0.11 pA/pF. Half-maximal voltage (V_ 1/2) and slope factor (k) values in activation curves in OMI cells were shifted to hyperpolarizating direction and k was increased. V_ 1/2 and k values of inactivation were similar among the three groups. Time constants of recovery (τrev) in noninfarcted cells were slightly delayed, but there was no significant differences among the three groups. Conclusion: Imidapril can decrease I_ Ca-T densities of noninfarcted ventricular myocytes of OMI.