摘要
目的 研究心房颤动 (房颤 )患者心房肌电生理重塑机制并探讨缬沙坦在房颤患者治疗中的作用及可能机制。方法 经典两步酶解法分离单个心房肌细胞 ,膜片钳全细胞法记录离子电流 ,并分别观察缬沙坦 (10 μmol/L)对房颤组和窦性心律 (窦律 )组心房肌细胞各离子电流的影响。结果 (1)与窦律组比较 :房颤组心房肌细胞L型钙电流 (ICa L)密度降低 (P <0 0 0 1) ,瞬间外向钾电流 (Ito1)密度降低 (P <0 0 0 1) ,内向整流性钾电流 (IK1)在超极化状态密度增加 (P <0 0 5 )。两组超速激活延迟整流性钾电流 (IKur)和快速内向钠电流 (INa)差异无显著性。 (2 )缬沙坦灌流前后两组心房肌细胞各离子电流自身前后对比 :以 10 μmol/L缬沙坦灌流后 ,房颤组心房肌细胞INa密度峰值减少 6 5 6 8%(P <0 0 0 1) ,膜电位 +5 0mV时IKur密度减少 30 70 % (P <0 0 5 ) ,膜电位 - 12 0mV时IK1密度减少2 3 32 % (P <0 0 5 ) ;窦律组心房肌细胞仅INa密度峰值减少 5 9 4 9% (P <0 0 0 1) ,IKur和IK1无显著改变。缬沙坦对房颤和窦律组心房肌细胞Ito1及ICa L无显著影响。结论 心房肌细胞ICa L、Ito1密度降低而超极化状态时IK1密度增加 ,是房颤患者心房肌电生理重塑的重要离子基础 ;缬沙坦对房颤患者心房肌细胞离子电流表现出异?
Objective To study the mechanism of electrophysiological remodeling in patients with chronic atrial fibrillation (AF) and to investigate the possible mechanism of valsartan for the therapy in AF patients. Method Single myocytes were isolated by enzymatic dissociation with the chunk method and the ionic currents were recorded using patch clamp technique. Results (1) Compared to the stable sinus rhythm (SR) group: the I Ca L density was reduced by 74 48% ( P <0 001) and the I to1 density was reduced by 60 23% ( P <0 001) in AF group; the I K1 density was increased by 34 04% in AF at commened potential -120 mV ( P <0 01); the current densities of I Kur and I Na were unaffected by AF (2) The effects of valsartan (10 μmol/L ) on the ionic currents in human atrial myocytes showed that in AF group, I Na density was significantly decreased by 65 68% ( P <0 001), I Kur density was decreased by 30 70% at commened potential +50 mV ( P <0 05), and I K1 density was decreased by 23 32% at commened potential -120 mV ( P <0 05). With 10 μmol/L valsartan, only I Na density was significantly decreased by 59 49% in SR group ( P <0 001). Current densities and voltage dependences of I Ca L and I to1 in both SR and AF group were not significantly changed with administration of valsartan Conclusions Decreased I Ca L and I to1 and increased I K1 at hyperpolarizing potentials in AF patients′ atrial myocytes may result from the electrophysiological remodeling by AF. The different effect of valsartan on the currents in AF and SR patients′ myocytes suggests that valsartan may be beneficial to the recovering of remolded atria.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2004年第3期197-201,共5页
Chinese Journal of Cardiology
基金
广东省自然科学基金项目资助 ( 9812 )
