心肺复苏中使用肾上腺素和艾司洛尔对动作电位恢复性质的影响

Effects on electrical restitution of given esmoiol during cardiopulmonary resuscitation in a swine ventricular fibrmation model

摘 要：目的 探讨在心室颤动心肺复苏模型中联合应用肾上腺素和艾司洛尔对心肌动作电位恢复性质的影响,了解β1-肾上腺素能受体拈抗剂艾司洛尔防治室颤的潜在机制.方法 稳定动态刺激健康雄性大Yorkshire猪发生心室颤动,心外膜接触标记,同步记录左心室5个标测部位单极电图,构建心肌组织激动-恢复间期（activation-recovery intervals,ARIs）恢复曲线,应用Western blot免疫印迹技术半定量测定并比较肾上腺素组和艾司洛尔组心肌磷酸化RyR2通道蛋白表达水平的差异.两组间均数比较采用成组t检验,计数资料用χ~2检验.局部ARI恢复曲线的坡度值比较采用Student t-test检验.结果 在心肺复苏过程中使用肾上腺素导致心室肌RyR2通道高度磷酸化,显著增加局部ARI恢复曲线斜率和心室ARI恢复曲线的空间异质性.在复苏早期联合使用艾司洛尔可显著下调心肌RyR2通道在Ser^（2815）和Ser^（2809）两个位点上的磷酸化蛋白表达,并部分拮抗肾上腺素对ARI恢复曲线的影响,提高室颤阈值,减少除颤次数,显著下降自主循环恢复后室颤再发生率.结论 在复苏早期使用艾司洛尔拮抗心室肌RyR2通道过度磷酸化,降低ARI恢复曲线斜率,缩小ARI恢复曲线空间异质性,是β1-肾上腺素受体阻滞剂减少室颤发作的重要机制之一.

Objective To investigate the effect on electrical restitution of β1-adrenergic receptor antagonist esmolol administered during cardiopulmonary resuscitation in the porcine ventricular fibrillation model. Method Ventricular fibrillation untreated for four minutes was induced by dynamic steady state pacing protocol in 40 healthy male pigs, in which local unipolar electrograms were recorded using one 10-electrode catheter that was sutured to the left ventrieular epicarditan. During CPR, animals were randomized into two groups to receive saline as placebo or esmolol after two standards doses of epinephrine. At postresuscitation 2-hour, six pigs were randomly selected from each group and the second VF induction was performed. Local activation-recovery intervals （ARI） restitutions and the VF inducibility between control group and esmolol group were compared. Western blotting was performed to determine cardiac ryanodine receptor （RyR2） protein expression, and their phosphorylation status. Results No sig-nificant differences were observed at the restoration of spontaneous circulation between two groups. Higher postre-suseitation 2-hour survival rate was observed in the esmolol group. Esmolol significantly flattened ARI restitution slope, lessened regional difference of ARI restitution, decreased the VF inducibility, and alleviated RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR significantly improved postresuscitation 2-hour survival rate. Its effects on modulating electrical restitution property and intracellular calcium handling make up the most important reasons why β1-blockade significantly reduced the onset and maintenance of VF.