老龄大鼠缺血性室性心律失常时迷走神经刺激抗心律失常作用的丧失。
Loss of anti-arrhythmic effect of vagal nerve stimulation on ischemia-induced ventricular tachyarrhythmia in aged rats.
机构信息
Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, PR China.
出版信息
Tohoku J Exp Med. 2011 Jan;223(1):27-33. doi: 10.1620/tjem.223.27.
Reduced vagal activity is associated with increased risk for life-threatening arrhythmia during myocardial ischemia (MI); conversely, the increase in vagal tone may provide protective effect against ventricular arrhythmias. In fact, vagal nerve stimulation (VNS) exerted an anti-arrhythmic effect by preserving connexin 43 (Cx43), a gap junction protein in ventricles, in a rat model of MI. We investigated the effects of VNS on ventricular tachyarrhythmia during acute MI and the expression of Cx43 in aged rats. Both adult (3-4 months) and aged (≥ 24 months) male rats were subjected to ischemia of 30 min. VNS was applied before ischemia either alone or in combination with atropine (0.5 mg/kg) or carbenoxolone, a gap junction inhibitor (10 mg/kg). During the 30-min ischemia, the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) was higher in aged rats compared with adult rats. VNS significantly suppressed VT and VF in adult rats and these effects were eliminated by atropine or carbenoxolone. In contrast, VNS did not suppress VT and VF in the aged rats. Moreover, ischemia did not change the expression levels of total Cx43 protein in adult and aged rat ventricles. However, the expression level of total Cx43 protein was two times lower in sham-operated aged rats than that in sham-operated adult rats. Thus, in aged rats, loss of anti-arrhythmic effect of VNS is associated with reduced expression of Cx43 protein. These findings suggest that Cx43 may be an important target for inhibiting ischemia-induced VT in adult patients but not in aged patients.
迷走神经活动减少与心肌缺血（MI）期间危及生命的心律失常风险增加有关；相反，迷走神经张力的增加可能对室性心律失常提供保护作用。事实上，在 MI 大鼠模型中，迷走神经刺激（VNS）通过保留缝隙连接蛋白 43（Cx43）发挥抗心律失常作用，Cx43 是心室中的一种缝隙连接蛋白。我们研究了 VNS 在急性 MI 期间对室性心动过速的影响以及 Cx43 在老年大鼠中的表达。成年（3-4 个月）和老年（≥24 个月）雄性大鼠均接受 30 分钟的缺血。VNS 在缺血前单独或与阿托品（0.5mg/kg）或缝隙连接抑制剂 carbenoxolone（10mg/kg）联合应用。在 30 分钟的缺血期间，老年大鼠发生室性心动过速（VT）或心室颤动（VF）的发生率高于成年大鼠。VNS 显著抑制成年大鼠的 VT 和 VF，而阿托品或 carbenoxolone 消除了这些作用。相比之下，VNS 并没有抑制老年大鼠的 VT 和 VF。此外，缺血并未改变成年和老年大鼠心室中总 Cx43 蛋白的表达水平。然而，在假手术的老年大鼠中，总 Cx43 蛋白的表达水平比假手术的成年大鼠低两倍。因此，在老年大鼠中，VNS 抗心律失常作用的丧失与 Cx43 蛋白表达减少有关。这些发现表明，Cx43 可能是抑制成年患者缺血诱导性 VT 的重要靶点，但不是老年患者的靶点。
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