Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA.
Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1330-9. doi: 10.1152/ajpheart.00955.2009. Epub 2010 Feb 19.
The Cardiac Arrhythmia Suppression Trial demonstrated that antiarrhythmic drugs not only fail to prevent sudden cardiac death, but actually increase overall mortality. These findings have been confirmed in additional trials. The "proarrhythmic" effects of most currently available antiarrhythmic drugs makes it essential that we investigate novel strategies for the prevention of sudden cardiac death. Targeted ablation of cardiac sympathetic neurons may become a therapeutic option by reducing sympathetic activity. Thus cholera toxin B subunit (CTB) conjugated to saporin (a ribosomal inactivating protein that binds to and inactivates ribosomes; CTB-SAP) was injected into both stellate ganglia to test the hypothesis that targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced, sustained ventricular tachycardia in conscious rats. Rats were randomly divided into three groups: 1) control (no injection); 2) bilateral stellate ganglia injection of CTB; and 3) bilateral stellate ganglia injection of CTB-SAP. CTB-SAP rats had a reduced susceptibility to ischemia-induced, sustained ventricular tachycardia. Associated with the reduced susceptibility to ventricular arrhythmias were a reduced number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)), as well as a reduced left ventricular norepinephrine content and sympathetic innervation density. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing the susceptibility to ventricular arrhythmias.
心律失常抑制试验表明，抗心律失常药物不仅不能预防心脏性猝死，反而实际上增加了总死亡率。这些发现已在其他试验中得到证实。大多数目前可用的抗心律失常药物的“致心律失常”作用，使得我们必须研究预防心脏性猝死的新策略。心脏交感神经节靶向消融可能成为一种治疗选择，通过降低交感神经活性。因此，霍乱毒素 B 亚单位（CTB）与相思豆毒素（一种与核糖体结合并使其失活的核糖体失活蛋白；CTB-SAP）结合物被注入星状神经节，以检验靶向消融心脏交感神经元是否能降低清醒大鼠缺血诱导的持续性室性心动过速的易感性。大鼠被随机分为三组：1）对照组（无注射）；2）双侧星状神经节注射 CTB；3）双侧星状神经节注射 CTB-SAP。CTB-SAP 大鼠对缺血诱导的持续性室性心动过速的易感性降低。与室性心律失常易感性降低相关的是星状神经节和脊髓（T(1)-T(4)节段）中染色神经元数量减少，以及左心室去甲肾上腺素含量和交感神经支配密度降低。因此，从星状神经节逆行运输的 CTB-SAP 有效消融心脏交感神经元并降低室性心律失常的易感性。
