Free radical scavenger specifically prevents ischemic focal ventricular tachycardia.
Free radical scavenger specifically prevents ischemic focal ventricular tachycardia.
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DOI：
10.1016/j.hrthm.2008.12.032
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发表时间：
2009-04
期刊：
影响因子：
5.5
通讯作者：
Martins, James B.
中科院分区：
文献类型：
--
作者：
Xing, Dezhi;Chaudhary, Ashok K.;Miller, Francis J., Jr.;Martins, James B.
急性心肌缺血时局灶性室性心动过速（VT）与触发活动（TA）密切相关，清除活性氧（ROS）可阻断TA。本研究分析了急性给予活性氧清除剂2，2，6，6-四甲基哌啶-N-氧自由基（克里思）对VT和TA的影响。本文研究了43只α-氯醛糖麻醉的冠状动脉闭塞犬。三维激动标测有助于定位局灶性或折返性室速的起源。给予克里思（30 mg/kg，iv）或溶剂。使用标准微电极技术和ROS测量研究了从VT起源部位切除的内皮细胞。折返和局灶性室性心动过速诱导均具有高度可重复性。克里思阻断了11只犬中6只的局灶性VT（p<0.05），但9只折返性VT犬中9只在克里思后继续诱发VT。克里思未改变有效不应期（168±3至171±3 ms）、平均血压（88±3至81±3 mmHg）和缺血范围（42±3% vs 40±4%）。在体外，克里思（10− 3 M，n=14）没有引起动作电位的变化。然而，TA与克里思的复合物从5.3±1.1可逆地衰减至0.4±0.4（n=15，p<0.05）。光泽精增强的荧光和二氢乙锭染色显示缺血性内皮细胞中ROS增加;克里思显著降低缺血部位的ROS。克里思是ROS的清除剂，在心肌缺血期间，在ROS增加的区域，可防止与局灶性室性心动过速相关的触发活动。抗氧化治疗在心肌缺血条件下阻断局灶性室性心动过速中可能起重要作用。
Focal ventricular tachycardia (VT) in acute myocardial ischemia is closely related to triggered activity (TA), which may be blocked by scavenging reactive oxygen species (ROS). This study analyzed effects of acutely administered ROS scavenger-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) on VT in vivo and TA in vitro. Forty-three alpha chloralose anesthetized dogs with coronary artery occlusion were studied. 3-D activation mapping helped to locate the origin of focal or reentrant VT. TEMPO (30mg/kg, iv) or vehicle was given. Endocardium excised from the site of origin of VT was studied using standard microelectrode techniques and measures of ROS. Reentry and focal VT induction were both highly reproducible. TEMPO blocked focal VT in 6 of 11 dogs (p<0.05), but 9 of 9 dogs with reentrant VT continued to have VT re-induced after TEMPO. TEMPO did not alter effective refractory period (168±3 to 171±3 ms), mean blood pressure (88±3 to 81±3 mmHg), and size of ischemia (42±3% vs 40±4%). In vitro, TEMPO (10−3M, n=14) produced no change in action potentials. Nevertheless, TA was reversibly attenuated from 5.3±1.1 to 0.4±0.4 complexes with TEMPO (n=15, p<0.05). Lucigenin-enhanced chemilumenescence and dihydroethidium staining showed increased ROS in ischemic endocardium; TEMPO dramatically reduced ROS in ischemic sites. TEMPO, a scavenger of ROS, prevented triggered activity associated with focal VT during myocardial ischemia in areas of increased ROS. Antioxidant therapy may play an important role in blockade of focal VT under the conditions of myocardial ischemia.
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DOI：
10.1152/ajpheart.00027.2004
发表时间：
2004-11-01
影响因子：
4.8
作者：
Xing, DZ;Martins, JB
通讯作者：
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DOI：
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发表时间：
2008-05-01
影响因子：
4.8
作者：
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DOI：
10.1124/jpet.106.101832
发表时间：
2006-07-01
影响因子：
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作者：
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Belardinelli, Luiz