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超声引导下注射 A 型肉毒毒素阻断心脏交感神经节改善慢性心肌梗死后大型动物模型的心脏重构。

Ultrasound-guided injection of botulinum toxin type A blocks cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic myocardial infarction.

机构信息

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China.

出版信息

Heart Rhythm. 2022 Dec;19(12):2095-2104. doi: 10.1016/j.hrthm.2022.08.002. Epub 2022 Aug 7.

Abstract

BACKGROUND

Strategies to improve various cardiovascular diseases by blocking cardiac sympathetic ganglion have been increasingly available currently. Botulinum toxin type A (BTA), a typical neurotoxin, has been shown to block neural transmission in a safe and long-lasting manner.

OBJECTIVE

The aim of the present preclinical study was to assess the efficacy of BTA microinjection to alleviate cardiac remodeling after chronic myocardial infarction (MI) by blocking cardiac sympathetic ganglion in a canine model.

METHODS

Beagles were randomly divided into a control group (saline microinjection with sham surgery), an MI group (saline microinjection with MI), and an MI + BTA group (BTA microinjection with MI). Ultrasound-guided percutaneous BTA or saline injection into the left stellate ganglion (LSG) was performed followed by MI induction via left anterior descending artery occlusion (LADO) or sham surgery. After 30 days, electrocardiography, Doppler echocardiography, LSG function, neural activity, and ventricular electrophysiological detection were performed in all experimental dogs. At the end, LSG and ventricular tissues were collected for further detection.

RESULTS

BTA treatment significantly inhibited LSG function and neural activity and improved heart rate variability. Additionally, BTA application alleviated ventricular remodeling, ameliorated cardiac function, and prevented ventricular arrhythmias after 30-day chronic LADO-induced MI.

CONCLUSION

Ultrasound-guided percutaneous microinjection of BTA can block cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic LADO-induced MI. Ultrasound-guided BTA microinjection has potential for clinical application as a novel cardiac sympathetic ganglion blockade strategy for MI.

摘要

背景

目前,通过阻断心脏交感神经节来改善各种心血管疾病的策略越来越多。肉毒毒素 A 型(BTA)是一种典型的神经毒素,已被证明能安全且持久地阻断神经传递。

目的

本临床前研究旨在评估 BTA 微注射通过阻断犬慢性心肌梗死(MI)后的心脏交感神经节来减轻心脏重构的疗效。

方法

比格犬随机分为对照组(假手术时盐水微注射)、MI 组(MI 时盐水微注射)和 MI+BTA 组(MI 时 BTA 微注射)。在超声引导下经皮将 BTA 或生理盐水注射至左侧星状神经节(LSG),然后通过左前降支闭塞(LADO)或假手术诱导 MI。30 天后,对所有实验犬进行心电图、多普勒超声心动图、LSG 功能、神经活性和心室电生理检测。最后,收集 LSG 和心室组织进行进一步检测。

结果

BTA 治疗显著抑制了 LSG 功能和神经活性,改善了心率变异性。此外,BTA 应用可减轻心室重构,改善心脏功能,并预防慢性 LADO 诱导的 MI 后 30 天的心室心律失常。

结论

超声引导下经皮 BTA 微注射可阻断心脏交感神经节,改善慢性 LADO 诱导的 MI 大动物模型中的心脏重构。超声引导下 BTA 微注射作为一种新型心肌梗死后心脏交感神经节阻断策略具有临床应用潜力。

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