心脏再同步治疗在左束分支消融和快速起搏诱发的异步心力衰竭模型中的益处
1Department of Cardiology, Shanghai Institute of Cardiovascular Diseases,Zhongshan Hospital, Fudan University, 2Department of Echocardiography, Shanghai Institute of Medical imaging, Shanghai Institute of Cardiovascular Diseases,Zhongshan Hospital, Fudan University, 3Department of Cardiac surgery, Shanghai Institute of Cardiovascular Diseases,Zhongshan Hospital, Fudan University
Summary
采用快速起搏联合左束分支消融法建立慢性心力衰竭 (HF) 模型。应用二维散斑跟踪成像和主动脉速度时间积分验证了该模型的左心室异步性和心脏再同步治疗的益处。
Abstract
现在人们已经认识到, 心力衰竭 (HF) 患者左束支阻滞 (LBBB) 从心脏再同步治疗 (crt) 获得了大量的临床好处, LBBB 已成为 CRT 反应的重要预测因素之一。传统的 tachypacing 诱发 HF 模型有几个主要的局限性, 包括没有稳定的 LBBB 和快速逆转左心室 (LV) 功能障碍停止后起搏。因此, 有必要建立一个具有孤立 LBBB 的慢性 HF 的最佳模型来研究 CRT 的优点。在本研究中, 建立了由左束支 (LBB) 消融和4周快速右心室 (RV) 起搏引起的异步 HF 犬模型。RV 和右心房 (RA) 起搏电极通过颈静脉的方法, 连同心外膜 LV 起搏电极, 被植入的 CRT 性能。本文介绍了射频导管消融、起搏引导植入和快速起搏策略的详细协议。术中还提供心内和表面电图, 以更好地了解 LBB 消融。采用二维散斑跟踪成像和主动脉速度时间积分 (aVTI) 验证了具有 LV 异步和 CRT 优点的慢性稳定 HF 模型。通过协调心室活化和收缩, CRT 制服 lv 机械工作和恢复 lv 泵功能, 其次是逆转的 lv 扩张。此外, 病理学研究显示, 显着恢复的心肌细胞直径和胶原体积分数 (CVF) 后 crt 的表现, 表明组织学和细胞反向重塑诱发的 crt。在本报告中, 我们描述了一种可行的和有效的方法来发展一个慢性异步 HF 模型, 这是适合研究结构和生物逆向重塑后, CRT。
Introduction
晚期慢性 HF 是导致各种心血管疾病死亡的主要原因。充血性心力衰竭患者 (CHF) 的一个子集也发展心室传导 discoordination, 加重症状和预后。CRT, 也称为心室起搏, 已被介绍为这些病人的替代治疗20年以上1,2。不幸的是, 大约20-40% 的患者对 CRT 反应不佳。此后, 为了最大限度地提高 CRT 响应3, 已经进行了许多研究。现在人们已经认识到, LBBB 患者比非 LBBB4更能受益于 CRT, 因为 LBBB 模式会导致较大的心脏不同步, 因为间隔和侧壁之间的壁运动自由不对称。.同时, 最近的研究已经开始探索与 CRT5相关的基因表达和分子重塑的变化。伴随着 CRT 诱导的结构反向重构, 细胞和分子恢复到正常水平是非常感兴趣的6。因此, 有必要建立一个独立 LBBB 的 CHF 的最佳模型, 以研究 CRT 的优点。
慢性, 快速心室起搏曾经用来产生 CHF 的犬模型。RV 起搏无疑会产生延迟的 LV 收缩作为 LBBB 收缩模式的模型。然而, 这种类型的功能异步与完整的传导系统可能不会模拟解剖 LBBB, 并没有被认为是一个适当的模型, 研究 CRT 性能, 其本质是协调受损的电激活和心肌收缩。在停止起搏后, 快速恢复 lv 收缩力和部分恢复 lv 尺寸也报告了7。
实验研究通过射频消融诱导慢性 LBBB 建立异步心室收缩8。全球泵功能减少和区域无效机械工作的结合, 可能会导致心力衰竭, 产生心脏低效和心脏重塑在组织, 细胞和分子水平。在 LBBB 的心脏, 工作负荷是最低的隔膜和最高的 LV 侧壁。因此, 心脏重塑最明显的侧壁9。本研究的目的是: (i) 采用快速 RV 起搏与 LBB 消融相结合的方法, 在室和脑室机械异步的情况下, 推进一种稳定、慢性 HF 模型;(ii) 确认 dyssynchronous HF 在我们的模型和 CRT 的好处, 协调收缩的二维散斑跟踪超声心动图和 aVTI;(iii) 初步探讨 CRT 诱发的细胞反向重塑。
Protocol
十五只雄性猎犬 (12 至18月大, 体重约 10.0-12.0 公斤) 被购买并接受实验。所有程序均遵照美国国立卫生研究院出版的《护理和使用实验动物指南》 (85-23 号修订版 1996), 并经复旦大学中山医院动物护理委员会批准。大学.图 1显示了所有协议步骤的示意图工作流。 1. 手术前准备和基线数据收集 剃掉一个后肢的头发, 以便静脉穿刺。用静脉导管 (22 克, 0…
Representative Results
成功的 LBB 消融: 图 2表示导管消融过程中的典型表面和心内心电图。测量的平均 LBP 为18.8 ±2.8 ms, 比基线 h-v 间隔短10毫秒 (28.8 ±2.6 ms, p < 0.01)。在 LBB 消融后, QRS 持续时间从59.2 ±6.8 ms 延长到94.2 ±8.6 ms (p < 0.01)。心电图的丢失证实了成功的 LBB 消融。 ?…
Discussion
扩张型心肌病是充血性心力衰竭的主要病因, 其特点为心室扩张、收缩功能不全、LVEF 减少、舒张期异常 (11)。由于慢性心动过速介导 HF 是公认的临床条件, 快速起搏的心房或心室至少3至4周作为一种常用的动物模型诱发 CHF11。快速起搏后, 血流动力学的变化发生在24小时后, 心脏功能持续恶化长达3至5周。然而, 从起搏诱发的 HF 的恢复是这个模型的戏剧性和独特的…
Disclosures
The authors have nothing to disclose.
Acknowledgements
这项工作由中国国家自然科学基金 (81671685) 和上海卫生与计划生育委员会 (201440538 号) 资助。
Materials
| Closed iv catheter system (0.9mm×25mm) | Becton Dickinson Medical | 5264442 | Used as venous retention needle |
| Sodium pentobarbital | Sigma-Aldrich Company | 130205 | For anesthesia |
| Pet clipper | Wuhan Shernbao pet supplies Co., Ltd. | PGC-660 | For hair shaving |
| Electrocardiograph | Shanghai photoelectric medical electronic instrument Co., Ltd. | ECG-6511 | For electrocardiogram recording |
| Echocardiograph | GE-Vingmed Ultrasound Company | VIVID E9 | For echocardiographic assessment |
| EchoPAC software | GE healthcare | Version201 | Offline analysis |
| Laryngoscope | Shanghai Medical Instrument Co., Ltd | Orotracheal intubation | |
| Endotracheal tube | SIMS Portex Inc, UK | 274093 | Orotracheal intubation |
| Volume cycled respirator | Newport Corporation | C100 | Artificial ventilation |
| HeartStart XL Defibrillator/Monitor | Philips Medical Systems | M4735A | Electrocardiogram monitor during operation |
| Benzalkonium Bromide Tincture | Shanghai Yunjia Pharmaceutical Co., Ltd. | H31022694 | Used for skin disinfection |
| Rib retractor | Shanghai Medical Instrument Co., Ltd. | For thoracotomy | |
| 4-0 suture | Shanghai Pudong Jinhuan Medical Products Co., LTD. | 24L1005 | Suture of LV epicardial electrode |
| 2-0/T suture | Shanghai Pudong Jinhuan Medical Products Co., LTD. | 11M0505 | Suture of pacing leads, fascia, vessels, etc. |
| 0-suture | Shanghai Pudong Jinhuan Medical Products Co., LTD. | 11P0501 | Skin suture |
| penicillin powder | North China Pharmaceutical Co., Ltd. | F6034105 | |
| DSA X-ray machine | Philips | Allura Xper FD10 | X-ray for fluoroscopy |
| LV pacing electrode | Medtronic, Inc. | LBT 4965 | |
| RV pacing electrode | St. Jude Medical | Tendril 1888 | |
| RA pacing electrode | St. Jude Medical | IsoFlex 1642T | |
| Pacemaker pulse generator | Medtronic, Inc. | Enpulse E2DR01 | For rapid RV pacing |
| CRT pulse generator | St. Jude Medical | Anthem PM 3212 | For CRT performance |
| Multi-channel electrophysiologic recorder | GE Medical Systems | 2003232-004 | For surface and intracardiac electrogram |
| Catheter input module | GE Medical Systems | 301-00202-08 | Multiple pole switches for stimulation or recording |
| Radiofrequency generator | Johnson-Johnson Company | ST-4460 | For RF current delivery |
| Cordless return electrode | Covidien | E7509 | For current circuit formation |
| Cordis 6-Fr sheath | Johnson-Johnson Company | 504-606X | Access for mapping catheter |
| Cordis 7-Fr sheath | Johnson-Johnson Company | 504-607X | Access for mapping and ablation catheter |
| 6-Fr quadripolar catheter | Johnson-Johnson Company | F6QRA005RT | Mapping catheter |
| 7-Fr 4mm-tip steerable ablation catheter | St. Jude Medical | 402823 | Mapping and ablation catheter |
| Prucka Cardio-Lab®2000 | GE Medical Systems | 6.9.00.000 | Software package for electrogram recording |
| Heparin | Haitong Pharmaceutical Co., Ltd | 160505 | Anticoagulant during catheter ablation |
| Digital image analysis system | Leica Microsystems | Qwin V3 | For histologic analysis |
References
- Bristow, M. R., et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 350 (21), 2140-2150 (2014).
- Cleland, J. G., et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 352 (15), 1539-1549 (2005).
- Rickard, J., et al. Predictors of response to cardiac resynchronization therapy: A systematic review. Int J Cardiol. 225, 345-352 (2016).
- Ponikowski, P., et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 18 (8), 891-975 (2016).
- Yang, S., et al. Glycoproteins identified from heart failure and treatment models. Proteomics. 15 (2-3), 567-579 (2015).
- Barth, A. S., et al. Cardiac resynchronization therapy corrects dyssynchrony-induced regional gene expression changes on a genomic level. Circ Cardiovasc Genet. 2 (4), 371-378 (2009).
- Howard, R. J., Stopps, T. P., Moe, G. W., Gotlieb, A., Armstrong, P. W. Recovery from heart failure: structural and functional analysis in a canine model. Can J Physiol Pharmacol. 66 (12), 1505-1512 (1988).
- Vernooy, K., et al. Cardiac resynchronization therapy cures dyssynchronopathy in canine left bundle-branch block hearts. Eur Heart J. 28 (17), 2148-2155 (2007).
- Spragg, D. D., Kass, D. A. Pathobiology of left ventricular dyssynchrony and resynchronization. Prog Cardiovasc Dis. 49 (1), 26-41 (2006).
- Wang, J., et al. Effect of Cardiac Resynchronization Therapy on Myocardial Fibrosis and Relevant Cytokines in a Canine Model With Experimental Heart Failure. J Cardiovasc Electrophysiol. 28 (4), 438-445 (2017).
- Houser, S. R., et al. Animal models of heart failure: a scientific statement from the American Heart Association. Circ Res. 111 (1), 131-150 (2012).
- Shinbane, J. S., Wood, M. A., Jensen, D. N., Ellenbogen, K. A., Fitzpatrick, A. P., Scheinman, M. M. Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. J Am Coll Cardiol. 29 (4), 709-715 (1997).
- Helguera, M. E., Trohman, R. G., Tchou, P. J. Radiofrequency catheter ablation of the left bundle branch in a canine model. J Cardiovasc Electrophysiol. 7 (5), 415-423 (1996).
- Blanck, Z., Deshpande, S., Jazayeri, M. R., Akhtar, M. Catheter ablation of the left bundle branch for the treatment of sustained bundle branch reentrant ventricular tachycardia. J Cardiovasc Electrophysiol. 6 (1), 40-43 (1995).
- Auger, D., et al. Effect of induced LV dyssynchrony by right ventricular apical pacing on all-cause mortality and heart failure hospitalization rates at long-term follow-up. J Cardiovasc Electrophysiol. 25 (6), 631-637 (2014).
- Delgado-Montero, A., et al. Additive Prognostic Value of Echocardiographic Global Longitudinal and Global Circumferential Strain to Electrocardiographic Criteria in Patients With Heart Failure Undergoing Cardiac Resynchronization Therapy. Circ Cardiovasc Imaging. 9 (6), e004241 (2016).
- Delgado, V., et al. Assessment of left ventricular dyssynchrony by speckle tracking strain imaging comparison between longitudinal, circumferential, and radial strain radial strain in cardiac resynchronization therapy. J Am Coll Cardiol. 51 (20), 1944-1952 (2008).
- Risum, N., et al. Variability of global left ventricular deformation analysis using vendor dependent and independent two-dimensional speckle-tracking software in adults. J Am Soc Echocardiogr. 25 (11), 1195-1203 (2012).
- Barold, S. S., Ilercil, A., Herweg, B. Echocardiographic optimization of the atrioventricular and interventricular intervals during cardiac resynchronization. Europace. 10 (Suppl 3), iii88-iii95 (2008).
- Höke, U., et al. Relation of Myocardial Contrast-Enhanced T1 Mapping by Cardiac Magnetic Resonance to Left Ventricular Reverse Remodeling After Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy. Am J Cardiol. 119 (9), 1456-1462 (2017).
- Osmancik, P., Herman, D., Stros, P., Linkova, H., Vondrak, K., Paskova, E. Changes and prognostic impact of apoptotic and inflammatory cytokines in patients treated with cardiac resynchronization therapy. Cardiology. 124 (3), 190-198 (2013).
- Francia, P., et al. Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure. Int J Cardiol. 153 (3), 306-310 (2011).
Cite This Article
Wang, J., Nie, Z., Chen, H., Shu, X., Yang, Z., Yao, R., Su, Y., Ge, J. Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing. J. Vis. Exp. (130), e56439, doi:10.3791/56439 (2017).