心动过速诱发的心肌病作为猪慢性心力衰竭模型的研究
Summary
本文提出了一种在猪中产生心动过速诱发心肌病的方案。该模型是研究进展性慢性心力衰竭的血流动力学和应用治疗效果的有效方法。
Abstract
许多实验都需要一种稳定可靠的慢性心力衰竭模型来了解血流动力学或检测新治疗方法的效果。在此, 我们提出了这样一个模型的心动过速诱发心肌病, 可以产生的快速心脏起搏在猪。
一个单一的起搏铅被引入 transvenously 完全麻醉健康的猪, 到右心室的顶端, 并固定。它的另一端然后隧道背到旁地区。在那里, 它连接到一个内部的改良心脏起搏器单元, 然后植入皮下袋。
经过 4-8 周的快速心室起搏率为 200-240 节拍/分钟, 体格检查显示严重心力衰竭的迹象-呼吸急促, 自发性窦性心动过速, 和疲劳。超声心动图和 X 线显示所有心脏室、积液和严重收缩功能障碍的扩张。这些发现与失代偿性扩张型心肌病有很好的对应, 在停止起搏后也保留下来。
这种模型的心动过速诱发心肌病可用于研究进展性慢性心力衰竭的病理生理学, 尤其是血液动力学的变化所造成的新的治疗方式, 如机械循环支持。这种方法很容易执行, 结果是健壮和重现性的。
Introduction
新的心力衰竭治疗方法 (HF) 的多样性, 特别是在全球范围内使用的机械循环支持和体外膜氧合 (ECMO) 在临床实践中, 反映在前体实验试验。主要关注的是血液动力学的变化所造成的检查治疗方式, 即系统性血压1, 心肌收缩力, 压力和体积变化的心脏室和心脏工作2,3,动脉血流在全身和外周动脉, 以及代谢补偿4 -区域组织饱和度, 肺灌注和血气分析。其他研究是针对循环支持的长期影响5, 伴随炎症, 或发生溶血。所有这些类型的研究需要一个稳定的 biomodel 充血性 HF。
对于急性 HF2、6、7、8的实验模型, 大多数已发表的左心室 (LV) 表现和机械循环支持的血流动力学实验进行了研究。,9,10, 甚至在完全完整的心脏上。另一方面, 在临床实践中, 机械循环支持经常被应用于一种在以前存在慢性心脏病的基础上发展的循环失代偿状态。在这种情况下, 适应机制得到充分发展, 并可发挥重要作用, 不一致的结果观察, 根据 “尖锐或慢性” 的潜在心脏病11。因此, 一个稳定的慢性 HF 模型可以为病理生理机制和血流动力学提供新的见解。虽然有理由使用慢性 HF 模型是稀缺的-时间消耗准备, 心律不稳, 伦理问题和死亡率-他们的优势是明确的, 因为他们提供长期神经体液激活的存在,全身适应, 心肌细胞功能改变, 心肌和瓣膜结构改变12,13。
一般而言, 用于血流动力学研究的动物模型的可用性和多样性是广泛的, 为许多特定需求提供了选择。对于这些实验, 主要是猪, 犬, 绵羊, 或小鼠模型, 正在选择和提供一个良好的模拟预期的人体反应14。此外, 单器官实验的形式越来越频繁15。为了可靠地模仿 HF 的病理生理学, 循环正在被人为地恶化。对心脏的损伤可能是由各种方法造成的, 往往是由缺血、心律失常、压力超负荷或 cardiotoxic 作用引起的, 这些都导致了模型的血流动力学恶化。为了产生一个真正的慢性 HF 模型, 必须为发展整个生物体的长期适应提供时间。心动过速诱发的心肌病 (TIC) 是一种可靠稳定的模型, 可以通过实验动物快速心脏起搏产生。
结果表明, 在易感性的心脏, 长期持续不断的失常可能导致收缩功能障碍和扩张与减少的心脏输出。被称为 TIC 的条件首先在 1913年16中被描述, 在 1962年17的实验中被广泛使用, 现在已经是公认的紊乱。它的起源可能存在于各种类型的心律失常-室性和心室心动过速可导致收缩功能的渐进性恶化, 心室扩张, 以及包括腹水, 肿鼓, 嗜睡等症状的渐进性临床征象, 最终心脏失代偿导致晚期 HF, 如果不治疗, 死亡。
通过在动物模型中引入高速率心脏起搏, 观察了循环抑制的相似效应。在猪模型中, 心房或心室心率超过200次/分钟, 足以诱发末期 HF 在 3-5 周 (渐进期) 与 TIC 的特点, 虽然个体差异确实存在18, 19. 这些发现与失代偿性心肌病有很好的对应, 重要的是, 在停止起搏 (慢性相位)19,20,21,22,23。
猪、犬或绵羊 TIC 模型反复准备研究 HF14的病理生理学, 因为对 LV 的改变模仿扩张型心肌病24的特点。血流动力学特征有很好的描述-心室终末期舒张压增高, 心输出量降低, 系统性血管阻力增加, 心室扩张。相比之下, 墙体肥大没有被一致观察, 甚至壁薄也被一些研究人员描述为25,26。随着心室尺寸的发展, 房室瓣膜的返流发展为26。
在这份出版物中, 我们提出了一个协议, 以产生 TIC 长期快速心脏起搏在猪。本 biomodel 是研究失代偿性扩张型心肌病、慢性心力衰竭患者血流动力学及应用治疗效果的有力手段。
Protocol
这项实验性议定书是由查尔斯大学第一医学院的机构动物专家委员会审查和批准的, 并在大学生理学系的实验实验室进行, 第一院医学, 查尔斯大学在布拉格捷克共和国根据246/1992 号法令, 关于保护动物免受虐待。根据2011《国家科学院出版社出版的第八版实验动物护理指南》, 对所有动物进行了治疗和照顾。所有的程序都是按照标准的兽医惯例进行的, 在每项研究完成后, 动物被牺牲, 尸检执行。由?…
Representative Results
测试模型:在失代偿性慢性 HF 症状出现后, 麻醉和人工通气再次按照上述原则进行, 但由于心脏输出量降低27, 剂量调整。由于麻醉药可能 cardiodepressive 的影响, 需要对重要功能进行仔细的密集监测。 动物被附着在仰卧位, 所有侵入的方法开始。采用标准经皮腔内鞘, 对股静脉、动脉和颈静脉进行穿?…
Discussion
慢性 HF 是严重的健康问题, 对发病率和死亡率有很大的贡献。HF 在人类中的发病机制和进展是复杂的, 因此适当的动物模型对于研究其潜在的机制和测试旨在干预本病严重疾病进展的新疗法是至关重要的。为了研究其发病机理, 大型动物模型被用于实验测试。
一般来说, 慢性 HF 的外科模型密切模仿这种疾病。与急性 hf 模型相比, 慢性 hf 模型可以更深入地了解病理生理学, 但代?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
这项工作得到了查尔斯大学研究资助 GA 英国538216号和 ga 英国1114213号的支持。
Materials
| Medication | |||
| midazolam | Roche | Dormicum | anesthetic |
| ketamine hydrochloride | Richter Gedeon | Calypsol | anesthetic |
| propofol | B.Braun | Propofol | anesthetic |
| cefazolin | Medochemie | Azepo | antibiotic |
| Silver Aluminium Aerosol | Henry Schein | 9003273 | tincture |
| povidone iodine | Egis Praha | Betadine | disinfection |
| morphine | Biotika Bohemia | Morphin 1% inj | analgetic |
| Tools | |||
| Metzenbaum scissors, lancet with #22 blade, DeBakey forceps, needle driver | basic surgical equipment | ||
| cauterizer | |||
| 2-0 Vicryl | Ethicon | V323H | absorbable braided suture |
| 2-0 Perma-Hand Silk | Ethicon | A185H | silk tie suture |
| 2-0 Prolene | Ethicon | 8433H | non-absorbable suture |
| Diagnostic devices | |||
| ESP C-arm | GE Healthcare | ESP | X-ray fluoro C-arm |
| Acuson x300 | Siemens Healthcare | ultrasound system | |
| Acuson P5-1 | Siemens Healthcare | echocardiographic probe | |
| Acuson VF10-5 | Siemens Healthcare | sonographic vascular probe | |
| 3PSB, 4PSB and 6PSB | Transonic Systems | perivascular flow probes | |
| TS420 | Transonic Systems | perivascular flow module | |
| TruWave | Edwards Lifesciences | T001660A | fluid-filled pressure transducer |
| 7.0F VSL Pigtail | Transonic Systems | pressure sensor catheter | |
| INVOS 5100C Cerebral/Somatic Oximeter | Somanetics/Medtronic | near infrared spectroscopy | |
| CCO Combo Catheter | Edwards Lifesciences | 744F75 | Swan-Ganz pulmonary artery catheter |
| Vigillace II | Edwards Lifesciences | VIG2E | cardiac output monitor |
| 7.0F VSL Pigtail | Transonic Systems | pressure-volume catheter | |
| ADV500 | Transonic Systems | pressure-volume system | |
| LabChart and PowerLab | ADInstruments | data acquisition and analysis system | |
| Prism 6 | GraphPad | statistical analysis software | |
| Pacing devices | |||
| ICS 3000 | Biotronic | 349528 | pacemaker programmer |
| ERA 3000 | Biotronic | 128828 | external pacemaker |
| Effecta DR | Biotronic | 371199 | dual-chamber pacemaker |
| Tendril STS | St. Jude Medical | 2088TC/58 | ventricular pacing lead |
| Lead permanent adapter | Osypka | Article 53422 | convergent "Y" connecting part |
| Lead permanent adapter | Osypka | Article 53904 | convergent "Y" connecting part |
| Tear-Away Introducer 7F | B.Braun | 5210593 | tear away introducer sheath |
| Split Cath Tunneler | medComp | AST-L | tunneling tool |
| infusion line | MPH Medical Devices | 2200045 | connecting line |
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Tags
Tachycardia-induced CardiomyopathyChronic Heart Failure ModelSwineDilated CardiomyopathyVentricular DilationVentricular RemodelingChronic Heart DiseaseMinimal Invasive MethodSurgical TechniquesReproduciblePathophysiologyTherapeuticsCardiac PacingBiventricular DilationHeart Failure ProgressionAnesthesiaJugular VeinCarotid ArteryPacemaker ImplantationSeldinger TechniqueGuide WirePeel Away Sheath
Cite This Article
Hála, P., Mlček, M., Ošťádal, P., Janák, D., Popková, M., Bouček, T., Lacko, S., Kudlička, J., Neužil, P., Kittnar, O. Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine. J. Vis. Exp. (132), e57030, doi:10.3791/57030 (2018).