药理试验药物的疗效在心包目标交付模型在猪
Summary
We have developed a swine model for the target delivery of pharmacological agents within the pericardial space/fluid. Using this approach, the relative benefits of administered agents on induced atrial fibrillation, relative refractory periods and/or ischemic protection can be investigated.
Abstract
迄今为止，许多药剂用于治疗或预防心脏直视例心律失常创建不希望的全身性副作用。例如，静脉内给予抗心律失常药物可以产生全身性的压降在已经受损的心脏的病人。在执行开放式心脏手术，外科医生通常要么创建一个小口或形成心包支架创造适宜的操作领域。此为目标的药理递送（抗心律不齐或缺血预处理剂）直接连接到心肌组织而不不良副作用访问收益的机会。
我们已经制定了心包液中测试药物制剂为目标交付猪模型。而完全麻醉，每只动物用Swan-Ganz导管仪器以及左和右心室压力导管和起搏引线置于右心耳和右心室。然后进行内侧胸骨和心包访问摇篮创建的;暴跌起搏导线被放置在左心耳和双极起搏引线放置在左心室。利用程序员和心脏标测系统，房室结（AVN）的不应期，心房和心室测定。此外，制作心房颤动（AF）利用诱导房颤一个草刺激和时间进行了观察。这些测量被处理，以及30分钟和心包治疗后60分钟之前进行。对选定的研究中加入额外的时间点。随后心脏被cardiopleged并在四室的工作模式重新加进的。压力测量和功能进行了记录复苏后1小时。此治疗策略模型使我们能够观察药理学试剂的可能降低期间和AF心律失常和/或缺血性损伤，发生率的影响之三心脏直视手术。
Introduction
目前在开放式心脏手术，医生使用抗心律失常等治疗药物全身。然而，这可能是许多患者，特别是那些谁已经在临床上损害问题。例如，静脉内治疗可导致血压或肾功能不全的全身滴;进一步，它们可以创建麻醉管理问题和/或其它长期副作用。
在这里，我们创建了一个模型来测试药物给药制剂进入心包空间的功效。例如，这种方法可用于测试抗心律失常药物，研究可能增加心脏功能和/或外科手术后的心肌的促进恢复化合物。已经有目标交付的治疗进入心包腔与静脉给药观察的优点： 例如 ，我们的实验室证明antiar的本地化交付节奏的药物，如美托洛尔，是针对心律失常的发生保护，同时尽量减少在血压1降低。这一目标的投放策略也提供了更高的管理焦点浓度，同时尽量减少系统水平的机会。例如，高含量的脂肪酸静脉内递送的浓度可能会导致溶血，但是心包输送最小化这一问题2。
本研究范例包括三个主要的目标，以确定心包递送化合物的功效：1） 在原位测定心房心室节点的不应期，心房和心室，治疗前和30分钟和60分钟后处理的; 2）相对治疗 30和60分钟后处理（经常被添加额外的时间点），它已被重新加进3 INC后的心脏3）功能分析之前， 现场 AF负担泸定血流动力学监测，心脏率，从冠状静脉窦采样心脏代谢（乳酸和葡萄糖），射血分数（EF％）和室壁厚度（厘米）来监控每10分钟后复苏这一治疗策略模型使我们能够观察到的影响药剂可以减少期间和心脏手术或移植后心律失常和/或缺血性损伤的发生率。
Protocol
Representative Results
Discussion
这里，我们已经证明用于测试目标递送化合物的潜在功效进入心包空间中的独特的方法。本研究范例可以用于测试目前市场释放药物产品或实验化合物，从而提供了直接的平移应用到各种临床设置。在这一治疗策略有交付药品，心包内的两个主要的临床应用：1）开放式心脏或微创心脏外科手术; 2）心脏移植和器官保存。此外，本研究范例具有可以被分析，以便更好地了解自己这些描述的治疗策略…
Disclosures
The authors have nothing to disclose.
Acknowledgements
We would like to give a big thanks to the Visible Heart Laboratory staff and students that have helped with this project: Nate Menninga, Lars Mattison and Megan Schmidt.
Materials
| SelectSecure® 3830 lead | Medtronic | N/A | Pacing Lead |
| C304 Deflectable Catheter | Medtronic | N/A | Steerable catheter for placing leads |
| SelectSecure® 3830 lead | Medtronic | N/A | active fixation pacing leads |
| Grass S48 Stimulator | N/A | N/A | Electrical Stimulator |
| Premium 6500 Unipolar Pacing | N/A | Plunge pacing lead for LAA | |
| EnSite™ Cardiac Mapping | N/A | Electrophysiology mapping system | |
| CareLink Programer 2092 | Medtronic | N/A | programmer for pacing leads |
| GEM II ® pacemaker | Medtronic | N/A | pacemaker can |
| DLP ® Aortic Root Cannula | Medtronic | N/A | aortic root cannula for transplant |
| C-Arm Fluoroscopy | Ziehm | N/A | fluoroscopic imaging |
| Oscilliscope | Tektronix | N/A | |
| 11F Hemostasis introducer | SafeSheath | N/A | Hemostasis introducers |
| Swan-Ganz Catheter 8.0F | ICU Medical | N/A | thermal dilution catheter |
| Venogram balloon | Oscor | N/A | pressure monitoring |
| Ultraview SL | Spacelabs | N/A | EKG and blood pressure |
| s/5 Avance | General Electric | N/A | Anesthesia machine |
| Atrial 6492 – Unipolar Temporary Atrial Pacing Lead | Medtronic | N/A | temporary pacing lead |
| VIVID i | General Electric | 2D electrocardiography unit |
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