应用心脏爬行机器人的注射热敏感的反重塑剂治疗心肌梗塞外文资料翻译

1、应用心脏爬行机器人的注射热敏感的反重塑剂治疗心肌梗塞摘要：注塑机械膨化剂进入左心室（左室）心壁,进而作为一种治疗后心肌梗死 （mi） 舒解重塑心肌的药剂.后心肌（米）心脏的机器人履带的本身作为微创、 高度精确的心外膜注射的理想工具。最优膨松剂开发，我们集团使用的热固性水凝胶带来了若干工程的障碍，包括系统冷却小型化的注射时，机器人在温暖的环境生活病人的导航。我们在这篇文档演示的集成的微型冷却和喷射系统在现时 heartlander 爬行机器人，是完全生物相容性和有能力的热固性水凝胶注入密集的动物组织的多个，而整个系统沉浸在 37 水浴中。一 引言 注射的局部加劲进入左心室 （lv）心肌墙材料的提

2、出作为防止舒解 lv 改造由于心肌梗死 （mi） 开发的墙高应力的新型疗法。我们以前使用过基于共聚 n-异 (nipaam)、 丙烯酸 (aac) 和羟乙基将 （hemaptmc） 甲基丙烯酸甲酯-poly(trimethylene carbonate) mi 的小鼠模型的可生物降解，热致感应水凝胶。注射后的液体进入温暖的组织，它经过重组成为半刚性凝胶，进而提供机械大容量注入心肌，有助于预防拖延重构的削弱脑梗死区 1 中的区域。在人类的临床应用中，微创交付系统本质上是可取的。微创心脏外科 (中等收入国家） 技术的发展的主要目的已改善手术后恢复时间和减少固有的开放的方式，比如，疼痛、 感染、 手

3、术并发症和切口裂开的体会。剑突下的方法，就是这样一个技术，利用一个小腹部切口，利用小的腹部切口，是一种显示出较大的希望，因为它完全，避免了开胸手术，能抽出人类患者常规气管内麻醉与肺通缩的技术。不幸的是，正如我们以前有图猪模型中所示，通过该途径由于使用刚性传统的外科仪器仪表和直接的可视化的心包空间的方法会与重大 hemodynamiccompromise 和致命性心律失常 2 的风险相关，由于在此方法中涉及解决风险的方案，我们建议利用 heartlander 爬行机器人系统提供此水凝胶心外膜注射。心脏（图1）设计一个微型移动机器人用于介入微创心脏，并已显示出遍历整个的心外膜表面钕对闭胸心脏不停跳

4、猪模型体内 3、 4 执行准确放置心外膜注射剂的能力。这这种能力，通过一个强大的工具提供增强的起源微创访问使 heartlander 提供的水凝胶 subxiphoid 的手术方法。在此方法中所涉及的主要工程障碍是冷却工作头的机器人，为了防止水凝胶注射系统中过早地设置所需的小型化的喷射系统。保温材料是因为注射针的小直径不切实际的。半导体影响冷却需要复杂的光刻技术创建必要的热电偶路口的圆柱面上。此外，热电偶冷却需要电流传递到针本身内微米的心肌，有可能产生心律失常的危险。我们假设，往复的针系统，与供冷、 不育 0.9%生理盐水，一件夹克同轴能充分小型化在 heartlander 中的作用。为了满足

5、条件的成功，系统将不得不必须满足以下的条件： (1) 针直径 25 ga 防止泄漏回或心肌的损伤，（2） 足够导电嵌入式防止凝胶设置同时针针的冷却是注入的位置 （即，深埋在温暖心肌），（3）允许足够的停留时间注入 0.5 毫升 在凝胶的心肌中每个站点（4） 冷却水管连接到外部的凝胶体，从病人，允许执行重复注射剂在心肌梗死治疗迈克尔 体育查普曼热 sensitiveanti 重塑剂注射 heartlander 爬行机器人的多个应用程序的能力的粘性的凝胶，（6） 的迅速注入流 （5） 足够低阻力大约一米水库机器人的设备的整个长度，l.何塞 洛佩斯 冈萨雷斯、 克娜 e.播音、 kazuro l.藤

6、本隆宏、 zuwei 马、 威廉 瓦格纳、 马可 a.宰纳提和卡梅隆 n.里维耶尔 32 国际年会 ieee embs 图1 heartlander 机器人系统 （箭头） 模拟在硅橡胶橡胶心表面上爬行。阿根廷布宜诺斯艾利斯，8 月 31 日-9 月 4 日，2010978-1-4244-4124-2/10/$25.00 2010 ieee 5428 站点没有针堵塞、 (7) 生理安全和冷却方法的生物相容性和最后 (8) heartlander 的基本功能的运动没有阻抗车削、 导航和心外膜表面遵守。我们在此报告是成功建设这样一个系统完全集成到 heartlander 机器人成功建设。我们示范性的

7、扩增，动物组织中的多个站点注入 37 c 的水中浸泡的整个仪器与系统的能力。我们进一步证明了广泛的安全边距中的系统热配置文件和修改的 heartlander 机器人运动系统的全部功能。二 方法a.心脏爬行机器人 其他地方详细如3 描述 heartlander 爬行机器人的设计与施工的 heartlander 爬行机器人。简单地说，如图所示，在图 2 中，heartlander 系统，由两个爬网英尺 （b、 c）组成和任何附加的外科仪器仪表、 操作结束工作头 （a），在此情况下注射针 (d)。这头是程序集，引入病人的身体，剑突下切口，和其中抓取心脏的表面上的部分。脐组成的几个线性渠道，作为连接到

8、任何美联储通过经营通道的 1-2 毫米直径的外科设备驱动器仪器和运算符两端的这头。动机和转向部队会透过两个镍钛合金丝 (e) 和 (f) 管供应真空的脚到心脏表面的粘附传送。两个真空分庭 (g) 交替坚持和释放，以便在寸蠕虫时尚分别移动，以提供向前或向后的运动的双脚。转向被通过弯曲的前脚轨迹变两种镍钛合金驱动器电线的紧张局势。心包空间导航使用 ct 成像制导、 磁力跟踪器线圈系统，引用的外部胸墙上的裂痕。b.热固性凝胶的合成和热固性凝胶的性能详细的描述 1。简单地说，凝胶是一种共聚物的 n-异 (nipaam)、 丙烯酸 (aac) 和羟乙基甲基丙烯酸甲酯-poly(trimethylene

9、carbonate) （hemaptmc） 的水溶液。一达到大于约 24 c 的温度下，聚合物经历的驱逐水从它的矩阵和解决方案作为密集的、 弹性的凝胶留下灵活地增强心肌肌肉组织的力学性能优异的相变。这种材料是生物相容性和生物可降解的，它慢慢吸收和过去的几周，几个月发生的愈合过程时从注射部位中删除的物质。c.注塑和冷却系统的工作 心脏通道是重新设计的，以容纳22 ga 薄壁通道的标准不锈钢皮下油管、 领先的脐和终止连接到包含液态水凝胶的注射器的女性鲁尔连接器中。这种注射器相互感触的手，以导管为了完成针插入和撤回在下前脚组织目标的工作通道。此指南频道由 16ga 薄壁聚四氟乙烯管材，自由运行通过端

10、口的前后脚和硬性的组成图2 标准的心脏和心脏系统（下）改性集成冷却和喷射系统（上）。（参见方法标记的关键部分。）附贴于前脚，向下弯曲成机械加工丙烯酸体内的前脚，从90 度圆弯道开始，引导进入组织的针。为了判断此折弯，针提示 （最远端约30 厘米，) 水凝胶的通道机械加工成 25ga 镍钛合金管材，本身银焊接到 22ga 水凝胶传递通道，也是机械联动的注射和戒断的行动。ptfeguide 通道将终止在近端 （外部、 或运算符） 中女性的 luerconnector，而其本身的端点连接到三路 90oluer 适配器。针管大多会通过同轴通过此通道，从而通过直手臂的橡胶隔膜的防泄漏轴承表面行为往复式行

11、动的注射油管注射器大多会通过退出三路适配器。正交港三路适配器的通过内联流量调节器阀与标准四油管连接的 0.9%无菌生理盐水 (本身沉浸在冰水浴） 的加压水库。因此，冷生理盐水流经油管，并通过为针提示的同一通道退出 heartlander 前脚。此盐渍的污水流排水渠的心肌、 心包切口、 并在表面上。d.体外组织模型作为一个概念性证明和初步试验的坚固性，我们模拟条件是将猪模型心肌注射使用温暖的鸡（家鸡）胸大肌肌组织体外淹没在37水浴。在各种试验，心脏的应用和手动移动的表面肌肉样品。注射了 0.25-0.5 毫升 aliquots 和直观地视察了切口通过注射部位，注射后的 5 分钟。相同的机器人也被

12、移动到自动方式类似组织样品，以方便其移动使用模拟合成心包。e.温度测量流出的温度是衡量一个快速反应的微型双热电偶0.0095”最大外径（12167号，电阻，inc .），插入则逆行。使用专用的计算机接口设备和软件欧米茄文书模型 hh127） 录得的数据。三 结果a .定性注射观察以模拟一个典型的情况的病人我们手动引导一个完全组装的心脏5注射部位的肌肉组织样品与整个系统埋在人体体温的水里。我们注入深度为5毫米，等约60的注射，用针在收回的位置，模拟心脏导航为它在模式网站下的“运动”。水套冷却流量维持在0.25毫升/秒，整个实验注射了0.5毫升，30秒完成使用手动压注射器，由于流动性长和狭窄的油管

13、和相对粘性凝胶溶液，传导冷却的针尖通过其延伸到流动水夹克足以防止任何过早凝胶在所有在这个时间。平面切片的组织样本显示完整的固化胶，没有观察到泄漏回到通过轨道的无刷镍针（见图3）。优化系统包括手动曲柄和往复组件。机械优势提供更大的注射压力，从而更迅速和容积精密注射，同时保持与外科医生一致的感官反馈。b.定量热性能进行评估的安全裕度系统（即，其抗过早凝胶失效模式）与针的注射位置，延长超过5毫米的心脏工作头，我们记录的流出温度的水凝胶在不同流量的加冰盐水（约2丙）通过引导渠道/套组件。结果显示在图4。这一数据表明，广泛的业务安全幅度低于目标温度最高17碳，这是3下面第一个观察到的趋势在凝胶粘度 1。

14、这些测量数据进行在动态平衡条件下的恒流的水和水。流量为0.1毫升/秒大约维持在10水凝胶，从而提供了一个良好的安全边际。这些流动率是一个不可忽视的。图3。结果成功的体外实验。固化水凝胶是看见一个白色夹杂在肌肉体积样品的鸡胸大肌肌，大约5毫米以下的表面（虚线椭圆）。一个没有泄漏，完全封闭针轨道可以观察。图4。出水凝胶温度在不同利率的冷却水流量在37水环境，表现出有效的冷却针内容即使在延长（即，注入的）位置。把蓝色的痕迹（一）：冷却水温度在退出点从心脏前足。紫色固体微量（乙）：凝胶温度在针尖与针在收回的位置。红点跟踪（三）：凝胶温度在针尖与针延长5毫米从心脏到温暖的水环境，模拟病人流体的浪费，可以

15、很容易地回收，通过抽吸导管引入到低一点的心包经同一手术孔的机器人。c .心脏运动观测基本系统操作参数是心脏任何子系统通过部署工作头不妥协的能力，坚持和自由爬行，释放在心脏表面。我们有一些关注线性针和水套装配传授过度扭转刚度的头部，其之间的两只脚。如果是这样的话，减少直径的组成部分可能是必要的。然而在操作方面，心脏爬在其正常操作参数驱动线张力和真空室而爬行在干、湿纸巾的表面硅橡胶。没有返回了错误的导航系统。四 探讨我们已经成功地证明了一个优雅的简单的小型冷却和喷射系统，完全集成到现有的平台的心脏爬行机器人。我们有能力进行反复注射在多个温暖的动物组织网站，同时保护injectedmaterial过

16、早冷却，表明可以在系统的体内试验，进行心外膜注射猪经剑突下心包空间的方法，即使没有进一步的优化。此外，迅速调整和部署的心脏平台在这一具有挑战性的应用，我们已经证明了鲁棒性和灵活性的心脏系统。这表明心脏的能力，作为车辆的一个完全新的外科干预系统显示平台本质上是高度适应各种仪表子系统，最终将为用户需要的心脏外科医生，参考文献 1k .l-藤，卓马，d .m.j .尼尔逊，爪，关，k鸢多，和w . r .瓦格纳，”的合成，表征及疗效的一种可生物降解，温敏水凝胶设计应用在慢性心肌梗死，”材料，卷30，页4357-4368，六月2009。 2t横，t，d施瓦茨曼，和m . a .zenati，”影响，剑

17、突下视频pericardoscopy与刚性轴对心脏血流动力学的猪模型，“创新，第五卷，1号，第51-54，2010 - 1。 3 n.patronik，t .，m . a .c.zenati，和更多，”一个微型移动机器人导航定位在跳动的心脏，”杂志。机器人。，25卷，5号，第1109-1124，2009。 4t.a大田，patronik，d施瓦茨曼，c.家，和m . a .zenati，“微创心外膜注射使用半自主机器人装置，“循环，118卷，第14页s115-s120，2008，增刊。附件2：外文原文32nd annual international conference of the iee

18、e embsbuenos aires, argentina, august 31 - september 4, 2010application of the heartlander crawling robot for injection of a thermally sensitive anti-remodeling agent for myocardial infarction therapyabstract the injection of a mechanical bulking agent into the left ventricular (lv) wall of the hear

19、t has shown promise as a therapy for maladaptive remodeling of the myocardium after myocardial infarct (mi). the heartlander robotic crawler presented itself as an ideal vehicle for minimally-invasive, highly accurate epicardial injection of such an agent. use of the optimal bulking agent, a thermos

20、etting hydrogel developed by our group, presents a number of engineering obstacles, including cooling of the miniaturized injection system while the robot is navigating in the warm environment of a living patient. we present herein a demonstration of an integrated miniature cooling and injection sys

21、tem in the heartlander crawling robot, that is fully biocompatible and capable of multiple injections of a thermosetting hydrogel into dense animal tissue while the entire system is immersed in a 37c water bath. 1 introduction injection of a locally stiffening material into the left ventricular (lv)

22、 myocardial wall has been proposed as a novel therapy to prevent maladaptive lv remodeling due to high wall stresses that develop after myocardial infarction (mi). we have previously used a biodegradable, thermoresponsive hydrogel based on copolymerization of n-isopropylacrylamide (nipaam), acrylic

23、acid (aac) and hydroxyethyl methacrylate-poly(trimethylene carbonate) (hemaptmc) in a mouse model of mi. upon injection of the liquid into warm tissue, it undergoes reorganization into semi-rigid gel, providing mechanical bulk to the injected region of myocardium, aiding in prevention of dilatory re

24、modeling of the weakened infarct zone 1. for a clinical application in humans, a minimally-invasive delivery system is inherently desirable. the principal motivation for development of minimally invasive cardiac surgery (mics) techniques has been to improve post-surgical recovery times and reduce th

25、e complications of this work was supported in part by the u.s. national institutes of health under grant r01 hl078839. m.p. chapman was with the heart lung and esophageal surgery institute, university of pittsburgh, pittsburgh, pa 15213 usa. he is now with the department of general surgery, medical

26、college of georgia, augusta, ga 30912 usa. j. l. lpez gonzlez is with the university of valladolid, spain. b. e. goyette, and c. n. riviere (e-mail:) are with the robotics institute, carnegie mellon university, pittsburgh,pa 15213 usa. k. l. fujimoto, z. ma, and w. r. wagner are with t

27、he university of pittsburgh center for biotechnology and bioengineering, pittsburgh, pa 15213 usa. m. a. zenati is with the division of cardiac surgery, university of pittsburgh, pittsburgh, pa 15213 usa. surgery inherent in an open approach, such as pain, infection, and wound dehiscence. the subxip

28、hoid approach, utilizing a small abdominal incision, is one such technique that shows much promise, as it avoids thoracotomy entirely, and could spare a human patient general endotracheal anesthesia and lung deflation. unfortunately, as we have previously shown in a porcine model, approaches to the

29、pericardial space through this route using traditional rigid surgical instrumentation and direct visualization are associated with significant hemodynamiccompromise and risk of lethal arrhythmia 2. as a solution to the risks involved in this approach we propose to utilize the heartlander crawling ro

30、bot system to deliver this hydrogel for epicardial injection. heartlander (fig. 1) is a miniature mobile robot designed for minimally invasive cardiac intervention, and has already shown its capability to traverse the entire epicardial surface nd to perform accurately-placed epicardial injections on

31、 closed-chest beating porcine models in vivo 3, 4. this ability to provide enhanced minimally invasive access to the epicardium makes heartlander a powerful tool to deliver the hydrogel via a subxiphoid surgical approach. a major engineering obstacle involved in this approach is cooling the miniatur

32、ized injection system required for the working head of the robot, in order to prevent the hydrogel from prematurely setting up in the injection system. insulation is impractical owing to the small diameter of the injection needle. peltier effect cooling would require complicated lithography on a cyl

33、indrical surface to create the necessary thermocouple junctions. also, thermocouple cooling would require the delivery of electrical current to the needle itself, within micrometers of the myocardium, potentially creating a risk for arrhythmia. we hypothesized that a reciprocating needle system, coa

34、xial with a jacket supplying cold, sterile 0.9% saline solution, could be adequately miniaturized to function in heartlander. in order to meet criteria for success, the system would have to have to meet criteria for: (1) needle diameter 25 ga to prevent leak back or myocardial injury, (2) sufficient

35、 conductive cooling of the imbedded needle to prevent gel setting while the needle is in the injected position (i.e., buried in warm myocardium), (3) sufficient permissible dwell time in the myocardium to inject 0.5 ml of the gel at each site, (4) cooling of the entire length of plumbing for the dev

36、ice, connecting the robot to an external reservoir of gel, approximately one meter from the patient, (5) sufficiently low resistance to flow to permit rapid injection of the viscous gel, (6) the ability to perform repeated injections at multiple application of the heartlander crawling robot for inje

37、ction of a thermally sensitiveanti-remodeling agent for myocardial infarction therapy michael p. chapman, jose l. lpez gonzlez, brina e. goyette, kazuro l. fujimoto, zuwei ma, william r. wagner, marco a. zenati, and cameron n. riviere 32nd annual international conference of the ieeeembsfig. 1. the h

38、eartlander robotic system (arrow) crawling on the surface of a silicone rubber heart analog. buenos aires, argentina, august 31 - september 4, 2010978-1-4244-4124-2/10/$25.00 2010 ieee 5428 sites without needle clogging, (7) physiologic safety and biocompatibility of the cooling method and, lastly (

39、8) no impedance to heartlanders basic functions of locomotion, turning, navigation, and adherence to the epicardial surface. we report herein the successful construction of such a system, fully integrated into the heartlander robot. we demonstrate the ability for the system to inject multiple sites

40、in animal tissue ex vivo, with the entire apparatus immersed in 37c water. we further demonstrate a wide safety margin in the systems thermal profile and the full functionality of the modified heartlander robots locomotion system. ii. methodsa. heartlander crawling robot the design and construction

41、of the heartlander crawling robot are described in detail elsewhere 3. briefly, as shown in fig. 2, the heartlander system consists of a working head (a), comprising two crawling feet (b, c) and the operating end of any attached surgical instrumentation, in this case the injection needle (d). this h

42、ead is the portion of the assembly that is introduced into the patients body, through the subxiphoid incision, and which crawls on the surface of the heart. as umbilicus consisting of several linear channels, connects this head to the drive apparatus and operator ends of any surgical equipment fed t

43、hrough the 1-2 mm diameter operating channel. the motive and steering forces are transmitted via two nitinol wires (e) and a tube (f) supply vacuum for adhesion of the foot to the cardiac surface. two vacuum chambers (g) alternately adhere and release in order to allow the two feet to move separatel

44、y in an “inch worm” fashion to provide forward or backward locomotion. steering is accomplished by bending the trajectory of the front foot by varying the tension in the two nitinol drive wires. navigation in the pericardial space is accomplished using ct image guidance and a magnetic tracking coil

45、system, referenced to external fiducials on the chest wall. b. thermosetting hydrogel the synthesis and properties of the thermosetting hydrogel are described in detail elsewhere 1. briefly, the gel is an aqueous solution of a copolymer of n-isopropylacrylamide (nipaam), acrylic acid (aac) and hydro

46、xyethyl methacrylate-poly(trimethylene carbonate) (hemaptmc). upon reaching temperatures greater than approximately 24oc, the polymer undergoes a phase transition in which it expels water from its matrix and leaves solution as a dense, elastic gel with excellent mechanical properties for flexibly re

47、inforcing myocardial muscle tissue. the material is both biocompatible and biodegradable at a very slow rate, allowing it to be absorbed and removed from the injection site as the healing process occurs over the course of weeks to months. c. injection and cooling system the working channel of heartl

48、ander was re-engineered to accommodate a 22 ga thin-walled channel of standard stainless steel hypodermic tubing, leading up the umbilicus and terminating in a female luer connector attached to the injection syringe containing the liquid hydrogel. this syringe is moved reciprocally by hand, with res

49、pect to the guide tube of the working channel in order to accomplish needle insert and withdrawal at the tissue target under the front foot. this guide channel consists of 16ga thin wall ptfe tubing, running freely through a port in the rear foot and rigidly fig. 2. standard heartlander system (bott

50、om) and heartlander modified to integrate the cooling and injection systems (top). (refer to methods section for labeling key.) 5429 affixed to the front foot, opening into a curved channel machined in the acrylic body of the front foot, making a 90o circular bend downward to guide the needle into t

51、he tissue. in order to negotiate this bend, the needle tip (the most distal 30 cm, approximately) of the hydrogel channel is machined into 25ga nitinol tubing, itself silver-soldered into the 22ga hydrogel delivery channel, which is also the mechanical linkage for the actions of injection and withdr

52、awal. the ptfeguide channel terminates at the proximal (external, or operator) end in a female luerconnector, which itself attaches to a three-way 90oluer adapter. the needle-tube assembly passes coaxially through this channel and thus through the straight arm of the three-way adapter to exit throug

53、h a rubber septum which acts a leak-proof bearing surface for the reciprocating action of the injection tubing-syringe assembly. the orthogonal port of the three-way adaptor is connected to a pressurized reservoir of 0.9% sterile saline solution (itself immersed in an ice-water bath) via standard iv

54、 tubing with an inline flow regulator valve. thus, cold saline solution flows through the guide tubing and exits the front foot of heartlander via the same channel as the needle tip. this saline effluent stream drains onto the surface of the myocardium, and out of the pericardial incision. d. tissue

55、 model ex vivo 待添加的隐藏文字内容2 as a proof of concept and an initial trial of ruggedness, we simulated conditions of myocardial injection within our living swine model using warmed chicken (gallus gallus domesticus) pectoralis muscle tissue ex vivo submerged in a 37c water bath. in various trials, heartl

56、ander was applied and moved manually over the surface of the muscle sample. injections were made in 0.25-0.5 ml aliquots and were inspected visually by incision through the injection site, 5 minutes after the injection. the same robot was also moved in automated fashion over similar tissue samples,

57、using a synthetic pericardium analog to facilitate its movement. d. temperature measurement outflow temperatures were measured with a rapid-response miniature bifilar thermocouple of 0.0095” maximum outer diameter (no. 12167, rtd, inc.), inserted retrograde. data were recorded with a dedicated compu

58、ter interface device and software (model hh127, omega instruments). iii. resultse. qualitative injection observations in order to simulate a typical injection scenario in a patient, we manually guided a fully assembled heartlander to 5 injection sites on the muscle tissue sample with the entire system submerged in human body-temperature water. we injected at a depth of 5 mm and waited approximately 60 s between injections, with the needle in the withdrawn position, to simulat