HeartWare公司微型轴流式心室辅助装置.doc

HeartWare Miniature Axial-Flow Ventricular Assist DeviceHeartWare公司微型轴流式心室辅助装置Pulsatile ventricular assist devices have successfully provided circulatory support for many patients throughout the past quarter century; however, persistent complications have hindered expanded clinical application of this technology. Although the use of smaller, continuous-flow ventricular assist device pumps has reduced the frequency and severity of some adverse events, design enhancement may further improve outcomes for patients who require long-term left ventricular support. One new product, the HeartWare, Inc., miniature ventricular assist device, features a wide-bladed rotor design in an axial-flow pump with a strong, passively suspended magnetic rotor. The operating range of 16,000 to 28,000 rpm can provide up to 10 L /min of flow. The wide blades portend minimal cel -lular trauma.过去四分之一个世纪以来，对于许多患者来说，脉动式心室辅助装置已成功地为其提供了血液循环支持。然而，持续的并发症阻碍了这项技术的临床应用和推广。虽然使用了更小的、连续流动式的心室辅助泵，减少了并发症的频率和一些不良症状的严重程度。通过精心和巧妙的设计，可进一步改善患者长期左心室血液循环支持的效果。，HeartWare公司的一款新的产品微型心室辅助装置，采用宽叶片的转子轴流式设计，采用了强劲的被动悬浮磁转子泵。该装置的工作范围为16000到28000 RPM，可以提供高达10 L/min的流量。宽叶片设计能够实现对血液细胞的最小损伤。This new device has not yet been approved for use in human beings. As a test, we implanted it in a calf, and we continuously monitored the devices performance and the hemodynamic results over 30 days. No mechanical failure occurred, and no thrombi were noted upon explantation of the device. The animals circulation was stable during the test period, and no end-organ abnormalities were found upon autopsy. The potential benefits of this miniature ventricular assist device are its increased availability to a broader patient population, a lower risk of infection, simplified implantation procedures, and improved durability. Further in vivo testing is planned. Herein, we discuss the unique design of the HeartWare miniature ventricular assist device, our feasibility study of its performance, and the possibilities for its use in human beings. (Tex Heart Inst J 2009;36(1):12-6)这种新的装置尚未批准用于临床治疗。作为测试，我们将它植入小牛体内，连续超过30天对该装置的性能和血流动力学结果进行监测，没有发生机械故障和形成血栓。在测试过程中，动物的血液循环稳定。在验尸期间，并没有发现器官异常情况。这个微型心室辅助装置的潜在好处是它的供血量增大，适用于更多的患者群体，简化了植入手术，从而使手术感染的风险较低，并且提高了耐用性。进一步体内试验正在计划之中。文章中讨论了HeartWare微型心室辅助装置的独特设计，其性能的可行性研究，以及应用于人类的可能性。Implantable, pulsatile-flow ventricular assist device (VAD) systems have been used successfully for a quarter of a century as a bridge to heart transplantation, as a bridge to myocardial recovery, and as destination therapy. Early designs were influenced by the idea that mechanical blood pumps must mimic the natural heart with regard to blood flow rate and intermittent changes in pressure (pulsatility). Accordingly, VAD pumps have been designed with stroke volumes in the range of 50 to 100 mL and pumping rates of 50 to 120 beats/min. However, these devices are large and are compatible only with patients of larger body sizes. Furthermore, complications related to device operation or implantation have hampered the effectiveness of these VADs. Design technology has evolved so that newer, smaller, and more reliable VADs can now create continuous blood flow, unlike that produced by natural-heart or pulsatile VADs.植入式脉冲流动心室辅助装置（VAD）系统已成功使用了四分之一个世纪，用于心脏移植，心肌恢复的桥梁，并成为最终的治疗方案。早期的设计方案受到了一些观点的影响，即机械血液泵必须模仿自然心脏在血压下血液流速和间歇性的变化。因此，VAD泵的设计输送血液体积在50至100毫升之间，泵的频率为50120次/分钟的范围内。然而，这些装置过大，仅适合较大身形的患者。此外，由于该装置的手术或植入存在并发症，因此阻碍了这些VAD的有效性。设计技术的发展，研发出新型，更小，更可靠的VAD，可以提供连续的血流量，不再像自然心脏或搏动性VAD。The miniature VAD (MVAD, HeartWare, Inc.; Miramar, Fla) is a small pump with a wide-bladed rotor design and magnetically suspended impeller that generates axial blood flow. This design portends improved durability and performance. The MVAD is not yet approved for use in human beings. In this report, we present the unique design features of this new VAD, our feasibility study of its performance in a calf, and the devices possibilities for use in human patients who require long-term left ventricular support.微型VAD（MVAD，HeartWare公司）是一个体积很小的泵体，宽叶片转子的设计，以及磁悬浮叶轮产生轴向的血流量。这样的设计预示着更加耐用和更好的性能。MVAD尚未批准用于人类临床治疗。在这份报告中，我们给出了这个新型VAD独一无二的设计特点，以及在植入小牛的可行性研究，并验证了其在需要长期左心室支持设备的人类患者的可能性。Materials and Methods材料和方法Device Description设备描述The HeartWare MVAD is a small axial-flow pump that can generate blood flow up to 10 L/min (Fig.1). The displacement volume is 15 cc. The cylindrical titanium housing contains an electromagnetic motor stator with an external power supply (Fig.2). Within the housing is a wide-bladed rotor that creates axial flow through the device.HeartWare公司的MVAD是一个很小的轴流式泵体，它可以产生高达10升/分钟（如图1）的血流量。置换血量为15毫升。圆筒状的钛壳体与外部电源（如图2）包含一个电磁电动机定子。在壳体内，是一个宽叶片转子，通过该装置形成轴向流动。The rotor is constructed of magnetic and biocompatible material, which is hard enough to render a coating unnecessary. The hydrodynamic thrust bearings are larger and wider than the area between the blades where blood flows (Fig.3); this affords sufficient area for passive radial rotor suspension, and for the accommodation of magnets that create a strong electromagnetic coupling. The configuration confers good systemic power efficiency and passive motor constraint. The passive rotor-suspension system obviates mechanical bearings and other rotor-support structures. The outflow is angled at 90 from the pump housing and is attached to a 10-mm double-woven outflow graft for anastomosis to the aorta. Small wires from the pump motor are tunneled subcutaneously and exit through the skin, where they are connected to external power and control units. The pump speed is adjustable from 16,000 to 28,000 rpm, and the current can be monitored continuously to ensure proper functioning of the pump. Pump flow is monitored by means of an ultrasonic flow probe on the outflow graft.构成转子的磁性和生物相容性材料硬度足够高，因此不必使用涂层。流体动力学推力轴承血液流过的面积比叶片的更大更宽（如图3），这提供了足够的面积用于悬浮被动径向转子，并且使磁铁产生了强烈的电磁耦合。这些结构赋予了系统良好的电源效率和被动转子约束。被动转子悬挂系统，省去了机械轴承和转子支持结构。从泵壳体流出的角度为90，并且连接到10mm长的双编织移植物接合处的主动脉上。泵电机细小的电源线从皮下通过和退出，并且连接到外部电源和控制单元上。泵的转速是可以调节的，从16000到28000RPM，目前还可以进行连续监测，以确保泵的正常运转。泵的流量通过装在移植体的超声波气流探测器进行监测。Fig. 1 The HeartWare MVAD pump, held in an adult human hand.图1 成年人手中的HeartWare公司的MVAD泵体Fig. 2 The internal components of the Heart Ware MVAD pump, and the locations of the motor stator and the rotor (arrows).图2，HeartWare公司MVAD泵体的内部组件，以及电动机定子和转子（箭头）的位置。Fig. 3 A) Schematic drawing of the wide-bladed rotor of the HeartWare MVAD, with the blood-flow channels and hydrodynamic bearings identified. B) Photograph of the rotor.图3 A）HeartWare公司的MVAD泵体宽大并且装有叶片的转子，带有血流流通通道的流体动力学轴承。B）转子的照片Feasibility Study in a Calf在小牛上的可行性研究We implanted the HeartWare MVAD in a Jersey calf for an intended 30-day pilot test. The animal was prepared for surgery in standard fashion, and all care was provided in accordance with the “Guide for Care and Use of Laboratory Animals” (NIH publication 85-23, revised 1996). Baseline laboratory values, including blood cell counts, coagulation test results, and blood chemistries, were obtained before the induction of anesthesia. Anesthesia was induced by use of intravenous thiopental (10mg/kg) and was maintained by means of inhaled isoflurane (1%-2%). 我们在一头新泽西州的小牛身上植入了HeartWare公司的MVAD，进行为期30天的试验测试。动物手术前的准备，完全按照“实验动物护理和使用指南”（NIH85-23出版，1996年修订）进行。基本的实验室检查结果，包括血液细胞计数，凝血试验，以及血液化学检测。这些检查是在麻醉诱导之前进行的。麻醉诱导是通过静脉注射硫喷妥钠（10mg/kg体重）进行的，并且保持吸入异氟醚（1-2）。Electrocardiographic (ECG) readings, arterial line pressure, and pulse oximetry were monitored continuously during implantation, and also postoperatively. A left thoracotomy between the 5th and 6th ribs exposed the left ventricular apex and the descending thoracic aorta. A pulmonary artery catheter was inserted via the right atrial appendage, and hemodynamic data were recorded, including central venous pressure, pulmonary artery pressure, and systolic, diastolic, and mean arterial blood pressures. Heparin (300 U/kg) was administered for anticoagulation before anastomosis of the outflow graft to the descending aorta. Cardiopulmonary bypass was not necessary during this operation. 在手术后和植入过程中连续监测心电图（ECG）的读数，动脉血管压力，和脉搏血氧饱和度。在第5根和第6根肋骨之间的左侧开胸，暴露出左心室心尖部和胸降主动脉。通过肺动脉导管插入右心耳，同时记录血液流动力学数据，包括中央静脉压，肺动脉压和收缩压，舒张压和平均动脉血压。降主动脉移植吻合之前，需要使用抗凝肝素（300 U/kg）。在此操作过程中，不需要进行体外循环。After the attachment of a sewing ring to the left ventricular apex, a ventriculotomy was performed with a circular knife. The MVAD pump was inserted into the left ventricle and was secured to the sewing ring by the tightening of a locking screw. After complete de-airing of the system, the clamp on the outflow graft was removed, and normal operation of the MVAD was initiated. A 10 mm Transonic flow probe (Transonic Systems Inc.; Ithaca, NY) was attached to the outflow graft and was monitored by use of an HT-205 flow meter (Transonic). Once the MVAD was operating satisfactorily, hemodynamic and laboratory data were recorded. 左心室心尖部的缝合环安装后，用一个圆形刀进行心室切开术。MVAD血泵插入左心室，并固定缝合环的锁紧螺钉拧紧。整个系统排气完成后，除去流出移植处的夹子，MVAD血泵开始进行正常操作。10毫米的跨音速流动探头（Transonic系统公司，伊萨卡，NY）连接到移植处的出口，并且使用HT-205流量计（Transonic）进行了监测。一旦MVAD血泵运作良好，将记录血泵的血液流动力学数据和实验室数据。The heparin was reversed with protamine sulfate (500 mg over 30 min). The MVAD driveline and flowprobe cable were positioned so that they would exit the thoracotomy toward the back of the animal. Chest tubes were placed, and the thoracotomy was closed. Anesthesia was discontinued; the animal was placed in a stanchion and was then transferred to a recovery area. Postoperatively, the calfs vital signs and the pump-operating values were recorded daily, at scheduled intervals.肝素硫酸鱼精蛋白逆转（500毫克，30分钟）。MVAD血泵动力传动系统和流量探头电缆被定位，以便它们将退出朝向动物背部的开胸。胸管放置完成，并且关闭开胸。停止麻醉动物放置在一个支柱上，然后将其转移到恢复区域。手术完成后，每天在预定的时间间隔内记录小牛的生命体征及血泵的运行参数。Results of the Feasibility Study可行性研究的结果No mechanical or medical complications were observed during the postimplantation period, and the animals hemodynamic levels were stable throughout the study (Fig. 4). Weekly laboratory values were within normal ranges (or they reflected expected changes), with the exception of the hemoglobin and hematocrit values, which decreased during week 2 (Table I). These values returned to normal by week 4.在植入后观察发现，小牛没有出现机械或医疗并发症，整个研究过程中，动物的血液动力学水平是稳定的（如图4）。每周化验值均在正常范围内（或反映了预期的变化），异常的血红蛋白和红细胞压积值，在第2周下降（见表一）。这些实验数值第4周恢复正常。The calf received no transfusions during the implantation procedure or the study period. The pump speed of the MVAD ranged from 19500 to 21300 rpm, and mean daily left VAD flow rates of 4.250.75 L/min (range, 3.55.1 L/min) were maintained (Fig. 5). Thermodilutional cardiac output measurements during the initial 8 postoperative days indicated that the VAD flow rate was, on average, 79.4% of the total cardiac output. Arterial blood pressure was maintained within a normal range; the average daily systolic, diastolic, and mean arterial pressures were 120 15.2, 73.4 11.8, and 89.0 12.1 mmHg, respectively (Fig. 6).小牛在植入过程中或研究期间没有进行输血。MVAD血泵的转速范围为19500-21300rmp，即平均每天离开植入式脉冲流动心室辅助装置（VAD）的流速保持在4.250.75升/分钟（范围为3.5-5.1升/分钟）（如图5）。手术后最初的8天期间，热稀释法测量的心脏输出血量表明，VAD的流量的平均值为心脏总输出血量的79.4。动脉血压保持在正常范围内，每日平均收缩压、舒张压和平均动脉压力分别为12015.2、73.411.8和89.012.1毫米汞柱（如图6）。The average pulse pressure was 46.8 9.2 mmHg, indicating that some pulsatility was maintained and that there was less than maximal unloading of the left ventricle. The plasma free hemoglobin peaked at 100 mg/dL on the 1st postoperative day. This value stabilized at 10 mg/dL during weeks 3 and 4. On day 31, the calf was euthanized in accordance with protocol, and a same-day autopsy was performed. The explanted pump was free of thrombi, and no thermal damage to it was identified. No renal, hepatic, splenic, or brain abnormalities were evident in the calf.平均脉冲血压为46.89.2毫米汞柱，表明一些脉动得以维持，并且小于左心室的最大卸载值。手术后第1天，血浆中游离的血红蛋白达到100 mg/dL。血浆中游离的血红蛋白值在第3周和第4周期间稳定在10mg/dL。第31天，根据相关协议，对小牛实施安乐死，并在同一天进行尸检。植入的血泵没有形成血栓，并确定没有受到热损伤。没有发现小牛的肾，肝，脾，或大脑出现明显的发育异常。Fig. 5 Daily flow rates were 4.25 0.75 L /min (range, 3.55.1 L/min). Thermodilutional cardiac output measurements during the initial 8 postoperative days indicated that the MVAD flow rate was, on average, 79.4% of the total cardiac output. MVAD = miniature ventricular assist device.图5 每天血液流量分别为4.250.75升/分钟（范围为3.5-5.1升/分钟）。手术后最初的8天期间，热稀释法测量的心脏输出血量表明，VAD的流量的平均值为心脏总输出血量的79.4。MVAD=微型心室辅助装置。Fig. 6 Plots of the average daily values of the arterial systolic, diastolic, mean, and pulse pressures, over the duration of the study图6在研究期间平均每日的动脉收缩压，舒张压，平均脉压数值图 Discussion讨论Continuous flow VADs afford several potential advantages over pulsatile-flow VADs. The smaller size of continuous-flow VADs enables their application in patients of a broader range of body sizes. Smaller pumps can be implanted with less-invasive surgery. Unlike the pulsatile-flow VADs, they generally do not need to be placed in an abdominal pocket: a difference that reduces patients susceptibility to infection. These continuous-flow devices are simpler than the pulsatile devices, with a single moving part the rotor which portends greater durability. 连续流量的VAD具有超过脉冲式流量VAD的几个潜在的优势。更小尺寸的连续流量VAD，在更加广泛的身形尺寸的患者身上得到更多的应用。较小的血泵可以减少移植手术的伤害。与脉动流VAD不同的是，它们一般不需要放置在腹部口袋内：减少了患者的感染。连续流量设备要比脉冲式设备简单的多，只包括一个运动部件转子这表明将更加耐用。Most axial-flow VADs contain a rotor held in position by 2 bearings that are lubricated by circulating blood. In contrast, most blood pumps that have magnetically suspended impellers generate flow by centrifugal force and do not use bearings, which reduces component wear. A theoretical advantage of magnetically suspended pumps with non-contact bearings is that there is no friction or heat generation; the absence of frictional heat should result in less thrombogenesis and thus less need for anticoagulation therapy in patients.大多数轴流VAD包含保持在适当位置的转子，2个轴承通过血液循环进行润滑。相反，大多数血泵通过磁悬浮叶轮离心力产生流量，不使用轴承，从而降低了部件的磨损。非接触式轴承的磁悬浮血泵的理论优点是，没有摩擦或产生热量。缺少摩擦热将减少血栓的形成，从而减少了需要抗凝治疗的患者。Complications in human patients who have received VAD support have been reduced by improved supportive care gained from experience, and by the refinement of blood-pump technology. Smaller axial-flow VADs have been shown in clinical studies to be more durable and lead to fewer complications than the older, pulsatile VADs. Axial-flow devices can be implanted without the use of cardiopulmonary bypass. Smaller left VADs require less invasive surgery for implantation, which minimizes postoperative bleeding complications. Less surgical and coagulopathic bleeding reduces infection rates, which is noteworthy because postoperative bleeding and infection continue to be the chief causes of morbidity and death after VAD implantation.通过精心的支持性护理和血泵技术的精细发展，接受VAD治疗的人类患者的并发症已经减少了。在临床研究中已经显示，相对于传统的脉冲式VAD，小型的轴流VAD更加耐用，并且导致的并发症更少。可以植入轴流设备，而无需使用体外循环。小型的左侧VAD需要微创手术植入，最大限度地减少术后出血等并发症。减少手术出血和凝血障碍，降低感染率是值得重视的，因为术后出血和感染仍然是VAD植入后发病率和死亡率的首要原因。During this pilot study of the HeartWare MVAD, the ideal pump speed for optimal clinical support was not fully studied. The maximum speed setting is 28000 rpm; in this study, the speed was set at 21300 rpm at highest. The thermodilutional cardiac output values and the calculated pulse pressure indicate that there was continuous but submaximal unloading of the left ventricle. While this may be the optimal support, further characterization of this system is necessary.HeartWare公司的MVAD血泵试验性研究中，对于获得最佳临床支持的血泵的理想转速没有得到充分的研究。最大转速设置为28000转。在这项研究中，最高设定转速为21300rpm。热稀释法测量的心脏输出值和所计算的脉冲压力表明，左心室具有连续的，但是第二最大卸载值。虽然这可能是最佳的血泵支持，但是需要对该系统做进一步鉴定。The MVAD features additional refinements that could continue the trend toward better long-term outcomes in VAD usage. The small, efficient rotor allows the housing to be miniaturized and to be manufactured in a variety of configura