CN106659150A - 用于维护被收获的待移植心脏的设备 - Google Patents
用于维护被收获的待移植心脏的设备 Download PDFInfo
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- CN106659150A CN106659150A CN201580022610.4A CN201580022610A CN106659150A CN 106659150 A CN106659150 A CN 106659150A CN 201580022610 A CN201580022610 A CN 201580022610A CN 106659150 A CN106659150 A CN 106659150A
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- heart
- module
- infusion liquid
- centrifugal pump
- duricrust
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Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0242—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
- A01N1/0247—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0242—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
- A01N1/0252—Temperature controlling refrigerating apparatus, i.e. devices used to actively control the temperature of a designated internal volume, e.g. refrigerators, freeze-drying apparatus or liquid nitrogen baths
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- A—HUMAN NECESSITIES
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- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0263—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
- A01N1/0273—Transport containers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/362—Heart stimulators
- A61N1/3621—Heart stimulators for treating or preventing abnormally high heart rate
- A61N1/3622—Heart stimulators for treating or preventing abnormally high heart rate comprising two or more electrodes co-operating with different heart regions
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- A—HUMAN NECESSITIES
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- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/38—Applying electric currents by contact electrodes alternating or intermittent currents for producing shock effects
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- A61N1/3968—Constructional arrangements, e.g. casings
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
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- Agricultural Chemicals And Associated Chemicals (AREA)
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- Agricultural Machines (AREA)
Abstract
一种维持和监控被切除的供体心脏的设备、***和方法。该设备包括将被切除心脏接收并且浸没在不断循环的灌注液中的第一部件,包括用于调节灌注液的温度和氧含量的装置的第二部件。第一部件包括一体的一对除颤垫。第一导管基础结构使第一模块、第二模块和被切除的供体心脏的主动脉互连,将灌注液从第一模块通过第二模块推到主动脉内。第二导管基础结构使第一模块与右心房和左心房相连接,用于将灌注液从第一模块推到心房内。第三导管基础结构使第一模块与肺动脉连接并且为来自肺动脉的灌注液液流提供后压力。
Description
技术领域
本发明涉及用于被收获(harvested)的供体心脏的体外灌注和维护的设备、***、和方法,并且更具体涉及被收获的供体心脏的移植适宜性的移植前评估。
背景技术
心力衰竭侵袭着10%的北美洲人并且是最主要的出院诊断。诊断出心力衰竭就伴随着与主要的癌症差不多的生存希望。对于患有心力衰竭的患者来说它们的康复选择能力有限,实际上极少策略能够使心脏重新具有活力。对于患有终末期心力衰竭的患者来说心脏移植仍是金标准的治疗干预方法,每年都有日益增加的个人被添加到移植等待者名单中。然而,这种维持生命的干预的更加广泛的应用受可用供者的限制。来自InternationalSociety of Heart and Lung Transplantation Registry的数据显示心脏移植术在合适的供者方面呈下降型(2007,Overall Heart and Adult Heart TransplantationStatistics)。在过去的十年间已经有二百五十八个加拿大人在等待心脏移植的过程中死去(2000-2010;Heart and Stroke Foundation of Canada)。同样,在美国,仅仅在2010年就有304个患者在等待心脏移植的过程中死去(Organ Procurement and TransplantationNetwork,US Dept.of Health&Human Services)。这种现象主要是由于适当的器官供者短缺而造成的,并且正在全球范围内经历着。
心脏从供者移除并且成功地移植到受者体内最关键的是时间。下面的原则总体适用于在从供体移除和移植之间的时间段期间进行最佳的供体心脏保存:(i)最小化细胞肿胀和水肿,(ii)防止细胞内酸中毒,(iii)防止由氧自由基造成的伤害,和(iv)提供在再灌注期间进行高能磷酸化合物和ATP再生的基体。进行移植的供体心脏的两个主要来源是由于头部钝伤或脑内出血引起的脑功能不可逆地丧失、但仍有呼吸并且被划分为“脑死亡”供体的患者,以及患有循环衰竭死亡并且被称为“非心跳”供者的患者。
脑死亡器官供者在人工呼吸条件下可维持一延长时间段,用于在他们体内提供相对血液动力学稳定性,直到器官检索或提取(organ retrieval)时。因此,心脏灌注是不能妥协通融的(uncompromised)并且器官功能性理论上得以维持。然而,脑死亡自身可能会深度影响心脏功能。对脑死亡的体液反应的特征是循环中的儿茶酚胺类显著升高。对此“儿茶酚胺风暴”的生理学反应包括血管收缩、高血压和心动过速,所有这些都将增加心肌氧需量。在冠脉循环中,在脉管***中循环的儿茶酚胺显著增加的水平导致血管收缩,这继而损害心肌氧供应并且可能导致心内膜下缺血。在下面的脑死亡中观察到心肌氧供应和需求之间的这种不平衡是与心脏功能损失密切相关的一个因素(Halejcio-Delophont等人,1998,Increase in myocardial interstitial adenosine and net lactate production inbrain-dead pigs:an in vivo microdialysis study.Transplantation 66(10):1278-1284;Halejcio-Delophont等人,1998,Consequences of brain death on coronaryblood flow and myocardial metabolism.Transplant Proc.30(6):2840-2841)。脑死亡后发生的结构性心肌损失的特征是肌细胞崩溃、收缩带坏死、心内膜下大出血、水肿和间质单核细胞浸润(Baroldi等人,1997,Type and extent of myocardial injury related tobrain damage and its significance in heart transplantation:a morphometricstudy.J.Heart Lung Transplant 16(10):994-1000)。虽然没有直接心脏损伤,但脑死亡供者通常呈现出降低的心脏功能,并且当前的观点是只有25%的心脏可从种供者人群恢复用于移植。
已经研发出用于从非心跳供者收获移植用心脏的明确规定的标准(Kootstra等人,1995,Categories of non-heart-beating donors.Transplant Proc.27(5):2893-2894;Bos,2005,Ethical and legal issues in non-heart-beating organdonation.Transplantation,2005.79(9):p.1143-1147)。非心跳供者具有极少的脑功能但不满足脑死亡的标准,因此不能合法宣布为脑死亡。在非常清楚患者没有恢复希望时,医生和家庭必须一致同意撤走支撑措施。在医疗上,直到这时,非心跳患者通常利用机械强制呼吸以及静脉注射强心剂或血管加压药来支撑。然而,只有单一***器官出现衰竭(神经***)的那些可以考虑进行器官捐献。撤走生命支撑、最常见的是停止机械强制呼吸,之后就是缺氧心脏停搏,然后在允许进行器官获取之前患者必须保持心搏停止五分钟。因此,非心跳供者在心脏停搏后必须暴露于可变时长的热缺血,这可能导致不同程度的器官损伤。然而,在热缺血持续时间不过长的情况下,从非心跳供者获得的许多类型的器官,即肾、肝、肺,在移植后能够恢复功能的成功率与从脑死亡的心跳供者移植器官的情况差不多。
已经研发出许多灌注设备、***和方法用于所收获的器官的体外维护和运输。多数采用低温环境来降低器官新陈代谢,降低器官能量需求,延迟高能磷酸盐储备消耗,延迟乳酸积累,以及减缓与中断充氧血的供应有关的形态和功能退化。在这些***中,所收获的器官通常被灌注包含低温的抗氧化剂和丙酮酸盐的防腐溶液来维持它们的生理学功能。然而,已经发现在脉冲式加压的低温***中、在所收获的器官的延长维护期间引起了自由基和催化酶的量的增加。在这种***中的波动的灌注压力可能会通过冲刷掉它们的血管内皮细胞衬里而损坏这些器官以及使下面的组织受伤。此外,所收获的器官将洗提增加细胞内的、内皮的和薄膜成分的量,导致它们进一步生理虚弱。
这些领域的技术人员已经认识到了低温设备、***和方法的缺点,并且研发出可替代的设备、***和方法用于将所收获的器官保存和维护在约25℃至约35℃范围内的温度,通常称为“常温”温度。常温***典型地利用以下述中的一种或多种增补的基于Viaspan配方的灌注液:作为蛋白质和胶体源的血清白蛋白,用于增强生活力和细胞功能的微量元素,用于氧化磷酸化支撑的丙酮酸盐和腺苷,作为附着因子的铁传递蛋白;用于新陈代谢支撑的胰岛素和糖,用于清除有毒自由基以及浸透源的谷胱甘肽,作为浸透源的环式糊精,清除剂,以及细胞附着和生长因子的增效剂,用于微脉管新陈代谢支撑的高Mg++浓度,用于生长因子强化和止血的黏多糖,以及内皮生长因子(Viaspan包括乳糖酸钾,KH2PO4,MgSO4,蜜三糖,腺苷,谷胱甘肽,别嘌呤醇,和羟乙基淀粉***)。其它常温灌注液已经被研发出来并且被使用(Muhlbacher等人,1999,Preservation solutions fortransplantation.Transplant Proc.31(5):2069-2070)。虽然在常温***中所收获的肾和肝可被维持超过十二小时,但很显然地,所收获的心脏被脉冲式灌注常温浸泡、维护超过12小时会导致心脏的生理学功能退化和不可逆的变虚弱。使用常温、连续脉冲式灌注***进行所收获的心脏的维护的另一不利因素是从供者切除心脏、将其安装在常温灌注***内、然后开始和稳定化灌注过程所需的时间。在被切除的心脏被稳定之后,其生理学功能即被确定,并且如果满足移植条件的话,则尽可能快地将切除的心脏运输到移植设施。
当前的技术采用闭塞式滚子泵将灌注液液流供应到离体(isolated)的主动脉根内。利用此方法,如果没有显著升高的收缩应力,心脏就不能抵抗泵而喷射。此外,当前市场上没有除提供被切除心脏的新陈代谢评估之外还允许对右和左心室进行心脏收缩和心脏舒张功能的综合性评估的装置。
发明内容
本公开涉及用于维护和监控被切除供体心脏的生理学功能的设备、***、和方法。
本设备包括将切除的心脏接收并且浸没在不断循环的灌注液中的第一部件,包括用于调节灌注液的温度和氧含量的装置的第二部件,包括非闭塞性离心泵用于在保存模式中将灌注液泵送到被切除的心脏的离体大动脉根内并且用于在工作/评估模式中对射血提供非闭塞性阻力(后负荷)的第三部件,以及包括非闭塞性离心泵用于在工作/评估模式中提供被切除的心脏的填充(前负荷)的第四部件。通过将泵定位在心脏下面,与泵的非闭塞性特性相结合,在心肌功能不良或心律失常的情况下提供被切除的心脏的紧缩。在当前的设计中,避免了需要重力作为向被切除心脏提供前负荷或后负荷的能量源,从而允许本公开设备的紧凑、便携式设计。
本***总体上包括安装被切除心脏的设备,其中该设备与下述互连:(i)灌注液泵送***,(ii)用于监控至和从被安装心脏的主动脉、肺动脉、肺静脉和下腔静脉的灌注液液流的流量传感器,(iii)可与被切除心脏互连的ECG设备,和(vv)使被切除心脏与利用独立于载荷的指数和依附于载荷的指数来监控被切除心脏的生理学功能的仪器互连的探针。
附图说明
下面结合对附图的参考来描述本发明,图中:
图1是根据本公开的一个实施例的用于所收获的供体心脏的示例性维护设备的示意图;和
图2是本公开的所收获的供体心脏维护设备的起搏器,ECG监控,和除颤器部件的示例性实施例的局部放大图。
具体实施方式
除非以其它方式指出,在这里使用的所有技术和科学术语具有与本发明所属领域内的普通技术人员通常理解的相同的含义。为了使在这里描述的本发明能够得到完全的理解,提供了下面的术语和定义。
词语“包括”或其变异词应理解为隐含包括所指出的整数或整数组但不排除任何其它整数或整数组。
术语“大于”和“约”是指在给定值或范围的20%内,优选10%内,并且更优选5%内。
如在这里所使用的术语“调整(modulate)”是指通过增大到该装置的信号以最大该装置的输出或通过减小到该装置的信号以减小该装置的输出,来调节该装置的操作。
术语“后负荷”是指心脏腔为了收缩而产生的平均张力。也可以理解为心脏要喷射血而必须克服的“载荷”。因此,后负荷是大动脉的大血管顺应性、波反射和小血管阻力(左心室后负荷)或类似肺动脉参数(右心室后负荷)的结果。
术语“前负荷”是指单一心肌肌细胞在收缩前的伸张并且因此与肌小节长度有关。因为肌小节长度在在完整的心脏中不能确定,所以使用前负荷的其它指标、比如心室舒张末期容积或压力。作为例子,在静脉血回流增加时前负荷增大。
术语“心肌细胞”是指心肌肌肉细胞。
术语“血搏出量”(SV)是指在单一收缩过程中由右/左心室喷射的血量。它是舒张期末容积(EDV)和收缩末期容量(ESV)的差。从数学上讲,SV=EDV-ESV。血搏出量受前负荷、后负荷和收缩力(缩小力)的影响。在正常的心脏中,SV不太受后负荷影响,而在衰竭的心脏中SV对后负荷的变化非常敏感。
术语“每搏作功”(SW)是指左或右心室分别为了向主动脉或肺动脉喷射血搏出量而所做的功。由压力/容积环封闭的面积是心室每搏作功的量度,其是血搏出量和平均大动脉或肺动脉压力(后负荷)的积,取决于所考虑的是左心室还是右心室。
术语“射血分数”(EF)是指在每次收缩过程中被喷出心室的舒张末期容积的分数。从数学上讲,EF=SV/EDV。健康心室的射血分数通常大于0.55。低EF一般表示收缩功能障碍并且严重的心力衰竭可能导致EF低于0.2。EF还用作心脏的收缩力(缩小力)的临床指示。增大收缩力导致EF增大,而减小收缩力则减小EF。
术语“收缩末期压力-容量关系”(ESPVR)说明的是在任一给定左心室容积下左心室所能够产生的最大压力,或者可选地,在任一给定右心室容积下右心室所能够产生的最大压力。这意味着,对于任一给定收缩状态,PV环都不能跨过限定ESPVR的线。ESPVR的斜率(Ees)代表收缩末弹性,其提供心肌收缩性指数。ESPVR对前负荷、后负荷和心率的变化相对不敏感。这使其成为优于诸如射血分数、心排血量和每搏输出量的其它动力参数,的改进的收缩功能的指标。此ESPVR随着收缩力(缩小力)增大而变陡并且向左移位。此ESPVR随着收缩力(缩小力)减小而变平坦并且向右移位。
术语“前负荷补充搏功关系”(PRSW)是心肌收缩力的量度,是SW和EDV之间的线性关系。
术语“压力-容积面积”(PVA)是指心室收缩产生的总机械能。这等于被包含在PV环内的每搏作功(SW)和弹性势能(PE)的和。从数学上来讲,PVA=PE+SW。
术语“Langendorff灌注”是指经由主动脉以相反的方式用富含营养的氧合液灌注被切除心脏的方法。向后的压力致使主动脉瓣关闭从而迫使溶液进入通常向心脏组织供血的冠状血管内。这向心脏肌肉供给营养和氧,允许其在从动物身上去除之后继续跳动若干小时。
如这里所使用的术语“工作心脏”是指通过经由左心房进行的心室充盈而对被切除心脏进行的临床体外冠状动脉灌注,以及通过心脏的收缩功能和规律的心律驱动的、从左心室经由主动脉的喷射。被切除心脏通过套管附接到Langendoff准备中的灌注液存储器和循环泵。在“工作心脏”模式下,灌注液通过被切除心脏的流动在与Langendoff灌注期间灌注液流动相反的方向上。
术语“缺血”指的是当血流和氧被阻止到达心脏时发生的情况。
如这里所使用的术语“导管”是指管道和/或套管。
本公开有关于一种将被切除心脏保持在持续的Langendorff灌注环境下直到移植的设备、***和方法。本设备和***是可以传授的,并且可与用于监控被切除心脏的生理学环境和功能的心脏监控设备和微处理器共同操作。
本公开的一个实施例有关于一种用于将被切除心脏接收和保持在持续的Langendorff灌注环境下直到移植的示例性模块式设备。此示例性设备包括两个模块。第一模块包括硬壳存储器,在这里也称为存储器,用于将被切除心脏容纳于其中,用适当的灌注液溶液持续浸泡。在硬壳存储器内,被切除心脏安装在架子上并且被浸没。硬壳存储器被提供有四个端口(即两个出口端口和两个进入端口),它们被已经与被切除心脏的右心房、左心房、主动脉和肺动脉互联的导管可密封地接合。第二模块是包括下述的灌注液调温设备:(i)用于加热灌注液溶液并且将其保持在用户指定温度(通常被称为正常温度)的热交换器,和(ii)用于将灌注液溶液中的溶解氧水平保持在95%饱和度以上并且通过添加二氧化碳而保持PH平滑的充氧器。这两个模块通过可与泵、比如离心泵相接合的导管基础结构互连。合适的离心泵的例子是离心泵(ROTAFLOW是Maquet CardiopulmonaryAG Corp.,Hirrlingen,Fed.Rep.Ger.的注册商标),Medtronic的离心血泵BIO-PUMP是Medtronics Bio-Medicus Inc.,Minnetonka,MN,USA的注册商标),Sorin的RevOlution 5 blood pump(Sorin Group USA,Arvada,CO,USA)。操作过程中,离心泵将来自第一模块(即硬壳存储器)的恒定的灌注液液流提供至第二模块(即灌注液调温设备)。第一模块另外被提供有用于接收来自心脏监控设备的引线的端口,用于接合被切除心脏上和/或中的特定部位。每个模块可被进行单独的组装和制备以与多个单元一起使用,从而以便根据需要快速组装和配置该设备,以接收和维持被切除心脏。
根据本公开的一个实施例的示例性设备10在图1中公开了。该设备包括:(i)第一部件,其是容纳着可拆除支撑(未示出)的硬壳存储器20,所述可拆除支撑用于在其上和其中安装被切除心脏100,和(ii)第二部件,其是包括热交换器36和充氧器37的灌注液调温装置35。硬壳存储器20可另外具有用于监控硬壳存储器20中的灌注液水平的水平传感器(未示出)。这两个部件通过第一导管基础结构互连,所述第一导管基础结构包括:(i)出口线30,出口线30在一端与设置在硬壳存储器20的底部附近的端口22可密封地连接,并且在其另一端与第一离心泵32的入口可密封地连接。第一离心泵32的出口与线34可密封地连接,线34与通向灌注液调温装置35的热交换器36的入口可密封地连接。线40与来自灌注液调温装置35的充氧器37的出口可密封地连接。线40的另一端与Y-接头42可密封地连接,Y-接头42使来自灌注液调温装置35的经调温的灌注液的液流的一部分转向到净化线50内,净化线50与设置在硬壳存储器20上的第一进入端口26可密封地连接。灌注液调温装置35的液流的剩余部分通过Y-接头42转向到与集成压力端口46互连的流量传感器44内,所述集成的压力端口46可夹锁(clampable)到被收获心脏的主动脉150内。操作过程中,流量传感器44测量从灌注液调温装置35进入主动脉150的经调温的灌注液的大动脉流。从硬壳存储器20出来进入灌注液调温装置35的灌注液通过在热交换器36中加热而调节至从约20℃至约37℃范围的常温,然后在流到线40内之前通过充氧器37充氧,再传送到主动脉150内。主动脉150中的舒张压可被指定,并且通过计算机控制反馈精细(tightly)调节,来调整离心泵32。在评估模式期间,随着向左心房内供应液流,心脏将灌注液向回喷射通过线40,同时离心泵32提供阻力(后负荷)。以这种方式,心脏能够抵抗着通过来自离心泵32的灌注液的液流传送的后负荷压力而跳动。
第二导管基础结构包括线60a,线60a在一端与设置在硬壳存储器20底部附近的第二出口端口24可密封地连接,并且在其另一端与进入第二离心泵62的入口可密封地连接。第二离心泵62的出口与终止于Y-接头64的线60b可密封地连接。Y-接头64将加压后的灌注液液流分到两个线70,80内。线70首先与阻断钳夹72、其次与流量传感器74、然后与集成压力端口76互连。线70的终端可***所收获的心脏100的右心房130内。应注意阻断钳夹72优选是伺服致动的局部阻断钳夹,其可变化的状态使得能够调节进入右心房130内的灌注液的流速,并且因此还能够用于调节被传递至所收获心脏100的压力。线80首先与流量传感器82、然后与集成压力端口84互连。线80的终端可***被收获心脏100的左心房140内。应注意线70,80另外被提供有气泡检测器(未示出)。在评估模式期间,泵62将灌注液液流从压力端口84,76供应到反馈环下面的右心房和左心房(前负荷压力)内,同时进入右心房和左心房的不同液流控制通过钳夹72的调节来提供。在例如由于心律失常或心脏功能不良而引起心脏过量增压的情况下,来自泵62的灌注液液流被减少,从而通过使灌注液被动地向回逆行流经泵62而允许发生心脏减压。
第三导管基础结构包括可夹锁到被收获心脏100的肺动脉160上的线96。线96依次与压力端口90、流量传感器92、和第三离心泵94可密封地连接。线96的终端与设置在硬壳存储器20上的第二进入端口28可密封地连接。泵94通过参考来自压力端口90的反馈、对泵94进行计算机控制的调整来为右心室提供阻力(后负荷压力)。
图2示意出在本公开的示例性设备中的、用于在存储和运输期间的功能条件下维持所收获的心脏的示例性监控和维护装置。来自ECG监控装置170的引线172例如与被收获心脏100的右心室110和左心室120可接合,用于监控被收获心脏100的电活动。可选地,ECG引线可被一体地引入到硬壳存储器20的壁内。来自双腔起搏器190的引线192与被收获心脏100的右心房130和右心室110可接合。虽然双腔起搏器与本公开的设备10一起使用是首选的,但用具有与右心房或右心室可接合的单一引线的单腔起搏器来替代也是可选的。两个除颤器垫184被以彼此面对的方式一体地设置在硬壳存储器20的内表面上,并且通过引线182连接到除颤器。ECG监控装置170,起搏器190和除颤器180可安装在一支撑上,该支撑被提供(未示出)为硬壳存储器20的一体部件。可选地,ECG监控装置170,起搏器190和除颤器180可被一体地引入到运输容器的外壳内,所述运输容器被配置为在其中接收硬壳存储器20。
一旦被切除心脏100被安装到可拆除支撑上并且被放置在硬壳存储器20内,线40的终端即被夹锁到主动脉150内,线70被***右心房130内,线80被***左心房140内,并且线96被夹锁到肺动脉160内。这样,适当的灌注液,比如全血、用柠檬酸盐和/或磷酸盐和/或葡萄糖修改(amend)的全血、修改的克雷布斯液、Viaspan、修改的Viaspan溶液等,被添加到硬壳存储器20内,直到心脏100被完全浸没。应注意硬壳存储器20可另外被提供有水平传感器(未示出)和灌注液(未示出)的补偿供应以根据需要传送到硬壳存储器20,以便在本公开的设备中在存储和运输期间被切除心脏100保持完全浸没。
当处于操作过程中时,泵32持续地从硬壳存储器20从出口端口22抽取灌注液到线30内、到灌注液调温装置35内,其中灌注液通过被加热到常温温度而进行调温,然后被充氧。经调温和加压调温的灌注液被输送到Y-接头42,Y-接头42将经调温的灌注液的一部分转向到净化线50内,用于通过进入端口26输送回到硬壳存储器20内,在这里它围绕着心脏100循环并且浸泡心脏100。经加压调温的灌注液的剩余液流被通过流量传感器44和集成的压力端口46传送到主动脉150内。应注意当被切除心脏100安装在组装设备10中时净化线50被定位在组装设备10中的最高点,以便被心脏喷射出的任何空气能够立即经由净化线50流出并且回到硬壳存储器20。
前负荷离心泵62将灌注液从硬壳存储器通过出口端口24抽取出来进入线60b然后将灌注液推至Y-接头64,在那里液流被分成两条线70,80。灌注液被推动通过线70、通过计算机控制的伺服致动的局部阻断钳夹72、流量传感器74、和集成压力端口76到达右心房130内。伺服致动的局部阻断钳夹72的可变状态使得进入右心房130的灌注液流速能够得到精确调节。并行地,灌注液被推动通过线80、通过流量传感器82和集成的压力端口84进入左心房140。
流入主动脉150,右心房130,和左心房120内的加压灌注液流入右心室140内,然后通过肺动脉160流出进入线96,首选通过集成的压力端口90、然后通过流量计92、接着通过后负荷离心泵94,用于调节右心室后负荷压力(该压力通过流量计92进行测量),最后通过入口端口28回到硬壳存储器20。经由线40进入主动脉150的经调温灌注液的加压液流通过离心泵32供应并且被大动脉流量传感器44监控。进入主动脉150然后流出肺动脉160的经调温的灌注液的加压液流使心脏100维持在Langendorff离体根灌注状态。为了在工作模式中维持和评估心脏的功能,需要对前负荷进行精确调节。因此连接到右心房和左心房的线70,80分别包括3/8"管道并且接收来自前负荷泵62的灌注液的加压液流。右心房液流压力通过流量传感器74监控而左心房液流压力通过流量传感器82监控。计算机控制的伺服致动的局部阻断钳夹72使得到右心房130和左心房140的灌注液的速率、以及因此被施加到接收腔的压力能够得到精确控制。流量计44,74,82,92和集成的压力点46,76,84,90可连接到计算机并且与其通信用于持续监控和整合流速和压力,以能够实现持续地评估心脏功能,即右心室每搏动功和左心室每搏动功,同时改变对灌注液液流的阻力(即,后负荷)。应注意,在灌注开始之前灌注液中的血细胞比容,Ca++,K+,NaHCO3,Na+,pO2,CO2,和葡萄糖的水平必须得到平衡。在使用血库CPD供者血的情况下,混乱的(deranged)K+和Ca++浓度可能不允许自我平衡的稳态(homeostatic prime)。这可以通过使用林格氏液作为冲洗剂进行血液过滤来调节。理想地,所有这些值都应该在正常生理学范围内开始,并且应该通过在线连续血气分析监控。灌注液的首要目的是避免导致组织水肿和维持离子均衡以保持心肌功能。
本公开的另一示例性实施例涉及一支撑,该支撑用于在其上安装和从其上拆卸模块和泵。该支撑可另外具有安装座,用于安装心脏监控设备和/或计算机设备和/或用于显示被切除心脏的生理学环境和功能的监控器。该支撑可以是安装在轮子上的支架***,以便该设备能够在医疗设施内运输,例如,在外科手术室、分段运输间、装配间和拆卸间之间。该支撑可以是具有两个相对侧壁并且另外两侧上具有开口门的柜体。可选地,该支撑可以是这样的柜体,其三个固定的侧壁是对置设置的壁并且具带开口门的一侧。这些侧壁和门可被绝缘和/或带衬垫。该支撑可被配置为通过车辆或飞机运输。
本公开的另一示例性实施例涉及一种用于接收、灌注和维持和评估被切除的供体心脏的***。该***总体上包括与下述互连的上述设备:(i)灌注液-处理***,(ii)灌注液泵送***,(iii)用于监控至和从被安装心脏的主动脉、右心房、左心房和肺动脉腔静脉的灌注液液流的流量传感器,(iv)可与被安装心脏互连的ECG设备,(v)可与被安装心脏互连的起搏器,(vi)可与一对除颤器垫互连的除颤器,所述一对除颤器垫和该设备的硬壳存储器部件的内表面是一体的,和(vii)可使被切除心脏与利用独立于载荷的指数和依附于载荷的指数来监控心脏的生理学功能的仪器互连的探针。适当的灌注液-处理***的例子是通常用于冠状动脉架桥外科手术的体外循环机。
本公开的设备、***和方法的示例性用法总体上包括灌注液的选择、准备和平衡的步骤,通过如下设置***的步骤:使灌注液-处理***和带有套管的双向灌注液泵送***与互连,其中所述套管随后被与所述接收、维持和评估用设备的盖上的适当端口互连,为该互连的***填装灌注液的步骤,将被切除心脏安装到设有该设备的支撑上的步骤,以及然后将适当的套管安装到该心脏的主动脉、肺动脉、肺静脉和腔静脉内的步骤,从心脏和套管内排出(express)空气的步骤,以及在从约25℃至约35℃范围的常温下开始Langendorff灌注的步骤。
Claims (6)
1.一种用于被切除的供体心脏的维护和运输的模块式灌注设备,包括:
第一模块,其包括带有可拆除支撑的硬壳存储器,所述可拆除支撑用于在其上定位和安装被切除心脏,所述硬壳存储器具有与所述硬壳存储器的内表面接合的一对相反的除颤器垫;
第二模块,其包括与充氧器连通的热交换器;
支撑,用于使第一模块和第二模块可脱开地安装于其上;
第一导管基础结构,其使第一模块、第二模块和被切除的供体心脏的主动脉互连,所述第一导管基础结构具有用于从第一模块向第二模块推动灌注液的第一离心泵;
第二导管基础结构,其使第一模块与被切除的供体心脏的右心房和左心房相连接,所述第二导管基础结构具有用于从第一模块向所述右心房和左心房推动灌注液的第二离心泵;和
第三导管基础结构,其使第一模块与被切除的供体心脏的肺动脉相连接,所述第三导管基础结构具有用于向来自肺动脉的灌注液流提供后压力的第三离心泵。
2.根据权利要求1所述的模块式灌注设备,还包括用于使第一模块,第二模块,第一离心泵,第二离心泵和第三离心泵可脱开地安装于其上的支撑。
3.根据权利要求2所述的模块式灌注设备,其中,所述支撑包括用于包装所安装的第一模块,第二模块,第一离心泵,第二离心泵和第三离心泵的外壳。
4.根据权利要求1所述的模块式灌注设备,还包括ECG监控装置。
5.根据权利要求1所述的模块式灌注设备,还包括心脏起搏器。
6.根据权利要求1所述的模块式灌注设备,还包括与所述一对除颤器垫连通的除颤器。
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EP3122180A4 (en) | 2018-01-03 |
EP4023066A1 (en) | 2022-07-06 |
CA3164819A1 (en) | 2015-10-01 |
CN113229273B (zh) | 2023-01-31 |
BR112016021971A2 (zh) | 2017-08-15 |
AU2015234580B2 (en) | 2018-11-15 |
US10327442B2 (en) | 2019-06-25 |
AU2015234580A1 (en) | 2016-10-27 |
EP3122180B1 (en) | 2022-05-11 |
BR112016021971B1 (pt) | 2022-05-17 |
EP3122180A1 (en) | 2017-02-01 |
CN106659150B (zh) | 2021-06-01 |
CN113229273A (zh) | 2021-08-10 |
CA2943633A1 (en) | 2015-10-01 |
ES2916212T3 (es) | 2022-06-29 |
CA2943633C (en) | 2023-06-20 |
US20190387736A1 (en) | 2019-12-26 |
WO2015143552A1 (en) | 2015-10-01 |
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