CN1195457C - 用于覆盖左心房附件口的屏障装置 - Google Patents
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Abstract
本发明公开了一种用于心房附件口的膜。该膜防止心房附件内的血凝块从该心房附件中溢出和进入血流中,血凝块的溢出和进入血流将导致血管堵塞,引起中风和心脏病。该膜相对于血流是可渗透或不可渗透的。该膜设置成盖住左心房附件的口而延伸。该膜的外周的直径大于口的相应尺寸。还提供有固定装置,用于使膜的外周直接与环绕该口的心房壁配合。该固定装置可以位于膜和心房壁之间,或者该固定装置可以从该膜并穿过该口向远处延伸。
Description
技术领域
本发明涉及用于或跨过心房附件口的膜结构,以便防止血栓离开心房附件。
背景技术
多种心脏病(例如冠状动脉疾病、二尖瓣疾病)对心脏有着各种不利的影响。某些心脏疾病例如二尖瓣疾病的不利影响是心房(或心耳)纤颤。心房纤颤可能导致血液汇集到左心房附件内。血液汇集还可能自发产生。当血液汇集到心房附件中时,血凝块可能在该心房附件中形成和积聚,它们自身不断累积,并从心房附件往外传播到心房内。然后,这些血凝块能够进入体循环或肺循环,且当它们从心房附件中出来、在血流中自由运动并在远处栓塞到动脉系统内时,将引起严重的问题。当从心房附件延伸到心房中的血凝块断裂和进入血液供给时,也产生类似的问题。因为血从左心房和心室供给心脏和大脑,从心房附件出来的血凝块可能阻塞心脏和大脑中的血流,引起心脏病发作、中风或其它器官局部缺血。因此,需要找到一种装置,该装置将防止血凝块在心房附件中形成,且一旦形成血凝块,将防止这些血凝块离开心房附件到达病人的心脏、肺、大脑或其它循环系统,这可能导致心脏病发作、中风或其它器官局部缺血。
美国专利5865791涉及减小血瘀区域,最终减少血栓在该区域中的形成,尤其是在有心房纤颤的病人的心房附件内。尤其是,专利′791涉及用于固定心房附件的方向的方法和装置,该方法和装置将防止随后形成血栓。在专利′791中,通过将该附件拉起并将一个环环绕该附件而放置以形成一个心房附件袋,再将它从心脏的其余部分上切下,从而将该附件从心房上取下。
美国专利5306234涉及一种通过手术来封闭心房和心房附件之间的通道或割断心房附件的方法。
其它治疗方法包括手术去除心房附件,以便防止在心房附件中形成血瘀。
发明内容
本发明提供了一种用于盖住病人的左心房附件的口而固定的装置,包括:一膜,该膜可盖住左心房附件的口而延伸,该膜的外周的尺寸大于该口的相应尺寸;其特征在于,该膜有可渗透的结构,该可渗透结构允许血液流过该膜,但是基本防止血栓通过,以及固定装置,用于将该膜的外周固定而直接与口周围的心房壁配合,其中,该固定装置包括用于穿透围绕着所述口的心房壁和心房附件的壁这二者中的至少一个的装置。
该膜基本防止在心房附件中形成的血凝块离开该心房附件。如果允许该血凝块离开心房附件并进入血流中,可能导致心脏病发作、中风或其它栓塞现象。该膜通过直接固定在口上或口附近的心房壁上的固定装置而跨过心房附件的口而永久性地布置。
该膜有效防止左心房附件内血凝块离开并进入心房。它可以比该附件的口更大,并在比该口更大的区域内延伸。该膜通过导管而经皮肤传送到心房附件口,然后可以膨胀,以便跨过或盖住该口而定位。
根据一个实施例,该膜对于血流是不可渗透的。该膜防止左心房附件中的血栓离开并进入血流。该膜还防止血液流入或流出左心房附件。
根据另一实施例,该膜自身是可渗透的,以便允许血液流过该膜。通过允许该血液流过该膜,该可渗透结构以可控制的方式使得心房附件和心房之间的压力梯度减至最小。而且,该可渗透膜作为滤器,允许血液流过,但是基本防止血栓通过。
该可渗透过滤膜可以最终由细胞渗透。该可渗透的过滤膜允许组织沿该结构的外周开始生长。该组织生长使得在过滤膜周边附近的不可控制的泄漏减至最小,还可以有助于使跨过该口的过滤膜固定在包围该口的组织上。该过滤膜可涂覆有抗凝血剂或其它化合物如肝素,或者可对其进行处理,以防止血栓在过滤膜表面上形成,从而延长其开放期,或者直到它被细胞渗透和/或发展成内皮覆层。
可以有多种将该膜固定在跨过心房附件口的位置处的装置。直接用于固定该膜的固定装置可以由涂布在该膜和口或心房壁之间的可生物相容的粘接剂提供。这样,该膜可以直接粘接在组织上。在另一实施例中,通过利用钉子、夹子、缝合线、丝线、倒钩、尖头或其它方式的固定件来形成直接固定,该钉子、夹子、缝合线、丝线、倒钩、尖头或其它方式的固定件穿过该口或心房壁的组织。在另一实施例中,利用与膜相连的结构进行直接固定,该结构通过该口并伸入心房附件的内部并与心房附件的内部配合,其中,心房附件的内壁还可以包括延伸到心房附件内的该口的任意部分。该直接固定装置可以提供使该膜在附件口周围自己定心的特征。
发明目的
本发明的一个目的是提供一种在心房和心房附件之间的膜,以便防止血凝块在它们之间流动。
本发明的一个目的是提供一种膜,该膜通过直接固定在该口上或直接固定在靠近该口的心房壁上,从而永久性植入到心房和心房附件之间。
本发明的一个目的是提供一种在心房和心房附件之间的膜,该膜对于血流是不可渗透的或者使血栓不能通过。
本发明的一个目的是提供一种在心房和心房附件之间的过滤膜,以便例如允许血液流过该滤器,从而例如降低心房和心房附件之间的血液动力压差。
本发明的一个目的是防止血凝块在心房附件内形成。
本发明的一个目的是将一个不形成血栓且生物相容的表面跨过心房附件的口而定位,该不形成血栓且生物相容的表面将防止形成血凝块。
本发明的一个目的是提供一种可渗透的过滤膜表面,该过滤膜表面最后可以衬有内皮或心内细胞衬。
本发明的一个目的是通过过滤膜来合适地使心房附件相对于血栓通道而与心房隔开,同时使得血液可以通过该过滤膜而流通。
本发明的一个目的是以最小侵入来防止血凝块在心房附件中形成和从该心房附件中溢出。
本发明的一个目的是通过用在膜上的或从该膜上洗提的肝素或其它抗血栓形成的物质或其它化合物而防止形成血栓。
本发明的一个目的是保证该膜定心而跨过或盖住心房附件的口。
本发明的一个目的是将膜精确布置而跨过或盖住心房附件的口。
通过下面的详细说明并结合附图,可以更了解本发明的其它目的、优点和新颖性特征。
附图的简要说明
图1是心脏的局部剖视图,表示根据本发明导管利用逆行方法(retrograde)而从主动脉进入左心房附件。
图2是心脏的局部剖视图,表示根据本发明导管利用横过隔膜方法(transeptal)而从股静脉或上腔静脉进入左心房附件。
图3是心脏的局部剖视图,表示根据本发明导管从颈静脉或可选择从股静脉进入右心房附件。
图4是心脏的一部分的局部剖视图,表示心房和它的相关心房附件。
图5是传送导管的局部剖视图,根据本发明,该传送导管中有盘、弹簧和膜。
图6是根据本发明盘、弹簧和膜在离开图5的传送导管并膨胀之后的示意图。
图7是心脏的一部分的局部剖视图,表示心房及其相关心房附件,根据本发明,该心房及其相关心房附件有盘、膜和在该盘和膜之间的弹簧。
图8是心脏的一部分的局部剖视图,表示处于皱缩(collapsed)位置的心房及其相关心房附件。
图9是心脏的一部分的局部剖视图,表示心房及其相关心房附件,根据本发明,该心房及其相关心房附件有盘、弹簧、膜和在导管内的真空装置。
图10是心脏的一部分的局部剖视图,表示心房及其相关心房附件,根据本发明,表示了一个折叠的伞状物,用于进入心房附件。
图11是心脏的一部分的局部剖视图,表示心房及其相关心房附件,根据本发明,表示了在心房附件中打开的该伞状物,以便将该伞状物固定在心房附件的壁上。
图12是心脏的一部分的局部剖视图,表示心房及其相关心房附件,根据本发明,表示了该伞状物和跨过心房附件的口而定位的膜。
图13是心脏的一部分的局部剖视图,表示心房及其相关心房附件,根据本发明,表示了由于盘和弹簧将心房附件压向膜而使容积减至最小的心房附件。
图14是根据本发明的过滤膜和用于安装该过滤膜的装置的另一实施例的透视图。
图15是根据本发明的、图14中所示的过滤膜和装置的剖视图。
图16是根据本发明的、图15中的装置的一部分的放大图。
图17是表示根据本发明的、图14中的装置处于安装初始阶段时的局部剖视图。
图18是类似于图17的局部剖视图,表示在本发明的步骤中处于后期阶段。
图19表示了根据本发明的过滤膜和用于安装该过滤膜的装置的另一
实施例。
图20是根据本发明的、图19所示的过滤膜和装置的放大图。
图21是根据本发明的、图19-20所示的用于安装过滤膜的装置的平面展开图。
图22是根据本发明的、图21中的装置的一部分的放大透视图。
图23是根据本发明的、图21所示的装置处于膨胀结构时的平面展开图。
图24是根据本发明的、图20中的过滤膜和用于安装该过滤膜的装置的透视图,表示处于膨胀结构。
图25是本发明的过滤膜的一个实施例的纵剖图。
图26是本发明的过滤膜的另一实施例的纵剖图。
图27是本发明的过滤膜的又一实施例的纵剖图。
图28是本发明的过滤膜的又一实施例的纵剖图。
图29是表示根据本发明的、图19-28的过滤膜处于安装步骤的初始阶段时的局部剖视图。
图30是类似于图29的局部剖视图,表示在本发明的步骤中处于后期阶段。
图31是类似于图30的局部剖视图,表示在本发明的步骤中处于更后期阶段。
图32是类似于图31的视图,表示图19-23所示装置的另一可选实施例。
图33是类似于图32的局部剖视图,表示在本发明的步骤中处于后期阶段。
图34是类似于图33的局部剖视图,表示在本发明的步骤中处于更后期阶段。
图35(a)表示了根据本发明的、图19-20中所示的装置的另一可选实施例。
图35(b)表示根据本发明的、图35(a)中所示的装置处于膨胀结构。
图36是类似于图35(b)的视图,表示本发明的另一实施例。
图37是表示了根据本发明的过滤膜和用于安装该过滤膜的装置的又一实施例。
图38是根据本发明沿图37中的方向38的正视图。
图39是根据本发明沿图37中的方向39的正视图。
图40是表示根据本发明的、图37-39中的装置和附加装置的剖视图。
图41是表示根据本发明的、图37-39中的装置的第一安装结构的局部剖视图。
图42是与图41类似的局部剖视图,表示根据本发明的、图37-39中的装置的第二安装结构。
图43是表示本发明装置的另一实施例的局部剖视图。
图44表示了本发明的装置的又一实施例。
图45是根据本发明的、图44中的装置的端视图。
图46表示本发明的装置的又一实施例。
图47表示了根据本发明的、用于安装图44-46的装置的附加装置。
图48是根据本发明的、图47的装置的放大剖视图。
图49是图44-45中的装置的局部剖视图,表示在本发明的步骤中处于初始阶段。
图50是类似于图49的局部剖视图,表示在本发明的步骤中处于后期阶段。
图51表示了本发明的装置的又一实施例。
图52是根据本发明的、图51中的装置的端视图。
图53表示了根据本发明的、与图51-52中的装置一起使用的附加装置。
图54是根据本发明的、图51和53中的装置的放大剖视图。
图55是图51中的装置的局部剖视图,表示在本发明的步骤中处于初始阶段。
图56是与图55类似的局部剖视图,表示在本发明的步骤中处于后期阶段。
图57表示了本发明的装置的另一实施例。
图58表示了本发明的装置的又一实施例。
图59是图57中的装置的局部剖视图,表示在本发明的步骤中处于初始阶段。
图60是类似于图59的局部剖视图,表示在本发明的步骤中处于后期阶段。
图61是本发明的膜的另一实施例的简化视图。
图62是根据本发明的膜沿图61中的方向62的侧视图。
图63是根据本发明图61-62中的膜的局部剖视图,表示典型使用方法。
图64是本发明的膜的另一实施例的局部剖视图,表示典型使用方法。
图65是本发明的膜的又一实施例的简化视图。
图66是根据本发明的膜沿图65中的方向66的侧视图。
图67是根据本发明图65-66中的膜的局部剖视图,表示典型使用方法。
优选实施例的说明
尽管心房纤颤可能导致血液汇集到左心房附件中,且本发明将主要用于左心房附件,但是本发明也可以用于右心房附件,且通常用于跨过身体内的任意孔而布置,其中,能基本防止血凝块从腔体中溢出和进入血流中。
如图4中所示,当病人发生心房纤颤时,由于左心房附件13中的血液循环较弱,因此,血栓、血凝块或栓塞30(统称为血栓)可能通过血液汇集到左心房附件13内而形成。当血液汇集到左心房附件13内时,血栓30可能在左心房附件13内积聚,它们自身不断累积,并从心房附件13往外传播到左心房13内,从而离开心脏和进入血流中。一旦进入血流内,当血栓进入并固定在心脏、大脑或其它器官的动脉中时,该血栓可能堵塞流向心脏、大脑或其它器官或者末梢血管的血流。从而可能导致心脏病发作、中风或局部缺血。
为了防止血栓30在左心房附件13内形成或防止在左心房附件13内形成的血栓离开和进入血流从而可能导致心脏病发作、中风或局部缺血,膜40永久性固定而盖住或跨过心房附件13的口20。该膜40可以由生物相容的材料制成,例如:ePFTE(例如Gortex)、聚酯(例如Dacron)、PTFE(例如Teflon)、硅酮、氨基甲酸乙酯、金属纤维或其它生物相容的聚合物。
对于后面所述的各实施例,膜40对于血流来说可以基本是不可渗透的。对于不可渗透的膜,血液和血栓都不能流过该膜。如上所述,该结构防止心房附件内的血栓进入血流并引起心脏病发作、中风或局部缺血。该不可渗透的膜可以由上述材料制成,例如呈织物、编织物或基质形式的聚氨酯、聚酯(例如Dacron)、ePFTE(例如Gortex)。该不可渗透的膜还可以包括两种或更多材料的组合。在某些情况下,膜的外周可以由金属(例如不锈钢或镍钛诺)或塑料制成的支杆支撑或者由蜂窝结构(cells)或编织物支撑。(例如见图20、22、24、50、56)。该附加结构可以提供附加固定,以将膜的外周靠压在口周围的心房壁上,以便提供能防止泄漏的密封。
根据另一实施例,本文中所述的各膜结构40可以选择成对于流过的血流来说,基本为可渗透的。该可渗透的膜还可以作为过滤膜,其中,它基本防止血栓通过。该可渗透过滤膜的孔径范围可以为从大约50至大约400微米。还可以考虑,该孔可以根据情况更大或更小,只要该孔基本防止血栓通过即可。过滤膜的开口面积优选为总表面积的至少20%,不过,范围为大约25-60%为更优选。过滤膜的结构优选是两维筛网、蜂窝状基质、编织或非编织的网等。过滤膜还可以是细纤维的可渗透金属或金属网。该过滤膜可以涂覆有抗凝血剂,例如肝素或其它化合物,或者进行处理以提供抗血栓形成的特性。
如上所述,过滤膜的可渗透性允许血液流过,同时阻挡或防止形成于心房附件内的血栓、血凝块或栓塞通过和进入心脏心房并最终进入病人的血流中。
允许血液流过过滤膜的特性有多个优点。例如,在正常的心脏功能中,左心房附件固有地进行收缩,以便迫使血液流过心脏。该收缩导致血液流过左心房附件的口。允许血液流过过滤膜将大幅度减小在该附件和心房之间可能存在的压力梯度。
在从过滤膜结构植入心房附件中恢复的过程中,减小压力梯度将对病人有利。尤其是,当允许血液流过过滤膜并因此通过左心房附件的口时,心脏能够更加逐渐地适应该过滤膜的存在。
过滤功能还减小了在过滤膜外周附近泄漏的危险,或者减小了可能由于施加有压向过滤膜表面的压力而引起的过滤膜移动的危险。允许血液流过该过滤膜足够以可控制的方式释放该压力,从而减小该泄漏或移动。
组织向内生长可以提供将过滤膜固定在口上的附加固定。尤其是组织的生长可以沿过滤膜的外周或靠近口的支承结构进行。该组织生长和由可渗透结构提供的压力释放相结合,可以提供减小过滤膜外周附近泄漏的附加装置。组织生长可以最终覆盖过滤膜的附加表面区域。
跨过或盖住口20而布置的膜40将可以防止血栓形成。为了使该膜可以防止血栓形成,可以在膜40上采用肝素或其它抗凝血剂或抗血小板剂。
当采用可渗透过滤膜40时,细胞的生长可能导致内皮细胞最终覆盖该膜。内皮细胞有覆盖膜的光滑细胞壁,这将防止在膜上形成血栓。
图1和2表示了人的心脏的横截面,并表示了在左心房附件13中的血栓30。图中还表示了心房附件的口20,该口20将有盖住它的膜40,以便防止血栓30溢出心房附件13并进入左心房11,并因此进入血流中,而这将可能引起中风、心脏病发作或局部缺血。
图3表示了人体心脏的横截面,并表示了在右心房附件23中的血栓30。该右心房附件23可以以与左心房附件13相同的方式进行治疗。
图4表示了左心房11、口20和左心房附件13的横截面,该左心房附件13内有血栓30。
图5表示了传送导管125,包含有一个皱缩的膜40和一个通过在导管21上的弹簧90而与该膜40相连的皱缩盘130。盘130可以由柔性编织金属或内部夹有薄的可渗透聚合物的柔性编织金属制成。盘130还可以是聚合物织物。盘130是柔性的并进行压缩或折叠,这样,它能装入传送导管125中,并在从传送导管125中释放后能膨胀成所希望的形状。类似的,膜40进行压缩或折叠以便装入传送导管125,并在释放后膨胀成所希望的形状。膜40大于口20。图6表示了图5中的膜40、盘130和弹簧90在传送导管125外部处于膨胀状态时的形状。
图6表示了与膜40和盘130相连以便将它们压在一起的弹簧90。在其它实施例中,可以利用具有齿的弹性系绳或系绳和在膜40上形成棘爪的爪来将膜40和盘130拉在一起。因为膜40大于口20,膜40的外周与口周围的心房壁接触。
图7表示了图5中的装置,该装置用于有血栓30的左心房附件13。采用该装置后,弹簧90朝着膜40拉动盘130,从而使左心房附件13皱缩并将血栓30截留在该左心房附件中,如图8所示。弹簧90使膜40的外周固定而直接与口周围的心房壁配合。
图9表示了图7和8中的装置的一种可选实施例,其中,导管21配备有真空装置140,用于将左心房附件13内的血液和血栓30吸出。该真空装置140还有助于使左心房附件13皱缩,这样,弹簧90不需要象图7中那样大。
图10-12表示了本发明的另一实施例,该实施例利用伞的原理来将膜40固定而压靠口20。图10表示了进入左心房附件13的口20内的闭合伞撑杆160。膜40在伞撑杆160后面一定距离处,并在杆170上的齿195区域的底部。图11表示了在左心房附件13内部的伞撑杆,其中撑杆160打开。在杆170上的开伞结构175将撑杆推开到开伞位置。开伞结构175可以被推到开伞位置或有一个弹簧加载机构,以便将撑杆160推到打开位置。伞撑杆160的末端与口20周围的左心房附件壁配合,并防止该伞从左心房附件13中退回。与心房附件壁配合的伞撑杆160的末端可以是钝头或在端部有球状物或有衬垫,从而不会刺破左心房附件13。图21表示了通过使膜沿杆170啮合运动(ratcheting)而将膜40的外周拉起并压靠在口20周围的心房壁上。爪机构200与杆170上的齿195配合,并向前运动,以便将膜40定位而跨过口20,这样,膜40的外周与口周围的心房壁直接配合。
图13表示了压缩的左心房附件13,这样,心房附件的容积减小到几乎没有。通过使容积减小,心房附件不会有能够产生血栓的大量血液。在所示实施例中,盘130和弹簧90朝着膜40拉左心房附件13。尽管图13所示为用盘130和弹簧90作用在左心房附件上,但也可以采用其它任何能尽量减小心房附件容积的方法。
如图13中所示,膜40比口20大得多。该过大尺寸的膜40可以选择用于所有实施例,以便保证口20被完全盖住。弹簧90使膜40的外周固定而与口20周围的心房壁直接配合。膜40具有能阻挡或基本防止血栓、血凝块或栓塞进入心房和最终进入病人的血流中的结构。
图14-18表示了本发明的另一实施例,其中,膜40的外周通过可膨胀结构例如气球结构402而固定成与口20周围的心房壁直接配合。如图15所示,气球结构402可以由现有技术已知的聚合物材料或类似材料制成。管404与气球结构402的内腔连通,用于将盐水或其它合适流体引入气球结构402内。膜40以任意合适的方式安装在管404上,例如粘接、缝合或其它方式,并有一个孔406,该孔允许管404的端头部分进入,并作为气球引入孔408,能够将流体引入气球结构402中。
图14还表示了用于将流体引入气球结构402中的结构,例如导管装置410。导管装置410包括一个在其远端部分处的出口孔412,用于从该导管装置410中喷出流体。出口孔412可以与气球引入孔408相连,该气球引入孔408再与管404的内腔和气球结构402的内部连通。
图15表示了呈压紧结构在传送管422内的膜40、气球结构402、管404和安装在管404上的导管410。更尤其是,气球结构402处于皱缩状态,膜40是柔性的,并进行压缩或折叠以便装入传送管422中。膜40设计成能在从管422中释放后膨胀成盘状形状。图16表示了与导管410和管404之间的相互连接相关的某些结构。尤其是,导管410的出口孔412可以有细管424,该细管424安装在气球引入孔408内,并当出口孔412与进口孔408相连时使阀426保持在打开状态。当出口孔412离开气球引入孔408时,阀426可以封闭,以防止流体离开气球结构402,如图16所示。
传送管422可以在合适位置引入静脉或动脉系统,并能通过合适的引导和显影装置(未示出)而进入心脏的心房内。
图17表示了在安装过程后期的状态,其中,膜40、气球结构402、管404和导管410从传送管422(图17中未示出)中推进。气球结构402位于左心房附件13内,这样,膜40的外周位于口20周围的心房壁附近。随后将流体引入导管410,该流体经过管404,以便使气球结构402膨胀,如图18所示。气球结构402在心房附件13内膨胀,并将膜40固定就位。当导管410与气球引入孔408脱开并随后从心房中取出时,气球引入孔408中的阀机构426(图18中未示出)防止流体从该气球结构402中流出。如上所述,膜40可以有不可渗透的结构,该不可渗透的结构防止血栓离开心房附件13,且它还防止血液流过该膜40。或者,膜40可以有可渗透结构,它允许血液流过,但阻挡或基本防止血栓、血凝块或栓塞离开心房附件13和进入病人的血流中。
图19-31表示了用于将膜固定而横过左心房附件13的口20的又一实施例。图19表示了膜40、用于将该膜40固定而跨过心房附件13的口20的固定装置440和用于安装该固定装置440和膜40的导管装置442。如图20所示,固定装置440和膜40可以最初成压紧形状。固定装置440优选是一个可膨胀的管状装置,其初始直径444为大约1-3mm,初始长度446为大约0.5-6cm。固定装置优选是由柔性材料例如不锈钢、镍钛诺、尼龙、聚酯、PET或聚乙烯制成。固定装置440可以通过膨胀结构例如气球结构452或机械膨胀结构472或482而膨胀。或者,固定装置440可以自膨胀,这样,它通常偏压向膨胀状态,例如参考图24所述,并以约束状态进行布置,例如参考图20所述。用于约束该自膨胀装置的装置通常为管。
膜40安装在固定装置440的近端并呈松配合,该膜40稍微成锥形形状,并确定了一个中心开口448,该中心开口448允许导管装置442的导管450穿过该膜40,如本文详细所述。或者,膜40可以覆盖固定装置440的长度446上的很大部分,或者膜40可以以基本袜状的形式覆盖整个固定装置440。膜40可以由也具有弹性特征并可以从第一尺寸膨胀到第二尺寸的材料制成。
导管450将膨胀流体例如盐水或造影剂供给可膨胀结构例如气球结构452内,该可膨胀结构位于固定装置440的内腔内,以便当固定装置440位于心房附件13内时使该固定装置440径向膨胀。气球结构452可以包括一个远端的防止损伤的尖端部分454,例如一个柔性螺旋线圈或软塑料尖部。
图21和23表示了固定装置440的平面展开图。固定装置440的结构优选使得该装置在其初始形状(图21)时的长度446相对于它处于膨胀形状时的长度456(图23)能基本保持恒定。为了实现该膨胀,同时保持长度基本恒定,固定装置440的形状有几个蛇形段458、460和462。相邻的蛇形段通过多个纵向支杆相互连接,例如环457和460通过支杆464相互连接,环460和462通过支杆466相互连接。在装置440远端部分处的多个部件470提供了用于膜40的固定点。尤其是,径向部件471设置成沿径向向外延伸(图22),以便提供用于固定膜40的外周的位置并提供用于固定在心房壁上的表面。如本文所述,径向部件471可以通过膨胀部件例如气球而膨胀成沿径向向外的形状。在一个实施例中,部件471的材料或厚度可以选择而能使部件471的膨胀程度大于固定装置440的其余部分。或者,部件471可以由可自膨胀的材料制成,例如镍钛诺,其中,部件通常偏压向沿径向向外的形状。
图24表示了处于膨胀形状的固定装置440,其中,长度456相对于图20所示形状的长度446基本保持恒定。直径472远远大于直径444(图20),以便将其自身固定而压靠心房附件13的内部,并使膜40固定而与口20周围的心房壁直接配合,如本文所述。部件471沿径向向外延伸,并提供用于膜40外周的结构。
图25-28表示了膜40的几个实施例。如上所述,导管450穿过膜40中的开口458,以便将膨胀流体供给可膨胀的气球结构452。当气球结构452使固定装置440膨胀成如图24所示的膨胀形状之后,需要通过使气球结构452在近处穿过膜40,尤其是穿过开口458,从而除去气球结构452。图25-28所示的膜40的实施例可以有利于气球结构452通过或其它插入装置通过。
图25表示的膜40a有复合结构,包括过滤部分474a和弹性部分476a。过滤部分474a由过滤材料制成,它提供过滤血液的功能,以便允许血液流过,同时阻挡或基本防止血凝块、血栓或栓塞通过,如上所述。弹性部分476a由弹性材料制成,例如硅酮、氨基甲酸乙酯或其它类似材料,它能够拉伸,以便使开口458b放大,从而允许气球结构452或其它插入装置例如丝线、导管等通过,并随后返回其原始大小。孔458a的原始大小提供了与过滤部分474a的过滤材料类似的、防止血凝块、血栓或栓塞通过孔458a的特性。在该结构中,弹性材料476a基本跨过膜40a的整个直径472a延伸。
膜40b(图26)由过滤部分474b(即与过滤部分474a相同的材料)和弹性部分476b(即与弹性部分476a相同的弹性材料)构成。在膜40b中,过滤部分474b基本同心地环绕弹性部分476b。该弹性部分476b有开口458b,该开口458b能膨胀,以便允许气球结构452或其它插入装置通过,并返回其原始尺寸,以便提供与过滤部分474b的过滤材料基本相同的、防止血凝块、血栓或栓塞通过的特性。
膜40c(图27)由过滤部分474c(即与过滤部分474a相同的材料)和弹性部分476c(即与弹性部分476a相同的弹性材料)构成。在膜40c中,过滤部分474c基本同心地环绕弹性部分例如基本椭圆形的部分476c。该弹性部分476c有孔例如狭缝458c,该狭缝458c能膨胀,以便允许气球结构452或其它插入装置通过,并返回原始尺寸,以便提供与过滤部分474b的过滤材料基本相同的、防止血凝块、血栓或栓塞通过的特性。
膜40d(图28)可以由与上述过滤部分474a相同的材料构成,并成几个部分,例如部分475d和477d,它们在区域479d处交叠,以便形成一个用于气球结构452或其它插入装置的开口。还可以考虑利用过滤材料的三个或更多部分以与例如光学装置的“孔”结构类似的方式形成交叠结构。气球结构452可以通过在部分475d和477d之间的开口。在取出气球结构452之后,交叠结构基本封闭该开口,并提供与过滤部分475d和477d的过滤材料基本相同的、防止血凝块、血栓或栓塞通过的特性。
图29-31表示了用于将固定装置440和膜40安装在心房附件13内的步骤。在初始步骤中(图29),气球结构452和固定装置440一起以其初始的压紧结构形式插入心房附件13中。在图30中,膨胀流体经过导管450并通过孔453排出,以便充满气球结构452的内部。气球结构452膨胀,从而使固定装置440沿径向扩大,如上面参考图21-24所述。在优选实施例中,气球452的近端部分455设置成有更大的膨胀程度,以便使部件471沿径向向外偏转。或者,部件471可以设置成使在通过气球452膨胀时的膨胀程度比固定装置440的其余部分更大。在另一实施例中,部件471可以由能自膨胀的材料制成,例如镍钛诺,其中,部件471通常偏压向沿径向向外的形状。因此,膜40的外周膨胀而与口20周围的心房壁直接接触。部件471提供了附加的支承,从而使膜40的边缘能很好地密封。
如图31所示,固定装置440与心房附件13的内部配合,从而使膜40跨过口20而固定就位,这样,膜40的外周与口20周围的心房壁直接配合。通过使气球结构452返回其初始压紧结构(例如通过使膨胀流体从其中排出)和使气球结构通过开口458而退出,该气球结构452可以从心房附件13中取出。如上面参考图25-28所述,膜可以由弹性部分制成,该弹性部分可以膨胀以便允许气球结构通过它而收回,并随后使尺寸减小,从而防止血栓、血凝块和栓塞通过和进入心房。随后可以将导管结构442从病人中取出。或者,在固定装置440膨胀之后,气球结构452可以留在心房附件13内,并随后使气球结构452返回其初始压紧结构。例如,导管450可以以与导管410和管404(图16)类似的方式从气球结构452上脱开。或者,固定装置440可以由能自膨胀的材料制成,例如镍钛诺,其中,固定结构通常偏压向如图24所示的形状。为了将固定结构440安装到心房附件13内,可将固定结构440约束在一管中,固定结构440可以随后从管处布置并能够自膨胀成类似于图31所示的形状。
图32-34表示了本发明的另一实施例。固定装置460和气球装置462基本与前述固定装置440和气球装置452相同,它们的区别点将在下面介绍。固定装置460可以有多个配合件464,例如尖头、钩等,以便与心房附件的壁配合和/或刺入心房附件的壁,以便提供固定装置460的附加固定。气球结构452可以与固定装置460结合使用。或者,气球结构462可以设置成远端部分的膨胀程度比近端部分更大(图33)。该气球结构462的更大膨胀提供了作用在配合件464区域上的附加力,从而将该配合件压入心房附件13的壁中(图34)。
图35-36表示了用于使固定装置440(或460)在心房附件内沿径向扩大的可膨胀结构的另一实施例。代替气球结构(例如气球结构452)或者除气球结构之外,还可以考虑特别使用机械膨胀结构。图35(a)-(b)表示了可用于使固定装置440径向膨胀的机械膨胀结构472。如图35(a)所示,机械膨胀结构472可以有压紧形状,其中,多个接触件474确定了能够将该结构插入到固定装置440内的直径476。如图35(b)所示,机械膨胀结构472还有膨胀形状,其中,接触件474进一步间隔开,以便确定了一个较大直径477,其能够使固定装置沿径向放大到图21-24和30-31所示形状。连接结构可以包括连接件478和套筒479。套筒479有内螺纹(未示出),该内螺纹与在驱动螺杆部分481上的外螺纹480配合。驱动螺杆481的角度旋转使得套筒479纵向移动(如箭头所示),该套筒479与连接件478配合,以便可控制地使接触件474在压紧和膨胀形状之间运动。
图36表示了机械膨胀结构482,该机械膨胀结构482基本与机械膨胀结构472相同。套筒489与连接件478相互作用,以便可控制地使接触件474运动,如上面参考套筒479所述。套筒489可相对于细长件491而纵向滑动。还可以提供有锁定结构(未示出),以便固定该套筒489相对于细长件491的位置(从而固定接触件474的位置)。
在固定装置440(或460)膨胀之后,机械膨胀结构472和482可以留在心房附件13中。驱动螺杆481部分或细长件491可以分别与膨胀结构472或482脱开(未示出)。或者,利用基本与机械膨胀结构472/482类似的装置作为膜40的支承结构。根据该实施例,例如通过将膜40安装在接触件474的端部或通过基本围绕接触件474和连接件478,可以将膜40安装在结构472/482的端部。结构472/482可以位于心房附件13内,并如上述膨胀,这样,膜40跨过口20而延伸,以便允许血液流过,同时防止血栓通过膜40。驱动螺杆481或细长件491可以随后与装置472/482脱开。
图37-39表示了本发明的另一实施例。膜40可以通过固定装置500而安装和保持在心房附件13内,该固定装置500优选包括一对柔性丝线部分502a和502b,该丝线部分502a和502b优选是由例如镍钛诺、Elgiloy或不锈钢这样的材料构成,且丝线直径大约为0.005至0.020英寸。各丝线部分502a/502b可以包括弯曲部分504a/504b,一对支承件506a/506b和多个配合件508。弯曲部分504a/504b确定了一个基本封闭的部分,用于安装膜40。膜40通过缝合、粘接或其它合适方式而安装。配合件508设置成与心房附件13的内部配合,以便使膜40跨过口20而固定就位,如本文所述。配合件508可以有防止损伤的端头部分510。
图40表示了成压紧结构以便安装在心房附件13内的固定装置500和膜40。优选是,传送导管装置520用于将固定装置500和膜40引入心房附件。弯曲部分504a/504b在近侧朝着平行于导管520的纵向轴线的方向偏转,配合件508在远侧朝着平行于纵向轴线的方向偏转。内部件522可滑动地安装在导管520的内部,并可以相对于导管装置520沿纵向相对运动,以便布置和安装固定装置500和膜40。
图41-43表示了用于跨过口20安装膜的几种可选方式。如图41所示,弯曲部分504a/504b自身位于口20的壁内。配合件508通过与心房附件内部配合而提供附加支承。或者,弯曲部分504a/504b位于口的外部并在心房内。配合件508使膜40的外周保持与口20周围的心房壁直接配合。根据又一可选实施例,配合件508有尖锐的倒钩端头部分512,该倒钩端头部分512与心房附件的壁配合和/或刺入心房附件的壁中,以便使膜固定就位(图43)。
图44-45表示了本发明的另一实施例。固定装置650有:多个第一支撑丝线652,它们从支承环654朝着固定装置650的远端部分656而在远侧沿径向向外延伸;以及多个第二支撑丝线658,它们从支承环654朝着固定装置650的近端部分660而在近侧沿径向向外延伸。支撑丝线652/658可以由合金构成,例如镍钛诺,有形状记忆特征。支承环654使支撑丝线652/658保持合适形状,并可以由不透射线的材料制成,例如铂,以便提供装置位置的荧光图像。支撑丝线652可以有倒钩662或其它用于安装到心房附件内部的装置。支撑丝线652/658设置成分别在口的内部和外部与该口的壁配合。
支撑丝线658可以作为膜的安装结构。膜40安装在支撑丝线658上,并有上述特征。在一个实施例中,膜40是可渗透的,其中,允许血液流过该膜40,但是防止血栓、血凝块和栓塞通过。或者,对于血栓和血流,该膜40都是不可渗透的。膜40可以利用粘接、缝合、封装或其它方式与支撑丝线652相连。
图46中表示了本发明的另一实施例。固定装置670由编织网材料构成,而不是参考图44-45所述的支撑丝线652/658。远端部分672设置成与口的内部部分附近的心房附件壁配合,近端部分676设置成与口的外部部分配合,颈部部分674布置在该远端部分672和近端部分676之间。固定装置670的自膨胀编织网材料有与膜40类似的过滤特性,或者,膜安装在该网材料上,以便提供这些特性。
图47-48表示了用于传送和安装固定装置650和膜40和/或固定装置670的装置。导管装置620包括一个外鞘622和一个可滑动地容纳于该外鞘622内部的内部件624。该外鞘622和内部件624可以由例如聚合物材料制成,该材料有足够的柔性,以便能通过人体组织,同时还有足够的刚性,以便能相对纵向运动,从而布置和定位固定装置650。内部件624可以有远端部分626和肩部部分628。装置650的支撑丝线652(或装置670的远端部分672)在远侧朝着与导管装置620的纵向轴线平行的方向偏转,并通过外鞘622保持该偏转形状。类似的,支撑丝线658(或近端部分676)在近侧朝着与纵向轴线平行的方向偏转,并通过外鞘622保持该偏转形状。为了布置固定装置650,外鞘622相对于内部件624纵向运动。肩部628使固定装置650/670保持就位。当外鞘622缩回后,支撑丝线652/658(或部分672/676)的形状记忆特征使得该装置恢复到类似于图44(或图46)的形状。
图49-50更详细地表示了固定装置650/670和膜40的安装。如图49所示,导管装置622的一部分前进到心房附件13内。外鞘622可以收回,这使得支撑丝线652沿径向向外展开。医生可以利用环654的不透射线的特征来将该环654合适定位到口20内。外鞘622进一步收回,使得远端支撑丝线652和近端支撑丝线658沿径向向外展开,并与心房附件13的内部配合(图50)。倒钩662可以与心房附件的壁配合和/或刺入心房附件的壁,从而增加该固定装置650的稳定性。膜40由此跨过口20而定位,这样,膜40的外周固定而与口周围的心房壁直接配合。在一个实施例中,膜40是不可渗透的,并不允许血液或血栓流过,但是也可以采用过滤膜,从而允许血液流过该过滤膜,同时基本防止血栓、血凝块和栓塞离开心房附件13。支撑丝线658提供了附加固定,以便使膜40和口20周围的心房壁之间保持无泄漏的密封。
图51-52表示了本发明的又一实施例。固定装置700有多个从支承环704沿径向向外延伸的支撑丝线702。各支撑丝线702的第一部分706朝着固定装置700的近端部分708延伸,各支撑丝线702的第二部分710朝着远端部分712延伸。各支撑丝线702的远端部分710可以有尖锐的倒钩尖端714或其它用于安装在心房附件内部的装置。支撑丝线702可以由合金构成,与上述用于支撑丝线602的材料类似。支承环704使得支撑丝线702保持合适形状,它基本与上述支承环604类似。支撑丝线702的近端部分706和远端部分710设置成分别在口的外部和内部与口的壁配合。
膜40安装在支撑丝线702的近端部分706上,并可以有上述过滤特征,其中允许血液流过该膜40,但是防止血栓、血凝块和栓塞通过。或者,膜40对于血液和血栓都是不可渗透的。膜40可以利用粘接、缝合、封装或其它方式与支撑丝线702相连。
图53-54表示了用于传送和安装固定装置700和膜40的装置。导管装置620如上面参考图47-48所述。支撑丝线702朝着平行于导管装置620的纵向轴线的方向偏转,并通过外鞘622保持该偏转形状。为了布置固定装置700,外鞘622相对于内部件624沿纵向运动,肩部部分628使固定装置700保持就位。当外鞘622缩回后,支撑丝线702的形状记忆特征使得该装置恢复到类似于图51的形状。
图55-56更详细地表示了固定装置700和膜40的安装。如图55所示,导管装置622的一部分前进到心房附件13内。外鞘622可以收回,这使得支撑丝线702的远端部分710沿径向向外展开。外鞘622进一步收回,使得远端部分710与心房附件13的内部配合,而近端部分706与口20的外部配合(图56)。支撑丝线706提供了附加的固定,以便使膜40和口20周围的心房壁之间保持无泄漏的密封。倒钩714可以与心房附件的壁配合和/或刺入心房附件的壁,从而增加该固定装置700的稳定性。膜40由此跨过口20而定位,这样,膜的外周固定成与口20周围的心房壁直接配合。支撑丝线706提供了将膜固定在心房壁上的附加固定,以便提供无泄漏的密封。应当采用过滤膜,以便允许血液流过该膜,同时基本防止血栓、血凝块和栓塞离开心房附件13。
图57-58表示了本发明的另一实施例。固定装置750包括多个支撑丝线752,该支撑丝线752在远处从支承件754朝着远端部分756而沿径向向外延伸。各支撑丝线752可以有尖锐的倒钩尖端758或其它用于安装在心房附件内部的装置。支撑丝线752由合金构成,与上述用于支撑丝线602的材料类似。支承件754使得支撑丝线752保持合适形状。
支承件754的近端部分支承一个弯曲的膜安装结构760,该膜安装结构760确定了一个基本封闭的曲线。膜40安装在膜安装结构760上,并可以有上述过滤特性,其中允许血液流过该膜40,但是防止血栓、血凝块和栓塞通过。或者,该膜40对于血流和血栓都是不可渗透的。膜40可以利用粘接、缝合、封装或其它方式与膜安装结构760相连。
图58中所示的固定装置770基本与固定装置750相同,下面将介绍它们的区别点。例如,支承件754的近端部分支承着螺旋形状的膜安装结构772。膜40安装在螺旋形安装结构772上,基本如上述参考膜安装结构760所述。螺旋形形状可以例如有助于在安装过程中使安装结构减小成压紧形状。
图59-60表示了固定装置750(或770)和膜40在心房附件13中的安装。导管装置780用于传送和安装固定装置750和膜40。导管装置780与上面参考图55所述的导管装置620类似。导管装置780包括外鞘782和内部件784。内部件784优选有在其远端部分上的配合表面785。在安装过程中,支撑丝线752朝着平行于导管装置780的纵向轴线的方向偏转,并通过外鞘782(图74中未示出)保持该偏转形状。类似的,膜安装部分760(或772)折叠、滚卷或以其它方式压紧到外鞘782内部,如图59所示。
为了布置固定装置750,导管装置780的一部分前进到心房附件13内。外鞘782可以往回收回,这使得支撑丝线752由于其形状记忆特征而径向向外展开,如图所示。内部件784使固定装置750保持就位。
如图60所示,外鞘782进一步往回收回,使得支撑丝线752径向向外展开,并与心房附件的内部配合。倒钩758可以与心房附件的壁配合和/或刺入心房附件的壁,从而增加该固定装置700的稳定性。膜安装结构760(或722)同样可以返回其盘状形状,这样,膜40跨过口20而定位,从而将膜40的外周固定成与口周围的心房壁直接配合。膜40可以是可渗透的,以便允许血液流过该膜,同时基本防止血栓、血凝块和栓塞离开心房附件13。或者,该膜40对于血流和血栓都是不可渗透的。
图61-67表示了本发明的另外实施例,其中,膜40的大小可盖住心房附件的口20,并固定成与口周围的心房壁直接配合。因此,膜40的直径或其它尺寸大于口20的直径或相应尺寸,以便完全覆盖该口。尤其是,膜40确定有与口或口周围的心房壁直接配合的外周。
如图61-62所示,膜40有多个配合件400,该配合件400可以安装或位于膜40的外周上,并可以有杆部分402和有倒钩的自由端404,这样,该杆部分402和有倒钩的自由端404可以从配合件400上沿径向向外延伸。
如图63所示,膜40安装成盖住口20。配合件400刺入口20的壁内或刺入口周围的心房壁内,以便将膜40直接安装在口20上或安装在口周围的心房壁上。有倒钩的自由端404防止配合件400从壁上缩回,并有助于将膜40固定就位,如图所示。膜40有防止血栓离开心房附件并进入血流中的结构。可以选择采用可渗透的过滤膜,该过滤膜允许血液流过,同时基本防止血栓通过。
图64表示了另一实施例,其中,膜40盖住心房附件13的口20。生物相容的组织粘接剂420例如纤维蛋白胶或氰基丙烯酸酯或类似材料可以涂布在膜的外周上,并用于将该膜40直接安装在口20上或安装在口20周围的心房壁上。膜40防止血栓离开心房附件并进入血流。可以选择采用可渗透的过滤膜,该过滤膜允许血液流过,同时基本防止血栓通过。
图65-66表示了本发明的又一实施例,其中,膜40有多个配合件430。各配合件430安装在膜40的外周上,并有:细长的杆部分432,该杆部分432在远侧沿纵向延伸;以及有倒钩的自由端434,该有倒钩的自由端434可以从该细长杆部分432沿径向向外延伸。杆部分432比上面参考图61-63所述的杆部分402长得多。配合件430确定了一个间距436或在除了径向凸出的倒钩状自由端434之外的相对配合件430之间的距离,该间距或距离与口20的内径尺寸相近。位于膜40的相对侧上的配合件430之间的该间距436提供了使配合件在口20和心房附件13的内部定心的特性。
如图67所示,膜40安装成盖住口20。细长的杆部分432伸入到口20或心房附件13内一定距离,有助于使膜40在口20内定心。有倒钩的自由端434与心房附件13的内壁配合,从而防止配合件430从壁上缩回,并将膜40固定成与口20或口20周围的心房壁直接配合,如图所示。膜40有防止血栓离开心房附件并进入血流中的结构。可以选择采用可渗透的过滤膜,该过滤膜允许血液流过,同时基本防止血栓通过。
上述装置可以经皮肤分别传送到左右心房附件13、23。该装置中可以有能够通过超声波、X射线或其它方式来增强显影或成像的材料,从而使得该装置能够更容易地进行植入并相对于心房附件13的口20而精确定心。这可以包括布置在膜、连接元件或锚固件上的关键位置处的小珠。参考图1,可以看见,导管21通过主动脉12进入心脏,并进入左心室16和通过二尖瓣17再进入左心房附件13,以便布置如上述实施例的一个中的膜40。在图2中,导管21从股静脉进入心脏,并通过下腔静脉18到达右心房,然后通过卵圆窝19或通过隔膜29进入左心房11,再进入左心房附件13,以便将膜40布置在左心房附件13上。图3表示了用于右心房附件23的导管21。导管21可以通过颈静脉28或通过股静脉到达下腔静脉18,再进入心脏。
应当知道,本发明可以通过以多种方式将膜40跨过心房附件13和23的口20安装而实施。所有通过左心房附件13进行表示和说明的上述实施例也可用于右心房附件23。也可以采用固定装置与粘接剂、尖头、柱形结构、锚固件、盘、系绳或弹簧的任意组合。膜还可以透入心房附件并提供有使该过滤膜装置牢固锁定就位的装置。当优选是具有可渗透特征时,虽没有在本文中列出,但是提供有能使血液流过并基本防止血凝块离开心房附件的膜的其它装置也可以使用。
显然,在上面的指导下,可以对本发明进行多种变化和改变。应当知道,在附后的权利要求的范围内,本发明可以以与特别介绍的方式不同的方式实施。
Claims (14)
1.一种用于固定在病人的左心房附件的口上的装置,包括:
一膜,该膜可在左心房附件的口上延伸,该膜的外周的尺寸大于该口的相应尺寸;
其特征在于,该膜有可渗透的结构,该可渗透结构允许血液流过该膜,但是基本防止血栓通过,以及
固定装置,用于将该膜的外周固定而直接与口周围的心房壁配合,其中,该固定装置包括用于穿入围绕着所述口的心房壁和心房附件的壁这二者中的至少一个的装置。
2.根据权利要求1所述的装置,其中:该固定装置位于膜的外周和该口周围的心房壁之间。
3.根据权利要求2所述的装置,其中:该固定装置还包括涂布在膜的外周和该膜周围的心房壁之间的粘接剂。
4.根据权利要求3所述的装置,其中:该粘接剂是氰基丙烯酸酯。
5.根据权利要求2所述的装置,其中:该固定装置包括多个配合件,该配合件在膜外周上的多个位置处安装于该膜上。
6.根据权利要求5所述的装置,其中:该配合件可穿入口周围的心房壁。
7.根据权利要求6所述的装置,其中:各配合件包括倒钩结构,以便穿入所述口周围的心房壁,从而防止该配合件离开心房壁。
8.根据权利要求5所述的装置,其中:各配合件包括一杆部分,该杆部分从膜的外周向远侧延伸,并至少部分伸入该口内。
9.根据权利要求8所述的装置,其中:安装在膜的相对侧上的配合件确定了基本与该口的内部尺寸相同的间距。
10.根据权利要求8所述的装置,其中:各配合件包括倒钩结构,以便穿入所述心房附件的内壁。
11.根据权利要求1所述的装置,其中:该固定装置在远处从该膜伸入到口内并穿入所述左心房附件的内部的一部分。
12.根据权利要求11所述的装置,其中:该固定装置可根据位于该固定装置的内部中的膨胀结构的膨胀而扩大。
13.根据权利要求11所述的装置,其中:该固定装置弹性偏压向与左心房附件的内壁配合的扩大形状,并可以约束成减小的尺寸结构,以便安装在左心房附件内。
14.根据权利要求1所述的装置,其中:该固定装置安装在膜的外周上,并设置成从该口沿径向向外延伸,以便将膜的外周固定成与口周围的心房壁直接配合。
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2000
- 2000-08-18 US US09/642,291 patent/US6652555B1/en not_active Expired - Lifetime
- 2000-10-23 JP JP2001532690A patent/JP2003512128A/ja not_active Withdrawn
- 2000-10-23 IL IL14913300A patent/IL149133A0/xx unknown
- 2000-10-23 CN CNB008148856A patent/CN1195457C/zh not_active Expired - Fee Related
- 2000-10-23 CA CA002386894A patent/CA2386894A1/en not_active Abandoned
- 2000-10-23 EP EP04000434A patent/EP1433437A2/en not_active Withdrawn
- 2000-10-23 AU AU21195/01A patent/AU779674B2/en not_active Ceased
- 2000-10-23 AT AT00984598T patent/ATE264658T1/de not_active IP Right Cessation
- 2000-10-23 ES ES00984598T patent/ES2219428T3/es not_active Expired - Lifetime
- 2000-10-23 WO PCT/US2000/041414 patent/WO2001030267A1/en active IP Right Grant
- 2000-10-23 DE DE60010105T patent/DE60010105T2/de not_active Expired - Fee Related
- 2000-10-23 EP EP00984598A patent/EP1223890B1/en not_active Expired - Lifetime
-
2003
- 2003-09-05 US US10/655,867 patent/US20040049210A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1223890B1 (en) | 2004-04-21 |
CA2386894A1 (en) | 2001-05-03 |
JP2003512128A (ja) | 2003-04-02 |
WO2001030267A1 (en) | 2001-05-03 |
US20040049210A1 (en) | 2004-03-11 |
DE60010105T2 (de) | 2004-08-26 |
US6652555B1 (en) | 2003-11-25 |
ES2219428T3 (es) | 2004-12-01 |
EP1433437A2 (en) | 2004-06-30 |
CN1384726A (zh) | 2002-12-11 |
AU2119501A (en) | 2001-05-08 |
DE60010105D1 (de) | 2004-05-27 |
EP1223890A1 (en) | 2002-07-24 |
IL149133A0 (en) | 2002-11-10 |
ATE264658T1 (de) | 2004-05-15 |
AU779674B2 (en) | 2005-02-03 |
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