CH-VAD动物实验抗凝管理研究

VAD绵羊模型常用来验证装置血液相容性、生物安全性和工作可靠性以及对动物生理状态的影响,且需要有效、安全的抗凝管理方案,以降低血栓和出血风险.研究拟讨论绵羊植入CH-VAD后应用肝素和华法林钠的抗凝效果,为后期动物长期存活实验和临床应用提供抗凝数据.选择健康绵羊6只,构建动物左心室→心室辅助装置→降主动脉血流旁路,建立CH-VAD动物模型.术中一次性静脉注射肝素250 U/kg.术后前4d连续静脉滴注肝素50 U/kg·h,使活化全血凝固时间(ACT)和活化部分凝血酶时间(aPTT)1.5～2.0倍于基值.术后第3d开始口服华法林钠,并调整用量使国际标准化比值(INR)在1.2～2.0目标范围内.动物存活期间密切观察有无出血并发症.实验终止后,观察血泵内部、人工血管、吻合口等血液流道内有无血栓.宏观检查主要脏器是否充血、梗死,取典型部分做HE染色,观察组织病理学变化.6例绵羊整个实验过程无严重出血并发症.绵羊模型术中ACT值为(326±33)s.术后前4 d ACT基本保持在(157 ±28)s,在基值的1.5-2.0倍内,aPTT上升缓慢,第4d刚达到目标范围下限.除Sheep4血泵转子背部有小块纤维组织外,其他血泵泵体、出入口、人工血管、吻合口内均无血栓和纤维组织.病理学检查显示在此抗凝方案下绵羊终末期器官基本没有血栓、坏死和微栓子存在.CH-VAD绵羊模型中,植入后初期连续静脉滴注肝素保持ACT 1.5～2.0倍于基值、后期口服华法林钠使INR值在1.2～2.0范围内能够很好的控制血栓和出血并发症,可以作为CH-VAD后期动物实验抗凝方案参考.     

ChinaHeart左心辅助装置的动物在体存活实验

验证磁悬浮离心式左心辅助装置—ChinaHeart VAD的在体血液相容性和可靠性,评估其对实验动物主要终末器官的影响。通过6例健康绵羊的在体存活实验进行评估。在心脏不停跳的情况下,装置入口插入左心尖,出口与降主动脉吻合。术前和术后做血常规、生化及血凝检查,术后连续监测动物存活及辅助装置运行状况。择期动物安乐死后,进行终末主要脏器的宏观和病理学检查。4只羊术后3～28 h内因麻醉或手术意外死亡;2只羊成功复苏并分别辅助20 d和38 d后施行安乐死。对于成功存活的2例实验动物,术后护理期间血常规、生化和血凝检查结果均在正常范围内,辅助装置无机械故障发生。尸检时1只羊(存活20 d)血泵泵体内发现一肉眼可见小块血栓沉积,其余无血栓形成;组织病理检查发现2只羊左肺贴近辅助装置部位均可见有小叶性肺炎,其余终末脏器无明显病变发生。ChinaHeart VAD在体辅助期间血液相容性能良好,对各主要终末脏器无显著影响,具有较好的可靠性;动物存活实验中麻醉呼吸管理和手术操作也至关重要。     

Animal survival experiment of 20mL pediatric Luo-Ye ventricular assist pump

目的 采用自行研制的20 mL小儿罗叶泵行动物存活实验,明确其对血细胞和重要器官的影响,探讨临床应用的可行性.方法 健康山羊6只,体重(18±3.3)kg.经左侧第5肋间进胸,以左室心尖及降主动脉的插管方式建立左心辅助循环.止血关胸,清醒后拔除气管插管,动物置于专用饲养笼内.辅助期间持续静脉给予肝素抗凝,维持激活全血凝固时间(activated clotting time,ACT)在180～250 s.经颈动、静脉置管监测中心静脉压和血压.在辅助前,辅助后1 h、3h、6 h、10 h、16 h、24 h及存活期间每24 h监测血浆游离血红蛋白,在辅助前及存活期间每24 h检测血常规、肝肾功能、凝血指标.实验结束时取动物心、肝、肾、肺观察病理变化.结果 开胸后插管时发生顽固性室颤死亡1只,其余5只成功进行存活实验,平均存活时间(79.8±60)h.其中因栓塞死亡1只,胸腔出血、肺部感染死亡1只,肝素连接管脱落出血致失血性休克1只,反复气胸、ACT过高致脏器出血1只.1只山羊在存活至预定的7 d时,再次麻醉插管,开胸撤离辅助装置,关胸后顺利拔除气管插管,动物存活.辅助过程中肝素抗凝剂量25～35u/(kg*h),所维持的ACT具足够的抗凝效果.中心静脉压、平均动脉压、肝肾功能在辅助前后无明显变化.血浆游离血红蛋白由辅助前的(2.227±1.321)mg/dL升高到辅助72h的(8.873±2.510)mg/dL,二者相比有统计学差异,但在正常生理值范围内.除第1例因抗凝不足产生肾栓塞外,其余4例心、肝、肾、肺的病理检查均无栓塞.结论 20mL小儿罗叶泵血液相容性好,对肝肾功能无不良影响,具备用于临床的条件.     

20mL小儿罗叶泵的动物存活实验

目的 采用自行研制的20 mL小儿罗叶泵行动物存活实验,明确其对血细胞和重要器官的影响,探讨临床应用的可行性.方法 健康山羊6只,体重（18±3.3）kg.经左侧第5肋间进胸,以左室心尖及降主动脉的插管方式建立左心辅助循环.止血关胸,清醒后拔除气管插管,动物置于专用饲养笼内.辅助期间持续静脉给予肝素抗凝,维持激活全血凝固时间（activated clotting time,ACT）在180～250 s.经颈动、静脉置管监测中心静脉压和血压.在辅助前,辅助后1 h、3h、6 h、10 h、16 h、24 h及存活期间每24 h监测血浆游离血红蛋白,在辅助前及存活期间每24 h检测血常规、肝肾功能、凝血指标.实验结束时取动物心、肝、肾、肺观察病理变化.结果 开胸后插管时发生顽固性室颤死亡1只,其余5只成功进行存活实验,平均存活时间（79.8±60）h.其中因栓塞死亡1只,胸腔出血、肺部感染死亡1只,肝素连接管脱落出血致失血性休克1只,反复气胸、ACT过高致脏器出血1只.1只山羊在存活至预定的7 d时,再次麻醉插管,开胸撤离辅助装置,关胸后顺利拔除气管插管,动物存活.辅助过程中肝素抗凝剂量25～35u/（kg＊h）,所维持的ACT具足够的抗凝效果.中心静脉压、平均动脉压、肝肾功能在辅助前后无明显变化.血浆游离血红蛋白由辅助前的（2.227±1.321）mg/dL升高到辅助72h的（8.873±2.510）mg/dL,二者相比有统计学差异,但在正常生理值范围内.除第1例因抗凝不足产生肾栓塞外,其余4例心、肝、肾、肺的病理检查均无栓塞.结论 20mL小儿罗叶泵血液相容性好,对肝肾功能无不良影响,具备用于临床的条件.     

磁悬浮离心血心室辅助装置在体实验及其血液相容性

背景：磁悬浮离心血心室辅助装置独特的心尖插管设计,可以在心脏不停跳状态下完成左心室插管,明显缩短手术时间,避免体外循环的有害影响。 目的：验证磁悬浮驱动离心式左心室辅助装置的在体可靠性。 方法：将磁悬浮驱动离心式左心室辅助装置装置入口通过不停跳方式植入绵羊左心尖,出口与降主动脉吻合。手术前后行全血、生化以及血凝检查,期间不间断采集与辅助装置主体血心室辅助装置功能相关的数据,并做主要脏器宏观和病理检查。 结果与结论：在体辅助38 d期间辅助装置无机械故障发生,心室辅助装置的流入和流出道未见血栓沉积,血液和生化检查结果均在正常范围。实验羊无明显并发症,主要脏器宏观和病理检查表明无缺血或梗死。证实磁悬浮驱动离心式左心室辅助装置具有良好的在体血液相容性和可靠性。     

左心室辅助装置(LVAD)建立动物体外循环的初步报告

实验的目的是在体外模拟试验的基础上检查左心室辅助装置植入动物体内的性能,是否可维持动物的循坏,以研制可供植入的左心室辅助装置。因R波心电触发同步装置的体外试验尚未完成,故进行了本组预试性试验。以左心室辅助装置(LVAD)代替人工心肺机的滚压泵搏动血流,和人工肺(氧合袋)一起构成动物的心肺旁路。本组试验共进行过五次。     

应用左心辅助装置(LVAD)对正常犬进行辅助循环效应的实验研究

七条犬应用左心辅助装置进行辅助循环,犬平均存活时间为17～45.5(24.5)小时,血泵输出量为883mL/分。死亡原因:室颤3例,出血及肺部并发症4例。左心辅助装置进行辅助循环的血液动力学效应是,心率减慢,心输出量和尿排出量增加,主动脉收缩压、左室收缩压和左室舒张末压降低。主动脉舒张压升高和冠伏动脉灌注增强。实验室检查:血浆游离血红蛋白逐渐增加而血浆纤维蛋白含量逐渐减少。尿素氮、CO_2结合率和血浆钾、钠含量均维持在正常范围。尸解显示在心肌、肝、肾、脾、肺及脑组织中可见局部出血、间质水肿及细胞坏死。     

超声引导经皮肺穿刺在周围型肺部肿块诊断中的应用价值

目的探讨超声引导经皮肺穿刺在肺部肿块诊断中的临床应用价值及其影响因素。方法经超声、X射线、CT或MRI发现的80例88个肺部肿块,其中男性62例（77.5%）,女性18例（22.5%）;年龄23～81岁,平均年龄58.3岁。在超声引导下行穿刺细胞学和/或组织病理学活检,分析假阴性结果及影像表现。结果所有病例穿刺全部成功。其中12例单一细胞学检查,病理阳性率58.3%（7/12）;28例单一组织病理学检查,病理阳性率92.9%（26/28）。另40例同时做细胞学和组织病理学检查阳性率为97.5%（39/40）。结论超声检查及对肺部肿块穿刺活检在肺部肿块的定位及定性诊断中有着重要的临床价值。若同时对肺部肿块作细胞学和组织病理学检查可提高检查阳性率。     

外置主动脉旁反搏装置的慢性动物实验研究

验证主动脉旁反搏辅助装置(paraaortic counterpulsation device,PACD)置于动物体外并进行短期辅助的可行性及该装置的生物学相容性。小尾寒羊5只,体重42.6±4.5 kg,全麻后左第4肋进胸,将PACD(每搏量为60ml)的人工血管与胸降主动脉吻合,气体管道连接IABP主机,利用体表心电或主动脉压力触发驱动装置反搏。PACD置于动物体外固定后关胸。记录反搏前后主动脉压力变化,定时测定凝血及肝、肾功能、血浆游离血红蛋白(PFH)等指标。4例顺利完成PACD短期(7 d)辅助实验,1例PACD辅助54 h后死亡。PACD辅助后主动脉收缩压(SAP)、主动脉舒张压(DAP)较辅助前显著下降(P<0.01),舒张期主动脉平均压(MADP)显著增加(P<0.01);肝、肾功能轻度损害。辅助期间PFH均在生理可接受范围内变化。PACD易植入,有良好的生物学相容性,可置于动物体外并进行短期(7 d)循环辅助。     

新型国产二尖瓣夹合器系统的动物实验研究

通过动物实验,对一种新型国产二尖瓣夹合器系统的可行性和安全性进行评价。14只正常三元杂交系猪分为实验组10只和对照组4只,实验组植入新型二尖瓣夹合器系统,对照组行传统二尖瓣修复术。分别于术前、术后不同时间点行超声心动图检查、血液检查,术后140 d对动物安乐死取材,进行心脏及主要脏器大体、病理检查,观察植入后的情况。实验组共8只动物、对照组共4只动物达到实验终点,所有动物术中未出现夹合器脱落、心脏破裂、瓣膜损伤、顽固性心律失常、脏器栓塞、心力衰竭、死亡等严重并发症。超声显示,所有夹合器均固定在二尖瓣处,不同时间点二尖瓣平均跨瓣压差、左心室射血分数等两组间均未见具有统计学意义的差异。血液学检查,未见植入器械对肝肾功能产生明显影响。病理检查提示,夹合器周围瓣叶呈现慢性炎症、黏液样变性、少量出血,未引起二尖瓣及心脏组织损伤,未出现心脏血栓、感染,各脏器也未见血栓栓塞。动物实验结果表明,新型国产二尖瓣夹合器系统生物相容性好,能够有效固定在二尖瓣处而不引起严重的相关并发症。     

Short-term in vivo preclinical biocompatibility evaluation of FW-II axial blood pump in a sheep model

We investigated the outcome of FW-II axial pump on healthy sheep (weight, 60-70 kg) for 2 weeks by perioperatively hematological and chemical tests, and circulating activated platelet and leukocyte-platelet aggregates measurements by flow cytometry assays. Complete necropsy and histopathological examinations and thorough pump inspection were performed at study termination for evidence of thrombi. In this experimental series, one sheep died of pulmonary edema, the other four sheep reached the scheduled endpoint of 14 days without device-related problems, and flow range was maintained at 2.5-4.0 L/min. The number of red blood cells and platelets decreased within first 3 days but increased gradually after the first postoperative week. In all animals, serum glutamic oxaloacetic transaminase increased significantly after surgery but gradually returned to normal limits within 2 weeks. Platelet activation, granulocyte-platelet aggregates, and monocyte-platelet aggregates reached the peak at postoperative day 2. Postexplant examinations indicated round thrombus in the hub areas of pumps. No evidence of ischemia or infarction was found in the explanted hearts, livers, spleens, kidneys, and brains of the five animals. Our results demonstrate that FW-II ventricular assist device (VAD) is a promising device for left ventricular (LV) support with moderate anticoagulation.     

The use of extracorporeal membrane oxygenation in patients with therapy refractory cardiogenic shock as a bridge to implantable left ventricular assist device and perioperative right heart support

Implantation of left ventricular assist device (LVAD) as a bridge to recovery or transplantation is a widely accepted treatment modality. Preexisting organ dysfunction is thought to unfavorably affect patient survival after implantation of a ventricular assist device (VAD). We present our experience using extracorporeal membrane oxygenation (ECMO) in patients with cardiogenic shock to stabilized organ function prior to LVAD implantation. Between September 2006 and March 2008, five patients in cardiogenic shock with preexisting organ dysfunction (impaired liver and kidney function) were supported with ECMO before LVAD implantation. ECMO-LVAD interval was 8 ± 4 days. All patients were transferred to a LVAD. At the LVAD implantation time, glutamic-oxaloacetic transaminase (GOT) decreased from 206.25 ± 106.93 Ul ⁻¹ to 70.6 ± 32.9 U l⁻¹, glutamic-pyruvic transaminase (GPT) decreased from 333.5 ± 207.3 U l⁻¹ to 77.8 ± 39.7 U l⁻¹, and creatinine decreased from 2.2 ± 0.9 mg dl⁻¹ to 1.2 ± 0.2 mg dl⁻¹. One patient died while on LVAD support due to not device related sepsis. One patient received successful heart transplantation. Overall survival was 80%. In all patients, we removed the ECMO 3 days after LVAD implantation. After removal of the ECMO there was no right heart failure. ECMO support can immediately stabilize circulation and provide organ perfusion in patients with cardiogenic shock. After improvement of organ function, LVAD implantation can be performed successfully in this patient collective. To avoid right ventricular failure, the ECMO should not be removed at the time of LVAD implantation, and used as a right ventricular support for the immediate postoperative period.     

Clinical experience and patient outcomes associated with the TandemHeart percutaneous transseptal assist device among a heterogeneous patient population

There is a paucity of literature describing the outcomes associated with the use of TandemHeart percutaneous ventricular assist device (PVAD). The literature is limited by analyzing only subsets of patients. We present the clinical outcomes and safety associated with the use of TandemHeart among a series of heterogeneous patients requiring PVAD support. We reviewed the clinical experience, hemodynamic variables, survival outcomes, and complications associated with the implantation of TandemHeart support device among 25 patients presenting to our institution. Indications for PVAD implantation were cardiogenic shock (56%), ST-segment elevation myocardial infarction (STEMI) (20%), postpericardiotomy (16%), and high-risk percutaneous coronary interventions (PCI) or ventricular tachycardia (VT) ablation (8%). TandemHeart was used for an average of 4.8 ± 2.1 days and demonstrated significant hemodynamic improvements (pre- and postimplantation left ventricular ejection fractions were 21.5% ± 15% and 24.5% ± 10.5%, respectively [p = 0.06]). The cardiac index improved from a mean 2.04 ± 075 L/min/m2 to 2.45 ± 073 L/min/m2 (p = 0.09). The mixed venous oxygen saturation (SVO2) increased from 55.14 ± 13.34 to 66.43 ± 7.43 (p = 0.008) after implantation. TandemHeart was used as a bridge to left ventricular assist device implantation (44%) or recovery (20%). Thirty-six percent of patients died on support or shortly after PVAD removal. Thirty, 90-day, and long-term (>90 days) survival rates were 56%, 52%, and 36%, respectively. Procedure-related complications were reported in 13 patients (56%), and the majority (90%) was related to vascular access (bleeding or pseudoaneurysm). The TandemHeart device is a safe therapeutic option as a bridge-to-recovery or bridge-to-bridge for patients with hemodynamic compromise regardless of the etiology. The favorable hemodynamic profile, postimplantation survival rates, and manageable complications support its use to assist hemodynamic recovery in patients refractory to conventional therapy.     

Recovery of organ dysfunction during bridging to heart transplantation in children and adolescents

The beneficial effects of ventricular assist devices on organ dysfunction during bridging to heart transplantation have been widely reported in the adult population. In contrast, the use of ventricular assist devices used as bridge-to-transplant in children is limited. To evaluate organ recovery during ventricular support in pediatric transplant candidate, respiratory, renal and hepatic function were reviewed retrospectively. The Thoratec device (stroke volume 65 ml) and the HIA-Medos-system (stroke volume 25/10 ml) were used as bridge-to transplant in 11 children and adolescents who were in low-output-syndrome despite maximal pharmacological support. Prior to implantation five patients were mechanically ventilated, six patients underwent cardiopulmonary resuscitation, eight patients had anuria (one treated by hemofiltration), three patients had liver dysfunction and four patients had signs of severe infection. At the time of implantation one patient was supported by the intraaortic balloon pump and one by the femorofemoral bypass for rapid hemodynamic stabilization. Eight patients were treated using the Thoratec device (one of these by Nova cor on the left side), three by the HIA-Medos system. The support time ranged between seven and 140 days. Seven patients could be extubated within three days. Renal function recovered in all pts. Liver enzymes decreased in all pts without reaching normal values. Bilirubin values also decreased in survivors but increased to 9.3 mg/dL in non-survivors. At least seven patients underwent successful heart transplantation, three patients died because of multiorgan failure after extended transfusion and one patient because of technical failure. In our experience the hemodynamic situation was sufficient in all bridging to transplant candidates. In all patients who underwent successful transplantation, transplantability was associated with rapid organ recovery within seven days after initiating mechanical assistance. Extended blood tranfusions, combined failure of three organs and increasing bilirubin values during support seem to be predictors of poor outcome.     

Papillary muscle rupture after myocardial infarction during left ventricular assist device support

We report a rare case of papillary muscle rupture due to myocardial infarction during left ventricular assist device support. A 69-year-old woman with cardiogenic shock due to acute myocardial infarction requiring venoarterial extracorporeal membrane oxygenation support was transferred for further surgical intervention. Six days after the event, extracorporeal membrane oxygenation was decannulated, and an extracorporeal left ventricular assist device was implanted. On postoperative day 11, she suffered from sudden onset hypoxia due to pulmonary edema. Transesophageal echocardiography showed new onset severe mitral regurgitation. No further surgical intervention was performed according to the family’s wishes, and she passed away on the 22nd postoperative day. Autopsy findings revealed papillary muscle rupture. Although the left ventricle is unloaded by the left ventricular assist device, papillary muscle rupture should be recognized as a possible complication after myocardial infarction.     

完全磁悬浮心室辅助装置的体外模拟循环系统实验研究

目的研究我国自主研发的第3代完全磁悬浮心室辅助装置(CH-VAD)对于心衰患者的循环辅助效果。方法建立一套体外模拟循环系统(mock circulatory system,MCS)。该系统能够模拟人体健康休息状态以及心力衰竭状态,并与CH-VAD协同工作,测试CH-VAD在连续流状态下的辅助效果。另外,对CH-VAD的搏动流控制方法进行测试,该模式采用正弦波速度波形,使CH-VAD的运行与MCS心室周期同步。结果 CH-VAD在正常连续流状态下能够使心衰状态的血流动力学参数(动脉压、心排量)恢复到正常范围。初步的搏动流测试结果显示,当前的速度搏动幅值对血流动力学影响较小,搏动流状态下与连续流状态所对应的平均动脉压、动脉脉压、平均心排量与心排量波形等差异不大。结论 CH-VAD能够通过搏动控制器产生一定程度的速度搏动,提供足够的心室辅助,并可以进一步改良优化,提供符合生理条件的搏动血流。所研制的MCS能够提供心室辅助装置以及其他机械循环辅助装置一个有效、可控的体外测试平台,是机械循环辅助装置设计、优化和验证的重要工具。     

Early decision for a left ventricular assist device implantation is necessary for patients with modifier A

Refractory ventricular tachyarrhythmias are life threatening, especially in patients with stage D heart failure, and left ventricular assist device therapy is virtually the sole option to resolve the fatal conditions in many cases. The Interagency Registry for Mechanically Assisted Circulatory Support defines modifier A as complicating recurrent ventricular tachyarrhythmias. However, the optimal timing to implant a left ventricular assist device remains to be determined in less sick patients with modifier A. We experienced three patients with stage D heart failure with revised modifier A, i.e., at least two appropriate operations of implantable cardiac defibrillators within 2?weeks. Two of them were rescued by extracorporeal left ventricular assist device implantation, but one died because of an electrical storm before left ventricular assist device support was available. We would like to emphasize that we should consider implantable left ventricular assist device therapy as soon as possible for those who are assigned modifier A to prevent sudden arrhythmic death.     

Identification of device malfunction in patients supported with the HeartMate XVE left ventricular assist system

Predicting end-of-life for left ventricular assist devices is important to determine timing of device removal. A retrospective analysis was performed on 46 patients undergoing implantation of the latest HeartMate XVE from July 1, 2003, through March 31, 2006. Devices were assessed by analysis of motor current waveforms and quantification of the titanium or copper particles within dust localized to the driveline vent filter by optical, polarized light, scanning electron microscopy, and energy dispersive x-ray spectroscopy. Assessments were performed monthly for patients supported > or =330 days or for unexpected device alarms. Thirty-one (67%) patients were supported for <330 days and 15 (33%) were supported for > or =330 days. No malfunctions occurred in patients supported <330 days. For patients supported > or =330 days, five had abnormal current waveforms or copper and titanium dust localized to the vent filter. One underwent urgent transplantation, three underwent device replacement (one death; two ongoing), and one is with ongoing support. Of the remaining 10 patients, seven underwent transplantation; two remain on device; and one died while on left ventricular assist device support. There were no unexpected device failures. Bearing wear of the HeartMate XVE is predictable by analysis of current waveforms or titanium and copper dust within the vent filter.     

Successful use of temporary right ventricular support to avoid implantation of biventricular long-term assist device: a transcutaneous approach

Severe right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is a serious complication with a poor prognosis. The most effective therapy for these patients is an upgrade to biventricular mechanical support. However, it is well recognized that primary and secondary biventricular ventricular assist device implantation is associated with higher mortality rates. We report on three patients with cardiogenic shock, who were provided on an emergency basis with a percutaneous extracorporeal life support (ECLS) system by the femoral vessels. After stabilization, a LVAD was implanted. To avoid secondary RV failure, the ECLS was switched to a transcutaneous RV assist device (RVAD) as a temporary RV support. The arterial cannula was removed from the femoral artery, and a prosthesis-supported cannula was sutured to the pulmonary artery and passed through a subxiphoid exit. The femoral vein cannula was left in situ. Both cannulae were connected to a centrifugal pump. Two patients could be weaned from the RVAD; the system was explanted under local anesthesia. One patient died due to internal bleeding. In conclusion, the ease of device implantation, weaning, and explantation justifies a liberal use of temporary RV support to avoid implantation of the problematic long-term biventricular assist devices.