Ⅰ型血泵左心辅助循环动物实验研究

为了对Ⅰ型血泵进行深入研究以便在此基础上进行改进，我们选择９只心脏正常犬进行左心辅助动物实验，以验证该泵的血液动力学输出性能、对心脏的辅助功能及对血液的破坏程度。在动物实验中，血泵放入胸腔内，进口通过静脉插管经左心房耳插入左心房，出口经过动脉插管插入升主动脉。输液、测试、辅助管路接通后，控制血泵的辅助流量为心输出量的２５～３０％左右。结果显示：１．辅助流量在５００～６００ｍｌ／ｍｉｎ时，主动脉收缩压可达１３０ｍｍＨｇ，证明Ⅰ型血泵输出性能满足辅助时生理血液动力学要求。２．辅助后，主动脉舒张压和心脏总输出量均升高，提示此血泵对冠状动脉血流量的增加及心脏泵血具有辅助功能。３．辅助４小时后，血浆中游离血红蛋白含量由２．４ｍｇ／ｄｌ升高到３．１ｍｇ／ｄｌ，纤维蛋白未发生明显变化，说明此血泵对血液有较轻的破坏     

左心辅助对犬右心室的影响

目的 :观察左心辅助对犬右心室的影响。方法 :2 1条健康犬按不同左心辅助流量随机分为 3组 ,每组 7条。Ⅰ组辅助流量为 5 0ml·kg- 1 ·min- 1 ;Ⅱ组辅助流量为 70ml·kg- 1 ·min- 1 ;Ⅲ组辅助流量为 90ml·kg- 1 ·min- 1 。应用气动左心辅助装置行左心房至升主动脉辅助 5h。观察辅助前 ,辅助 5h ,停辅助 10min等时间位点的右心血流动力学变化。结果 :辅助 5h ,Ⅰ、Ⅱ、Ⅲ组左房压 (LAP) ,平均肺动脉压 (MPAP) ,全肺阻力 (TPR) ,右室最大压力上升速率 (Rvdp dtmax)均较辅助前明显减小 (P <0 0 5 ) ,且辅助流量越大下降幅度越明显 (P <0 0 5 ) ,Ⅰ、Ⅱ组右心排血指数 (PCI)较辅助前明显增高 (P <0 0 5 ) ,Ⅲ组无明显变化 (P >0 0 5 ) ,Ⅰ、Ⅱ组右心搏动指数 (RCWI)无明显变化 (P >0 0 5 ) ,Ⅲ组明显减小 (P <0 0 5 ) ,停辅助 10min时各组右心血流动力学指标均恢复至辅助前 (P >0 0 5 )。结论 :左心辅助流量越大对右心血流动力学影响越明显 ,短期左心辅助不会导致右心室的功能减退     

新型气动左心辅助循环装置动物存活实验

目的　应用自行研制的气动左心辅助泵 (罗叶泵 )进行动物存活实验 ,探讨其对血流动力学、血液有形成分和肝肾功能的影响及其临床应用的可行性 ;方法　健康山羊 12只 ,体重 2 9.7～ 39.4kg ,平均 34.1kg ,从左心房至降主动脉间转流 ,进行左心辅助循环 (LVAD) ,辅助频率为 6 0次 /分 ,流量为 2～ 3L/min ;结果　本组山羊LVAD时间为 13～174小时 ,平均 89小时 ,LVAD过程中 ,动物血压、中心静脉压稳定 ,尿液正常 ,肝肾病理检查未见坏死及出血灶 ;肌酸激酶同功酶、乳酸脱氢酶在辅助 4 8小时较术前明显升高 ,分别为 396 8.70± 15 6 1.2 5U/L ,2 0 18 0 0± 6 4 9 12U/L ,但 72小时后逐渐恢复正常 ,游离血红蛋白LVAD 4 8小时为 4 81 12± 116 .16mg/L ,在LVAD 72小时降至正常范围 (2 91.13±12 1.13mg/L) ;结论　罗叶泵能有效地维持血流动力学稳定 ,性能稳定、可靠 ,说明该血泵已具备条件进行短期临床试用     

左室辅助循环对急性左心衰犬肾素血管紧张素系统影响

目的:研究不同辅助流率对急性左心衰时肾素血管紧张素系统(RAS)的影响。方法:对20条急性左心衰犬进行高、中、低流量的180 min左室辅助,观察其对血液动力学及RAS的影响。结果: 左室辅助循环可使急性左心衰犬平均左房压、血浆肾素、血管紧张素Ⅱ迅速下降,平均主动脉压、左室搏功指数均升高。 结论:不同辅助流量对急性左心衰时左心血液动力学支持均有效,但以中流量效果最佳。神经内分泌因子是评价LVAD效果敏感而有效的指标。     

左室辅助循环对急性左心衰犬肾素血管紧张素系统影响

目的:研究不同辅助流率对急性左心衰时肾素血管紧张素系统(RAS)的影响.方法:对20条急性左心衰犬进行高、中、低流量的180 min左室辅助,观察其对血液动力学及RAS的影响.结果:左室辅助循环可使急性左心衰犬平均左房压、血浆肾素、血管紧张素Ⅱ迅速下降,平均主动脉压、左室搏功指数均升高.结论:不同辅助流量对急性左心衰时左心血液动力学支持均有效,但以中流量效果最佳.神经内分泌因子是评价LVAD效果敏感而有效的指标.     

双心室辅助对缺血性左右心功能不全血流动力学影响的实验研究

比较在缺血性左右心功能不全时左心辅助和双心室辅助对血流动力学的不同影响 ,为自制气动隔膜泵(罗叶泵 )的临床应用提供实验依据。采用 8只健康成年犬 ,植入左心辅助装置和右心辅助装置。结扎左前降支 ,3mins后在窦房结支发出处远侧端结扎右冠状动脉 ,以建立缺血性左右心功能不全的动物模型。先行左心辅助 5mins,再行双心室辅助。分别记录中心静脉压 ,心输出量 ,平均动脉压 ,肺动脉压 ,肺毛细血管楔压等血流动力学指标。结果表明 :双心室辅助时心输出量显著上升 (0 .82 2± 0 .0 9L / min vs 1.33± 0 .12 L / m in,P<0 .0 1)与正常对照值相比无显著差异 ;平均动脉压上升达正常范围 (37.4± 8.8mm Hg vs 84.2± 9.7mm Hg,P<0 .0 1) ;中心静脉压显著下降 (14.6± 2 .3cm H2 O vs 4.2± 1.5 cm H2 O,P<0 .0 1) ;肺动脉压无显著性变化 ;肺毛细血管楔压下降 (14± 3.9vs 1.6± 0 .9mm Hg,P<0 .0 1)。结论是全心功能不全时 ,单纯应用左心辅助并不能有效地改善血流动力学状况 ,应用双心室辅助可提高心输出量和动脉压至正常水平 ,可最大限度地减少心脏作功 ,降低氧耗 ,促进心肌组织的修复和代谢。因此 ,在左右心功能明显受损对药物和主动脉内球囊反搏 (IABP)治疗无效时 ,单行左心辅助应慎重 ,双心室辅助是推荐     

飞龙掌血水提物对心肌缺血兔心功能和血液动力学的影响

目的:观察飞龙掌血(Toddalia asiatica Lam)水提物(飞龙一号,F01)对急性心肌缺血动物模型心脏功能和血液动力学的影响。方法:新西兰兔作不开胸膜冠脉左前降支高位结扎造成急性心肌缺血, 观测结扎后及F01 ip对动物心功、血液动力学的影响。结果:冠脉左前降支结扎后,LVEDP显著升高(P＜0.05),t-dp/dt max 无明显变化,其余各项参数均明显降低(P＜0.05或P＜0.01)。F01(268 mg/kg)腹腔注射后,除有关左室作功和心肌耗氧的参数(HR、TTI和TTI×HR)继续降低外,其余各项参数的变化均显著逆转,恢复或接近结扎前的水平, 用药后1.5 h的作用较0.5 h更明显。结论:F01可显著减少急性缺血心肌的作功和耗氧,通过纠正心脏对氧的供需平衡失调,改善心脏收缩、舒张功能和泵血功能,从而发挥对缺血心肌的保护作用。     

一种经皮植入式左心辅助装置的泵流量测试

目的 研究设计一种能用于心血管急危重症的经皮植入式左心辅助装置（血泵）。方法 根据机翼理论,设计一种经皮植入的左心辅助装置,通过测量3种不同参数（叶片旋转角度、血泵出水口距离、血泵出水口长度）的血泵所能产生的流量,最终选择最优化的血泵设计。结果 经过简易流量测定装置测量,当血泵采取单叶设计,血泵叶片的旋转角度为720°时,或血泵出水口与叶片的距离为0 mm时,血泵出水口长度为4 mm时,血泵流量最大。结论 选择能产生最大流量的参数值,研制出一种可在体外正常运转的经皮植入式左心辅助装置,为最终研制一种可用于临床的经皮植入式左心辅助装置提供理论和数据支持。     

轴流泵在左心辅助装置中的应用

轴流泵在左心辅助装置中的应用北京心肺血管医疗研究中心─安贞医院蔺嫦燕左心辅助循环是通过一种辅助泵的装置，将左心的血液引流到泵内再注入主动脉系统，从而减轻左心室负担。采用这种血泵进行辅助循环时，通过左心室顺应性的改变和射血阻抗的降低，能明显改善左心室的...     

基于左心辅助的血液循环系统的控制研究

本文提出一种基于左心辅助的血液循环系统控制模型,该模型由左心血液循环系统和旋转式心脏泵模型耦合而成。考虑心脏泵的水力特性,根据泵相似性原理提出了新型旋转式心脏泵的数学模型。泵模型耦合心血管系统后采用七阶集总参数非线性空间状态方程表示,控制变量为电机转速。本文采用泵心脏舒张期最小流量变化斜率作为反馈机制,确保最大灌注量的同时避免抽吸。通过Matlab对模型进行仿真,结果显示在开环控制下,心衰患者的血液循环系统各项血液动力特性均有改善。当转速为9 000r/min时,经左心辅助的患者每搏心输出量由最初34mL/s提高至正常水平82mL/s,左心室压力-容积环向左偏移并且面积减小,说明辅助装置能够明显改善泵血不足并帮助心室卸载。若持续提高泵转速,当转速达到12 800r/min时,会发生抽吸异常状况,这是因为转速过高导致静脉回流量不足而形成的。经采用反馈控制后,系统可有效避免抽吸现象。本文研究结果表明,基于左心辅助的血液循环系统的控制模型能在确保足量灌注量的同时避免抽吸异常状态。该模型反映了左心辅助装置与心血管系统的交互作用,为左心辅助心衰治疗和生理控制策略设计提供理论依据。     

The enabler cannula pump: a novel circulatory support system.

BACKGROUND: The enabler circulatory support system is a catheter pump which expels blood from the left or right ventricular cavity and provides pulsatile flow in the ascending aorta or pulmonary artery. It is driven by a bedside installed pulsatile driving console. The device can easily be implanted by a minimal invasive approach, similar to the Hemopump. PURPOSE: To demonstrate the hemodynamic performance of this new intracardiac support system. METHODS: In a series of 9 sheep, hemodynamic evolutions were recorded in various conditions of myocardial contractility (the non-failing, the moderately failing and the severely failing heart). Heart failure was induced by injection of microspheres in the coronary arteries. RESULTS: Introduction of the cannula through the aortic valve was feasible in all cases. Pump flow by the enabler was gradually increased to a maximum of 3.5 L/min. Diastolic (and mean) aortic blood pressure is significantly increased in the non-failing and moderately failing condition (counterpulsation mode). In heart failure, cardiac output is significantly increased by the pump (p < 0.0001). A drop in left atrial pressure (indicating unloading) is achieved in all conditions but reaches significant levels only during heart failure (p=0.0068). CONCLUSIONS: This new circulatory support system contributes to stabilization of the circulation in the presence of cardiac unloading. In heart failure it actually supports the circulation by increasing cardiac output and perfusion pressure.     

Ultrastructural changes in the ischemic zone bordering experimental infarcts in rat left ventricles.

Ultrastructural changes in myocardial cells from the ischemic border of infarcts (produced in rat left ventricles by ligating the anterior coronary artery in vivo) were examined 1 to 24 hours after ligation. Twenty-four hours after ligation, irreversibly injured cells showed a selective spreading of Z-band material over the I band; disappearance of M bands, prominent N bands, and disassembly of A bands were also noteworthy. Sixty minutes after ligation the cells of the ischemic border were ultrastructurally normal except for paradoxically relaxed sarcomeres, indicative of an inability to contract in response to the calcium influx produced by osmium tetroxide; progressive vacuolization of this zone was evident after 4 to 12 hours. Paradoxical relaxation may be an ultrastructural correlate of acute ischemic "pump failure".     

糖尿病在糖尿病大鼠心肌梗死后心力衰竭形成中的效应

目的： 评估糖尿病在链脲霉素（STZ）诱导的血糖不加控制的糖尿病大鼠急性心肌梗死（AMI）后心力衰竭(HF)形成中的效应。方法：所有SD大鼠随机分组,糖尿病组经腹腔内注射STZ（65mg/kg）诱导糖尿病,70 d后所有AMI组结扎冠状动脉左前降支建立AMI模型。确定AMI前后各时点观察大鼠的生存率,心肌超微结构的变化,进行血流动力学分析、心肌纤维化测定及左心肥厚的评估。结果：结扎左冠状动脉前降支后,糖尿病大鼠的左心功能恶化及左室重构的速度均较非糖尿病大鼠显著。在早期阶段,糖尿病与非糖尿病大鼠心肌纤维化相似,而1月后却出现显著差别。结论：糖尿病大鼠AMI后心力衰竭进展明显加速。     

A two and one half year clinical experience with a mechanical left ventricular assist pump in the treatment of profound postoperative heart failure.

A sac-type paracorporeal left ventricular assist pump was implanted in 9 patients suffering from profound left ventricular failure following open heart surgery. Two patients had good recovery of left ventricular function and were weaned from assist. One survived 14 months postoperatively. Primary causes of death among the remaining patients were (1) primary right ventricular failure, (2) assist pump inlet cannula obstruction and (3) excessive bleeding. The strategies developed or proposed to deal with these problems include, respectively: (1) biventricular assist for patients with concomitant right ventricular failure; (2) cannulation of the left atrium to avoid inlet cannula obstruction by the left ventricular wall and intraventricular septum; (3) more rapid selection of left assist candidates and more rapid implantation techniques to reduce the coagulopathy associated with prolonged cardiopulmonary bypass, and an effective autotransfusion system to augment blood replacement.     

A chronic heart failure model by coronary artery ligation in the goat

The availability of a reliable heart failure model in large animals is important. We report upon our efforts to develop a chronic heart failure model in seven goats using sequential ligation of the left anterior descending (LAD) coronary artery and its diagonal branch. After anesthesia and left thoracotomy, the LAD artery was ligated, and the diagonal vessel at the same level was ligated one hour later. Cardiac measurements were performed with a thermodilution catheter and by ultrasonography. Two months after the operation, the same measurements were made and animals were sacrificed for postmortem examinations of their hearts. Hemodynamic measurements, except cardiac output, showed no significant changes immediately after the coronary artery ligation. Echocardiographic measurements showed significant changes in the ejection fraction and fractional shortening without changes in left ventricular dimensions. Wall motion analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all animals immediately after coronary artery ligation. Five animals have undergone hemodynamic and ultrasonographic studies 2 months after coronary artery ligation. The results obtained from these animals showed significant increases in central venous pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary artery capillary wedge pressure, and a significant decrease in cardiac output. Increases in left ventricular dimensions and decreases in ejection fraction with fractional shortening in ultrasonographic studies were also observed. Pathologically, well-demarcated thin-walled anteroseptal infarcts, with chamber enlargement, were clearly seen with dilatation of the heart chambers in all specimens. Based on this study, we conclude that goats, like sheep, can provide a reliable model of chronic heart failure by coronary artery ligation and in view of the many advantages offered by goats, we believe that this animal model will be useful for cardiac experimentation.     

Increased contribution of alpha 1- vs. beta-adrenoceptor-mediated inotropic response in rats with congestive heart failure

AIM: In failing myocardium the mechanical response to beta-adrenoceptor stimulation is attenuated. Alternative signalling systems might provide inotropic support when the beta-adrenoceptor system is dysfunctioning. Accordingly, the inotropic responses to alpha 1- and beta-adrenoceptor stimulation by the endogenous adrenoceptor agonist noradrenaline in non-failing and failing rat hearts were compared. METHODS: Chronic heart failure was induced in male Wistar rats by coronary artery ligation. Corresponding sham groups were prepared. After 6 weeks, papillary muscles from non-failing and failing hearts were isolated. Receptor binding studies were performed in the corresponding myocardium. The alpha 1-adrenoceptor-mediated inotropic response was not changed while the beta-adrenoceptor-mediated response was substantially reduced in failing compared with non-failing myocardium. RESULTS: No change in potency for the agonists was observed at the alpha 1-adrenoceptors, while an increased potency for the agonists at the beta-adrenoceptors was found during heart failure. The lusitropic response to beta-adrenoceptor stimulation was intact during heart failure. No over all change in affinity or number of either adrenoceptor type was observed in receptor binding studies. The alpha 1-adrenoceptor-mediated inotropic response became dominating compared with the beta-adrenoceptor-mediated one in failing rat myocardium in contrast to the dominating role of the latter in non-failing myocardium. The attenuation of the beta-adrenoceptor-mediated inotropic response in rat failing myocardium was not because of a reduced number of receptors. CONCLUSION: Increasing contractility through stimulation of alpha 1-adrenoceptors in situ by the endogenous agonist may be an alternative way of inotropic support during heart failure and even more so during beta-adrenoceptor blockade.     

Measurement of hemodynamic changes with the axial flow blood pump installed in descending aorta

We have developed various axial flow blood pumps to realize the concept of the Valvo pump, and we have studied hemodynamic changes under cardiac assistance using an axial flow blood pump in series with the natural heart. In this study, we measured hemodynamic changes of not only systemic circulation but also cerebral circulation and coronary circulation under cardiac support using our latest axial flow blood pump placed in the descending aorta in an acute animal experiment. The axial flow blood pump was installed at the thoracic descending aorta through a left thoracotomy of a goat (43.8 kg, female). When the pump was on, the aortic pressure and aortic flow downstream of the pump increased with preservation of pulsatilities. The pressure drop upstream of the pump caused reduction of afterload pressure, and it may lead to reduction of left ventricular wall stress. However, cerebral blood flow and coronary blood flow were decreased when the pump was on. The axial flow blood pump enables more effective blood perfusion into systemic circulation, but it has the potential risk of blood perfusion disturbance into cerebral circulation and coronary circulation. The results indicate that the position before the coronary ostia might be suitable for implantation of the axial flow blood pump in series with the natural heart to avoid blood perfusion disturbances.     

The heart-pump interaction: effects of a microaxial blood pump

BACKGROUND: When we use rotary blood pumps as an assist device, an interaction takes place between the pump performance and the native heart function (native heart influences pump performance and vice versa). The interaction between native heart and rotary blood pump can be useful to predict recovery of the failing heart. METHODS: The rotary blood pumps used were microaxial catheter-mounted pumps with an external diameter of 6.4 mm (Impella, Aachen, Germany). The pump-heart interaction was studied in five juvenile sheep with a mean body weight of 68.5 +/- 8.7 kg. The pumps were introduced via the left carotid artery and placed in transvalvular aortic position. Recorded parameters were pump speed (rpm), generated flow (L/min) and differential pressure (mm Hg) obtained at high frequency rate of data recordings (25 sets of data per second). This allowed continuous analysis of the pump performance during cardiac cycle. Under clinical conditions the interaction was studied in a 60-year-old male, in whom the device was applied due to postcardiotomy heart failure after myocardial infarction. RESULTS: Heart-pump interaction was analyzed based on pump flow differential pressure. This relationship, analyzed continuously during cardiac cycle, presents as a loop. The dynamic contribution of the heart to the flow generated by the pump leads to continuous fluctuation in the pressure head and the creation of hysteresis. The improved function of the failing heart under clinical conditions after seven days of mechanical support was expressed by: increased hysteresis of the loop caused by increased gradient of flow generated during cardiac cycle, a more pronounced venticular ejection phase that indicates more dynamic heart contribution to the generated flow, and finally increased gradient of the differential pressure during cardiac cycle, caused predominantly by increased aortic pressure and decreased left ventricle pressure during diastolic phase. CONCLUSIONS: The heart-pump interaction based on the pump flow-differential pressure relationship can be useful in predicting the possibility to wean the patient from the device.     

Observation of cavitation pits on mechanical heart valve surfaces in an artificial heart used in in vitro testing

Our group has developed an electrohydraulic total artificial heart (EHTAH) with two diaphragm-type blood pumps. Cavitation in a mechanical heart valve (MHV) causes valve surface damage. The objective of this study was to investigate the possibility of estimating the MHV cavitation intensity using the slope of the driving pressure just before valve closure in this artificial heart. Twenty-five and twenty-three-millimeter Medtronic Hall valves were mounted at the inlet and outlet ports, respectively, of both pumps. The EHTAH was connected to the experimental endurance tester developed by our group, and tested under physiological pressure conditions. Cavitation pits could be seen on the inlet valve surface and on the outlet valve surface of the right and left blood pumps. The pits on the inlet valves were more severe than those on the outlet valves in both blood pumps, and the cavitation pits on the inlet valve of the left blood pump were more severe than those on the inlet valve of the right blood pump. The longer the pump running time, the more severe the cavitation pits on the valve surfaces. Cavitation pits were concentrated near the contact area with the valve stop. The major cause of these pits was the squeeze flow between the leaflet and valve stop.     

太子参对心肌梗死后慢性心衰大鼠心功能与基质金属蛋白酶表达的影响

目的：研究太子参对心肌梗死诱导的慢性心衰大鼠心功能与基质金属蛋白酶（MMPs）表达和活性的作用。方法:采用结扎大鼠冠状动脉复制急性心肌梗死诱导慢性心衰动物模型，以血流动力学指标分析心功能，RT-PCR分析MMP-2与MMP-9的mRNA表达，酶谱法分析MMP-2与MMP-9的活力。结果:大鼠冠脉结扎6周后，心功能显著紊乱；左心室组织MMP-2与MMP-9 mRNA水平显著提高、酶活力增加。太子参水煎液连续灌胃给药5周，可显著改善心衰大鼠的血流动力学，抑制左心室组织MMP-2与MMP-9的活力和mRNA的水平增加（与模型组比较，差异显著，P<0.01，P<0.05）。结论:大鼠冠脉结扎6周形成慢性心衰模型，太子参水煎液可改善大鼠冠脉结扎所诱导的心衰，其机制可能与MMPs的表达和活性有关。