In vivo studies of the MagScrew total artificial heart in calves

The purpose of this study was to evaluate the in vivo pump performance of our total artificial heart (TAH), the "MagScrew TAH." The TAH consists of a blood pump and control logic developed at the Cleveland Clinic and the MagScrew actuator and electronic control system developed by Foster-Miller Technologies, Inc. (Albany, NY). MagScrew TAH implantation was performed in two calves. Study durations were 50 and 5 days. The causes of termination were prosthetic valve endocarditis in one case and cable failure in the other. Mean left pump flow ranged from 8.0 to 9.7 L/min, with left atrial pressure of 3.0 to 16.0 mm Hg. Preload sensitivity of the MagScrew TAH demonstrated a Frank-Starling response to preload in automatic mode. The relationship between right and left atrial pressure was well balanced. Mean arterial pressure and mean pulmonary artery pressure were maintained within physiologic ranges over study duration. There were no signs of bleeding, hemolysis, or organ failure. The MagScrew TAH showed physiologic pump performance, and hemodynamics were well maintained without any organ failure. Further development testing will bring the MagScrew TAH to the point of preclinical readiness testing.     

Pressures generated within the chambers of the MagScrew TAH: an in vitro study

Incompetent inflow valves have been reported with clinical pulsatile left ventricular assist devices that use bioprosthetic valves. Suspected as the cause of premature valve failure within these devices, absolute pressures and instantaneous pressure changes were evaluated in the MagScrew total artificial heart (TAH). The MagScrew TAH is a passively filling pulsatile pump which uses a reciprocating magnetic actuating mechanism under various control modes to propel blood into circulation. Both right and left ejection speeds were modulated and optimized at the onset of hydraulic eject. These various speed profiles were evaluated in vitro at 220 beats per minute (bpm), 100% pump fill, mean aortic pressure of 100 mm Hg and mean pulmonary artery pressure of 20 mm Hg. The pressure inside the left and right pump chambers was measured with Millar Mikro-Tip catheter and captured using Power Lab at a rate of 40 kHz. The pump chamber peak pressure, operating with unmodified eject speeds, measured on average 183 mm Hg for the left and 133 mm Hg for the right. Eject speed profiling for both pumps reduced the peak pressure by 10% and 28% for the left and right pump, respectively. Future studies will assess software controlled optimization of the eject speed profiles under any operating condition and how effective it is in vivo.     

Total heart replacement using dual intracorporeal continuous-flow pumps in a chronic bovine model: a feasibility study

Continuous-flow pumps are small, simple, and respond physiologically to input variations, making them potentially ideal for total heart replacement. However, the physiological effects of complete pulseless flow during long-term circulatory support without a cardiac interface or with complete cardiac exclusion have not been well studied. We evaluated the feasibility of dual continuous-flow pumps as a total artificial heart (TAH) in a chronic bovine model. Both ventricles of a 6-month-old Corriente crossbred calf were excised and sewing rings attached to the reinforced atrioventricular junctions. The inlet portions of 2 Jarvik 2000 pumps were positioned through their respective sewing rings at the mid-atrial level and the pulseless atrial reservoir connected end-to-end to the pulmonary artery and aorta. Pulseless systemic and pulmonary circulations were thereby achieved. Volume status was controlled, and systemic and pulmonary resistance were managed pharmacologically to keep mean arterial pressures at 100+/-10 mmHg (systemic) and 20+/-5 mmHg (pulmonary) and both left and right atrial pressures at 15+/-5 mmHg. The left pump speed was maintained at 14,000 rpm and its output autoregulated in response to variations in right pump flow, systemic and pulmonary pressures, fluid status, and activity level. Hemodynamics, end-organ function, and neurohormonal status remained normal. These results suggest the feasibility of using dual continuous-flow pumps as a TAH.     

Preload sensitivity of the Jarvik 2000 and HeartMate II left ventricular assist devices

The in vitro sensitivity of continuous flow pumps to preload and afterload pressure has been well characterized. We compared flow in the Jarvik 2000 and HeartMate II continuous flow left ventricular assist devices (LVADs) at different inflow and outflow pressures and different pump speeds. This allowed us to measure the impact of a changing inflow pressure on the pump flow rate at different speeds but against a constant afterload. The resulting preload sensitivity curves showed that, overall, both LVADs have a mean preload sensitivity of 0.07 L/min/mm Hg in the physiologic ranges of pressures and flows encountered during normal operation. The HeartMate II pump had an increased preload sensitivity (up to approximately 0.1 L/min/mm Hg) as the preload was increased. The preload sensitivity of the Jarvik 2000 LVAD was more variable, having several peaks and troughs as the preload was increased. In future LVADs, improved preload sensitivity may allow passive regulation of pump output, optimize ventricular unloading, and decrease the risk of ventricular suction by the pump.     

Hemodynamics of a functional centrifugal-flow total artificial heart with functional atrial contraction in goats

Implantation of a total artificial heart (TAH) is one of the therapeutic options for the treatment of patients with end-stage biventricular heart failure. There is no report on the hemodynamics of the functional centrifugal-flow TAH with functional atrial contraction (fCFTAH). We evaluated the effects of pulsatile flow by atrial contraction in acute animal models. The goats received fCFTAH that we created from two centrifugal-flow ventricular assist devices. Some hemodynamic parameters maintained acceptable levels: heart rate 115.5 ± 26.3 bpm, aortic pressure 83.5 ± 10.1 mmHg, left atrial pressure 18.0 ± 5.9 mmHg, pulmonary pressure 28.5 ± 9.7 mmHg, right atrial pressure 13.6 ± 5.2 mmHg, pump flow 4.0 ± 1.1 L/min (left) 3.9 ± 1.1 L/min (right), and cardiac index 2.13 ± 0.14 L/min/m². fCFTAH with atrial contraction was able to maintain the TAH circulation by forming a pulsatile flow in acute animal experiments. Taking the left and right flow rate balance using the low internal pressure loss of the VAD pumps may be easier than by other pumps having considerable internal pressure loss. We showed that the remnant atrial contraction effected the flow rate change of the centrifugal pump, and the atrial contraction waves reflected the heart rate. These results indicate that remnant atria had the possibility to preserve autonomic function in fCFTAH. We may control fCFTAH by reflecting the autonomic function, which is estimated with the flow rate change of the centrifugal pump.     

MagScrew TAH: an update

The MagScrew Total Artificial Heart (TAH) system is the result of a close collaboration among the Cleveland Clinic Foundation, Foster Miller Technologies, Wilson Greatbatch Ltd, and Whalen Biomedical Inc. The system components are the thoracic blood pumping unit with attached compliance chamber and refill port, implantable electronic control unit, implantable battery pack, transcutaneous energy transmission system, external battery pack, and a telemetry system for communication with the electronic control unit. System in vitro tests are underway for system characterization and durability demonstration, whereas in vivo tests were conducted to evaluate system performance and biocompatibility under physiologic conditions. The passively filling pump uses a left master alternate left and right ejection control mode and has a Starling law-like response to venous pressure. The in vitro tests documented excellent hydraulic pump performance with high device output of over 9 l/min at left atrial pressures below 12 mm Hg. Atrial balance was well maintained under all test conditions. The in vivo tests demonstrated good biocompatibility without use of anticoagulant therapy. Experimental durations have ranged between 0 and 92 days. Postexplant evaluation of tissue samples did not reveal any sign of thromboembolic events or tissue damage due to device operation.     

Right-left ventricular output balance in the totally implantable artificial heart

Pneumatically powered artificial hearts readily accommodated the higher net stroke volumes by the right ventricle than from the left ventricle. We published that this discrepancy was approximately 8% of the left ventricular cardiac output. A variety of methods have been used to achieve balance between the right and left atrial pressures. Relatively large volume-displacement chambers (VDC) present potential problems, but do provide balance. The VDC in volumetrically coupled right-left stroke volumes was eliminated by using a small-diameter interatrial shunt (IAS). Preliminary studies demonstrated excellent balance in contracted and expanded blood volume (preload) and by hypotension and hypertension created with vasoactive drugs (afterload). At a mean aortic pressure of 120 mmHg, heart rate of 120 BPM, cardiac output of 8 L/minute and right atrial pressure of 13 mmHg, the peak IAS flow was 3.2 ml/beat in a right to left direction and 8.0 ml/beat in a left to right direction. The net left to right flow was 4.8 ml/beat. Over a wide range of preload (2 to 20 mmHg) and afterload (45 to 180 mmHg), the left atrial pressure was routinely 5 mm Hg more than the right atrial pressure. Elimination of the VDC reduces the number of components, volume, and weight of the totally implantable artificial heart. The IAS offers a simple solution to a very complex problem and provides a device that is simpler to implant and is possible to explant.     

Estimation of the following cardiac output using sympathetic tone and hemodynamics for the control of a total artificial heart.

A sympathetic neurogram is potentially useful for the development of a real time total artificial heart (TAH) control system. We used sympathetic tone and hemodynamic derivatives to estimate the following cardiac output in acute animal experiments using adult mongrel dogs. Moving averages of the mean left atrial pressure and mean aortic pressure were used as parameters of the preload and afterload, respectively. Renal sympathetic nerve activity (RSNA) was employed as a parameter of sympathetic tone. Equations for the following cardiac output were calculated using multiple linear regression analysis of the time series data. A significant correlation was observed between the estimated and following measured cardiac output. These results suggest the potential usefulness of the sympathetic neurogram for the real time TAH automatic control system.     

Continuous flow total artificial heart: modeling and feedback control in a mock circulatory system

We developed a mock circulatory loop and used mathematical modeling to test the in vitro performance of a physiologic flow control system for a total artificial heart (TAH). The TAH was constructed from two continuous flow pumps. The objective of the control system was to maintain loop flow constant in response to changes in outflow resistance of either pump. Baseline outflow resistances of the right (pulmonary vascular resistance) and the left (systemic vascular resistance) pumps were set at 2 and 18 Wood units, respectively. The corresponding circuit flow was 4 L/min. The control system consisted of two digital integral controllers, each regulating the voltage, hence, the rotational speed of one of the pumps. The in vitro performance of the flow control system was validated by increasing systemic and pulmonary vascular resistances in the mock loop by 4 and 8 Wood units (simulating systemic and pulmonary hypertension conditions), respectively. For these simulated hypertensive states, the flow controllers regulated circuit flow back to 4 L/min within seconds by automatically adjusting the rotational speed of either or both pumps. We conclude that this multivariable feedback mechanism may constitute an adequate supplement to the inherent pressure sensitivity of rotary blood pumps for the automatic flow control and left-right flow balance of a dual continuous flow pump TAH system.     

Acute in vivo evaluation of an implantable continuous flow biventricular assist system

An implantable biventricular assist device offers a considerable opportunity to save the lives of patients with combined irreversible right and left ventricular failure. The purpose of this study was to evaluate the hemodynamic and physiologic performance of the combined implantation of the CorAide left ventricular assist device (LVAD) and the DexAide right ventricular assist device (RVAD). Acute hemodynamic responses were evaluated after simulating seven different physiological conditions in two calves. Evaluation was performed by fixing the speed of one individual pump and increasing the speed of the other. Under all conditions, increased LVAD or RVAD speed resulted in increased pump flow. The predominant pathophysiologic effect of independently varying DexAide and CorAide pump speeds was that the left atrial pressure was very sensitive to increasing RVAD speed above 2,400 rpm, whereas the right atrial pressure demonstrated much less sensitivity to increasing LVAD speed. An increase in aortic pressure and RVAD flow was observed while increasing LVAD speed, especially under low contractility, ventricular fibrillation, high pulmonary artery pressure, and low circulatory blood volume conditions. In conclusion, a proper RVAD-LVAD balance should be maintained by avoiding RVAD overdrive. Additional studies will further investigate the performance of these pumps in chronic animal models.     

轴流泵式全人工心脏的体外测试及对负荷反应特性

目的 在体外模拟循环台测试轴流泵式全人工心脏的基本负荷反应特性，为探索生理性控制方案提供基础。方法 轴流泵式全人工心脏样机采用2个轴流泵共同设置在刚性外壳中，直径65 mm，长度70 mm。于模拟循环台上串联连接组成全人工心脏的2个轴流泵，在外周动脉和肺动脉阻力不变的条件下观测前、后负荷变化对心脏输出量的影响。结果 在前负荷固定不变的条件下，增加后负荷时心脏输出流量逐步下降，增大泵转速可对抗后负荷对输出量的抑制，泵转速设定为右心泵8 500 r/min、左心泵11 000 r/min时，心脏输出压力为13.3 kPa（100 mmHg）和输出量6 L/min。当后负荷增大到26.7 kPa（200 mmHg）时心输出量下降为0 L/min。在后负荷固定不变的条件下，前负荷的增加不导致心脏输出量明显改变。设定左心泵转速为11 000 r/min、右心泵转速8 500 r/min时前负荷由0.27 kPa（2 mmHg）增加到1.87 kPa（14 mmHg），流量基本维持在7 L/min。结论 轴流泵式全人工心脏对后负荷增加表现出明显的流量抑制趋势，此趋势可通过调节泵转速改善。轴流泵式全人工心脏对前负荷反应不明显，有别于自然心脏，其机制及调节意义尚待进一步研究。     

Analysis of the interventricular pressure waveform in the moving-actuator total artificial heart

Right and left filling pressures are important parameters in the automatic control of a total artificial heart (TAH) within normal physiologic ranges. Our TAH is composed of a moving actuator, right and left ventricles, and an interventricular space (IVS) enclosed by a semirigid housing. During operation of the TAH, the IVS volume is changed dynamically by the difference between the ejection volume of one ventricle and the inflow volume of the other. We measured the interventricular pressure (IVP) waveform by using a pressure sensor and analyzed the relationship between the IVP and the preload condition. From in vitro and in vivo experiments, we found that the measured filling pressures were linearly related to the negative peak value of the IVP. Additionally, we found that we could use the time interval from actuator start to the positive peak value of the IVP (outflow valve opening) as a useful parameter to estimate the blood filling volume of the diastole ventricle.     

叶轮泵式全人工心脏的结构设计及流体力学特性

目的通过模型样机研制和流体力学特性测试．探索以叶轮式血泵为结构基础的新型可完全植入的全人工心脏。方法全人工心脏模型样机分为左心泵和右心泵2个基本单位。2血泵均采用叶轮泵．共同设置在球形外壳中。2半球形外壳由高分子材料经激光快速成型制成．球形腔内设置固定左右心泵后对合为球形外壳．表面由医用聚氨酯橡胶涂层，直径55mm，总质量150g左右。在体外模拟循环台上对左心泵和右心泵的流体力学特性进行测试．主要观测指标为泵的转速、输出压力、流量、能耗和效率。模拟循环装置由模拟左右心房、血泵、阻力调节器、流量计串联组成，采用30％甘油水溶液作为循环介质。通过调节阻力测定特定泵转速下压力和流量。结果体外模拟测试表明全人工心脏模型样机可满足血液动力学基本要求，左心泵在9000-13000r／min转速条件下可以达到5-7L／min流量和13．3kPa（100mmHg）的压力输出，右心泵在约1／2左心泵转速和4．00kPa（30mmHg）后负荷下达到相似流量．可分别满足体、肺循环的要求。在该工作负荷条件下，2血泵的总效率约为14％。结论轴流泵作为人工心脏的血泵单位．流体力学特性可达到全人工心脏的基本要求．     

Influence of right ventricular pre- and afterload on right ventricular ejection fraction and preload recruitable stroke work relation.

When right ventricular (RV) afterload is abnormally increased, it correlates inversely with right ventricular ejection fraction (RVEF). We tested, whether this would be different with normal afterload. Additionally, we investigated whether previous studies on the slope of RV preload recruitable stroke work (SW) relation, which used rather non-physiological measures to change RV preload, could be transferred to more physiological loading conditions. RV volumes were determined by thermodilution in 16 patients with stable coronary artery disease and normal pulmonary artery pressure (PAP) at rest. Pre- and afterload were varied by body posture, nitroglycerin (NTG) application and by exercise at different body positions. At rest, the change from recumbent to sitting position decreased PAP, cardiac index (Ci), RV diastolic and systolic volumes, and RVEF. Additionally, mean pulmonary artery pressure (MPAP) correlated positively with both RVEF and cardiac index. After correction for mathematical coupling, the RV preload recruitable SW relation was: right ventricular stroke work index (RVSWi) (103 erg m-2)= 8.1 x (RV end-diastolic volume index -4.9), with n=96, r=0.57, P< or =0.001. Exercise abolished this correlation and led to an inverse correlation between RV end-systolic volume (ESV) and RVSW. In conclusion, (i) RVEF correlates positively with RV afterload when afterload varies within normal range; (ii) the slope of the RV preload recruitable SW relation, which is obtained at steady state under normal loading conditions, is substantially flatter than previously described for dynamic changes of RV preload. With increasing afterload, preload loses its determining effect on RV performance, while afterload becomes more important. This puts earlier assumptions of an afterload independent RV preload recruitable SW relation into question.     

婴幼儿心室辅助泵——20mL罗叶泵体外测试平台的建立和性能研究

目的 设计并制作基于婴幼儿心室辅助泵——罗叶泵的体外测试平台,分别完成20 mL婴幼儿罗叶泵的流体性能实验和耐疲劳实验。方法 将罗叶泵驱动装置、20 mL婴幼儿罗叶泵、前负荷腔、前负荷压力传感器、后负荷腔、前负荷压力传感器、心电监护器、阻尼器和流量计等按不同的实验目的组装成不同的测试平台,流体温度控制为37 ℃,分别用来完成20 mL婴幼儿罗叶泵的流体性能实验和耐疲劳实验。结果 所制作的流体性能实验平台能较好的模拟人体前后负荷;在固定泵输出压力时,测量了20 mL婴幼儿罗叶泵泵频率与泵前压力（前负荷）、泵后压力（后负荷）和流量的关系;所组装的耐疲劳实验平台能够测试罗叶泵的耐疲劳性能;20 mL婴幼儿罗叶泵在连续搏动70 d后,其形变率仅为4 %。结论 所组装的搏动泵测试平台能测试20 mL婴幼儿罗叶泵的流体性能和耐疲劳性能;所制作的20mL婴幼儿罗叶泵具有较好的稳定性和耐疲劳性。 更多还原     

Fuzzy logic automatic control of the Phoenix-7 total artificial heart

Automatic physiological control of the pneumatic Phoenix-7 total artificial heart (TAH) occupies a pivotal position for clinical application of the device. We developed a fuzzy logic automatic control algorithm for the Phoenix-7. The object of the automatic control system is to regulate the cardiac output at a level desirable for the given preload. The system uses cardiac output-type fuzzy pressure control combined with expert knowledge, most of which is of the form If condition, then action. As a demonstration of the utility of the control algorithm, the effects of inlet air pressures, aortic pressure, pulmonary artery pressure, and heart rate on the cardiac output were analyzed. In addition, an in vitro experiment was carried out that verified good performance of the control algorithm. This fuzzy logic control algorithm possesses the potential for totally automatic operation, eliminating any need for manual intervention under variable hemodynamic conditions.     

Advance in animal experiments with the undulation pump total artificial heart: 50 and 54 day survival periods with 1/R control

The undulation pump total artificial heart (UPTAH) is a unique, implantable, total artificial heart (TAH) that uses undulation pumps. To achieve long-term survival in animals with physiologic hemodynamic conditions, a control method based on conductance and arterial pressure was applied to UPTAH. With this control method, called 1/R control, survival periods of 50 days (No. 0016, 49.6 kg) and 54 days (No. 0030, 42.5 kg) were obtained in adult female goats. In No. 0016, 1/R control was applied to the left pump, whereas in No. 0030, it was applied to the right pump. Another pump was used for left-right balance control. The control stability was better in No. 0030 than in No. 0016. The sucking effect of the left atrium was remarkable in No. 0016, possibly because of a time delay when left-right balance control was performed with the right pump. In No. 0016, the cause of death was probably a thrombus flown from a panus in the left atrium. It is possible that the left atrial suction effect influenced the thrombus and panus formation in the left atrium. In No. 0030, the cause of death was a small rupture of the membrane in the right pump. The rupture may have been caused by excessive negative pressure inside the pump. This pressure resulted from suction of the right atrium because of an unexpected control excursion, which was probably caused by a software bug. It will be necessary to redesign the undulation pump and improve the software to achieve longer survival periods for animals with physiologic hemodynamic conditions.     

Computer-controlledin vitro model of the human left heart

The decision for surgical intervention in the treatment of stenosis and for regurgitation of the mitral valve demands an objective and quantitative evaluation of the severity of mitral valve disease. The availability of ultrasound techniques capable of analysing flow velocities across valves and to produce representative images of valve orifices has increased the interest in the hydraulics of cardiac valves. To isolate and study the determinants of transmitral flow, an in vitro model of the human left heart was built. From the model it is possible to differentiate the influence of the different determinants of left heart performance on transmitral flow: preload, compliance of the left atrium and ventricle, peripheral resistance (afterload) and heart rate. The mechanical part of the model consists of a reservoir connected to an elastic closed circuit (Latex pulmonary veins, left atrium, left ventricle and aortic arch) with replaceable mitral and aortic valves. The electronic part of the model drives and controls the hydraulic part, allowing the independent regulation and monitoring of left atrial and left ventricular pressures p, volumes V and 'pV-loops' throughout the cardiac cycle at different cardiac rhythms. Left atrial filling pressure and aortic resistance are variable in a controlled fashion. Echo-Doppler study of the mitral valve and the transmitral valve flow is possible both from an atrial and a ventricular window in the model. This technical note describes the model.     

Changes in atrial natriuretic factor during preload reduction with nitroglycerin in patients with congestive heart failure

Nine patients with congestive heart failure, New York Heart Association class II-III, were evaluated with right heart catheterization. Plasma atrial natriuretic factor (ANF) was determined in blood samples from the pulmonary artery simultaneously with recordings of right atrial, pulmonary arterial, pulmonary capillary wedge and systemic arterial pressures and heart rate during preload reduction with 0.5 mg nitroglycerin sublingually. Basal plasma ANF levels were higher in patients with congestive heart failure compared to normal controls, and correlated to right atrial, pulmonary arterial, and pulmonary capillary wedge pressures. After nitroglycerin all patients had reductions in right atrial, pulmonary arterial, and pulmonary capillary wedge pressures and a simultaneous decrease in plasma ANF concentrations, reaching lowest values after 10 min. Central pressures and plasma ANF rose to baseline values within 30 min. After nitroglycerin plasma ANF concentrations correlated to pulmonary arterial and pulmonary capillary wedge pressures, while changes in plasma ANF correlated to changes in right atrial and pulmonary arterial pressures. These results provide further evidence that ANF is released by a pressure-sensitive mechanism and demonstrates that ANF secretion in relation to central pressure variations is preserved in patients with congestive heart failure and that the response is rapid.     

Development of mechanical circulatory support devices at the University of Tokyo

The development of mechanical circulatory support devices at the University of Tokyo has focused on developing a small total artificial heart (TAH) since achieving 532 days of survival of an animal with a paracorporial pneumatically driven TAH. The undulation pump was invented to meet this purpose. The undulation pump total artificial heart (UPTAH) is an implantable TAH that uses an undulation pump. To date, the UPTAH has been implanted in 71 goats weighting from 39 to 72 kg. The control methods are very important in animal experiments, and sucking control was developed to prevent atrial sucking. Rapid left–right balance control was performed by monitoring left atrial pressure to prevent acute lung edema caused by the rapid increase in both arterial pressure and venous return associated with the animal becoming agitated. Additionally, 1/R control was applied to stabilize the right atrial pressure. By applying these control methods, seven goats survived more than 1 month. The maximum survival period was 63 days. We are expecting to carry out longer term animal experiments with a recent model of TAH. In addition to the TAH, an undulation pump ventricular assist device (UPVAD), which is an implantable ventricular assist device (VAD), has been in development since 2002, based on the technology of the UPTAH. The UPVAD was implanted in six goats; three goats survived for more than 1 month. While further research and development is required to complete the the UPVAD system, the UPVAD has good potential to be realized as an implantable pulsatile-flow VAD.