国内首例自制叶轮血泵作双心室辅助的临床试用

目的为抢救１名法洛三联症及术后低心排血量患者，将研制的离心型人工心脏叶轮血泵首次应用于临床。方法应用叶轮血泵行双心室辅助，左泵从左心房输送血液至主动脉，右泵从右心房输送血液至肺动脉。结果血泵工作４３小时，运行正常，患者心功能得到一定程度的恢复，主动脉平均压几次达到１０．６７ｋＰａ（８０ｍｍＨｇ），但因肾功能衰竭出现水肿，最终中止抢救拆除人工心脏泵。结论患者未能存活的原因有人工心脏使用不及时，生命体征好转后过早尝试降低辅助流量，以及使用升压药导致肾血流量灌注减小等。     

In Vivo Evaluation of the Miniaturized Gyro Centrifugal Pump as an Implantable Ventricular Assist Device

A miniaturized Gyro centrifugal pump has been developed to be incorporated into a totally implantable artificial heart. The Gyro PI (permanently implantable) model is a pivot bearing supported centrifugal pump with a priming volume of 20 ml. With the miniaturized actuator, the pump-actuator package has a height of 53 mm, a diameter of 65 mm, and a displacement volume of 145 ml. To evaluate the hemocompatibility and efficiency of the Gyro PI pump system, a plastic prototype (Gyro PI-601) was implanted into a bovine model as a left or right ventricular assist device (LVAD or RVAD), bypassing from the left ventricular apex to the descending aorta or from the right ventricular infundibulum to the main pulmonary artery. The calves were anticoagulated with heparin to maintain activated clotting times from 150 to 200 s. Four calves were supported for 23, 24, and 50 days in the LVAD studies, and 40 days in the RVAD study. The first calf died due to intrathoracic bleeding associated with sepsis. The second calf was euthanized for a low flow rate less than 2 L/min due to an obstructed inflow with growing pannus. The third and fourth calves were euthanized as scheduled. Renal and hepatic functions remained normal, and plasma free hemoglobin values were less than 8 mg/dL throughout the experiments. The fourth case showed flow rates of 4.83 ± 0.57 L/min, and input power of 6.16 ± 0.49 W, and the inside temperature of the actuator of 43.5 ± 0.52°C. The pumps implanted in the fourth calf demonstrated no thrombus formation at the autopsy. These in vivo experiments revealed that the Gyro PI pump can provide adequate flow as an easily implantable, efficient, antithrombogenic, and nonhemolytic centrifugal LVAD or RVAD with miniaturized actuators.     

The Pulsatile Impeller Pump for Left Ventricular Assist

Abstract: Because of severe hemolysis, especially on producing pulsatile flow by changing the rotating speed of the impellers, the traditional centrifugal pump was rarely used for long-term support of the failing heart. We therefore developed a motor driven pulsatile implantable impeller pump. The pulsatility was achieved by changing the rotating speed via introducing a square waveform voltage into the motor coil. The impeller vane was designed to have both radial and axial curves according to the stream surface and stream lines to reduce the thrombosis and hemolysis. Nine calves weighing 80 to 100 kg were used. With the calves under endotracheal general anesthesia, left posterolateral thoracotomy was performed to connect the inflow tube with the left atrial appendage and to anastomose the outflow tube with the descending aorta. The calves usually awoke and stood up within hours after discontinuation of anesthetics. Within 7 days, continuous monitoring of electrocardiogram, systemic and pulmonary arterial pressures, and central venous pressure were performed to adjust the pump flow to 40% to 50% of the cardiac output. During the survival of 4 to 54 days (mean 16.3 ± 19.3 days with two calves surviving longer than 1 month), no significant deterioration of liver or renal function was noted. Because of bleeding, hemoglobin reduced from 11.4 ± 1.8 to 9.0 ± 1.3 g/dl, and the hematocrit decreased from 34.5 ± 4.7 to 26.7 ± 4.6%. No significant changes of free hemoglobin were noted. In our results, the device revealed competent pulsatile function without severe blood damage or organ dysfunction.     

Anatomic Fitting of Total Artificial Hearts for In Vivo Evaluation

Successful anatomic fitting of a total artificial heart (TAH) is vital to achieve optimal pump hemodynamics after device implantation. Although many anatomic fitting studies have been completed in humans prior to clinical trials, few reports exist that detail the experience in animals for in vivo device evaluation. Optimal hemodynamics are crucial throughout the in vivo phase to direct design iterations and ultimately validate device performance prior to pivotal human trials. In vivo evaluation in a sheep model allows a realistically sized representation of a smaller patient, for which smaller third‐generation TAHs have the potential to treat. Our study aimed to assess the anatomic fit of a single device rotary TAH in sheep prior to animal trials and to use the data to develop a three‐dimensional, computer‐aided design (CAD)‐operated anatomic fitting tool for future TAH development. Following excision of the native ventricles above the atrio‐ventricular groove, a prototype TAH was inserted within the chest cavity of six sheep (28–40 kg). Adjustable rods representing inlet and outlet conduits were oriented toward the center of each atrial chamber and the great vessels, with conduit lengths and angles recorded for future analysis. A three‐dimensional, CAD‐operated anatomic fitting tool was then developed, based on the results of this study, and used to determine the inflow and outflow conduit orientation of the TAH. The mean diameters of the sheep left atrium, right atrium, aorta, and pulmonary artery were 39, 33, 12, and 11 mm, respectively. The center‐to‐center distance and outer‐edge‐to‐outer‐edge distance between the atria, found to be 39 ± 9 mm and 72 ± 17 mm in this study, were identified as the most critical geometries for successful TAH connection. This geometric constraint restricts the maximum separation allowable between left and right inlet ports of a TAH to ensure successful alignment within the available atrial circumference.     

Long-Term In Vivo Left Ventricular Assist Device Study for 284 Days with Gyro PI Pump

A totally implantable centrifugal artificial heart has been developed. The plastic prototype, the Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart (TAH), 2 week screening tests for anti-thrombogenecity, and a 1 month system feasibility study. Based upon these results, a metallic prototype, the Gyro PI 700 series, was subjected to long-term in vivo left ventricular assist device (LVAD) studies of over 1 month. The Gyro PI 700 series has the same inner dimension and same characteristics of the Gyro PI 601 such as an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI metallic pump is also driven with the Vienna DC brushless motor actuator like the PI 601. The pump-actuator package was implanted in 3 calves in the preperitoneal space, bypassing from the left ventricular (LV) apex to the descending aorta. Case 1 achieved a 284 day survival. Case 2 was euthanized early at 72 postoperative days as a result of the functional obstruction of the inlet port due to the excessive growth of the calf. There was no blood clot inside the pumps of either case. Case 3 is on-going (22 days on July 24, 1998). During these periods, all cases showed no physiological abnormalities. In conclusion, the PI 700 series pump has excellent results as a long-term implantable LVAD.     

Anatomical Consideration for an Implantable Centrifugal Biventricular Assist System

Abstract: A miniaturized pivot bearing-supported centrifugal blood pump (Gyro PI) has been developed as a long-term biventricular assist system (BiVAS). In this study we determined the anatomical configuration of this system using a bovine model. Under general anesthesia, a left lateral thoracotomy was performed to open the chest. Two Gyro PI-601 pumps for left and right assists were placed in the preperitoneal pocket by a subcostal abdominal incision. The left pump could be placed along the dome of the diaphragm just beneath the apex of the left ventricle. The right pump could be placed next to the left pump. The inlet and outlet ports of both pumps penetrated the diaphragm. The inlet port of the left pump, with a length of 55 mm, was inserted directly into the apex of the left ventricle. A woven Dacron graft (150 mm long, 11 mm inner diameter) was placed between the outlet port of the left pump and the descending aorta. As for the right pump. a 100 mm long and 120 degree angled inflow conduit was placed between the inlet port and the right ventricular infundibulum. The outlet port of the right pump was connected to the main trunk of the pulmonary artery using a 90 mm long, 11 mm inner diameter Dacron graft. We could perform biventricular assistance to confirm the anatomical feasibility of the Gyro implantable centrifugal BiVAS.     

In Vitro Evaluation of a Pulsatile Assist Device for a Centrifugal Pump Using a New Principle

Abstract: To induce a pulsatile flow in a centrifugal pump, we developed a new device (pulsatile assist device for centrifugal pump: PADCP) using a new concept. This device consists of a flexible polyurethane tube with an air chamber which is connected to the arterial side of the centrifugal pump circuit directly. A mock circulation system was used for evaluation of this PADCP. Thirty to 40 mm Hg of pulse pressure was obtained under 3–6 L/min of flow rate. By increasing the driving pressure of the PADCP from 200 to 600 mm Hg in a mock system, 4–48 mm Hg of pulse pressure was gained accompanied by a decrease in pump flow and increased left atrial pressure. The decreased pump flow and increased left atrial pressure were recovered easily by increasing the flow rate of the centrifugal pump. Pressures at the proximal site of the PADCP were less than 500 mm Hg. The PADCP was useful to induce a pulsatile flow in a centrifugal pump.     

In Vitro and In Vivo Testing of an Implantable Motor-Driven Left Ventricular Assist Device

Abstract: A totally implantable motor-driven left ventricular assist device (LVAD) has been developed and tested. The performance of this LVAD was tested in a mock circulatory system. This pump provided 8 L/min of output against a mean afterload of 120 mm Hg with a filling pressure of 20 mm Hg when the pump was operated in the fill/empty mode. The right and left pumps were tested in a mock loop. The right pump afterload was kept in the range from 23–32 mm Hg. With increase in the left pump afterload, the pump power output varied from 1.64 to 2.37 W. The instantaneous motor power input varied from 22.6 to 30.6 W with the total system efficiency ranging from 6.7 to 9.4%. To date, 4 in vivo studies have been conducted for up to 12 h. Two animals survived 12 and 10 h, respectively. Termination was due to bleeding in 1 animal, vent tube obstruction in 1, and respiratory failure in 2. All animals died of technical failure. Another experiment is to be undertaken, and a newly designed cannula is now being manufactured.     

Control and Driving of Pneumatic Total Artificial Hearts TNS-BRNO-II and-III in Long-Term Experiments

Hemodynamic analysis was carried out during long-term experiments with the pneumatic total artificial hearts TNS-BRNO-II and TNS-BRNO-III to determine standard methods of starting artificial hearts and criteria for their long-term operation in vivo. In long-term experiments, regulatory mechanisms automatically regulating the systole length and diastolic aspiration pressure have also been verified. Comparison of hemodynamic variables obtained from invasive measurements with pneumatic pressure curves permitted the control and monitoring of the experiment in its entirety by noninvasive methods only. The control of the artificial heart using the Chirasist TN 3 and Chirasist TN 4 was adapted to specific properties of the pumps, above all to the functions of the atypical inlet valves. The terminal stages of the experiments have shown that a 100-ml pump can ensure survival of experimental calves up to 210 kg body weight.     

Realization of a Permanent Implantable Pulsatile Impeller Heart with Magnetically Suspended Motor

Abstract: A permanent impeller heart that could work for years was once an idea. However, now this idea is turning into reality through the use of the magnetically suspended motor. Recently, with our implantable pulsatile impeller pump, 3 left ventricular assisted calves survived for about 2 months (62, 54, and 46 days, respectively). The termination of the experiments was related to wear of the mechanical bearing, which resulted in vibration of the rotor and pump failure. All the experimental animals were in good condition prior to pump failure. It seemed as if the experiments could have lasted indefinitely if the bearing had not failed. All the hematological and biochemical data of the calves remained in normal or acceptable ranges; neither blood damage nor organ dysfunction of any animal was detected. During autopsy, no severe thrombus formation was found in the pump or vessels although a low dose of heparin (0.548 g/h) was given to increase the activated coagulation time (ACT) to 1.5–2.0 times its normal value. To solve the problem of bearing wear, a magnetically suspended motor was investigated and applied to the impeller pump. On the opposite sides of a disc connected to the rotor, 2 permanent magnet rings were embedded, one for driving and the other for axial suspension. Because both the driving and suspending coils with iron cores attract the disc, no radial bearing was needed. This newly devised impeller heart promises to have long-term and permanent applications.     

Evaluation of Hemolysis in a Pulsatile Assist Device for Centrifugal Pump

Abstract: To evaluate the blood trauma caused by a new device for producing a pulsatile flow of the centrifugal pump, the pulsatile assist device for the centrifugal pump (PAD-CP) that we have developed, a hemolysis study was performed in vitro and in animal experimentation. For the in vitro testing, 2 identical sets of hemolysis test circuits were prepared with 2,400 ml of bovine blood. The 2 circuits were pumped simultaneously. Plasma total hemoglobin levels were less than 40 mg/dl after 3 h, under a pump flow of 2 L/min. Hemolysis increased to a severe level after 4 h of 4 L/min pump flow. The cause of this hemolysis was thought to be a vibration of the circuit because of incomplete compression of the polyurethane tube in the PADCP. Five adult sheep (average body weight, 47 kg) were used for in vivo evaluation of hemolysis. Hemolysis was less than 30 mg/dl of plasma hemoglobin after 4 h of open chest extracorporeal circulation with 3.0–3.6 Limin of flow rate using the PAD-CP. Other hematologic changes after PAD-CP driving were within normal limits. We conclude that the PAD-CP has proven to have possible clinical applications.     

Thrombotic Depositions on Right Impeller of Double‐Ended Centrifugal Total Artificial Heart In Vivo

The development of total artificial heart devices is a complex undertaking that includes chronic biocompatibility assessment of the device. It is considered particularly important to assess whether device design and features can be compatible long term in a biological environment. As part of the development program for the Cleveland Clinic continuous‐flow total artificial heart (CFTAH), we evaluated the device for signs of thrombosis and biological material deposition in four animals that had achieved the intended 14‐, 30‐, or 90‐day durations in each respective experiment. Explanted CFTAHs were analyzed for possible clot buildup at “susceptible” areas inside the pump, particularly the right pump impeller. Depositions of various consistency and shapes were observed. We here report our findings, along with macroscopic and microscopic analysis post explant, and provide computational fluid dynamics data with its potential implications for thrombus formation.     

In Vitro and In Vivo Validation Tests for Total Artificial Heart

Abstract: Properly planned in vitro and in vivo studies are mandatory to validate blood pump performance. However, standard procedures for in vitro and in vivo tests of total artificial heart (TAH) performance still do not exist. At Baylor College of Medicine, standard tests procedures for performance validation of the totally implantable TAH have been established. In this paper, these in vitro tests protocols (performance mapping tests, accelerated endurance test, hemolysis test, flow visualization tests, etc.) are described as well as in vivo test procedures (TAH implantation procedure, including surgical technique, postoperative management and tests, etc.). In addition, pathological protocols are presented. In our experience, these procedures are very simple, easy to perform, and inexpensive. These protocols are proposed as standard in vitro and in vivo tests for a TAH.     

叶轮泵辅助小公牛血液循环62天

为了对自制叶轮泵作在体评价，在小公牛身上进行左心室辅助实验。血液从左心房经血泵输送到主动脉，血泵流量调节为总流量的５０％左右。术前及术后连续检测动物的生理及血液生化参数。结果显示，叶轮泵能有效地辅助血液循环和恢复自然心脏的功能，并对动物的血液及器官功能不造成明显损害。一头小公牛在存活６２天后因右前腿受伤内出血引起败血症死亡，尸检未发现血管或血泵内有严重凝血及血栓。实验证明叶轮血泵的血液相容性和机械可靠性已达到中、长期使用的设计要求。     

Pulsatile Total Artificial Heart Using a Reversible Rotary Pump

Abstract: A pump circuit was assembled and examined for use as an implantable artificial heart. The circuit consisted of a gear pump and 4 artificial heart valves. Mitral and pulmonary arterial valves were placed at the inflow port of the pump, and aortic and tricuspid valves were placed at the outflow port. The mitral and the tricuspid valves were connected to each reservoir at 10 mm Hg, and the aortic and the pulmonary arterial valves were connected to the head tanks at 80 and 20 mm Hg, respectively. The pump discharged pulsatile flows into both systemic and pulmonary arteries alternately by switching the direction of rotation periodically. Because the rated discharge was 1.7 L/min for the gear pump used, the measured flow rate was 0.8-0.75 L/min at a heart rate of 60–110 bpm.     

Do We Really Need Pulse? Chronic Nonpulsatile and Pulsatile Blood Flow: From the Exercise Response Viewpoints

Abstract: The response of the body and the blood pump was evaluated in animals with a pulsatile artificial heart (total artificial heart [TAH]) and those with a nonpulsatile artificial heart (nonpulsatile biventricular bypass [NPBVB]) subjected to the same exercise load. The animals used in this study were 5 calves implanted with a pusher–plate type TAH (45–206 days) and 5 calves implanted with a nonpulsatile centrifugal pump (34–99 days). The pre–exercise pump flow rate was 92. 1 ± 8. 1 ml/kg/min for the TAH group and 94. 8 ± 9. 1 ml/kg/min for the NPBVB group, with no significant difference between the two groups. The workload was administered at a rate of 1. 5 mph for 15 min. The artificial heart driving conditions were kept constant throughout the test period. Sequential changes in hemodynamic response and metabolism were determined before, during, and for 30 min after exercise. Both TAH and NPBVB calves showed excellent tolerance of the workload (1. 5 mph exercise); in NPBVB calves, oxygen demand was compensated for by an increase in the arteriovenous oxygen difference during exercise; and norepinephrine showed a greater response in the NPBVB group. Based on the results presented, the nonpulsatile pump seems to lend itself to a mechanically driven artificial heart of the complete implantation type because of its small size, high efficiency, and the lack of need for a compliance chamber.     

Implantable Ventricular Assist Systems

A major goal of the Circulatory Support Program of the National Heart, Lung, and Blood Institute (NHLBI) is the development of a tether-free implantable ventricular assist system (VAS) to rehabilitate patients with advanced heart disease. In 1980, the NHLBI initiated a targeted program to develop and integrate implantable electromechanically powered VASs capable of operating for at least 2 years. The objectives of the program are to complete the development of the VAS and perform in vitro and in vivo evaluation studies. This article summarizes the research status of this NHLBI-sponsored program. It defines the VAS system requirements, describes the systems under development, identifies progress achieved to date, and identifies research challenges.     

Physiologic Control of Cardiac Assist Devices

Abstract: Total artificial hearts (TAHs) and biventricular assist devices (BVADs) have varying levels of acceptance and reliability, and the research on both focuses on their control mechanisms. Efforts generally aim to achieve a response to physiologic demand and left/right output balance, and beneficial cardiac output (CO) and effective control mechanisms have been achieved by eliciting a Starling-like response to preload and afterload. Such control mechanisms, however, generally base device output on a single parameter, such as the preload on the heart. Current TAHs and BVADs provide relatively fixed oxygen delivery to patients with large physiologically induced variations in oxygen consumption. This paper aims to document fluctuations in oxygen consumption that are normal in BVAD and TAH patients, identify a number of patient-generated signals that reflect these fluctuations, and describe a multitiered control algorithm based upon these signals. Such a control system may offer better response times and more physiologic cardiac outputs. There currently exists a microprocessor-based control mechanism that can be adapted to control TAHs and BVADs using input from a variety of sensors, and it can be found in modern implantable pulse generators (IPGs). Today's pacemakers are capable of rate control and can run diagnostic programs and store data that could be valuable in the evaluation of the patient's condition.     

Impeller design for a miniaturized centrifugal blood pump

The impeller design for a miniature centrifugal blood pump is an important consideration since the small diameter impeller requires higher rotational speed, which may cause more blood trauma compared to the larger diameter impeller. Three different impeller vanes (straight vanes with a height of 4 mm and 8 mm, and 8 mm curved vanes) of which the diameter was 35 mm were subjected to hydraulic performance and hemolysis tests in the same pump housing. Both straight vane impellers attained left ventricular assist condition (5 L/min against 100 mm Hg) at 2,900 rpm while the curved vane required 3,280 rpm. There was no significant hemolysis difference between the tall and short vanes. The curved impeller vanes did not exhibit sufficient hydraulic performance when compared to the straight vanes. The straight vane impellers, even with different heights, were incorporated into the same pump housings, and the vane heights did not drastically change the hydraulic performance or hemolysis.