Masaharu Yoshikawa

Development of a totally implantable biventricular bypass centrifugal blood pump system

BACKGROUND During the past 2 years, the development of a totally implantable biventricular bypass rotary blood pump system has been made. METHODS An extracorporeal gyro centrifugal pump, the CIE3, was miniaturized and developed into the PI601, a totally implantable plastic pump. Two-day anatomic and hemodynamic feasibility studies demonstrated that these two pump systems were easily implantable inside a calfs abdominal wall, directly under the diaphragm. The priming volume of the pump was 20 mL, with sufficient cardiac outputs at approximately 2,000 rpm and requiring less than 10 W of power. Two-week antithrombogenic screening tests also revealed these pump systems to be quite antithrombogenic. In addition, 1-month system reliability studies demonstrated fail-safe reliable performances. RESULTS AND CONCLUSIONS Encouraged by these preliminary studies, the PI601 model was converted to the permanently implantable titanium gyro pump PI702 model. The long-term implantations were initiated approximately 3 months ago, and two such long-term LVAD studies are currently underway with no sign of difficulty (October 10, 1997). They were followed 283 days and 72 days, respectively. Both terminated due to functional inflow obstruction. There were no blood clots or emboli at autopsy.

Blood trauma induced by clinically accepted oxygenators.

Hemolysis remains one of the most serious problems during cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and percutaneous cardiopulmonary support (PCPS). However, the hemolytic characteristics associated with oxygenators are not well defined. A specialized hemolysis test protocol for oxygenators was developed. A comparative study was performed following this protocol to determine the hemolytic characteristics of the clinically available oxygenators during CPB; pressure drop measurements in the blood chamber were also performed. Four oxygenators (Medtronic Affinity, Cobe Optima, Terumo Capiox SX25, and Bard Quantum) were evaluated. Fresh blood from healthy Dexter calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 5 L/min, similar to that used in CPB. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials (ASTM) standards. The NIH value, which was obtained from the circuit without an oxygenator, was subtracted from the primary NIH value, obtained from the circuit with an oxygenator to eliminate the effects of a centrifugal pump or other artifacts. The NIHO value was the lowest in the Affinity (0.0116 ± 0.0017) and increased from Affinity < Optima (0.0270 ± 0.0038) < Capiox (0.0335 ± 0.0028) < Quantum (0.0416 ± 0.0015 g/100 L). The Optima and Capiox did not demonstrate a significant difference. In addition, this NIHO value has a close relationship to the pressure drop. In conclusion, this new evaluation method is suitable to compare the biocompatibility performance of different types of clinically available oxygenators for CPB usage.

Feasibility of a miniature centrifugal rotary blood pump for low-flow circulation in children and infants.

In this study, a seal-less, tiny centrifugal rotary blood pump was designed for low-flow circulatory support in children and infants. The design was targeted to yield a compact and priming volume of 5 ml with a flow rate of 0.5–4 l/min against a head pressure of 40–100 mm Hg. To meet the design requirements, the first prototype had an impeller diameter of 30 mm with six straight vanes. The impeller was supported with a needle-type hydrodynamic bearing and was driven with a six-pole radial magnetic driver. The external pump dimensions included a pump head height of 20 mm, diameter of 49 mm, and priming volume of 5 ml. The weight was 150 g, including the motor driver. In the mock circulatory loop, using fresh porcine blood, the pump yielded a flow of 0.5–4.0 l/min against a head pressure of 40–100 mm Hg at a rotational speed of 1,800–4,000 rpm using 1/4” inflow and outflow conduits. The maximum flow and head pressure of 5.25 l/min and 244 mm Hg, respectively, were obtained at a rotational speed of 4,400 rpm. The maximum electrical-to-hydraulic efficiency occurred at a flow rate of 1.5–3.5 l/min and at a rotational speed of 2,000–4,400 rpm. The normalized index of hemolysis, which was evaluated using fresh porcine blood, was 0.0076 g/100 l with the impeller in the down-mode and a bearing clearance of 0.1 mm. Further refinement in the bearing and magnetic coupler are required to improve the hemolytic performance of the pump. The durability of the needle-type hydrodynamic bearing and antithrombotic performance of the pump will be performed before clinical applications. The tiny centrifugal blood pump meets the flow requirements necessary to support the circulation of pediatric patients.

Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application.

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 ± 0.56 ml/m2/L/min and 38.72 ± 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 ± 0.5 ml/m2/L/min and 24.7 ± 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.

LONG-TERM IN VIVO LEFT VENTRICULAR ASSIST DEVICE STUDY WITH A TITANIUM CENTRIFUGAL PUMP

A totally implantable centrifugal artificial heart has been developed. The plastic prototype, Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart, 2 week screening tests for antithrombogenicity, and 1 month system feasibility. Based on these results, a metallic prototype, Gyro PI 702, was subjected to in vivo left ventricular assist device (LVAD) studies. The pump system employed the Gyro PI 702, which has the same inner dimensions and the same characteristics as the Gyro PI 601, including an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI 702 is driven with the Vienna DC brushless motor actuator. For the in vivo LVAD study, the pump actuator package was implanted in the preperitoneal space in two calves, from the left ventricular apex to the descending aorta. Case 1 achieved greater than 9 month survival without any complications, at an average flow rate of 6.6 L/min with 10.2 W input power. Case 2 was killed early due to the excessive growth of the calf, which caused functional obstruction of the inlet port. There was no blood clot inside the pump. During these periods, neither case exhibited any physiologic abnormalities. The PI 702 pump gives excellent results as a long-term implantable LVAD.

Development of an antithrombogenic and antitraumatic blood pump: the Gyro C1E3.

The Gyro C1E3 is a centrifugal blood pump. Its antithrombogenic and antitraumatic blood features were demonstrated by prior studies. Based upon these studies, a mass production model of the C1E3 is becoming commercially available. Therefore, this feasibility study was conducted using the mass production models of the Gyro C1E3 for long-term cardiac assist in ex vivo animal experiments. Five healthy calves were used and 15 pump heads were applied for different time periods (Group 1, 30 days; Group 2, 14 days; Group 3, 10 and 7 days; Group 4, 4 days; and Group 5, 2 days). Activated clotting time (ACT) was kept at 200-250 sec. All five calves demonstrated neither abnormal signs nor abnormal blood examination data throughout the experiment. During necropsy, no thromboembolism was found in any downstream organs. Groups 1-4 showed thrombi inside the pump heads while two pumps in Group 5 had no thrombi formations. Bearing deformation or possible wear did not increase after 2 days of pumping. The C1E3 is capable of long-term assist circulation. However, after 2 days of pumping, careful observation is necessary since thrombi may occur inside the pump when ACT is controlled under 250 sec. During the weaning stage or low flow (under 2 L/min), over 250 sec of ACT is recommended to assure the safety of the patient.

One-Month Biocompatibility Evaluation of the Pediatric TinyPump in Goats

The TinyPump is an extracorporeal, magnetically driven centrifugal blood pump with its impeller suspended magnetically and hydrodynamically to provide short-term mechanical circulatory support for children and infants. We have previously demonstrated that the in vivo experiments of the experimental TinyPump showed acceptable stable performance at pump flows averaging around 1.0 L/min with low hemolytic and thrombogenic properties for up to 2 weeks. We present here the 1-month in vivo evaluation of the TinyPump, whose design was modified further for more durable operation. The pump was implanted as a left ventricular assist device in five goats (12.5-26.7 kg), with inflow inserted into the left ventricular apex and outflow anastomosed to the descending aorta. Five animals were supported for 110 pump days, with mean pump flow of 1.19 ± 0.03 L/min at a pump speed of 2679 ± 97 rpm. Two animals reached the scheduled end point of 30 days without device failure, and mean plasma-free hemoglobin was 1.7 ± 0.8 mg/dL. Hematologic and biochemical data of these two animals showed no evidence of cardiovascular, renal, or hepatic dysfunction. Although further experiments are needed, the modified TinyPump offers promise as a short-term mechanical circulatory support device in pediatric population.

Development of an implantable small right ventricular assist device.

Currently, at least two permanent implantable left ventricular assist devices (LVADs) are used clinically. Unfortunately, there is no small implantable right ventricular assist device (RVAD) available, even though at least 25-30% of this patient population has right ventricular failure. If a small implantable RVAD were available, biventricular assist could support patients with right ventricular failure. A small atraumatic and antithrombogenic RVAD is being developed to meet this clinical need. This small centrifugal blood pump, the Gyro PI pump, is 6.5 cm in diameter and 4.6 cm in height and has three unique characteristics to prevent thrombus formation: (1) the double pivot bearing and magnetic coupling system enable this pump to be completely sealless; (2) the secondary vanes at the bottom of the impeller accelerate the blood flow and prevent blood stagnation; and (3) the eccentric inlet port enables the top female bearing to be embedded into the top housing and decrease blood cell trauma. The inflow conduit consists of a wire reinforced tube and a hat-shaped tip that is biolized with gelatin to create a thrombus resistant material. This conduit is directly implanted into the right ventricle, and the outflow conduit is anastomosed to the PA. The pump can be implanted inside the abdominal wall or in the thoracic cavity. Biocompatibility of this pump was proved in two calves by thrombus free implantation as an LVAD for 284 days and 200 days. Two RVAD implantations were conducted, aiming for 1-month system feasibility studies. During the month, the RVADs operated satisfactorily without any thromboembolic incident. No blood clots or abnormal findings were seen inside the pump, nor were there abnormal findings in the explanted lungs except for small areas of atelectasis. The pump flow was 3.02 +/- 0.38 L/min in calf 1 and 3.75 +/- 1.18 L/min in calf 2. The power requirement was 7.28 +/- 0.43W for calf 1 and 14.52 +/- 3.93W for calf 2. The PaO2 was 72.0 +/- 3.60 mm Hg (calf 1) and 72.0 +/- 7.63 mm Hg (calf 2); PaCO2 was 38.3 +/- 2.17 mm Hg (calf 1) and 34.1 +/- 1.95 mm Hg (calf 2); and SaO2 was 94.1 +/- 1.37% (calf1) and 95.0 +/- 1.95% (calf 2). Gas exchange via the lungs was maintained. These studies indicate that the Gyro PI pump is suitable as a single implantable RVAD, and is a feasible RVAD as a part of a BiVAD system in terms of pump performance and thrombus resistance.

Reoperation of the proximal aorta: impact of presternotomy extracorporeal circulation on clinical outcomes

PurposeAdverse events can occur during a sternotomy for reoperation of the proximal aorta. Presternotomy extracorporeal circulation is often employed to avoid catastrophic events. The purpose of this study was to investigate the impact of presternotomy extracorporeal circulation on clinical outcomes of redo proximal aortic surgery.MethodsBetween January1990 and December 2005 a total of 21 aneurysms or dissections of the proximal aorta were repaired via a repeat sternotomy. Extracorporeal circulation was established before the sternotomy in 9 (49%) patients and after the sternotomy in 12 (51%) patients.ResultsThere were no statistically significant differences in the age, sex, emergency surgery, chronic obstructive pulmonary disease, and renal function between the groups. Femoral cannulation was used more often in the presternotomy extracorporeal circulation group (8/9, 89% vs. 1/12, 8.3%; P = 0.000). The difference in the pump time did not reach a statistically significant level. The 30-day and in-hospital mortality rates were 11% (1/9) and 11% (1/9) in the presternotomy extracorporeal circulation group and 0% (0/12) and 17% (2/12) in the poststernotomy extracorporeal circulation group. There were no statistically significant differences in stroke, respiratory failure, myocardial infarction, or renal failure. There was a trend toward a longer hospital stay in the presternotomy extracorporeal circulation group (85.8 vs. 48.1 days; P = 0.06).ConclusionPresternotomy extracorporeal circulation was not associated with any major adverse outcomes such as death, stroke, or renal failure.

CONTROL SYSTEM FOR AN IMPLANTABLE ROTARY BLOOD PUMP

Rotary blood pumps can be used for long-term left ventricular assist devices. These pumps have several advantages over the conventional pulsatile pumps including smaller size, higher efficiency, and simple design and construction. However, one of the difficulties associated with the rotary blood pump is the proper control method to maintain an optimum flow rate in different physiological conditions. The rotary blood pump can be controlled by two methods. The first is to utilize the measured pump flow rate from its servo signal. The second is to detect and avoid abnormal pumping conditions such as; back flow and sudden increase in the pressure head. This abnormal situation typically occurs from excessive suction of blood when there is a functional or mechanical occlusion in the inflow cannula. The ultrasound flow meter is durable and reliable but it is difficult to continually monitor the blood flow rate of an implantable pump. Therefore, another method is needed instead of the continuous flow monitoring. One chronic calf having an LVAD was subjected for the development of this control system. This calf survived more than 6 months. Voltage, current, motor speed, heart rate and the pump flow rate were recorded and stored at 30-min intervals in a computer. Utilizing these parameters, attempts were made (1) to achieve indirect flow assessments and (2) to reveal abnormal operating parameters of the centrifugal pump (1). Indirect flow measurement, the predicted pump flow rate was calculated from these pump derived parameters (required power, motor speed and heart rate). The value of the coefficient of determination (R) between the measured and estimated pump flow rate was 0.796. (2) Abnormal operating indicator, there was an association between the required current and pump flow waves. The current was differentiated, and then calculated to the power of the differentiated current. The normal range of this value was 0.02+/-0.54. In abnormal conditions, this abnormal operating indicator increased 500 times. The predicted flow estimation method and abnormal operating indicator were available from intrinsic operating parameters of the pump and need no sensors. These two methods were simple, yet they are possibly effective and reliable servo control methods for a rotary blood pump.