Coronary microembolization sheep model by adjusting the number of microspheres based on coronary blood flow.

BACKGROUND: A heart failure (HF) model using coronary microembolization in large animals is indispensable for medical research. However, the heterogeneity of myocardial response to microembolization is a limitation. We hypothesized that adjusting the number of injected microspheres according to coronary blood flow could stabilize the severity of HF. This study aimed to evaluate the effect of microsphere injection based on the left coronary artery blood flow in an animal model. METHODS: Microembolization was induced by injecting different numbers of microspheres (polystyrene, diameter: 90 µm) into the left descending coronary artery of the two groups of sheep (400 and 600 times coronary blood flow [ml/min]). Hemodynamic parameters, the pressure-volume loop of the left ventricle, and echocardiography findings were examined at 0.5, 1.5, 3.5, and 6.5 h after microembolization. RESULTS: End-diastolic pressure and normalized heart rate increased over time, and were significantly higher in 600 × coronary blood flow group than those in 400 × coronary blood flow group (p = 0.04 and p < 0.01, respectively). The maximum rate of left-ventricular pressure rise and normalized stroke volume decreased over time, and were significantly lower in 600 × coronary blood flow group than those in 400 × coronary blood flow group (p < 0.01 and p < 0.01, respectively). The number of microspheres per coronary blood flow was significantly correlated with the decrease in stroke volume and the maximum rate of left ventricular pressure rise in 6.5 h (r = 0.74, p = 0.01 and r = 0.71, p = 0.02, respectively). CONCLUSIONS: Adjusting the number of injected microspheres based on the coronary blood flow enabled the creation of HF models with different degrees of severity.

Feasibility study of an artificial placenta system consisting of a loop circuit configuration extracorporeal membrane oxygenation with a bridge circuit in the form of the umbilical arterial-venous connection.

We developed a new artificial placenta (AP) system consisting of a loop circuit configuration extracorporeal membrane oxygenation (ECMO) with a bridge circuit designed to be applied to the fetus in the form of an umbilical arterial-venous connection. We aimed to evaluate the feasibility of the AP system by performing a hydrodynamic simulation using a mechanical mock circulation system and fetal animal experiment. The effect of the working condition of the AP system on the fetal hemodynamics was evaluated by hydrodynamic simulation using a mechanical mock circulation system, assuming the weight of the fetus to be 2 kg. The AP system was introduced to two fetal goats at a gestational age of 135 days. The general conditions of the experimental animals were evaluated. The mock simulation showed that in an AP system with ECMO in the form of an umbilical arterial-venous connection in series, it could be difficult to maintain fetal hemodynamics when high ECMO flow was applied. The developed AP system could have high ECMO flow with less umbilical blood flow; however, the possibility of excessive load on the fetal right-sided heart should be noted. In the animal experiment, kid 1 (1.9 kg) was maintained on the AP system for 12 days and allowed to grow to term. In kid 2 (1.6 kg), the AP system could not be established because of the occlusion of the system by a thrombus. The developed AP system was feasible under both in vitro and in vivo conditions. Improvements in the AP system and management of the general fetal conditions are essential.

Assessment of ocular blood flow in continuous-flow ventricular assist device by laser speckle flowgraphy.

Although the influence of continuous-flow left ventricular assist device (CF-LVAD) support on peripheral circulation has been widely discussed, its monitoring modalities are limited. The aim of this study was to assess the peripheral circulation using the laser speckle flowgraph (LSFG) which can quantitatively measure the ocular blood flow. We implanted a centrifugal CF-LVAD (EVAHEART®; Sun Medical Technology Research Corporation, Nagano, Japan) in five adult goats (body weight 44.5 ± 2.9 kg) under general anesthesia. The waveform of the central retinal artery using the mean blur rate (MBR) for ocular blood velocity and fluctuations as a parameter of pulsatility were obtained before LVAD implantation and after LVAD full-bypass support. The MBR waveform and LSFG fluctuation data were compared with the waveform and pulsatility index of the external carotid artery using an ultrasonic flow meter to evaluate circulatory patterns at different levels. The MBR waveform pattern of the central retinal artery was pulsatile before LVAD implantation and less pulsatile under LVAD full bypass. The fluctuation was 14.7 ± 1.86 before LVAD implantation and 3.85 ± 0.61 under LVAD full bypass (p < 0.01), respectively. The fluctuations of LSFG showed a strong correlation with the pulsatility index of the external carotid artery meaning that similar changes in circulatory pattern were observed at two different levels. Measuring the ocular blood flow using LSFG has potential utility for the assessment of the status of the peripheral circulation and its pulsatility during CF-LVAD.

A Novel Extracorporeal Continuous-Flow Ventricular Assist System for Patients With Advanced Heart Failure　- Initial Clinical Experience.

BACKGROUND: Bridge-to-decision (BTD) devices providing temporary mechanical circulatory support should be introduced to patients with advanced heart failure. This study evaluated the effectiveness and safety of a BTD device comprising an innovative extracorporeal continuous-flow temporary ventricular assist device (VAD) driven by a novel hydrodynamically levitated centrifugal flow blood pump.Methods and Results:Nine patients, comprising 3 with dilated cardiomyopathy, 3 with fulminant myocarditis, and 3 with ischemic heart disease, and 6 males, whose mean age was 47.7±8.1 years, were enrolled into the study. Six patients had Interagency Registry for Mechanically Assisted Circulatory Support profile 1, and 3 were profile 2. The primary endpoint was a composite of survival free from device-related serious adverse events and complications during circulatory support. Eight patients received left ventricular support, of whom 3 received concomitant right ventricular support using extracorporeal membrane oxygenation circuits, as a consequence of severe respiratory failure. One patient with fulminant myocarditis received biventricular support using the novel VAD system. After 19.0±13.5 days, 3 patients were weaned from circulatory support, because their native cardiac function recovered, and 6 patients required conversion to a durable device as a bridge-to-transplantation. One patient had non-disabling ischemic stroke episodes, and no patients died. CONCLUSIONS: This novel extracorporeal VAD system with a hydrodynamically levitated centrifugal pump can safely and successfully bridge patients with advanced heart failure to subsequent therapeutic stages.

Preclinical biocompatibility study of ultra-compact durable ECMO system in chronic animal experiments for 2 weeks.

Although the innovation has come in ECMO field, many problems remain unresolved. One of the main problems is about long-term durability and biocompatibility. Another is the system's size, weight, and its complicated equipment. For the former problem, we have previously developed ECMO system which consists of a tiny, hydrodynamically levitated centrifugal pump (BIOFLOAT-NCVC), a membrane oxygenator with hollow polyolefin fibers (BIOCUBE-NCVC), and the circuit treated with a heparin-bonding material (T-NCVC coating), and reported three cases of animal experiments for 30-day heparin-free drive. For the latter problem, we have integrated these elements to the compact system with sensors of temperature, pressure, and SvO2, and blood flow. Its installation area is 595 cm2, weighs 8.9 kg with attachable oxygen cassette, and battery which could last an hour at least. To evaluate the biocompatibility of this system, this ECMO was installed in four goats. Scheduled duration was 14 days. Heparin was continuously infused to control their ACT between 150 and 200 s except one 2-week experiment without systemic heparinization. All of the four goats survived till the scheduled termination. Function of the pump and the oxygenator during ECMO was stable. No obvious adverse events were observed. All lab data were of normal range after 1 week. Small infarctions were found at kidneys, but they were not clinically significant. No thrombus was found in the pump system. The oxygenators were extremely clean except a little thrombus formation; while, the heparin-free examination revealed acceptable cleanliness. The present study revealed good anti-thrombogenicity of this ultra-compact durable ECMO system with heparinization. Our system encourages awake and extubated management, rehabilitation, inter-hospital transfer, and prehospital initiation of ECMO.

Miniaturized centrifugal ventricular assist device for bridge to decision: Preclinical chronic study in a bovine model.

We developed a novel miniaturized extracorporeal centrifugal pump "BIOFLOAT NCVC (Nipro Corporation Osaka, Japan) as a ventricular assist device (VAD) and performed a preclinical study that is part of the process for its approval as a bridge to decision by the pharmaceutical and medical device agencies. The aim of this study was to assess the postoperative performance, hemocompatibility, and anticoagulative status during an extended period of its use. A VAD system, consisting of a hydrodynamically levitated pump, measuring 64 mm by 131 mm in size and weighing 635 g, was used. We installed this assist system in 9 adult calves (body weight, 90 ± 13 kg): as left ventricular assist device (LVAD) in 6 calves and right ventricular assist device (RVAD) in 3 calves, for over 30 days. Perioperative hemodynamic, hematologic, and blood chemistry measurements were obtained and end-organ effects on necropsy were investigated. All calves survived for over 30 days, with a good general condition. The blood pump was operated at a mean rotational speed and a mean pump flow of 3482 ± 192 rpm and 4.08 ± 0.15 L/min, respectively, for the LVAD and 3902 ± 210 rpm and 4.24 ± 0.3 L/min, respectively, for the RVAD. Major adverse events, including neurological or respiratory complications, bleeding events, and infection were not observed. This novel VAD enabled a long-term support with consistent and satisfactory hemodynamic performance and hemocompatibility in the calf model. The hemodynamic performance, hemocompatibility, and anticoagulative status of this VAD system were reviewed.

Interventricular dyssynchrony during continuous-flow left ventricular assist device support: observation using the conductance method.

The purpose of this study was to observe and clarify the interventricular dysscynchrony caused by continuous-flow left ventricular assist device (CF-LVAD) support using the conductance method. During CF-LVAD support, the systolic phase of the left ventricle (LV) becomes shorter than that of the right ventricle (RV). Accordingly, timing of the systole and diastole during the cardiac cycle is not synchronous between the LV and RV. In this study, we evaluated this phenomenon in a normal heart model using the adult goat (n = 5, body weight 44.5 ± 2.9 kg). A centrifugal LVAD was implanted under general anesthesia. We inserted the conductance catheter into the RV and LV to obtain the pressure-volume relationship of the two ventricles simultaneously. We defined the dyssynchronous status as the sign (plus or minus) of the LV volume-change opposite to that of RV volume-change. Dyssynchronous phase of the cardiac cycle was observed in 5.6 ± 0.65% of hearts under LVAD pump-off and 25.3 ± 3.3% under LVAD full bypass, respectively (p < 0.05). To the best of our knowledge, this is the first experimental report clarifying interventricular dyssynchrony during CF-LVAD support using the conductance method. Quantification of this phenomenon under various support conditions and assessment of influences on the right ventricular function will be studied in future studies.

Evaluation of the Novel Centrifugal Pump, CAPIOX SL, in Chronic Large Animal Experiments.

In the development of a new device for extracorporeal circulation, long-term durability and biocompatibility are required. The CAPIOX SL Pump (SL pump, Terumo Corporation, Tokyo, Japan), which is a centrifugal pump using a two-pivot bearing, was developed with the hope of suppressing pump thrombus formation around the bearings. This study aimed to evaluate the in vivo performance of the SL pump in the condition assumed severe clinical situation for long-term extracorporeal membrane oxygenation (ECMO) support. Extracorporeal circulation using the SL pump was installed in three goats, with drainage from the inferior vena cava and infusion into the right jugular artery. The animals were maintained with target pump flow of 2.0-3.0 L/min for 3 or 7 days. Anticoagulation was performed by continuous infusion of heparin with a target activated coagulation time (ACT) of 200 ± 50 s. Blood tests were performed regularly. After 3 or 7 days, autopsies were performed on all animals. The pumps were disassembled and observed for thrombus formation. The results were compared with those of our previous study of the current model of the centrifugal pump (SP pump). All animals were successfully managed within target pump flows and ACT values during the scheduled period, with no adverse events. No thrombus formation was found around the bearing of the SL pump. The blood tests showed normal major organ functions, and platelet consumption and hemolysis were significantly lower in this study compared to the previous study of the SP pump. The CAPIOX SL Pump showed excellent durability and biocompatibility in a large animal experiment.

Novel temporary left ventricular assist system with hydrodynamically levitated bearing pump for bridge to decision: initial preclinical assessment in a goat model.

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. We developed a new temporary left ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing. We used three adult goats (body weight, 58-68 kg) to investigate the 30-day performance and hemocompatibility of the newly developed left ventricular assist system, which included the pump, inflow and outflow cannulas, the extracorporeal circuit, and connectors. Hemodynamic, hematologic, and blood chemistry measurements were investigated as well as end-organ effect on necropsy. All goats survived for 30 days in good general condition. The blood pump was operated at a rotational speed of 3000-4500 rpm and a mean pump flow of 3.2 ± 0.6 L min. Excess hemolysis, observed in one goat, was due to the inadequate increase in pump rotational speed in response to drainage insufficiency caused by continuous contact of the inflow cannula tip with the left ventricular septal wall in the early days after surgery. At necropsy, no thrombus was noted in the pump, and no damage caused by mechanical contact was found on the bearing. The newly developed temporary left ventricular assist system using a disposable centrifugal pump with hydrodynamic bearing demonstrated consistent and satisfactory hemodynamic performance and hemocompatibility in the goat model.

Impact of bypass flow rate and catheter position in veno-venous extracorporeal membrane oxygenation on gas exchange in vivo.

The clinical use of veno-venous extracorporeal membrane oxygenation (VVECMO) in adult patients with respiratory failure is rapidly increasing. However, recirculation of blood oxygenated by ECMO back into the circuit may occur in VVECMO, resulting in insufficient oxygenation. The cannula position and bypass flow rate are two major factors influencing recirculation, but the relationship and ideal configuration of these factors are not fully understood. In the present study, we attempted to clarify these parameters for effective gas exchange. VVECMO was performed in eight adult goats under general anesthesia. The position of the drainage cannula was fixed in the inferior vena cava (IVC), but the return cannula position was varied between the IVC, right atrium (RA), and superior vena cava (SVC). At each position, the recirculation rates calculated, and the adequacy of oxygen delivery by ECMO in supplying systemic oxygen demand was assessed by measuring the arterial oxygen saturation (SaO2) and pressure (PaO2). Although the recirculation rates increased as the bypass flow rates increased, SaO2 and PaO2 also increased in any position of return cannula. The recirculation rates and PaO2 were 27 ± 2% and 162 ± 16 mmHg, 36 ± 6% and 139 ± 11 mmHg, and 63 ± 6% and 77 ± 9 mmHg in the SVC, RA and IVC position at 4 L/min respectively. In conclusion, the best return cannula position was the SVC, and a high bypass flow rate was advantageous for effective oxygenation. Both the bypass flow rates and cannula position must be considered to achieve effective oxygenation.

Influence of a novel electrocardiogram-synchronized rotational-speed-change system of an implantable continuous-flow left ventricular assist device (EVAHEART) on hemolytic performance.

We developed a novel controller for a continuous-flow left ventricular assist device (EVAHEART) that can change the pump's rotational speed (RS) in synchronization with a patient's myocardial electrocardiogram (ECG) with the aim of facilitating cardiac recovery. We previously presented various applications of this system in animal models, but there remained a concern that the repeated acceleration and deceleration of the impeller may induce additional hemolysis. In this study, we evaluated the blood trauma and motor power consumption induced by our system in a mock circulation. We evaluated our system with a 60-bpm pulse frequency and a variance between the high and low RSs of 500 rpm (EVA-P; n = 4). The continuous modes of EVAHEART (EVA-C; n = 4) and ROTAFLOW (n = 4) were used as controls. The pumps were examined at a mean flow rate of 5.0 ± 0.2 L/min against a mean pressure head of 100 ± 3 mmHg for a 4-h period. As a result, the normalized indexes of the hemolysis levels of EVA-P and EVA-C were 0.0023 ± 0.0019 and 0.0023 ± 0.0025, respectively, and their difference was not significant. The estimated mean motor power consumptions of EVA-C and EVA-P were 6.24 ± 0.33 and 7.19 ± 0.93 W, respectively. When a novel ECG-synchronized RS-change system was applied to EVAHEART, the periodic RS change with a 500-rpm RS variance did not affect the hemolysis at a 60-bpm pulse frequency.

Development of a compact wearable pneumatic drive unit for a ventricular assist device.

The purpose of this study was to develop a compact wearable pneumatic drive unit for a ventricular assist device (VAD). This newly developed drive unit, 20 x 8.5 x 20 cm in size and weighing approximately 1.8 kg, consists of a brushless DC motor, noncircular gears, a crankshaft, a cylinder-piston, and air pressure regulation valves. The driving air pressure is generated by the reciprocating motion of the piston and is controlled by the air pressure regulation valves. The systolic ratio is determined by the noncircular gears, and so is fixed for a given configuration. As a result of an overflow-type mock circulation test, a drive unit with a 44% systolic ratio connected to a Toyobo VAD blood pump with a 70-ml stroke volume achieved a pump output of more than 7 l/min at 100 bpm against a 120 mmHg afterload. Long-term animal tests were also performed using drive units with systolic ratios of 45% and 53% in two Holstein calves weighing 62 kg and 74 kg; the tests were terminated on days 30 and 39, respectively, without any malfunction. The mean aortic pressure, bypass flow, and power consumption for the first calf were maintained at 90 x 13 mmHg, 3.9 x 0.9 l/min, and 12 x 1 W, and those for the second calf were maintained at 88 x 13 mmHg, 5.0 x 0.5 l/min, and 16 x 2 W, respectively. These results indicate that the newly developed drive unit may be used as a wearable pneumatic drive unit for the Toyobo VAD blood pump.

Experimental study of a novel method of cardiopulmonary resuscitation using a combination of percutaneous cardiopulmonary support and liposome-encapsulated hemoglobin (TRM645).

Percutaneous cardiopulmonary support (PCPS) has been applied for cardiopulmonary arrest (CPA). We have developed a novel method of cardiopulmonary resuscitation using PCPS combined with liposome-encapsulated hemoglobin (TRM645) to improve oxygen delivery to vital organs. Ventricular fibrillation was electrically induced to an adult goat for 10 min. Next, PCPS (30 ml/kg/min, V/Q: 1) was performed for 20 min. Then, external defibrillation was attempted and observed for 120 min. The TRM group (n5) was filled with 300 mL of TRM645 for the PCPS circuit. The control group (n5) was filled with the same volume of saline. The delivery of oxygen (DO2) and oxygen consumption (VO2) decreased markedly by PCPS after CPA, compared to the preoperative values. DO2 was kept at a constant level during PCPS in both groups, but VO2 slowly decreased at 5, 10, and 15 min of PCPS in the control groups, demonstrating that systemic oxygen metabolism decreased with time. In contrast, the decreases in VO2 were small in the TRM group at 5, 10, and 15 min of PCPS, demonstrating that TRM645 continuously maintained systemic oxygen consumption even at a low flow rate. AST and LDH in the TRM group were lower than the control. There were significant differences at 120 min after the restoration of spontaneous circulation (p<0.05).

Optimal drainage cannula position in dual cannulation for veno-venous extracorporeal membrane oxygenation.

INTRODUCTION:: Recently, the use of veno-venous extracorporeal membrane oxygenation for adult patients with severe acute respiratory failure has increased. We previously investigated the optimal return cannula position; however, the optimal drainage cannula position has not yet been fully clarified. The aim of this study was to investigate the optimal drainage cannula position. METHODS:: Veno-venous extracorporeal membrane oxygenation was performed in four adult goats (mean body weight 59.6 ± 0.6 kg). The position of the drainage cannula was varied among the right atrium, the upper inferior vena cava, and the lower inferior vena cava, whereas the position of the return cannula was fixed in the superior vena cava. The recirculation fraction and arterial oxygen saturation and pressure (SaO2, PaO2) were measured in all drainage cannula positions. RESULTS:: In the lower inferior vena cava drainage cannula position, the recirculation fraction was the lowest. In the lower inferior vena cava, upper inferior vena cava, and right atrium drainage cannula positions at 3 L/min, SaO2 and PaO2 after 20 min were 92.9% ± 4.9% and 75.1 ± 26.0 mm Hg, 99.5% ± 0.5% and 113.8 ± 20.9 mm Hg, and 93.8% ± 6.2% and 91.9 ± 17.7 mm Hg, respectively. CONCLUSION:: With respect to blood oxygenation, the optimal position for the drainage cannula was the upper inferior vena cava. These findings suggested that blood from the superior vena cava, inferior vena cava, and hepatic vein was most efficiently drained in the upper inferior vena cava cannula position.

The National Cardiovascular Center electrohydraulic total artificial heart and ventricular assist device systems: current status of development.

Electrohydraulic total artificial heart (EHTAH) and electrohydraulic ventricular assist device (EHVAD) systems have been developed in our institute. The EHTAH system comprises a pumping unit consisting of blood pumps and an actuator, as well as an electronic unit consisting of an internal controller, internal and external batteries, and transcutaneous energy transfer (TET) and optical telemetry (TOT) subunits. The actuator, placed outside the pericardial space, reciprocates and delivers hydraulic silicone oil to the alternate blood pumps through a pair of flexible oil conduits. The pumping unit with an external controller was implanted in 10 calves as small as 55 kg. Two animals survived for more than 12 weeks in a good general condition. The assumed cardiac output ranged between 6 and 10 L/min, the power consumption was 12-18 W, and the energy efficiency was estimated to be 9-11%. Initial implantation of subtotal system including electronic units was further conducted in another calf weighing 73 kg. It survived for 3 days with a completely tether free system. The EHVAD system is developed by using the left blood pump and the actuator of the EHTAH, which were packaged in a compact metal casing with a compliance chamber. In vitro testing demonstrated maximum output more than 9 L/min and more than 13% maximum efficiency. The initial animal testing lasted for 25 days. These results indicate that our EHTAH and EHVAD have the potential to be totally implantable systems.

Up to 151 days of continuous animal perfusion with trivial heparin infusion by the application of a long-term durable antithrombogenic coating to a combination of a seal-less centrifugal pump and a diffusion membrane oxygenator.

We developed a new coating material (Toyobo-National Cardiovascular Center coating) for medical devices that delivers high antithrombogenicity and long-term durability. We applied this coating to an extracorporeal membrane oxygenation (ECMO) system, including the circuit tube, cannulae, a seal-less centrifugal pump, and a diffusion membrane oxygenator, to realize prolonged cardiopulmonary support with trivial anticoagulant infusion. The oxygenator consisted of a hollow-fiber membrane made of polymethylpentene, which allows the transfer of gas by diffusion through the membrane. The centrifugal pump was free of seals and had a pivot bearing. We performed a venoarterial bypass in a goat using this ECMO system, and the system was driven for 151 days with trivial anticoagulant infusion. Plasma leakage from the oxygenator did not occur and sufficient gas-exchange performance was well maintained. In the oxygenator, thrombus formation was present around the top and the distributor of the inlet portion and was very slight in the outlet portion. In the centrifugal blood pump, there was some wear in the female pivot region and quite small amounts of thrombus formation on the edge of the shroud; the pivot wear seemed to be the cause of the hemolysis observed after 20 weeks of perfusion and which resulted in the termination of the perfusion. However, no significant amounts of thrombus were observed in other parts of the system. This ECMO system showed potential for long-term cardiopulmonary support with minimal use of systemic anticoagulants.

Effects of mechanical valve orifice direction on the flow pattern in a ventricular assist device.

We have been developing a pneumatic ventricular assist device (PVAD) system consisting of a diaphragm-type blood pump. The objective of the present study was to evaluate the flow pattern inside the PVAD, which may greatly affect thrombus formation, with respect to the inflow valve-mount orientation. To analyze the change of flow behavior caused by the orifice direction (OD) of the valve, the flow pattern in this pump was visualized. Particle image velocimetry was used as a measurement technique to visualize the flow dynamics. A monoleaflet mechanical valve was mounted in the inlet and outlet ports of the PVAD, which was connected to a mock circulatory loop tester. The OD of the inlet valve was set at six different angles (OD = 0 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, and 270 degrees, where the OD opening toward the diaphragm was defined as 0 degrees ) and the pump rate was fixed at 80 bpm to create a 5.0 l/min flow rate. The main circular flow in the blood pump was affected by the OD of the inlet valve. The observed regional flow velocity was relatively low in the area between the inlet and outlet port roots, and was lowest at an OD of 90 degrees. In contrast, the regional flow velocity in this area was highest at an OD of 135 degrees. The OD is an important factor in optimizing the flow condition in our PVAD in terms of preventing flow stagnation, and the best flow behavior was realized at an OD of 135 degrees.

Design progress of the ultracompact integrated heart lung assist device--part 1: effect of vaned diffusers on gas-transfer performances.

The integrated heart lung assist device (IHLAD) has been developed to overcome the problems of currently available extracorporeal membrane oxygenation devices. The integrated structure of a centrifugal blood pump and cylindrical bundle of polyolefin hollow-fibers has allowed a remarkably compact size for the device. This study deals with the design change of the IHLAD that added to the vaned diffuser between the impeller of the centrifugal pump and the hollow-fiber bundle with a view to enhancing the gas-transfer performance. Ex vivo gas-transfer performance tests were carried out, as well as hydrodynamic characteristics and hemolysis test using fresh goat blood. The oxygen transfer rate was generally improved, and the carbon dioxide removal rate was slightly improved. Intolerable amount of hemolysis (index of hemolysis= 0.177) was caused by the IHLAD, which must be resolved by improving the design in the future.

Design progress of the ultracompact integrated heart lung assist device--part 2: optimization of the diffuser vane profile.

The configuration of the vaned diffuser of the integrated heart lung assist device (IHLAD) has been revised to reduce mechanical blood trauma caused by the device. The flow visualization study of the flow near the diffuser vanes revealed the existence of a rotating stall which deteriorates the hydrodynamic performance of the device and augments the chance for blood cells to pass through the regions with intense shearing forces. Design changes of the diffuser included decrease in vane number from 7 to 5 and decrease in passage width from 3 mm to 2 mm. This design change was effective to suppress initiation of a rotating stall. Improvement of hydrodynamic performance and antihemolytic properties was confirmed with the newly designed configuration based on the flow visualization study.

At least thirty-four days of animal continuous perfusion by a newly developed extracorporeal membrane oxygenation system without systemic anticoagulants.

We developed an extracorporeal membrane oxygenation (ECMO) system with high antithrombogenicity and durability characteristics for prolonged continuous cardiopulmonary support. The oxygenator consists of a special hollow-fiber-type polyolefin gas-exchange membrane, which has an ultrathin dense layer in contact with the blood, in order to prevent plasma leakage during protracted use (Platinum Cube NCVC). The centrifugal pump (RotaFlow) is free of seals. The entire blood-contacting surface of the system is coated with a newly developed heparin material (Toyobo-NCVC coating). We performed a venoarterial bypass in a goat, and the ECMO system was driven for 34 days without systemic anticoagulants. Plasma leakage from the oxygenator did not occur, and sufficient gas exchange performance was maintained. Thrombus formation was hardly observed in the ECMO system except in the casing margins of the oxygenator. This ECMO system showed potential for long-term cardiopulmonary support with minimal or no use of systemic anticoagulants.