This review traces the evolution of centrifugal blood pumps in mechanical circulatory support (MCS) systems. Initially met with concerns over blood damage and thrombus formation, centrifugal pumps have become crucial components in ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) due to their simplified drive mechanisms and adaptability. This paper outlines three generations of centrifugal pump development: first-generation pumps with sealing components, second-generation pumps utilizing pivot bearings, and third-generation pumps employing contactless bearings. Each iteration addressed previous limitations, particularly regarding thrombus formation and durability. Current regulatory challenges surrounding the duration of pump use in MCS are examined, highlighting the discrepancy between approved usage times and clinical needs. This paper notes ongoing efforts to extend approved use periods, citing examples of pumps cleared for extended use in various jurisdictions. This historical perspective provides insights into the technological advancements that have enhanced the safety, efficacy, and durability of centrifugal blood pumps in MCS applications.

An extracorporeal membrane oxygenation (ECMO) system consisting of a heparin-coated membrane oxygenator with polymethylpentene hollow fiber membranes and a heparin-coated hydrodynamically levitated centrifugal pump was developed. The effect of heparin anticoagulation on the antithrombogenicity of the ECMO system under veno-arterial bypass was evaluated in an animal model. Veno-arterial bypass with the ECMO system was induced in goats. Ten goats were evaluated which were divided into heparin anticoagulation-free (HPF; n = 5) and heparin anticoagulation (HP; n = 5) groups. Evaluation of the ECMO system focused on thrombus formation and changes in blood test data. Veno-arterial bypass with the ECMO system was maintained for 2 weeks in both groups. The extent of thrombus formation in the oxygenators was suppressed in the HP group. The centrifugal pumps were free of major thrombus formation in both groups. From baseline to postoperative day (POD) 1, both groups showed significant decreases in platelet counts, with a significant reduction in von Willebrand factor (vWF) activity levels in the HPF group. Between PODs 1 and 14, POD differences were observed in platelet counts without group or interaction differences. The levels of vWF activity showed significant group differences, with the HPF group demonstrating lower values than the HP group, but no significant POD or interaction differences. Veno-arterial bypass with the ECMO system was sustained for 2 weeks regardless of heparin anticoagulation. Heparin anticoagulation suppressed the extent of thrombus formation in the oxygenators. The centrifugal pumps were free of major thrombus formation regardless of heparin anticoagulation.

Impella is a mechanical circulatory support device of a catheter-based intravascular microaxial pump for left ventricular support and unloading. However, nonclinical studies assessing the effects of the extended duration of left ventricular unloading on cardiac recovery are lacking. An animal model using Impella implanted with a less invasive procedure to enable long-term support is required. This study aimed to evaluate the feasibility of an animal model for long-term support with Impella 5.5 implanted through carotid artery access in sheep. Impella 5.5 was implanted in four sheep through the proximal region of the left carotid artery without a thoracotomy, and myocardial injuries were induced by coronary microembolization. Support by Impella 5.5 was maintained for 4 weeks, and the animals were observed. The position of Impella 5.5 and cardiac function was evaluated using cardiac computer tomography at 2 and 4 weeks after implantation. All four animals completed the 4-week study without major complications. The discrepancy in the Impella 5.5 flow rate between the conscious and anesthetized states was observed depending on the device’s position. Animals in whom the inflow was above the left ventricular papillary muscle had a relatively high flow rate under the maximum performance level without a suction alarm during the conscious state. Pathological changes in the aortic valve were observed. Cardiac function under the minimum performance level was observed with no remarkable deterioration. The animal model with myocardial injuries supported for 4 weeks by Impella 5.5 implanted through carotid artery access in sheep was feasible.

Extracorporeal centrifugal pumps are widely used in various forms of mechanical circulatory support, including extracorporeal membrane oxygenation and ventricular assist device. A durable centrifugal pump was developed by implementing a new hydrodynamic bearing design that prevents the impeller from touching to the casing wall and provides sufficient washout through the pump to prevent thrombus formation in the pump. The hydrodynamic bearings of the pump are composed of dual annular paths located on both sides of the impeller. Computational fluid dynamics analyses were performed on the flow field inside the pump to estimate the leakage flow through the gap and its impact on the pump efficiency and biocompatibility. The calculations were performed for motor speeds from 3000 to 5000 rpm and flow rates from 1.0 to 9.0 L/min. The leakage flow increased linearly with increasing pressure head of the pump, and the total leakage flow ranged from 2.0 to 27.3% of the total flow. The average wall shear stresses in the casing bottom ranged from 10.6 to 40.9 Pa. The leakage flow of the centrifugal pump with the hydrodynamically levitated impeller had a measurable impact on hydraulic energy losses while enhancing the washout flow to achieve good anti-thrombogenicity.

Asynchronous rotational-speed modulation of a continuous-flow left ventricular assist device (LVAD) can increase pulsatility; however, the feasibility of hemodynamic modification by asynchronous modulation of an LVAD has not been sufficiently verified. We evaluated the acute effect of an asynchronous-modulation mode under LVAD support and the accumulated effect of 6 consecutive hours of driving by the asynchronous-modulation mode on hemodynamics, including both ventricles, in a coronary microembolization-induced acute-myocardial injury sheep model. We evaluated 5-min LVAD-support hemodynamics, including biventricular parameters, by switching modes from constant-speed to asynchronous-modulation in the same animals (“acute-effect evaluation under LVAD support”). To determine the accumulated effect of a certain driving period, we evaluated hemodynamics including biventricular parameters after weaning from 6-hour (6 h) LVAD support by constant-speed or asynchronous-modulation mode (“6h-effect evaluation”). The acute-effect evaluation under LVAD support revealed that, compared to the constant-speed mode, the asynchronous-modulation mode increased vascular pulsatility but did not have significantly different effects on hemodynamics, including both ventricles. The 6 h-effect evaluation revealed that the hemodynamics did not differ significantly between the two groups except for some biventricular parameters which did not indicate negative effects of the asynchronous-modulation mode on both ventricles. The asynchronous-modulation mode could be feasible to increase vascular pulsatility without causing negative effects on hemodynamics including both ventricles. Compared to the constant-speed mode, the asynchronous-modulation mode increased pulsatility during LVAD support without negative effects on hemodynamics including both ventricles in the acute phase. Six hours of LVAD support with the asynchronous-modulation mode exerted no negative effects on hemodynamics, including both ventricles, after weaning from the LVAD.

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.

BACKGROUND A heart failure 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 heart failure. This study aimed to evaluate the effect of microsphere injection based on 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 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 hours 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 hours (r=0.74, p=0.01 and r=0.71, p=0.02, respectively). CONCLUSIONS Adjusting the number of injected microspheres based on coronary blood flow enabled the creation of heart failure models with different degrees of severity.

PurposeAn additional left ventricular (LV) unloading device could be effective for LV distension caused by V-A ECMO. However, the appropriate flow proportion between V-A ECMO and LV unloading devices has still been controversial. The purpose of this study was to evaluate the effect of flow proportion between V-A ECMO and LV unloading.MethodsMicrosphere was injected to the left anterior descending artery of 12 adult sheep to induce myocardial ischemia, aiming at the criteria of cardiac output to be less than 50% of that before the microsphere injection. V-A ECMO was established between the right atrium and the abdominal aorta. LV unloading was performed by venting blood from LV apex to the abdominal aorta using a centrifugal pump. V-A ECMO support and LV unloading were maintained for 6 hours with a total systemic flow to be 80-100ml/kg/min. We categorized into 3 groups based on different mechanical circulatory configurations and flow proportion: No LV unloading group (V-A ECMO without LV unloading), Low LV unloading group (LV unloading with V-A ECMO, ECMO: LV venting=3:1), and High LV unloading group (LV unloading with V-A ECMO, ECMO: LV venting=1:1). The LV and right ventricle (RV) functions of these 3 groups were investigated by analyzing hemodynamic parameters as well as the evaluation of LV pressure-volume loops and echocardiography.ResultsDuring the V-A ECMO support, LVEDP and potential energy of Low and High LV unloading groups were significantly lower than that of No LV unloading group (Figure1A). The RVDd/ LVDd ratio on echocardiography of High LV unloading group was higher than that of Low LV unloading group, while RVFAC of High LV unloading group was lower than that of Low LV unloading group (Figure 1B), suggesting that high LV unloading could be related to RV dysfunction.ConclusionLV unloading is mandatory for V-A ECMO in avoiding LV dysfunction, whereas excessive LV unloading has the possibility to cause RV dysfunction. An additional left ventricular (LV) unloading device could be effective for LV distension caused by V-A ECMO. However, the appropriate flow proportion between V-A ECMO and LV unloading devices has still been controversial. The purpose of this study was to evaluate the effect of flow proportion between V-A ECMO and LV unloading. Microsphere was injected to the left anterior descending artery of 12 adult sheep to induce myocardial ischemia, aiming at the criteria of cardiac output to be less than 50% of that before the microsphere injection. V-A ECMO was established between the right atrium and the abdominal aorta. LV unloading was performed by venting blood from LV apex to the abdominal aorta using a centrifugal pump. V-A ECMO support and LV unloading were maintained for 6 hours with a total systemic flow to be 80-100ml/kg/min. We categorized into 3 groups based on different mechanical circulatory configurations and flow proportion: No LV unloading group (V-A ECMO without LV unloading), Low LV unloading group (LV unloading with V-A ECMO, ECMO: LV venting=3:1), and High LV unloading group (LV unloading with V-A ECMO, ECMO: LV venting=1:1). The LV and right ventricle (RV) functions of these 3 groups were investigated by analyzing hemodynamic parameters as well as the evaluation of LV pressure-volume loops and echocardiography. During the V-A ECMO support, LVEDP and potential energy of Low and High LV unloading groups were significantly lower than that of No LV unloading group (Figure1A). The RVDd/ LVDd ratio on echocardiography of High LV unloading group was higher than that of Low LV unloading group, while RVFAC of High LV unloading group was lower than that of Low LV unloading group (Figure 1B), suggesting that high LV unloading could be related to RV dysfunction. LV unloading is mandatory for V-A ECMO in avoiding LV dysfunction, whereas excessive LV unloading has the possibility to cause RV dysfunction.

Mechanical circulatory support devices such as ventricular assist devices (VADs) are required for treatment of heart failure patients with small body size. However, clinically available rotary VADs which can be implanted in small pediatric patients still have not been developed. The implantable pediatric rotary VADs require compact device size, high mechanical durability and blood biocompatibility. Selection of impeller suspension methods is significant important for development of the rotary VADs. Magnetic suspension system is one of the strongest candidates to develop next generation VADs which can completely suspend a spinning rotor impeller without mechanical contact. Our research group has been developed an ultra-compact double stator self-bearing motor with 5-degrees of freedom (-DOF) control. The 5-DOF controlled self-bearing motor is 22 mm in diameter and 34 mm in height. This paper investigated magnetic suspension stability during pump operation. The developed maglev centrifugal blood pump produced flow rate of 0-3 L/min against head pressure of 60-100 mmHg at rotating speeds of 4000-5000 rpm. The centrifugal impeller was completely suspended with the proposed 5-DOF control concept. The results indicate sufficient pump performance for pediatric circulatory support and stable impeller suspension performance.

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.

The inflow cannula of left ventricular assist devices (LVAD) is connected with suturing, and the establishment of a convenient and less time procedure is required for a consistent connection. We have developed a self-connecting inflow cannula using the integrated low-level energies adhesion technique that enables tissue and metal adhesion only by applying heat and pressure for around a hundred seconds. In this study, we performed an animal experiment to identify issues with the device. The device connection was completed in about 6 minutes. Based on the experimental results, we improved the device; the adhesive area height is shortened from 15 mm to 10.5 mm to fit the ventricle wall thickness, and the number of vacuum slits is increased from two to three to improve the tissue adhesion. The adhesion strength of the device is improved by 40% from 36 kPa to 50 kPa.

16.3 mcg/min, p<0.01), and vasopressin (0.04 vs 0.12 units/min, p<0.01).Other hemodynamic and laboratory values remained stable.Conclusion: Steroid administration among patients with refractory vasoplegia reduced the need for vasoactive support in this cohort and may be considered as an adjunctive therapies in this population.Further research is needed to support these novel findings.

Extracorporeal membrane oxygenation (ECMO) is a respiratory or cardiac life support consisting of a vascular access cannula, a blood pump, and an artificial lung that removes carbon dioxide and adds oxygen. Venovenous ECMO is typically used for various forms of critical respiratory failure including severe pneumonia due to the new coronavirus, whereas venoarterial (VA) ECMO sees greater utilization in the patient with heart failure such as cardiac arrest or other clinical states in which cardiac dysfunction is a significant component of illness. The transference of gases occurs due to diffusion across the hollow fiber membranes packed in the module of the oxygenator. Emergence of microporous membrane tremendously enhanced gas diffusion, and currently microporous membrane with a dense layer on the blood-contacting surface is widely used for longer period of usage over weeks. As the usage period for respiratory failure is getting longer, development of more durable ECMO system is required in the future.

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 SvO(2), and blood flow. Its installation area is 595 cm(2), 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.

In order to use a transcutaneous energy transmission system safely, we have devised the emergency energy transfer system which is used when the electric power supply is stopped. Emergency port through the skin consists of two copper meshes arranged coaxially and filler silicones and the electric power is supplied to the embedded devices when the continuity needle of double pipe structure is stuck in the emergency port. We determined the dimensions of the emergency port and performed the continuity test. The emergency port was connected to light emitting diode and continuity was confirmed by turning on the light emitting diode. The continuity needle was stuck in the other three places in the emergency port. As a result of the experiment, we checked the current was flowed once. In the current structure, the continuity needle is easy to come off due to the elasticity of filler silicones. So that we will improve the structure of emergency port to prevent the continuity needle coming off.