Evaluation of cardiac beat synchronization control for a rotary blood pump on valvular regurgitation with a mathematical model.

We have studied the cardiac beat synchronization (CBS) control for a rotary blood pump (RBP) and revealed that it can promote pulsatility and reduce cardiac load. Besides, patients with LVAD support sometimes suffer from aortic and mitral regurgitation (AR and MR). A control method for the RBP should be validated in wider range of conditions to clarify its benefits and pitfalls prior to clinical application. In this study, we evaluated pulsatility and cardiac load reduction obtained with the CBS control on valvular failure conditions with a mathematical model. Diastolic assist could reduce cardiac load on the left ventricle by decreasing external work of the ventricle even in MR cases while it was not so effective in AR cases. Systolic assist can still promote pulsatility in AR and MR cases; however, aortic valve function should be carefully confirmed since pulse pressure can be wider not due to systolic assist but to AR.

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.

Mathematical evaluation of cardiac beat synchronization control used for a rotary blood pump.

We studied a control method of rotary blood pumps (RBPs), which is called as the cardiac beat synchronization (CBS) system. Usually, RBPs operate at constant target rotational speed, meanwhile, the CBS system modulates target speed synchronizing with cardiac beat. We built a computer simulation method to evaluate the CBS system. This simulator acquires a mathematical model of a circulatory system including a RBP and can provide us the theoretical hemodynamics when our control method is applied. We compared theoretical results with experimental ones with the model focusing on both pulsatility and aortic valve (AV) opening interval enhanced by the CBS system. Our simulator could reproduce behavior of the circulatory system whether the RBP is connected or not. Comparison among no RBP, constant assist, systolic assist, and diastolic assist modes indicated that pulsatility is enhanced with systolic assist theoretically. While systolic assist decreased AV opening interval, diastolic assist made it longer than the ones in other control strategies.

Quantification of interventricular dyssynchrony during continuous-flow left ventricular assist device support.

Under continuous-flow left ventricular assist device (CF-LVAD) support, the ventricular volume change and cardiac cycle between the left ventricle (LV) and right ventricle (RV) become dyssynchronous due to the shortening of the LV systole. The purpose of this study was to quantify interventricular dyssynchrony based on different CF-LVAD support conditions and assess its relationship with LV unloading. In this study, we evaluated seven goats (body weight 44.5 ± 6.5 kg) with normal hearts. A centrifugal LVAD was implanted under general anesthesia. We inserted the conductance catheters into the left ventricle (LV) and right ventricle (RV) to assess the volume signal simultaneously. We defined the interventricular dyssynchrony as a signal (increase or decrease) of LV volume (LVV) change opposite to that of RV volume (RVV) (i.e., (dLVV/dt) × (dRVV/dt) < 0). The duration of interventricular dyssynchrony (DYS) was reported as the percentage of time that a heart was in a dyssynchronous state within a cardiac cycle. The mean DYS of normal hearts, hearts with LVAD clamp and hearts supported by LVADs with a bypass rate of 50%, 75% and 100% were 5.6 ± 1.6%, 8.7 ± 2.4%, 8.6 ± 2.8%, 15.1 ± 5.1%, and 25.6 ± 8.0%, respectively. Furthermore, the DYS was found to be associated with the degree of LV stroke volume reduction caused by LV unloading. These findings may be useful for understanding interventricular interactions and physiology during CF-LVAD support. Influences on the right ventricular function and heart failure models warrant further study.

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.

One year Rat Study of iBTA-induced "Microbiotube" Microvascular Grafts With an Ultra-Small Diameter of 0.6 mm.

OBJECTIVE: The world's smallest calibre "microbiotube" vascular graft was recently developed, with an inner diameter of 0.6 mm. It was formed using in-body tissue architecture (iBTA) and has a high degree of patency and capacity for regeneration in the acute phase, 1 month after implantation. This consecutive study investigated the compatibility and stability of microbiotubes in the chronic phase of implantation for 12 months for potential application in microsurgery. METHODS: This was an in vivo experimental study. The microbiotubes were prepared by embedding the mould subcutaneously in rats for 2 months. Allogenic microbiotubes (n = 16) were implanted into the bilateral femoral arteries (inner diameter 0.5 mm) of eight Wistar rats in an end to end anastomosis manner for 12 months. Follow up 7-Tesla magnetic resonance angiograms were performed every 3 months. Histological observation was performed 12 months after implantation. RESULTS: All patent grafts (n = 12, patency 75%) one month after implantation maintained their patency up to 12 months without any abnormal morphological changes or calcification. Histological observation at 12 months showed that layered α-smooth muscle actin positive cells with a monolayer luminal covering of endothelial cells had formed from the proximal to the distal anastomoses. A thin elastic fibre layer formed in the luminal area. After implantation, all components of the microbiotube were similar to those of a native artery. CONCLUSIONS: This study suggests that microbiotubes have high compatibility, stability, and durability as replacement grafts over the short to mid-term period.

Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

BACKGROUND: 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. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. METHOD/DESIGN: NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device and the day of withdrawal of a trial device), and changes in left ventricular diastolic dimension (7 days after implantation of a trial device and the day of withdrawal of a trial device). ETHICS AND DISSEMINATION: We will disseminate the findings through regional, national, and international conferences and through peer-reviewed journals. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR; R000033243) registered on 8 September 2017.

Accurate Method of Quantification of Aortic Insufficiency During Left Ventricular Assist Device Support by Thermodilution Analysis: Proof of Concept and Validation by a Mock Circulatory System.

Aortic insufficiency (AI) is an intractable complication during long term left ventricular assist device (LVAD) support. Conventional evaluation of AI depends on ultrasound evaluation, which is mainly a qualitative, not a quantitative method. The pathophysiology of AI during LVAD is shunt formation. Conversely, the methods to quantify the shunt of congenital heart disease are already established, and among these is the thermodilution technique. To develop an accurate quantification method for AI (namely, a shunt), we have adopted this conventional thermodilution technique. The purpose of this study was to determine whether this technique could calculate the shunt magnitude accurately in a simulated cardiac circuit. The magnitude of AI was represented by the recirculation rate (RR), defined by regurgitant flow (RF) divided by pump flow (PF). A mock circulatory system for an LVAD endurance test (Laboheart NCVC; Iwaki & Co., Ltd, Tokyo, Japan) was used. A centrifugal LVAD was equipped in the Laboheart in parallel from the left ventricle to the aorta. A parallel shunt circuit was created across the aortic valve to mimic AI. To control the magnitude of AI, the resistance of the AI circuit was changed. Heart failure was simulated by controlling the parameters of the Laboheart. The LVAD was driven in full bypass condition, confirming that the heart did not eject forward flow via the aortic valve. PF, RF, and the temperatures of two points of the outflow graft measured with two thermistors were monitored. Analyses were started after confirming that circuit water temperature was the same as room temperature. Hot water was injected from a port between the two thermistors of the outflow conduit. The time-temperature curves of both thermistors were recorded, and RR was calculated. Two values of RR calculated in two different ways (by analyzing thermistors and by calculating from flowmeter values) were compared. Multiple measurements were done by changing the magnitude of AI. The existence of AI could be easily confirmed by analyzing the temperature data. There was a good correlation between RR by thermistor and RR by flowmeter data (r = 0.984). Furthermore, the two RR values were almost the same. This novel technique could provide an accurate method for quantifying AI during LVAD support. This method can be clinically applied by left-sided cardiac catheterization if a dedicated catheter with two thermistors and an injection hole is developed.

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.

Differences in clotting parameters between species for preclinical large animal studies of cardiovascular devices.

Several species of domestic animals are used in preclinical studies evaluating the safety and feasibility of medical devices; however, the relevance of animal models to human health is often not clear. The purpose of this study was to compare the clotting parameters of animal models to determine which animals most adequately mimic human clotting parameters. The clotting parameters of the different species were assessed in whole blood by in vitro thromboelastography using the clotting activators, such as tissue factor (extrinsic clotting screening test, EXTEM®) and partial thromboplastin phospholipid (intrinsic clotting screening test, IINTEM®). The measurements were performed using normal blood samples from humans (n = 13), calves (n = 18), goats (n = 56) and pigs (n = 8). Extrinsic clotting time (CT) and the intrinsic CT were significantly prolonged in calves compared to humans (249.9 ± 91.3 and 376.4 ± 124.4 s vs. 63.5 ± 11.8 and 192.5 ± 29.0 s, respectively, p < 0.01). The maximum clot firmness (MCF) in domestic animals (EXTEM®: 77-87 mm, IINTEM®: 66-78 mm) was significantly higher than that of humans (EXTEM®: 59.1 ± 6.0 mm, IINTEM®: 58.8 ± 1.5 mm, p < 0.01), and calves and goats exhibited longer time to MCF (MCF-t) than did humans and pigs (p < 0.01). Our results show that there are relevant differences in the four species' extrinsic and intrinsic clotting parameters. These cross-comparisons indicate that it is necessary to clarify characteristics of clotting properties in preclinical animal studies.

Left heart pressures can be the key to know the limitation of left ventricular assist device support against progression of aortic insufficiency.

Aortic insufficiency (AI) is a worrisome complication under left ventricular assist device (LVAD) support. AI progression causes LVAD-left ventricular (LV) recirculation and can require surgical intervention to the aortic valve. However, the limitations of LVAD support are not well known. Using an animal model of LVAD with AI, the effect of AI progression on hemodynamics and myocardial oxygen metabolism were investigated. Five goats (Saanen 48 ± 2 kg) underwent centrifugal type LVAD, EVAHEART, implantation. The AI model was established by placing a vena cava filter in the aortic valve. Cardiac dysfunction was induced by continuous beta-blockade (esmolol) infusion. Hemodynamic values and myocardial oxygen extraction ratio (O2ER) were evaluated while changing the degree of AI which was expressed as the flow rate of LVAD-LV recirculation (recirculation rate). Diastolic aortic pressure was decreased with AI progression and correlated negatively with the recirculation rate (p = 0.00055). Systolic left ventricular pressure (LVP) and mean left atrial pressure (LAP) were increased with AI progression and correlated positively with the recirculation rate (p = 0.010, 0.023, respectively). LVP and LAP showed marked exponential increases when the recirculation rate surpassed 40%. O2ER was also increased with AI progression and had a significant positive correlation with the recirculation rate (p = 0.000043). O2ER was increased linearly, with no exponential increase. AI progression made it difficult to reduce the cardiac pressure load, worsening myocardial oxygen metabolism. The exponential increase of left heart pressures could be the key to know the limitation of LVAD support against AI progression.

The angle of the outflow graft to the aorta can affect recirculation due to aortic insufficiency under left ventricular assist device support.

Aortic insufficiency (AI) is a crucial complication during continuous-flow left ventricular assist device (LVAD) support. Our previous clinical study suggested that a larger angle between the outflow graft and the aorta (O-A angle) could cause AI progression. This study examined the effect of the O-A angle on the hemodynamics of AI under LVAD support in an acute animal experimental model. An LVAD was installed in seven calves, with the inflow cannula inserted from the LV apex and with the outflow graft sutured at the ascending aorta. The AI model was made using a temporary inferior vena cava filter inserted from the LV apex and placed at the aortic valve. Cardiac dysfunction was induced by continuous beta-blocker infusion. Hemodynamic values and the myocardial oxygen extraction rate (O2ER) were evaluated at three O-A angles (45°, 90°, and 135°) over three levels of AI (none, Sellers I-II AI, and Sellers III-IV AI). The recirculation rate, defined as the percentage of regurgitation flow to LVAD output, was calculated. Systemic flow tended to decrease with a larger O-A angle. The recirculation rate was significantly increased with a larger O-A angle (22, 23, and 31% at 45°, 90°, and 135° in Sellers III-IV AI, respectively). Coronary artery flow was decreased at a larger O-A angle (86, 76 and 75 mL/min at 45°, 90°, and 135° in Sellers I-II AI, respectively, and 77, 67, and 56 mL/min at 45°, 90°, and 135° in Sellers III-IV AI, respectively). O2ER tended to increase with a larger O-A angle (40, 43, and 49% at 45°, 90°, and 135° in Sellers III-IV AI, respectively). A larger O-A angle can increase the recirculation due to AI and can be disadvantageous to LVAD-AI hemodynamics and myocardial oxygen metabolism.

Preclinical animal study of the NIPRO-ventricular assist device for use in pediatric patients.

Although the outcomes of patients with end-stage heart failure treated with implantable left ventricular assist devices have improved, extracorporeal left ventricular assist devices continue to play an important role, especially in pediatric patients. The present study aimed to examine the long-term biocompatibility of a small-sized extracorporeal pneumatic left ventricular assist device (NIPRO-LVAD) used in a 30- to 90-day animal experiment. The NIPRO-LVAD was designed for pediatric patients or small-sized adults. The left ventricular assist device system was installed in four adult Shiba goats weighing 25.7 ± 4.78 kg via a left thoracotomy. The outflow graft was sewn to the descending aorta and the inflow cannula was placed in the left ventricle through the left ventricular apex. Oral antiplatelet (aspirin) and oral anticoagulation therapies (warfarin) were also administered. Three out of four animals survived for a 30-day period and two goats survived for 90 days. One animal was killed early because of low pump flow due to obstruction of the inflow cannula by a left ventricular endocardial vegetation. The blood pump exhibited sufficient hydrodynamic performance with blood flows of 1.5-2.0 L/min. The animals' laboratory values were within normal limits by postoperative day 7. There was no significant thrombus formation on the housing, diaphragm, or valves of the explanted pumps. Based on the biocompatibility demonstrated in this animal study, the explanted small-sized pump may be suitable for use in left ventricular assist device systems for pediatric patients.

Wall thickness control in biotubes prepared using type-C mold.

A type-C mold based on in-body tissue architecture was previously developed for preparing small-diameter biotube vascular grafts with a 2-mm diameter and approximately 1-mm wall thickness. In this study, the type-C mold was modified for preparing large-diameter biotubes with controlled wall thicknesses. Four types of molds were assembled by inserting silicone center rods (outer diameters 11, 13, 15, 17 mm) into stainless steel cages (inner diameter 19 mm) and surgically embedded in the abdominal subcutaneous pouches of Holstein cows. After 8-12 weeks, connective tissues occupied the rod-cage gap in the molds to form biotubes. The wall thickness of the biotubes obtained after removing the molds was approximately 1-3 mm, which corresponded to approximately 80% of each gap distance. The breaking strength almost linearly increased with the wall thickness of the biotubes. The strength of the biotubes with wall thickness over 1.5 mm was higher than that of beagle blood vessels. The thickest biotubes were as strong as bovine pericardium and can be used as an alternative trachea graft because of their adequate lumen-holding force.

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.

The influence of pump rotation speed on hemodynamics and myocardial oxygen metabolism in left ventricular assist device support with aortic valve regurgitation.

Aortic valve regurgitation (AR) is a serious complication under left ventricular assist device (LVAD) support. AR causes LVAD-left ventricular (LV) recirculation, which makes it difficult to continue LVAD support. However, the hemodynamics and myocardial oxygen metabolism of LVAD support with AR have not been clarified, especially, how pump rotation speed influences them. An animal model of LVAD with AR was newly developed, and how pump rotation speed influences hemodynamics and myocardial oxygen metabolism was examined in acute animal experiments. Five goats (55 ± 9.3 kg) underwent centrifugal type LVAD, EVAHEART implantation. The AR model was established by placing a vena cava filter in the aortic valve. Hemodynamic values and the myocardial oxygen consumption, delivery, and oxygen extraction ratio (O2ER) were evaluated with changing pump rotation speeds with or without AR (AR+, AR-). AR+ was defined as Sellers classification 3 or greater. AR was successfully induced in five goats. Diastolic aortic pressure was significantly lower in AR+ than AR- (p = 0.026). Central venous pressure, mean left atrial pressure, and diastolic left ventricular pressure were significantly higher in AR+ than AR- (p = 0.010, 0.047, and 0.0083, respectively). Although systemic flow did not improve with increasing pump rotation speed, LVAD pump flow increased over systemic flow in AR+, which meant increasing pump rotation speed increased LVAD-LV recirculation and did not contribute to effective systemic circulation. O2ER in AR- decreased with increasing pump rotation speed, but O2ER in AR+ was hard to decrease. The O2ER in AR+ correlated positively with the flow rate of LVAD-LV recirculation (p = 0.012). AR caused LVAD-LV recirculation that interfered with the cardiac assistance of LVAD support and made it ineffective to manage with high pump rotation speed.

Long-term durability test of axial-flow ventricular assist device under pulsatile flow.

A long-term durability test was conducted on a newly developed axial-flow ventricular assist device (VAD) with hydrodynamic bearings. The mock circulatory loop consisted of a diaphragm pump with a mechanical heart valve, a reservoir, a compliance tank, a resistance valve, and flow paths made of polymer or titanium. The VAD was installed behind the diaphragm pump. The blood analog fluid was a saline solution with added glycerin at a temperature of 37 °C. A pulsatile flow was introduced into the VAD over a range of flow rates to realize a positive flow rate and a positive pressure head at a given impeller rotational speed, yielding a flow rate of 5 L/min and a pressure of 100 mmHg. Pulsatile flow conditions were achieved with the diastolic and systolic flow rates of ~0 and 9.5 L/min, respectively, and an average flow rate of ~5 L/min at a pulse rate of 72 bpm. The VAD operation was judged by not only the rotational speed of the impeller, but also the diastolic, systolic, and average flow rates and the average pressure head of the VAD. The conditions of the mock circulatory loop, including the pulse rate of the diaphragm pump, the fluid temperature, and the fluid viscosity were maintained. Eight VADs were tested with testing periods of 2 years, during which they were continuously in operation. The VAD performance factors, including the power consumption and the vibration characteristics, were kept almost constant. The long-term durability of the developed VAD was successfully demonstrated.