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.
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.
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.
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.
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.
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.
In large animal models of coronary microembolization, the heterogeneity of myocardial response to microembolization is a limitation. We demonstrated that adjusting the number of injected microspheres based on the left coronary blood flow enabled the creation of heart failure models with different degrees of severity. CBF, coronary blood flow; LV dP/dt max, maximum rate of left ventricular pressure rise; LVEDP, left ventricular end‐diastolic pressure; ME, microembolization; SV, stroke volume.
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.
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 (O
2
ER) 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). O
2
ER 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.
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.
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., (
d
LVV/
d
t) × (
d
RVV/
d
t) < 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.
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