Journal of Artificial Organs

Our group has developed an electrohydraulic total artificial heart (EHTAH) with two diaphragm-type blood pumps. Cavitation in a mechanical heart valve (MHV) causes valve surface damage. The objective of this study was to investigate the possibility of estimating the MHV cavitation intensity using the slope of the driving pressure just before valve closure in this artificial heart. Twenty-five and twenty-three-millimeter Medtronic Hall valves were mounted at the inlet and outlet ports, respectively, of both pumps. The EHTAH was connected to the experimental endurance tester developed by our group, and tested under physiological pressure conditions. Cavitation pits could be seen on the inlet valve surface and on the outlet valve surface of the right and left blood pumps. The pits on the inlet valves were more severe than those on the outlet valves in both blood pumps, and the cavitation pits on the inlet valve of the left blood pump were more severe than those on the inlet valve of the right blood pump. The longer the pump running time, the more severe the cavitation pits on the valve surfaces. Cavitation pits were concentrated near the contact area with the valve stop. The major cause of these pits was the squeeze flow between the leaflet and valve stop.

Alginate-based wound dressing materials have been widely used to promote wound healing and to reduce blood loss from wounds. However, recently a few drawbacks of well-established commercial alginate dressings have been reported. Therefore, we tried to develop a new alginate dressing to reduce the drawbacks. First, four new dressings with different calcium content were prepared, and the cytotoxicity of these four materials, and Kaltostat and Sorbsan, was tested in vitro by culture of fibroblasts with their extracts. Second, full-thickness wounds in pigs were used for the evaluation of wound healing in vivo. Finally, a newly developed alginate dressing was used clinically for treatment of split-thickness skin graft donor sites. The extract medium from ALG3, ALG4, Kaltostat, and Sorbsan induced a significant inhibitory effect on proliferation of fibroblasts. As for wound closure rate, the ALG2-covered wounds had the smallest wound area on day 15. Histologically, foreign-body reaction was least in ALG2-treated wounds. In a clinical study, the main drawback of ALG2 was leakage of wound exudate due to dissolution of the dressing material. However, the transparency of moistened ALG2 allowed easy evaluation of the wound, and after healing it was easy to remove ALG2 from the wound without injury to the reepithelialized skin because ALG2 was relatively nonadherent to the wound.

The dialyzer housing structure should be designed in such a way that high dialysis performance is achieved. To achieve high dialysis performance, the flow of the dialysis fluid and blood should be uniform, without channeling and dead spaces. The objective of this study was to evaluate the effect of fiber packing density on the flow of dialysis fluid and blood, and on the dialysis performance of a hollow-fiber dialyzer at defined flow rates for blood (Q B = 200 mL/min), dialysis fluid (Q D = 500 mL/min), and filtrate (Q F = 0 mL/min). We measured Q D, Q B, and solute clearance for 3 test dialyzers with dialyzer housing different diameters. To evaluate the flow of dialysis fluid and blood, we measured the residence time of the dialysis fluid and blood in the test dialyzers by use of the pulse–response method. We also measured the clearances of urea, creatinine, vitamin B12, and lysozyme to evaluate the dialysis performance of the test dialyzers. At packing densities ranging from 48 to 67%, higher packing densities and lower housing diameters of the dialyzer resulted in higher dialysis performance because the dialysis fluid and blood entered the hollow-fiber bundle smoothly and, hence, increased contact area between the dialysis fluid and the blood led to better dialysis performance.

For the continued development of improved mechanical circulatory systems, longer term evaluation of new devices in animal model experiments may be critical. The effects of anticoagulants in adult goats have not been well studied. We assessed the effects of oral warfarin in three adult goats during fasting or after feeding. The goats [weighing 57.8 ± 8.1 kg (53.0–67.2 kg)] were administered warfarin orally beginning at a dose of 5 mg/day and then increasing to 10, 20, 40, and 60 mg every 2 weeks. One goat (receiving 10 mg/day warfarin) was killed on day 27 because of the inability to stand. After administration of 60 mg warfarin, the remaining goat received no warfarin for 4 days to return to coagulated state. The goats were then fasted and treated with 40 mg warfarin. During warfarin administration, both goats required a dose of 60 mg/day to achieve International Normalized Ratios (INRs) of approximately 2.5; however, when, the animals were in the fasted condition, precipitous extension of INR was observed in 5 days. After resuming feeding, the INR was reduced to the proper range. We showed the tendency that warfarin therapy in goats required higher doses than the doses administered to human patients and that the effects of therapy were related to the feeding state. The results of this study provide important information for development of anticoagulation protocols to assess mechanical circulatory support devices for long-term use in preclinical examination.

Polymethylmethacrylate (PMMA) membrane is the first synthetic polymeric hollow fiber used in dialyzers that is known to adsorb β2-microglobulin. Polyester polymer alloy (PEPA), a blend of two polymers, i.e., polyarylate and polyethersulfone, is another dialysis membrane material with adsorption characteristics. In this study, the adsorption and permeation characteristics of BG-1.6PQ (PMMA) and FLX-15GW (PEPA) dialyzers were investigated by performing ultrafiltration experiments using chymotrypsinogen (molecular weight 25 000) and albumin (molecular weight 66 000) as test solutes. Although PMMA and PEPA had the same sieving coefficient for chymotrypsinogen at steady state, PMMA showed approximately 20% higher fractional adsorption than PEPA under the same initial concentrations. The fractional adsorption for albumin was approximately 20% in PEPA regardless of the ultrafiltration flow rate. The fractional adsorption for albumin in PMMA, however, increased as the ultrafiltration flow rate increased and reached 50%–60% after 10 h. Since PEPA has two skins, one inside and one outside the hollow fiber, proteins may have been adsorbed mainly by these two layers. However, since PMMA is a uniform membrane and since the higher the ultrafiltration flow rate, the higher the fractional adsorption found in PMMA, adsorption may be the result of the occlusion of the dense structure of the membrane. The amount of albumin loss is often clinically evaluated by measuring the amount of permeated albumin in the dialysate. However, when dialyzers with adsorption characteristics are examined, the loss by adsorption should also be taken into account.

A 4-year-old boy with atrioventricular discordance, double-outlet right ventricle, pulmonary stenosis, and mitral regurgitation, was undergoing anatomical repair consisting of Senning, Rastelli, Damus–Kaye–Stansel procedures, and a mitral valve repair, complained of post-operative excessive airway tract secretion, which ultimately developed into acute respiratory distress syndrome (ARDS) 28 days after the operation. The cause of the ARDS was thought to be frequent manual positive pressure recruitment and prolonged inhalation of pure oxygen. At 45 days after the operation, hypercapnia and respiratory acidosis turned out to be irreversible, and therefore, veno-arterial extracorporeal membrane oxygenation (ECMO) was established utilizing the Endumo®4000 system. Pulmonic interstitial inflammation gradually improved while resting the lung under ECMO support; however, effective ventilation volume decreased critically because a massive pulmonary hemorrhage occurred at 2 and 9 days after the initiation of ECMO. To maximize the effectiveness of respiratory physical therapy, “Awake ECMO” was started and tidal volume dramatically increased with a regained cough reflex. Five days later, he was successfully weaned off from ECMO, and discharged 7 months after the operation without any neurological and physiological sequelae.

The aim of this study was to evaluate flow from a new dispersive aortic cannula (Stealthflow) in the aortic arch using flow visualization methods. Particle image velocimetry was used to analyze flow dynamics in the mock aortic model. Flow patterns, velocity distribution, and streamlines with different shape cannulas were evaluated in a glass aortic arch model. We compared flow parameters in two different dispersive type cannulas: the Stealthflow and the Soft-flow cannula. A large vortex and regurgitant flow were observed in the aortic arch with both cannulas. With the Stealthflow cannula, a high-velocity area with a maximum velocity of 0.68 m/s appeared on the ostium of the cannula in the longitudinal plane. With the Soft-flow cannula, ‘multiple jet streams, each with a velocity less than 0.60 m/s, were observed at the cannula outlet. Regurgitant flow from the cannula to the brachiocephalic artery and to the ascending aorta on the greater curvature was specific to the Soft-flow cannula. The degree of regurgitation on the same site was lower with the Stealthflow cannula than with the Soft-flow cannula. The Stealthflow cannula has similar flow properties to those of the Soft-flow cannula according to glass aortic model analysis. It generates gentle flow in the aortic arch and slow flow around the ostia of the aortic arch vessels. The Stealthflow cannula is as effective as the Soft-flow cannula. Care must be taken when the patient has thick atheromatous plaque or frail atheroma on the lesser curvature of the aortic arch.

Recently, cavitation on the surface of mechanical heart valves (MHVs) has been studied as a cause of fractures occurring in implanted MHVs. In the present study, we investigated the mechanism of MHV cavitation associated with the Björk–Shiley valve and the Medtronic Hall valve in an electrohydraulic total artificial heart (EHTAH). The valves were mounted in the mitral position in the EHTAH. The valve closing motion, pressure drop measurements, and cavitation capture were employed to investigate the mechanisms for cavitation in the MHV. There are no differences in valve closing velocity between the two valves, and its value ranged from 0.53 to 1.96 m/s. The magnitude of negative pressure increased with an increase in the heart rate, and the negative pressure in the Medtronic Hall valve was greater than that in the Björk–Shiley valve. Cavitation bubbles were concentrated at the edge of the valve stop; the major cause of these cavitation bubbles was determined to be the squeeze flow. The formation of cavitation bubbles depended on the valve closing velocity and the valve leaflet geometry. From the viewpoint of squeeze flow, the Björk–Shiley valve was less likely to cause blood cell damage than the Medtronic Hall valve in our EHTAH.

Since the first use of a ventricular assist device in 1963 many extracorporeal and implantable pulsatile blood pumps have been developed. After the invention of continuous flow blood pumps the implantable pulsatile pumps are not available anymore. The new rotary pumps spend a better quality of life because many of the patients can go home. Nevertheless, the extracorporeal pulsatile pumps have some advantages. They are low-cost systems, produce less haemolysis and heart-recovery can be tested easily. Pump failure is easy to realize because the pumps can be observed visually. Pump exchange can be done easily without any chirurgic surgery. As volume displacement pumps they can produce high blood pressure, so they are the only ones suitable for pediatric patients. Therefore, they are indispensable for clinical use today and in the future. In this work, nearly all pulsatile blood pumps used in clinical life are described.