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Biomedical subjects

C Nojiri

Publications and source records attributed to C Nojiri.

At least 19 recordsLinked to original sources

Compact, reliable ventricular assist device as a bridge to recovery or for semipermanent use.

OBJECTIVES: The magnetically suspended centrifugal pump has gained attention as an implantable ventricular assist device for long-term use. We report recovery-oriented pump operation and results of a chronic animal experiment. METHODS: In an acute experiment in 8 sheep having microspheres injected to induce heart failure, left ventricular assist was implemented by 2 inflow cannulas, 1 each in the left atrium and left ventricle. The pressure-volume loop of the left ventricle and myocardial oxygen consumption were measured varying the assist rate. The chronic animal experiment used 10 sheep whose native heart was kept intact. Continuous hemodynamic monitoring and periodic blood sampling were conducted. RESULTS: In the acute study, myocardial oxygen consumption decreased proportionally with increasing assist rate in left atrial drainage, but was significantly less at a 100% assist rate in left ventricular drainage. External work in left ventricular drainage did not decrease until a 75% assist rate, suggesting that the left ventricle shape and size were maintained despite decreased myocardial oxygen consumption. In the chronic experiment, the pumping duration was 14 to 248 days. No thrombi or emboli in the pump or any major organ were found in sacrificed sheep after living more than 100 days. Hepatic and renal function were within an almost normal range throughout the experiment. CONCLUSION: Left ventricular blood drainage effectively reduced oxygen consumption, maintaining the shape of the left ventricle. The magnetically suspended centrifugal pump is suitable for recovery of a failing heart or semipermanent use.

Animals↗

Reliable long-term non-pulsatile circulatory support without anticoagulation.

OBJECTIVE: The Terumo implantable left ventricular assist system (T-ILVAS) consists of a titanium centrifugal pump with a unique magnetically suspended impeller producing continuous (non-pulsatile) flow up to 10 l/min. The interior surface is heparin-coated and there is no purge system. We implanted the device into six sheep to ascertain in-vivo haemodynamic function, mechanical reliability and biocompatibility. METHODS: The T-ILVAS was implanted via left thoracotomy without cardiopulmonary bypass. The inflow cannula was placed in the left ventricular apex and a Dacron outflow graft anastomosed to the descending aorta. All animals recovered well. No anticoagulation (heparin or warfarin) was given after the surgery. Suspension position, motor current, impeller speed and pump flow were continuously monitored and stored by on-line computer. Serial blood samples were collected to determine haematological and biochemical indices of renal function, liver function and haemolysis. All animals were electively euthanized between 3 and 7 months postoperatively. The explanted pumps were examined for mechanical reliability and thrombus formation. Major organs were examined macroscopically and histologically for thromboembolism. RESULTS: All animals appeared completely normal for up to 210 days. At speeds between 1500 and 2000 rev./min the device pumped up to 8 l/min capturing all mitral flow. There were no major complications (pump failure, thromboembolism, haemorrhage, or driveline infection). Indices of haemolysis, liver and renal function remained within normal limits. All pumps were mechanically sound and free from thrombus. One embolus was found in a sectioned kidney. CONCLUSION: The T-ILVAS successfully supported the systemic circulation without anticoagulation for up to 210 days. Mechanical reliability and biocompatibility were demonstrated. Organ function remained within normal limits during continuous non-pulsatile flow.

Animals↗

Development status of Terumo implantable left ventricular assist system.

We have been developing an implantable left ventricular assist system (T-ILVAS) featuring a magnetically suspended centrifugal pump (MSCP) since 1995. In vitro and in vivo studies using a prototype MSCP composed of a polycarbonate housing and impeller (196 ml) have demonstrated long-term durability and excellent blood compatibility for up to 864 days, and excellent stability of the magnetic bearing of the MSCP. These preliminary results strongly suggested that the magnetic bearing of the MSCP is reliable and is a most feasible mechanism for a long-term circulatory assist device. We have recently devised a clinical version pump made of titanium (180 ml) with a new position sensor mechanism and a wearable controller with batteries. Cadaver fit study confirmed that the Type IV pump could be implanted in a small patient with a body surface area as small as 1.3. The in vitro performance tests of the Type IV pump demonstrated excellent hydrodynamic performances with an acceptable hemolysis rate. New position sensors for the titanium housing showed more uniform sensor outputs of a magnetic bearing than in the prototype polycarbonate pump. The Type IV pump then was evaluated in vivo in 6 sheep at the Oxford Heart Centre. Four sheep were electively sacrificed at 3 months and were allowed to survive for more than 6 months for long-term evaluation. In this particular series of experiments, no anticoagulant/antiplatelet regimen was utilized except for a bolus dose of heparin during surgery. There was a left ventricular mural thrombi around the inflow cannula in 1 sheep. Otherwise, there was no mechanical failure nor sign of thromboembolism throughout the study.

Animals↗

Engineering analysis of diamond-like carbon coated polymeric materials for biomedical applications.

Diamond-like carbon (DLC) films have received much attention recently owing to their properties, which are similar to diamond: hardness, thermal conductivity, corrosion resistance against chemicals, abrasion resistance, good biocompatibility, and uniform flat surface. Furthermore, DLC films can be deposited easily on many substrates for wide area coat at room temperature. DLC films were developed for applications as biomedical materials in blood contacting-devices (e.g., rotary blood pump) and showed good biocompatibility for these applications. In this study, we investigated the surface roughness by Atomic Force Microscopy (AFM) and Hi-vision camera, SEM for surface imaging. The DLC films were produced by radio frequency glow discharge plasma decomposed of hydrocarbon gas at room temperature and low pressure (53 Pa) on several kinds of polycarbonate substrates. For the evaluation of the relation between deposition rate and platelet adhesion that we investigated in a previous study, DLC films were deposited at the same methane pressure for several deposition times, and film thickness was investigated. In addition, the deposition rate of DLC films on polymeric substrates is similar to the deposition rate of those deposited on Si substrates. There were no significant differences in substrates' surface roughness that were coated by DLC films in different deposition rates (16-40 nm). The surface energy and the contact angle of the DLC films were investigated. The chemical bond of DLC films also was evaluated. The evaluation of surface properties by many methods and measurements and the relationship between the platelet adhesion and film thickness is discussed. Finally, the presented DLC films appear to be promising candidates for biomedical applications and merit investigation.

Anticoagulants↗

Physical model-based indirect measurements of blood pressure and flow using a centrifugal pump.

This article describes a technique offering indirect measurements of pump pressure differential and flow with certain accuracy independent of changes in blood viscosity. This technique is based on noninvasive measurements of the motor current and rotation speed using the physical model equations of the centrifugal pump system. Blood viscosity included in the coefficients of the dynamic equations is first estimated, and then substitution of the estimated viscosity into the steady equations of the model provides pump flow and pressure differential. In vitro tests using a Capiox pump showed a sufficient linear correlation between actual values and their estimates for pressure differential and pump flow. An in vivo test using a 45 kg sheep showed that the proposed algorithm needs robustness for the convergence of estimates of viscosity. An overall evaluation, however, of the developed algorithm/model showed indications of success in terms of efficient computation and modeling.

Algorithms↗

Measurement of blood hematocrit inside the magnetically suspended centrifugal pump using an optical technique: application to assessment of pump flow.

To measure blood hematocrit inside the magnetically suspended centrifugal pump, we have performed both forward and backward light scattering measurements using a specially designed optical cell. In the forward scattering measurement, an optical fiber was used to guide the near infrared light at 780 nm into a 250 microns gap region, and the light that forward scattered toward a detector fiber was measured using a phototransistor. The light intensity decreased exponentially with an increase in the hematocrit to around 20%. The forward scattering method suffered from sensitivity at the hematocrit levels around 25-45% due to the diffusion effect. By making the optical path length larger than several millimeters, the sensitivity of the forward scattering method in terms of hematocrit change can be improved. In the back scattering method, however, better sensitivity in terms of hematocrit change from 0-50% was obtained. By making the optical fiber separation distance less than 1 mm, the system will measure the first order back scattering from the shallow layer while, by making the fiber separation distance larger than several millimeters, the system will primarily measure the diffuse reflectance from the deeper layer. Both approaches will yield sensitive optical intensity change in terms of the physiological hematocrit range.

Algorithms↗

Comparative study of biocompatibility between the open circuit and closed circuit in cardiopulmonary bypass.

The theoretical benefit of a centrifugal pump or heparin coating demonstrated through in vitro or in vivo studies is not recognizable in cardiopulmonary bypass (CPB) during chemical open heart surgery. The objective of this study was to investigate the influence of the interface of air and blood in current CPB with an open circuit system and its relative significance in relationship to the heparin dose and heparin coating. Using the same oxygenator and circuit, an open circuit and closed circuit CPB with the same priming volume were prepared for a 4 h perfusion experiment using diluted and heparinized (3.6 U/ml) fresh human blood. In these experiments, both heparin-coated and noncoated circuits were examined. Blood was sampled before and 2, 30, 60, 120, and 240 min after the start of perfusion, and the platelet and white blood cell counts and beta-thromboglobulin (beta-TG) and C3a levels were measured. The amount of adsorbed protein in the hollow fibers was also measured after retrieval. Although the results demonstrated significantly better biocompatibility of the heparin-coated circuit than the noncoated circuit, the difference between the open and closed circuits was unexpectedly small and insignificant with either the heparin-coated circuit or noncoated circuit. In contrast, the C3a level was higher in the closed circuit than the open circuit. However, the amount of adsorbed protein was markedly lower in the closed circuit (0.7 microgram/cm2) than in the open circuit (11.1 micrograms/cm2). An immunoblot of the adsorbed protein showed a higher density of fibrinogen bands and conversion to fibrin in the open circuit. We speculate that the lower blood C3a level in the open circuit suggests that C3a was taken in by the adsorbed protein. In conclusion, analysis of the adsorbed protein indicates the lower biocompatibility of the open circuit. Similar experiments with less heparin use and more severe conditions will be necessary to elucidate the essential benefit of making a CPB closed circuit.

Adsorption↗

Photochemical grafting of alpha-propylsulphate-poly(ethylene oxide) on polyurethane surfaces and enhanced antithrombogenic potential.

The aim of this study is the grafting of photoreactive alpha-propylsulphate-poly(ethylene oxide) (PEO-SO3), one end of which is capped with an azidophenyl group, on polyurethane (PU) surfaces via a photochemical technique. The anti-Factor Xa activity and the platelet adhesion characteristics of the modified PU surface were evaluated by a chromogenic assay method and by a flow-controlled chamber method, respectively. X-ray photoelectron spectroscopy analysis showed that PEO-SO3 was covalently grafted on the PU surface. The grafted surface showed anti-Factor Xa activity in the presence of antithrombin III, and significantly reduced platelet adhesion characteristics as compared with those of the unmodified PU surface. These results suggest that the grafting of PEO-SO3 improves the antithrombogenicity of PU surfaces.

Antithrombin III↗

Nonthrombogenic polymer vascular prosthesis.

Although many synthetic vascular grafts have been developed and evaluated experimentally or clinically, none of them have met long-term patency when applied as a small diameter vascular substitute. We have recently developed a small caliber vascular graft (3 mm i.d.) using a nonthrombogenic polymer coating. The graft consists of three layered structures: Dacron for the outer layer, polyurethane in the middle layer, and a HEMA/styrene block copolymer (HEMA-st) coating for the inner layer. HEMA-st is an amphiphilic block copolymer composed of 2-hydroxyethyl methacrylate and styrene which has demonstrated improved blood compatibility over existing biomedical polymers in both in vitro and ex vivo experiments. Ten grafts were evaluated in a dog bilateral carotid replacement model. The grafts were electively retrieved at 7, 14, 30, 92, and 372 days after implantation. All grafts were patent without detectable thrombi along the graft length including anastomotic sites. Scanning electron micrographs of retrieved graft lumen showed fairly clean surfaces covered with a homogenous protein-like layer without microthrombi or endothelial cell lining. The thickness of the surface protein layer measured by a transmission electron microscopy was what can be described as monolayer protein adsorption regardless of implantation periods of as much as 372 days. A stable monolayer adsorbed protein layer formed on HEMA-st surfaces demonstrated nonthrombogenic activities in vivo and secure long-term patency of small caliber vascular grafts with the absence of an endothelial cell lining.

Animals↗

In vitro evaluation of platelet/biomaterial interactions in an epifluorescent video microscopy combined with a parallel plate flow cell.

Suitable evaluation systems are critical for ranking various biomaterials in order to develop a method to design and synthesize nonthrombogenic biomaterials. We have recently developed an in vitro test system to evaluate platelet/biomaterial interactions in whole blood. The system consists of a parallel plate flow cell and epifluorescent video microscopy (EVM). A glass coverslip coated with a polymer was incorporated into the flow cell, and blood was perfused using a syringe pump via a polymer-coated PVC tubing connected to the flow cell. Whole human blood was anticoagulated with heparin (2 U/ml), and the platelets were labeled with the fluorescent dye mepacrine (5 microM). This system permitted real-time and dynamic observations of platelet/biomaterial interactions in whole blood under a defined flow condition. In order to evaluate the feasibility of this system, two different segmented polyether-polyurethanes (SPEUs), PU-PTMG(650) and PU-PTMG(2000), were chosen as test polymers. Surface characteristics verified with electron spectroscopy for chemical analysis (ESCA) and contact angle measurements showed similar results in both SPEUs. Blood was perfused at a wall shear rate of 200 s-1 for 20 min. Excitation light was applied for 2 s at 1 min intervals. The real-time image was then analyzed at each time point for the percentage of surface area of platelet coverage. Plasma beta-thromboglobulin (beta-TG) levels were also measured before and after each run. PU-PTMG(650) showed a significantly higher number of adhered platelets than PU-PTMG(2000) at each time point.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

Pulsatile flow and simple flow control method during weaning period in centrifugal pump: toward more expanded usage in open heart surgery.

To expand the usage of the centrifugal pump (CP) in open heart surgery, we performed two studies. In the first, we evaluated pulsatile flow in the CP. In vitro pump performance of the Terumo Capiox pump (TCP) and the Sarns Delphin pump (SDP) and increase of free hemoglobin (mg/dl) after driving 6 h were investigated using bovine blood. A roller pump (RP) was used as a comparison. Equally effective pulsatile flow was obtained in both CPs. Hemolysis was less severe in TCP (120 mg/dl) than SDP (210 mg/dl) and RP (320 mg/dl). In the second study, we evaluated a simple flow control method. Flow rate was easily controlled with step-wise clamping of 3-pronged tubing (Triple-flow) without changing rotational speed, regardless of afterload. Fluctuation of flow was much less with this method than with the rotational speed change method. The use of pulsatile flow of TCP, with its minimum increase of hemolysis and the easier flow control method during the weaning process, may expand the usage of CP in open heart surgery.

Animals↗

The margin of safety in the use of a straight path centrifugal blood pump.

A new centrifugal blood pump with a rotor that arranges 6 straight paths radially was developed for open heart surgery and temporary circulatory support. We describe comparative studies of the margin of safety in the practical use of the new pump. This pump was evaluated for temperature increase, cavitation, and pressure sensitivity. Two commercially available centrifugal pumps, the Biomedicus cone type and the Sarns 3M impeller type, were used as control pumps. The temperature increase in the new pump was four times slower than in the impeller pump when the outlet and the inlet of the pump was clamped. No sign of cavitation was observed when 0.1 ml air was introduced to the pump inlet under a negative pressure of 200 mm Hg in fresh bovine blood. As for pressure sensitivity of centrifugal pumps in practical applications, circuit resistance was a more essential factor than flow-pressure curves of the pump.

Animals↗

Tricuspid valve replacement with the bileaflet St. Jude Medical valve prosthesis.

Case histories of 39 patients who underwent tricuspid valve replacement with the St. Jude Medical prosthesis between June 1979 and August 1992 were reviewed in March 1993. The average patient age at the time of the operation was 46 +/- 11 years (range from 17 to 68 years). Concomitant mitral and/or aortic valve replacements were performed in 30 patients. All patients were given warfarin to maintain thrombotest between 10% to 25%. This number was between 2.8 to 1.6 times the control value in the International Normalized Ratio of prothrombin time. Three operative deaths occurred (7.7%). Among six late deaths, two patients died suddenly of unknown causes, and the remaining patient deaths were not valve-related. The actuarial survival rate at 14 years was 54.7%. Valve thrombosis occurred in one patient and was successfully treated with intravenous urokinase. This was the only valve-related complication (0.67%/patient-year). No reoperations were necessary in the tricuspid position. In conclusion, the St. Jude Medical valve is our choice of prosthesis for tricuspid valve replacement in adult patients who can receive proper anticoagulation therapy.

Adolescent↗

[True aneurysm of mitral valve secondary to aortic valvular infective endocarditis].

A case of the mitral valve aneurysm with aortic valvular infective endocarditis is reported. A 30-year-old male who had the history of Streptococcus viridans endocarditis underwent aortic and mitral valve replacement. The aortic valve was bicuspid and had the perforation in its non-coronary cusp, and histology in its specimen showed post-inflammatory vascularization and disorganization of architecture. A gigantic aneurysm was visible in the anterior leaflet of the mitral valve, but both anterior and posterior leaflets had no inflammatory change in histology. In this case, the "jet" of blood produced by aortic valve perforation involved the mitral valve. This aneurysmal change was so called "jet lesion" secondary to aortic valve endocarditis.

Adult↗

Development of the Terumo Capiox centrifugal pump and its clinical application to open heart surgery: a comparative study with the roller pump.

We have developed the Terumo Capiox centrifugal pump (CXP), which consists of a rotor having a unique straight-path design to reduce pump rotational speed without decreasing hydraulic efficiency. The CXP was tested in vitro for blood trauma with a specially designed test circuit using fresh bovine blood. The Biopump (BP) (Medtronic, Minneapolis, MN, U.S.A.) and the roller pump (RP) were used as controls. The CXP demonstrated the smallest elevation of free plasma hemoglobin compared with the BP and the RP. The CXP was then applied to cardiopulmonary bypass (CPB) in 10 patients (CXP group) who underwent elective coronary artery bypass grafting (CABG), and the results were compared with those for a comparable roller pump group (RP group). Free plasma hemoglobin level, platelet count, and serum beta-thromboglobulin (beta-TG) level were measured during CPB. There were no CXP-related complications nor hemodynamic abnormalities during CPB. The CXP group demonstrated less hemolysis and less platelet depletion than the RP group. Furthermore, the serum beta-TG level was significantly lower in the CXP group than in the RP group. The CXP showed excellent hemodynamic performance with less blood trauma both in vitro and in clinical application to open heart surgery. Thus, the CXP has significant potential to be safely applied to CPB for open heart surgery and circulatory support.

Animals↗

A straight path centrifugal blood pump concept in the Capiox centrifugal pump.

This article describes comparative studies of a newly developed "straight path" centrifugal pump (Capiox centrifugal pump) targeted for open-heart surgery and circulatory support. A unique straight path design of the rotor was very effective in reducing the pump's rotational speed and prime volume. This pump was evaluated for hydraulics, hemolysis, depriming characteristics, cavitation, and heat generation. Two commercially available centrifugal pumps, the Biomedicus cone-type pump and the Sarns 3M impeller-type pump, were used as controls. The new pump required the lowest pump speed to produce the same flow rates under the same pressure loads and demonstrated the lowest hemolysis and the lowest temperature rise with the outlet clamped. The air volume required to deprime the new pump was one-third to one-half that for the other pumps, and no sign of cavitation was observed even if a small amount of air was introduced to the pump inlet under a negative pressure of 200 mm Hg.

Animals↗

[Successful repair of partial atrioventricular septal defect in a 70-year-old female patient].

A 70-year-old female with partial atrioventricular septal defect underwent a total correction of the anomaly. The patient was in NYHA functional class II. Preoperative cardiac catheterization demonstrated a primum-type atrial septal defect through which 33% of left to right shunt occurred and a cleft of mitral valve causing moderate regurgitation. The operative procedure as our routine for this anomaly consisted of suture of mitral septal commissure and closure of atrial septal defect with autologous pericardial patch. Postoperative examination showed satisfactory competence of mitral valve and improved functional capacity. A successful correction for the case aged more than 66 with this anomaly has not been reported so far in Japanese literature. We conclude that surgical treatment should be basically considered for this anomaly in spite of senility.

Aged↗