Julie Glueck

Protein adsorption onto ceramic surfaces

Ceramics seldom have been used as blood-contacting materials. However, alumina ceramic (Al2O3) and polyethylene are incorporated into the pivot bearings of the Gyro centrifugal blood pump. This material combination was chosen based on the high durability of the materials. Due to the stagnant flow that often occurs in a continuous flow condition inside a centrifugal pump, pivot bearing system is extremely critical. To evaluate the thombogenicity of pivot bearings in the Gyro pump, this study sought to investigate protein adsorption, particularly albumin, IgG, fibrinogen, and fibronectin onto ceramic surfaces. Al2O3 and silicon carbide ceramic (SiC) were compared with polyethylene (PE) and polyvinylchloride (PVC). Bicinchoninic acid (BCA) protein assay revealed that the amount of adsorbed proteins onto Al2O3 and SiC was significantly less than that on PVC. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that numerous proteins adsorbed onto PVC compared to PE, Al2O3, and SiC. Identification of adsorbed proteins by Western immunoblotting revealed that the adsorption of albumin was similar on all four materials tested. Western immunoblotting also indicated lesser amounts of IgG, fibrinogen, and fibronectin on Al2O3 and SiC than on PE and PVC. In conclusion, ceramics (Al2O3 and SiC) are expected to be thromboresistant from the viewpoint of protein adsorption.

Development of a Pivot Bearing Supported Sealless Centrifugal Pump for Ventricular Assist

Since 1991, in our laboratory, a pivot bearing-supported, sealless, centrifugal pump has been developed as an implantable ventricular assist device (VAD). For this application, the configuration of the total pump system should be relatively small. The C1E3 pump developed for this purpose was anatomically compatible with the small-sized patient population. To evaluate an-tithrombogenicity, ex vivo 2-week screening studies were conducted instead of studies involving an intracorpore-ally implanted VADs using calves. Five paracorporeal LVAD studies were performed using calves for longer than 2 weeks. The activated clotting time (ACT) was maintained at approximately 250 s using heparin. All of the devices demonstrated trouble-free performances over 2 weeks. Among these 5 studies, 3 implantations were subjected to 1-month system validation studies. There were no device-induced thrombus formations inside the pump housing, and plasma-free hemoglobin levels in calves were within the normal range throughout the experiment (35, 34, and 31 days). There were no incidents of system malfunction. Subsequently, the mass production model was fabricated and yielded a normalized index of hemolysis of 0.0014, which was comparable to that of clinically available pumps. The wear life of the impeller bearings was estimated at longer than 8 years. In the next series of in vivo studies, an implantable model of the C1E3 pump will be fabricated for longer term implantation. The pump-actuator will be implanted inside the body; thus the design calls for substituting plastic for metallic parts.

Characteristics of a Blood Pump Combining the Centrifugal and Axial Pumping Principles: The Spiral Pump

Two well-known centrifugal and axial pumping principles are used simultaneously in a new blood pump design. Inside the pump housing is a spiral impeller, a conically shaped structure with threads on the surface. The worm gears provide an axial motion of the blood column through the threads of the central cone. The rotational motion of the conical shape generates the centrifugal pumping effect and improves the efficiency of the pump without increasing hemolysis. The hydrodynamic performance of the pump was examined with a 40% glycerin-water solution at several rotation speeds. The gap between the housing and the top of the thread is a very important factor: when the gap increases, the hydrodynamic performance decreases. To determine the optimum gap, several in vitro hemolysis tests were performed with different gaps using bovine blood in a closed circuit loop under two conditions. The first simulated condition was a left ventricular assist device (LVAD) with a flow rate of 5 L/min against a pressure head of 100 mm Hg, and the second was a cardiopulmonary bypass (CPB) simulation with a flow rate of 5 L/min against 350 mm Hg of pressure. The best hemolysis results were seen at a gap of 1.5 mm with the normalized index of hemolysis (NIH) of 0.0063 ± 0.0020 g/100 L and 0.0251 ± 0.0124 g/100 L (mean ± SD; n = 4) for LVAD and CPB conditions, respectively.

Blood trauma induced by clinically accepted oxygenators.

Hemolysis remains one of the most serious problems during cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and percutaneous cardiopulmonary support (PCPS). However, the hemolytic characteristics associated with oxygenators are not well defined. A specialized hemolysis test protocol for oxygenators was developed. A comparative study was performed following this protocol to determine the hemolytic characteristics of the clinically available oxygenators during CPB; pressure drop measurements in the blood chamber were also performed. Four oxygenators (Medtronic Affinity, Cobe Optima, Terumo Capiox SX25, and Bard Quantum) were evaluated. Fresh blood from healthy Dexter calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 5 L/min, similar to that used in CPB. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials (ASTM) standards. The NIH value, which was obtained from the circuit without an oxygenator, was subtracted from the primary NIH value, obtained from the circuit with an oxygenator to eliminate the effects of a centrifugal pump or other artifacts. The NIHO value was the lowest in the Affinity (0.0116 ± 0.0017) and increased from Affinity < Optima (0.0270 ± 0.0038) < Capiox (0.0335 ± 0.0028) < Quantum (0.0416 ± 0.0015 g/100 L). The Optima and Capiox did not demonstrate a significant difference. In addition, this NIHO value has a close relationship to the pressure drop. In conclusion, this new evaluation method is suitable to compare the biocompatibility performance of different types of clinically available oxygenators for CPB usage.

Biocompatibility of alumina ceramic and polyethylene as materials for pivot bearings of a centrifugal blood pump

The double pivot bearings in the Gyro C1E3 centrifugal blood pump incorporate a high-purity alumina (Al2O3) ceramic and an ultra-high-molecular-weight polyethylene (UHMWPE). This centrifugal pump has been developed as a completely sealless pump for long-term usage. The combination of Al2O3 and UHMWPE are the materials of choice for the acetabular bearing in artificial joints, which have proven to be clinically reliable for over 10 years. Previous studies have examined the biocompatibility of Al2O3 and UHMWPE as bulky implant materials. The present study investigated this material as a blood-contacting material using a standard assessment in vitro and in vivo analysis. The examined items were systemic toxicity, sensitization (guinea pig maximization test), cytotoxicity (elution test), mutagenicity (Ames test), direct contact hemolysis, and thrombogenicity. The studies were performed according to the United States Pharmacopoeia and published previous studies. The samples of both Al2O3 and UHMWPE demonstrated no differences from the negative controls in all tests. These findings indicate that both Al2O3 and UHMWPE are biocompatible materials for double-pivot bearings in the centrifugal blood pump.

Hemolytic characteristics of oxygenators during clinical extracorporeal membrane oxygenation.

A connection was previously reported between the hemolytic characteristics associated with oxygenators and the pressure drop measurements in the blood chamber under experimental conditions simulating their use in cardiopulmonary bypass. We examined this association during extracorporeal membrane oxygenation (ECMO) conditions. Three oxygenators for ECMO or pediatric cardiopulmonary bypass (Menox EL4000, Dideco Module 4000, and Mera HPO-15H) were evaluated. Fresh blood from healthy Dexter strain calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 1 L/min, similar to that in ECMO. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials standards, as was previously reported. The NIHO value was the lowest in the Menox (0.0070 ± 0.0009) and increased from Menox to Dideco (0.0113 ± 0.0099) to Mera (0.0164 ± 0.0043); however, there were no significant differences among the oxygenators. This NIHO value has a close correlation to the pressure drop. In conclusion, this evaluation method is also applicable to comparison of the biocompatibility performance of different types of clinically available oxygenators for ECMO.

Operating point control system for a continuous flow artificial heart: In vitro study

We proposed and developed a practical and effective servo control system for rotary blood pumps. A rotary blood pump for assisting the failing natural heart should be operated only in physiologically acceptable conditions. The operation of a rotary blood pump is based on the rotational speed of the impeller and pressure head. If the pump flow and the pressure head are set within an acceptable range, the driving condition is deemed normal condition, and this control system maintains the preset operating point by applying proportional and detective control (PD control). If the pump flow or pressure head is outside the acceptable range, the driving condition is determined to be abnormal condition, and this system operates the pump in a recovery fashion. If the driving condition is kept under abnormal conditions of sudden decrease of the flow, the condition is termed a suction condition. The controller releases the pump from the suction condition and later returns it to the normal condition. In this study, we evaluated these servo control modes of the centrifugal pump and confirmed whether the performance of this proposed operating point control system was practical.

Comparative in vitro encrustation studies of biomaterials in human urine.

A new dynamic in vitro human urine model was developed to compare biomaterial encrustation. The model incorporates a capacity to study seven biomaterials, a daily urine inflow of 500 ml, a reservoir capacity of 700 ml, and a turnover rate of four days. Encrustation studies performed for 2 weeks in sterile and infected (Proteus Vulgaris) urine on segmented polyether polyurethane, polyester polyurethane, silicone (Mitsui), silicone (Dow Corning), biothane, biolor 1 and biolor 11 demonstrated that biolor 11 (silicone-carbon composite) caused the least encrustation. Encrustation analysis showed brushite in the sterile model and struvite and ammonium acid urate in the infected mode I. Biolor II should have beneficial applications in catheters, stents and prosthetics which come in contact with urine.

Development of an antithrombogenic and antitraumatic blood pump: the Gyro C1E3.

The Gyro C1E3 is a centrifugal blood pump. Its antithrombogenic and antitraumatic blood features were demonstrated by prior studies. Based upon these studies, a mass production model of the C1E3 is becoming commercially available. Therefore, this feasibility study was conducted using the mass production models of the Gyro C1E3 for long-term cardiac assist in ex vivo animal experiments. Five healthy calves were used and 15 pump heads were applied for different time periods (Group 1, 30 days; Group 2, 14 days; Group 3, 10 and 7 days; Group 4, 4 days; and Group 5, 2 days). Activated clotting time (ACT) was kept at 200-250 sec. All five calves demonstrated neither abnormal signs nor abnormal blood examination data throughout the experiment. During necropsy, no thromboembolism was found in any downstream organs. Groups 1-4 showed thrombi inside the pump heads while two pumps in Group 5 had no thrombi formations. Bearing deformation or possible wear did not increase after 2 days of pumping. The C1E3 is capable of long-term assist circulation. However, after 2 days of pumping, careful observation is necessary since thrombi may occur inside the pump when ACT is controlled under 250 sec. During the weaning stage or low flow (under 2 L/min), over 250 sec of ACT is recommended to assure the safety of the patient.

Recent advances in the gyro centrifugal ventricular assist device

The gyro pump was developed as an intermediate-term assist pump (C1E3) as well as a long-term centrifugal ventricular assist device (VAD). The antithrombogenic design concept of this pump was confirmed throughout three 1 month ex vivo studies. The normalized index of hemolysis (NIH) of this gyro C1E3 model was lower than that of the BP-80. In the next step, a miniaturized centrifugal blood pump (The Gyro permanently implantable model PI-601) has been developed for use as a permanently implantable device after design optimization. A special motor design of the magnet circuit was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height, 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. This pump can provide 5 L/min against 120 mm Hg total pressure head at 2,000 rpm. The NIH value of this pump was comparable to that of the BP-80. The gyro PI-601 model is suitable for a VAD. The expected life from the endurance study is approximately 8 years. The evolution from C1E3 to the PI-601 converts this pump to a totally implantable centrifugal pump. Recent technologic advances in continuous flow devices are likely to realize a miniaturized and economical totally implantable VAD.