Development of a New Hollow Fiber Silicone Membrane Oxygenator: In Vitro Study

An experimental silicone hollow fiber membrane oxygenator for long-term extracorporeal membrane oxygenation (ECMO) was developed in our laboratory using an ultrathin silicone hollow fiber. However, the marginal gas transfer performances and a high-pressure drop in some cases were demonstrated in the initial models. In order to improve performance the following features were incorporated in the most recent oxygenator model: increasing the fiber length and total surface area, decreasing the packing density, and modifying the flow distributor. The aim of this study was to evaluate the gas transfer performances and biocompatibility of this newly improved model with in vitro experiments. According to the established method in our laboratory, in vitro studies were performed using fresh bovine blood. Gas transfer performance tests were performed at a blood flow rate of 0.5 to 6 L/min and a V/Q ratio (V = gas flow rate, Q = blood flow rate) of 2 and 3. Hemolysis tests were performed at a blood flow rate of 1 and 5 L/min. Blood pressure drop was also measured. At a blood flow rate of 1 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 72.45 +/- 1.24 and 39.87 +/- 2.92 ml/min, respectively. At a blood flow rate of 2 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 128.83 +/- 1.09 and 47.49 +/- 5.11 ml/min. Clearly, these data were superior to those obtained with previous models. As for the pressure drop and hemolytic performance, remarkable improvements were also demonstrated. These data indicate that this newly improved oxygenator is superior to the previous model and may be clinically acceptable for long-term ECMO application.     

Preclinical evaluation of a new hollow fiber silicone membrane oxygenator for pediatric cardiopulmonary bypass: ex-vivo study.

Based on the results of many experimental models, a hollow fiber silicone membrane oxygenator applicable for long-term extracorporeal membrane oxygenation (ECMO) was developed. For further high performance and antithrombogenicity, this preclinical model was modified, and a new improved oxygenator was successfully developed. In addition to ECMO application, the superior biocompatibility of silicone must be advantageous for pediatric cardiopulmonary bypass (CPB). An ex vivo short-term durability test for pediatric CPB was performed using a healthy miniature calf for six hours. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal pump. For six hours, the O2 and CO2 gas transfer rates were maintained around 90 and 80 ml/min at a blood flow rate of 2 L/min and V/Q=3, respectively. The plasma free hemoglobin was maintained around 5 mg/dl. These data suggest that this newly improved oxygenator has superior efficiency, less blood trauma, and may be suitable for not only long-term ECMO but also pediatric CPB usage.     

Development of silicone rubber hollow fiber membrane oxygenator for ECMO

Silicone rubber hollow fiber membrane produces an ideal gas exchange for long-term ECMO due to nonporous characteristics. The extracapillary type silicone rubber ECMO oxygenator having an ultrathin hollow fiber membrane was developed for pediatric application. The test modules were compared to conventional silicone coil-type ECMO modules. In vitro experiments demonstrated a higher O2 and CO2 transfer rate, lower blood flow resistance, and less hemolysis than the conventional silicone coil-type modules. This oxygenator was combined with the Gyro C1E3 centrifugal pump, and three ex vivo experiments were conducted to simulate pediatric V-A ECMO condition. Four day and 6 day experiments were conducted in cases 1 and 2, respectively. Case 3 was a long-term experiment up to 2 weeks. No plasma leakage and stable gas performances were achieved. The plasma free hemoglobin was maintained within a normal range. This compact pump-oxygenator system in conjunction with the Gyro C1E3 centrifugal pump has potential for a hybrid total ECMO system.     

Gas-exchange function of a preprimed pediatric oxygenator stored for one year for emergency cardiopulmonary bypass

To save priming time and perform more rapid initiation of emergency cardiopulmonary bypass for acute cardiopulmonary failure, an extracorporeal circuit with a hollow-fiber oxygenator (EL-2000 for pediatric use; Kurary Co. Ltd., Osaka, Japan) was preprimed, and the gas-exchange function was evaluated after 1 year of storage. EL-2000 has a dense polyolefin membrane with a surface area of 0.3 m2. When the bypass flow rates were 250, 500, 1,000, and 1,500 ml/min with 100% oxygen at the same flow rate as the bypass blood flow (namely, V/Q = 1) to the oxygenator, oxygen transport rates of the stored oxygenator were 19.6 +/- 0.3, 38.3 +/- 0.41, 64.4 +/- 0.9, and 76.4 +/- 2.7 ml/min (n = 5, mean +/- SD), respectively. PCO2 differences between pre- and postoxygenator blood (delta PCO2) were 18.6 +/- 1.4, 12.0 +/- 1.6, and 4.4 +/- 1.2 mm Hg at V/Q = 1 and the same bypass blood flow rates, respectively, excluding 1,500 ml/min, the data for which were excluded because of preparatory failure. PCO2 removal indices (defined as the ratio of delta PCO2 to PCO2 in preoxygenator blood) were 0.45 +/- 0.03, 0.29 +/- 0.12, and 0.10 +/- 0.03, respectively. Though the evaluation was done using only a single oxygenator, we feel strongly that the gas-exchange function of the preprimed dense-membrane hollow fiber oxygenator will be preserved even after 1 year of storage.     

Development of a new silicone membrane oxygenator for ECMO.

Two types small and efficient ECMO oxygenators were developed utilizing the most up to date hollow fiber technology. Newly silicone hollow fibers possess sufficient mechanical strength while maintaining ultra thin walls of 50 micro meter. Two types of oxygenators were made with this fiber. The fiber length for the type 1 module is 150mm with a priming volume 194 cc (surface area 1.3 m(2)) and type 2 has a fiber length of 100 mm with a 144 cc priming volume (the surface area 0.8 m(2)). The studies were performed at 0.5, 1.0 and 2.0 L/min of blood flow and these oxygenators demonstrated. O(2) gas transfer rate of 69+/-4 ml/min/L for type 1 and 68+/-6 ml/min/L for type 2. The CO(2) gas transfer rate was 25+/-2 ml/min/L for type 1 and 32+/-2 ml/min/L for type 2. These results demonstrate type 2 oxygenator has similar gas exchange capabilities to those of Kolobows' oxygenator which has about 2.0 times larger surface area. Additionally, comparative hemolysis tests were preformed with this new oxygenator and the Kolbow. The NIH value was 0.006 (g/100 L) for the type 1 oxygenator and 0.01 (g/100 L) for the Kolbow oxygenator. These results suggested that this ECMO oxygenator had sufficient gas exchange performance in spite of being smaller and induced minimal blood damage.     

Extracorporeal membrane oxygenator compatible with centrifugal blood pumps

Coil-type silicone membrane oxygenators can only be used with roller blood pumps due to the resistance from the high blood flow. Therefore, during extracorporeal membrane oxygenation (ECMO) treatment, the combination of a roller pump and an oxygenator with a high blood flow resistance will induce severe hemolysis, which is a serious problem. A silicone rubber, hollow fiber membrane oxygenator that has a low blood flow resistance was developed and evaluated with centrifugal pumps. During in vitro tests, sufficient gas transfer was demonstrated with a blood flow less than 3 L/min. Blood flow resistance was 18 mm Hg at 1 L/min blood flow. This oxygenator module was combined with the Gyro C1E3 (Kyocera, Japan), and veno-arterial ECMO was established on a Dexter strain calf. An ex vivo experiment was performed for 3 days with stable gas performance and low blood flow resistance. The combination of this oxygenator and centrifugal pump may be advantageous to enhance biocompatibility and have less blood trauma characteristics.     

Description of a flow optimized oxygenator with integrated pulsatile pump

Extracorporeal membrane oxygenation (ECMO) is a well-established therapy for several lung and heart diseases in the field of neonatal and pediatric medicine (e.g., acute respiratory distress syndrome, congenital heart failure, cardiomyopathy). Current ECMO systems are typically composed of an oxygenator and a separate nonpulsatile blood pump. An oxygenator with an integrated pulsatile blood pump for small infant ECMO was developed, and this novel concept was tested regarding functionality and gas exchange rate. Pulsating silicone tubes (STs) were driven by air pressure and placed inside the cylindrical fiber bundle of an oxygenator to be used as a pump module. The findings of this study confirm that pumping blood with STs is a viable option for the future. The maximum gas exchange rate for oxygen is 48mL/min/L(blood) at a medium blood flow rate of about 300mL/min. Future design steps were identified to optimize the flow field through the fiber bundle to achieve a higher gas exchange rate. First, the packing density of the hollow-fiber bundle was lower than commercial oxygenators due to the manual manufacturing. By increasing this packing density, the gas exchange rate would increase accordingly. Second, distribution plates for a more uniform blood flow can be placed at the inlet and outlet of the oxygenator. Third, the hollow-fiber membranes can be individually placed to ensure equal distances between the surrounding hollow fibers.     

Pressure drop, shear stress, and activation of leukocytes during cardiopulmonary bypass: a comparison between hollow fiber and flat sheet membrane oxygenators

The membrane oxygenator is known to be superior to the bubble oxygenator, but little information is available about the difference between the hollow fiber and flat sheet membrane oxygenators with regard to pressure drop, shear stress, and leukocyte activation. In this study, we compared these 2 types of membrane oxygenators in patients undergoing cardiopulmonary bypass (CPB) surgery with special focus on leukocyte activation and pressure drop across the oxygenators. Plasma concentration of elastase, a marker indicating leukocyte activation, increased to 593+/-68% in the flat sheet oxygenator group versus 197+/-42% in the hollow fiber oxygenator group (p<0.01) at the end of CPB compared to their respective baseline concentrations before CPB. Pressure drop across the oxygenator was significantly higher in the flat sheet group than in the hollow fiber group throughout the entire period of CPB (p<0.01). High pressure drop across the oxygenator as well as the calculated shear stress was positively correlated with the release of elastase at the end of CPB (r = 0.760, p<0.01, r = 0.692, p<0.01). However, this positive correlation existed in the flat sheet oxygenator but not in the hollow fiber oxygenator. Clinically, both membrane oxygenators have satisfactory performance in O2 and CO2 transfer. These results suggest that a higher pressure drop across the flat sheet oxygenator is associated with more pronounced activation of leukocytes in patients undergoing cardiopulmonary bypass.     

Retrospective analysis comparing hollow fiber and silicone membrane oxygenators for neonates on ECMO

There is little information showing the use of microporous polypropylene hollow fiber oxygenators during extra-corporeal life support (ECLS). Recent surveys have shown increasing use of these hollow fibers amongst ECLS centers in the United States. We performed a retrospective analysis comparing the Terumo BabyRx hollow fiber oxygenator to the Medtronic 800 silicone membrane oxygenator on 14 neonatal patients on extracorporeal membrane oxygenation (ECMO). The aim of this study was to investigate the similarities and differences when comparing pressure drops, prime volumes, oxygenator endurance, and gas transfer capabilities between the two groups.     

Laboratory evaluation of a new membrane oxygenator with a built-in hemoconcentrator

In order to facilitate the handling of cardiopulmonary bypass (CPB) and simplify the circuit, we have developed a new membrane oxygenator with a hemofiltration function. The hollow fiber units for gas exchange and hemofiltration were combined in concentric circles in a cylindrical housing. The total priming volume was 190 ml. Because we used a silicon-coated hollow fiber membrane for gas exchange, this oxygenator was completely resistant to serum leakage. The gas exchange and hemofiltration sections both have a blood-outside flow configuration. All blood flows in a radial direction from around the central core to the surrounding hollow fiber units, first to the hemofiltration portion and then to the gas exchange section. Filtered fluid was easily collected through a stopcock mechanism. The oxygen transfer rate was 312 ml/min at a blood flow rate of 6 L/min, and the ultrafiltration rate was 3.5 L/hour at a blood flow rate of 4 L/min with 25% hematocrit and 200 mmHg transmembrane pressure in an in vitro study. The pressure drop was 62 mmHg at a blood flow rate of 4 L/min. We found no adverse effects in an in vivo study using a mongrel dog. In conclusion, this durable combined device could achieve excellent and simplified hemoconcentration by having all the blood in the unit flow through the hemofiltration portion, and may be useful not only in CPB during open heart surgery, but also in extracorporeal membrane oxygenation.     

Technical Indicators to Evaluate the Degree of Large Clot Formation Inside the Membrane Fiber Bundle of an Oxygenator in an In Vitro Setup

The most common technical complication during ECMO is clot formation. A large clot inside a membrane oxygenator reduces effective membrane surface area and therefore gas transfer capabilities, and restricts blood flow through the device, resulting in an increased membrane oxygenator pressure drop (dpMO). The reasons for thrombotic events are manifold and highly patient specific. Thrombus formation inside the oxygenator during ECMO is usually unpredictable and remains an unsolved problem. Clot sizes and positions are well documented in literature for the Maquet Quadrox‐i Adult oxygenator based on CT data extracted from devices after patient treatment. Based on this data, the present study was designed to investigate the effects of large clots on purely technical parameters, for example, dpMO and gas transfer. Therefore, medical grade silicone was injected into the fiber bundle of the devices to replicate large clot positions and sizes. A total of six devices were tested in vitro with silicone clot volumes of 0, 30, 40, 50, 65, and 85 mL in accordance with ISO 7199. Gas transfer was measured by sampling blood pre and post device, as well as by sampling the exhaust gas at the devices’ outlet at blood flow rates of 0.5, 2.5, and 5.0 L/min. Pre and post device pressure was monitored to calculate the dpMO at the different blood flow rates. The dpMO was found to be a reliable parameter to indicate a large clot only in already advanced “clotting stages.” The CO₂ concentration in the exhaust gas, however, was found to be sensitive to even small clot sizes and at low blood flows. Exhaust gas CO₂ concentration can be monitored continuously and without any risks for the patient during ECMO therapy to provide additional information on the endurance of the oxygenator. This may help detect a clot formation and growth inside a membrane oxygenator during ECMO even if the increase in dpMO remains moderate.     

Impact of hollow-fiber membrane surface area on oxygenator performance: Dideco D903 Avant versus a prototype with larger surface area

This study compares the gas transfer capacity, the blood trauma, and the blood path resistance of the hollow-fiber membrane oxygenator Dideco D 903 with a surface area of 1.7 m2 (oxygenator 1.7) versus a prototype built on the same principles but with a surface area of 2 m2 (oxygenator 2). Six calves (mean body weight: 68.2 +/- 3.2 kg) were connected to cardiopulmonary bypass (CPB) by jugular venous and carotid arterial cannulation, with a mean flow rate of 4 l/min for 6 h. They were randomly assigned to oxygenator 1.7 (N = 3) or 2 (N = 3). After 7 days, the animals were sacrificed. A standard battery of blood samples was taken before the bypass, throughout the bypass, and 24 h, 48 h, and 7 days after the bypass. The oxygenator 2 group showed significantly better total oxygen and carbon dioxide transfer values throughout the perfusion (p < .001 for both comparison). Hemolytic parameters (lactate dehydrogenase and free plasma hemoglobin) exhibited a slight but significant increase after 5 h of bypass in the oxygenator 1.7 group. The pressure drop through the oxygenator was low in both groups (range, 43-74 mmHg). With this type of hollow-fiber membrane oxygenator, an increased surface of gas exchange from 1.7 m2 to 2 m2 improves gas transfer, with a limited impact on blood trauma and no increase of blood path resistance.     

Studies on ECMO. (III)--Study on pumpless A-V ECMO

Silicon hollow fiber membrane oxygenator is considered to be useful for long term extracorporeal membrane oxygenation (ECMO) and blood usually flows inside of the fiber (inside flow type). But if it flows outside of the fiber (outside flow type), the pressure drop is supposed to be less than that of inside flow type. In this study the oxygenator of an outside flow type was used. At first, the pilot study was done to evaluate the capability of this oxygenator as an outside flow type. The pressure drop was 50 mmHg at the blood flow of 400 ml.min-1. At this blood flow and same gas flow, CO2 transfer rate was 22.3 ml.min-1. In the second study, the effects of pumpless arterio-venous ECMO (pumpless A-V ECMO) were studied in 8 dogs under mechanical hypoventilation. During ECMO, there were no significant changes in hemodynamics when the blood flow rate was 15% of cardiac output. PaO2 and PaCO2 recovered considerably. In conclusion, pumpless A-V ECMO using this membrane oxygenator of outside flow type is effective for CO2 removal and considered to be clinically useful.     

Development of a new hollow fiber silicone membrane oxygenator for ECMO: the recent progress.

Throughout the last 50 years, many improvements have been made for a more effective oxygenator. A large plate type membrane oxygenator, used by Clowes, and a coil type, used by Kolff, has evolved into the small hollow fiber oxygenator. The complex bubble oxygenator, or rotating disk oxygenator, has become a small disposable bubble oxygenator. The currently available oxygenators are extremely small, efficient, and can be used for extended periods of time. However, there are some problems with extracorporeal membrane oxygenation (ECMO). Currently in the United States, there are no clinically applicable hollow fiber ECMO oxygenators available, in spite of the extended ECMO application. Therefore, the development of a small, yet efficient, silicone hollow fiber membrane oxygenator for long-term ECMO usage was attempted. Based on the results of many experimental models, preclinical oxygenator models for long-term ECMO were developed in our laboratory using an ultra-thin silicone rubber hollow fiber membrane.     

Silicone-Coated Polypropylene Hollow-Fiber Oxygenator: Experimental Evaluation and Preliminary Clinical Use

Background. A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-μm ultrathin silicone layer (cyclosiloxane) was developed. Animal experimental and preliminary clinical studies evaluated its reliability in bypass procedures.

Methods. Five 24-hour venoarterial bypass periods were conducted on dogs using the oxygenator (group A). In 5 controls, bypass periods were conducted using the same oxygenator without silicone coating (group B). As a preliminary clinical study, 14 patients underwent cardiopulmonary bypass with the silicone-coated oxygenator.

Results. Eight to 16 hours (mean, 12.2 hours) after initiation of bypass, plasma leakage occurred in all group B animals, but none in group A. The O₂ and CO₂ transfer rates after 24 hours in group A were significantly higher than at termination of bypass in group B (p < 0.005 and p < 0.03, respectively). Scanning electron microscopy of silicone-coated fibers after 24 hours of bypass revealed no damage to the silicone coating of the polypropylene hollow fibers. In the clinical study, the oxygenator showed good gas transfer, acceptable pressure loss, low hemolysis, and good durability.

Conclusions. This oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.     

The detection of microemboli in the middle cerebral artery during cardiopulmonary bypass: a transcranial Doppler ultrasound investigation using membrane and bubble oxygenators

Twenty-seven patients were examined who were undergoing cardiopulmonary bypass (CPB) surgery with either a bubble oxygenator or a capillary membrane oxygenator. The latter incorporated an arterial filter and bubble trap. A noninvasive Doppler ultrasound technique is described for monitoring irregularities in the Doppler flow signals attributable to gaseous microemboli detected in the middle cerebral artery during CPB. The ultrasound index for detecting gaseous microemboli (MEI) indicated the presence of such microemboli in 22 of the 27 patients during insertion of the aortic cannula. Measurements during CPB showed the MEI ranged from 4 to 39 in the 17 patients with a bubble oxygenator. However, all 10 patients with a membrane oxygenator had an MEI of 0. Varying the gas flow rates in 3 patients with bubble oxygenators showed a change in MEI from 4 +/- 4 (SD) at a flow rate of 2 L/min to 17 +/- 9 at a flow rate of 5 L/min. This observation supports the assumption that the MEI is providing quantitative information regarding the presence of gaseous emboli in the middle cerebral artery.     

In vivo evaluation of a phosphorylcholine coated cardiopulmonary bypass circuit

A complete phosphorylcholine coated cardiopulmonary bypass circuit, including the Dideco D901 oxygenator, was tested for gas transfer, blood path resistance, and biocompatibility in a standardized setting. Blood compatibility was tested by measuring complement and platelet activation. Three dogs (mean body weight 28 +/- 3 kg) were placed on cardiopulmonary bypass at a flow rate of 600 mL/min during 6 hours. The animals were weaned from cardiopulmonary bypass and sacrificed electively after 7 days. Oxygen and carbon dioxide transfer were 26.6 +/- 2.4 mL/min and 33.0 +/- 1.9 mL/min, respectively. Mean pressure drop across the oxygenator was 52.6 +/- 0.2 mmHg. The respective baseline values for thromboxane B2, prostaglandin E2 and platelet factor 4 were 1817 +/- 283 pg/mL, 12783 +/- 2109 pg/mL, and 0.35 +/- 0.08 IU/mL. Thromboxane B2 and prostaglandin E2 increased slightly to 2881 +/- 868 pg/mL and 18083 +/- 3144 pg/mL at 30 minutes of bypass, whereas platelet factor 4 values remained stable curing the procedure. Concentrations of complement split products C5a were only mildly increased. After use scanning electron microscopy was performed on the inner housing, heat exchanger, and outer surface of the hollow fibers. No thrombi nor organized cellular deposits were found on any of the components. Phosphorylcholine coating of CPB seems to be very promising regarding platelet activation and complement activation.     

Experimental evaluation of the Medtronic Maxima Forté hollow fiber membrane oxygenator.

A new hollow fiber membrane oxygenator, the Medtronic Maxima Forté, was tested for gas transfer, blood path resistance and blood handling characteristics in a standardized setting with surviving animals. Three calves (mean body weight: 71 +/- 9.6 kg) were placed on cardiopulmonary bypass at a mean flow rate of 50 ml/kg/min for six hours. The circuit included the Maxima Forté oxygenator. The animals were weaned from cardiopulmonary bypass and then from the ventilator. After seven days, the animals were sacrificed electively. Physiologic blood gas values could be maintained throughout perfusion in all animals. Mean pressure drop through the oxygenator varied between 49 mmHg and 66 mmHg. The respective baseline values for red blood cell count, white blood cell count and platelets were 8.90 +/- 1.26 10(6)/mm3, 7.46 +/- 3.17 10(3)/mm3. and 680 +/- 216 10(3)/mm3. Red blood cell and platelet counts dropped slightly to 7.26 +/- 1.61 10(6)/mm3 and 400 +/- 126 10(3)/mm3 at the end of the bypass, whereas the white blood cell count increased up to 9.13 +/- 5.25 10(3)/mm3. All three cell lines returned to near their baseline values after seven days. Blood trauma evaluated as a function of plasma hemoglobin (plasma Hb) and lactate dehydrogenase (LDH) showed stable values during all the perfusion time. Both peaked at 24 hours before returning to their baseline values at seven days. LDH showed a statistically significant variation: 3255 +/- 693 IU at 24 hours versus 2029 +/- 287 IU at baseline (p = 0.04). The variation of plasma Hb was not statistically significant (93.5 +/- 7.7 mumol/l at 24 hours versus 77.3 +/- 52.3 mumol/l at baseline) indicating a weak effect of the perfusion on blood trauma. The Medtronic Maxima Forté hollow fiber membrane oxygenator offered good gas exchange capabilities, a low pressure drop, and low blood trauma over a prolonged perfusion time of six hours in this evaluation.     

A Newly Developed Silicone-Coated Membrane Oxygenator for Long-Term Cardiopulmonary Bypass and Cardiac Support

Abstract: The surface of polypropylene hollow fiber was successfully coated with a very thin (0.2 μm) silicone layer. Experimental studies were performed in long-term (6 h) normothermic cardiopulmonary bypass (CPB) using 10 goats. A conventional membrane oxygenator (Mera Exce-lung HPO-lSH, MERA, Tokyo, Japan) was used for 5 goats as a control (Group C) and a new silicone-coated membrane oxygenator, which is of the same construction as that of the one used for Group C, for 5 (Group S). The O₂transfer and CO₂removal functions showed the same ranges. In the other parameters, there were no differences between the 2 groups. As for hemolysis, however, the plasma free hemoglobin of Group S was lower than that of Group C. Currently, 3 chronic percutaneous cardiopulmonary support (PCPS) experimental models have been conducted, and there has been no evidence of thromboembo-lism or deterioration of the oxygenator. In conclusion, this new oxygenator is suitable not only for CPB, but also for long-term cardiac support.     

Development of a novel polyimide hollow-fiber oxygenator

We have developed a membrane oxygenator using a novel asymmetric polyimide hollow fiber. The hollow fibers are prepared using a dry/wet phase-inversion process. The gas transfer rates of O(2) and CO(2) through the hollow fibers are investigated in gas-gas and gas-liquid systems. The polyimide hollow fiber has an asymmetric structure characterized by the presence of macrovoids, and the outer diameter of the hollow fiber is 330 microm. It is found that the polyimide hollow-fiber oxygenator can enhance the gas transfer rates of O(2) and CO(2), and that the hollow fiber provides excellent blood compatibility in vitro and in vivo.