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

Silicone-Coated Polypropylene Hollow-Fiber Oxygenator: Experimental Evaluation and Preliminary Clinical Use Takatsugu Shimono, MD, Yu Shomura, MD, Iwao Hioki, MD, Akira Shimamoto, MD, Hironori Tenpaku, MD, Yasumi Maze, MD, Koji Onoda, MD, Motoshi Takao, MD, Hideto Shimpo, MD, and Isao Yada, MD Department of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, Tsu, Japan

Background. A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-mm 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.

H

Material and Methods

eparin-coated microporous polypropylene hollowfiber oxygenators are antithrombogenic and biocompatible [1–3] and are commonly used for cardiopulmonary bypass (CPB) and prolonged extracorporeal circulation such as extracorporeal membrane oxygenation (ECMO). However, because of serum leakage, there is still concern regarding their durability [4, 5]. Fifteen years ago, a silicone hollow-fiber membrane oxygenator was developed at our institute [6]. The gas permeability of this oxygenator was not optimal because of the thick walls of its fibers. Recently, a membrane oxygenator (Mera Excelung Binding Prim) composed of microporous polypropylene hollow fibers in which the blood contact surface is coated with a 0.2-mm ultrathin silicone layer (cyclosiloxane) based on IVOX fiber technology (Cardiopulmonics, Inc, Salt Lake City, UT) [7] was developed by Senko Medical Instrument Mfg Co, Ltd (Tokyo, Japan) (Fig 1). We evaluated gas transfer and hemolysis with the use of this oxygenator on venoarterial extracorporeal circulation in animals, after which we evaluated the oxygenator during clinical CPB.

Accepted for publication Dec 24, 1996. Address reprint requests to Dr Shimono, Department of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu Mie 514, Japan.

© 1997 by The Society of Thoracic Surgeons Published by Elsevier Science Inc

(Ann Thorac Surg 1997;63:1730 – 6) © 1997 by The Society of Thoracic Surgeons

Animal Experiments Ten venoarterial (V-A) bypass periods were conducted on mongrel dogs weighing 19 to 29 kg using Nikkiso HMP 17 centrifugal pumps (Nikkiso Co, Ltd. Tokyo, Japan). The silicone-coated microporous hollow fiber membrane oxygenator, Mera Excelung Binding Prim HPO 08 (membrane area, 0.8 m2; Senko Medical Instrument Mfg Co) was used in 5 dogs (group A), and a conventional microporous hollow-fiber membrane oxygenator, Mera Excelung HPO 08 (microporous polypropylene hollow fiber oxygenator; membrane area, 0.8 m2; Senko Medical Instrument Mfg Co) was used in the other 5 dogs (group B). The silicone-coated microporous polypropylene hollow-fiber membrane oxygenators, which are designed so that blood flow is directed externally to individual fibers and gas flow within individual fibers, have the same design as Mera Excelung HPO 08 except for the addition of an ultrathin silicone coating on the microporous polypropylene hollow fiber. All the dogs were anesthetized with intravenous injection of 25 mg/kg pentobarbital and 0.08 mg/kg pancuronium and were intubated. A 12F arterial catheter was inserted into the ascending aorta via the right common carotid artery and a 16F venous catheter was inserted into the superior vena cava via the right external jugular vein. A femoral artery catheter was placed for blood sampling 0003-4975/97/$17.00 PII S0003-4975(97)00119-7

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Fig 1. Findings of hollow fibers by scanning electron microscopy (35,000) before 53% reduction. (A) Uncoated polypropylene hollow fibers; many micropores are identified. (B) Silicone-coated polypropylene hollow fibers; micropores are completely covered with an ultrathin silicone layer.

and arterial pressure monitoring. Figure 2 shows a schematic drawing of an experimental V-A bypass circuit. The circuit was primed with 5 mL/kg of 20% mannitol, 5 mL/kg of 6% hydroxyethyl starch, lactated Ringer’s solution, and 200 mL of heparinized blood (100 units per

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100 mL) taken from blood donor dogs on the same day. The total priming volume was 500 mL. Whole blood activated clotting time was maintained at greater than 350 seconds for the duration of V-A bypass with the use of intermittent intravenous heparin administration. The blood flow rate was maintained at 750 mL/min. The inspired oxygen fraction of the gas flow was maintained at 1.0 and the gas flow/blood flow ratio at 1:1. The inspired oxygen fraction of the respiration of all the dogs was changed from 0.2 to 1.0 during V-A bypass to keep a constant level of venous oxygen tension. The V-A bypass periods in both groups were conducted under the same conditions. The V-A bypass periods were scheduled for 24 hours but were terminated 2 hours after the occurrence of severe plasma leakage, if it occurred. Preoxygenator and postoxygenator blood samples for blood gas analysis (GEM-STAT Blood Gas/Electrolyte Monitor; Mallinckrodt Sensor System Inc, Ann Arbor, MI) were obtained from inlet and outlet ports of the oxygenators at 30 minutes after the initiation of bypass, and every 2 hours until termination of bypass. Total hemoglobin level and hematocrit were measured simultaneously using the blood sampled from the inlet port just before the initiation of bypass, 30 minutes after the initiation of bypass, and every 2 hours until the termination of bypass. Oxygen and carbon dioxide transfer rates were calculated using standard formulas (Appendix 1). Plasma free hemoglobin was measured just before the initiation of bypass and every 2 hours after the initiation of bypass until the termination of bypass. Total protein level was measured just before the initiation of bypass, 2, 4, and 8 hours after the initiation of bypass, and at the termination of bypass in both groups. The levels of plasma free hemoglobin and total protein were corrected for hematocrit to eliminate the influence of hemodilution. All oxygenators were rinsed with 2 L of cold saline solution immediately after the termination of V-A bypass, and hollow fibers were sampled near the inlet portion of the oxygenators and fixed with 0.02% glutaraldehyde buffer solution. After completion of fixation, scanning electron microscopic examinations were conducted using GSM-6301 F (GEOL, Tokyo, Japan). All animals were treated in accordance with the “Guide for the Care and Use of Laboratory Animals” published by the National Institutes of Health (NIH publication 86-23, revised 1985).

Preliminary Clinical Use for Cardiopulmonary Bypass

Fig 2. Schematic drawing of an experimental circuit for venoarterial bypass.

The Mera Excelung Binding Prim HPO 15 H-C (membrane area, 1.2 m2) and Binding Prim HPO 25 H-C (membrane area, 1.8 m2) oxygenators (Senko Medical Instrument Mfg Co), which have the same design as Mera Excelung HPO 15 H and HPO 25 H except for the addition of an ultrathin silicone coating on the microporous polypropylene hollow fiber, were used for clinical CPB. From June 1996 to August 1996, 6 patients weighing 55 kg or less underwent CPB with Binding Prim HPO 15 H-C (group A) and from August 1996 to December 1996, 8 patients underwent CPB with Binding Prim HPO 25

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Fig 3. Representative finding of oxygenator at a termination of experimental venoarterial bypass. (A) There is no plasma leakage in group A. (B) There is severe plasma leakage in group B.

H-C (group B). All these patients had given informed consent. Total bypass flows of 2.5 mL z min21 z m22 were obtained using roller pump. The flows were calculated by one stroke volume of roller pump times the revolutions per minute. The inspired oxygen fraction was adjusted to keep the arterial oxygen tension level at more than 450 mm Hg, and the gas flow/blood flow ratio was adjusted to keep the arterial CO2 tension level between 35 mm Hg and 45 mm Hg according to the alpha-stat method. Whole blood activated clotting time was maintained at greater than 400 seconds for the entire duration of CPB with intermittent intravenous heparin administration. Preoxygenator and postoxygenator blood samples were obtained from inlet and outlet ports of the oxygenators at 30 minutes and 2 hours after the initiation of CPB. These blood samples underwent blood gas analysis by GEM-STAT Blood Gas/Electrolyte Monitor. In all patients, blood pressure was measured continuously at the inlet and outlet ports of the oxygenators using pressure transducers (Baxter Japan, Tokyo, Japan) and an amplifier/monitor (model WS 880R; Nihon Koden Inc, Tokyo, Japan). The pressure drop between the inlet and outlet ports of the oxygenators was calculated. Plasma free hemoglobin level was measured just before the initiation of bypass and 1 hour after the initiation of CPB. The levels of plasma free hemoglobin were corrected for hematocrit to eliminate the influence of hemodilution.

Statistical Analysis Data are presented as the mean 6 the standard deviation except where otherwise indicated. A paired Student’s t test was used to compare changes over time, and an unpaired Student’s t test was used to compare values

between groups A and B. The significant difference was defined as p less than 0.05.

Results Animal Experiments Severe plasma leakage (Fig 3) occurred in the 5 dogs in group B at 8 hours, 10 hours, 13 hours, 14 hours, and 16 hours (mean, 12.2 hours) after the initiation of bypass, and bypass was terminated at 10 hours, 12 hours, 15 hours, 16 hours, and 18 hours (mean, 14.2 hours), respectively. However, plasma leakage did not occur at any time during the 24-hour perfusion period in any experiment in group A, and all animals completed the 24 hours of bypass in group A. Changes in O2 transfer rate are shown in Figure 4. The mean O2 transfer rates in group A were 48.9 6 6.0 mL z min21 z m22 at 30 minutes after the initiation of bypass and 59.7 6 6.6 mL z min21 z m22 after 24 hours (p 5 0.0691). The mean O2 transfer rates in group B were 59.3 6 15.6 mL z min21 z m22 at 30 minutes after the initiation of bypass and 34.1 6 7.4 mL z min21 z m22 at the termination of V-A bypass (mean perfusion period of 14.2 hours) (p , 0.02). The mean venous O2 tension levels and inspired oxygen fraction in group A were 49.6 6 5.7 mm Hg and 0.21 at 30 minutes after the initiation of bypass and 35.8 6 5.1 mm Hg and 1.0 after 24 hours, respectively. The mean venous O2 tension level and inspired oxygen fraction in group B were 49.4 6 6.3 mm Hg and 0.22 6 0.05 at 30 minutes after the initiation of bypass and 29.6 6 3.4 mm Hg and 0.95 6 0.11 at the termination of V-A bypass, respectively. The mean O2 transfer rate after 24 hours in group A was significantly higher than the rate at termination of bypass in group B (p , 0.005). Figure 5 shows changes in the CO2 transfer rate during

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Fig 4. Changes in O2 transfer rate during experimental venoarterial bypass.

Fig 6. Changes in plasma free hemoglobin level during experimental venoarterial bypass.

bypass. The mean CO2 transfer rates in group A were 51.6 6 42.8 mL z min21 z m22 at 30 minutes after the initiation of bypass and 47.3 6 15.9 mL z min21 z m22 after 24 hours (p 5 0.2944). The mean CO2 transfer rates in group B were 70.0 6 23.8 mL z min21 z m22 at 30 minutes after the initiation of bypass and 21.7 6 14.6 mL z min21 z m22 at the termination of V-A bypass (p , 0.02). The mean CO2 transfer rate after 24 hours in group A was significantly higher than the rate at termination of V-A bypass in group B (p , 0.03). Changes in plasma free hemoglobin level are shown in Figure 6. The mean plasma free hemoglobin levels in group A were 31.8 6 22.1 mg/dL just before the initiation of bypass and 183.4 6 168.9 mg/dL after 24 hours. The mean plasma free hemoglobin levels in group B were 27.6 6 19.1 mg/dL just before the initiation of bypass and 134.0 6 148.7 mg/dL at the termination of bypass. There were no significant differences in the plasma free hemoglobin levels between group A and group B at 2, 4, 6, and 8 hours after the initiation of bypass. Changes in total protein level are shown in Figure 7. There was no significant difference between group A and

group B at any sampling point during the 8-hour perfusions. However, the total protein level at the termination of bypass in group B was significantly lower than the level at the termination of the bypass in group A (p , 0.005). Figure 8 shows representative appearances of hollow fibers by scanning electron microscopy. Figure 8A shows a silicone-coated polypropylene hollow fiber that was sampled from the oxygenator of group A, and Figure 8B shows an uncoated polypropylene hollow fiber that was sampled from the oxygenator of group B. There were a few scattered platelet adhesions on the surface of the silicone-coated hollow fiber (group A), whereas there were scattered aggregated platelet adhesions on the surface of the uncoated fiber (group B). Figure 8C shows the surface of the silicone-coated fiber under high magnification rate (35,000). No damage was observed on the silicone layers coated on polypropylene hollow fibers.

Fig 5. Changes in CO2 transfer rate during experimental venoarterial bypass.

Preliminary Clinical Use for Cardiopulmonary Bypass The preoperative patient characteristics and the types of procedures done are shown in Table 1. There were no

Fig 7. Changes in plasma total protein level during experimental venoarterial bypass.

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deaths or complications associated with use of this oxygenator on CPB in all patients. The air in the CPB circuit could be vented through the fibers of the oxygenator because of the ultrathin silicone layer, and it was easy to vent the air from the CPB circuit. Figure 9 shows changes in oxygen and carbon dioxide tensions during CPB. The arterial oxygen tension was 495 6 35 mm Hg at 90 minutes after the initiation of CPB in group A and 576 6 51 mm Hg in group B. The arterial carbon dioxide tension was 38.3 6 2.8 mm Hg at 90 minutes after the initiation of CPB in group A and 37.6 6 4.1 mm Hg in group B. The arterial oxygen and carbon dioxide tensions were maintained throughout CPB. Pressure loss between inlet and outlet ports of the oxygenators is shown in Figure 10. The pressure loss under the total bypass flow was kept at less than 170 mm Hg in group A and less than 160 mm Hg in group B. The plasma free hemoglobin levels were 8.5 6 8.3 mg/dL just before the initiation of CPB and 33.5 6 17.2 mg/dL 1 hour after the initiation of CPB in group A, and 13.4 6 5.9 mg/dL just before the initiation of CPB and 34.5 6 16.2 mg/dL 1 hour after in group B.

Comment

Fig 8. Representative findings of fibers by scanning electron microscopy. (A) The finding of a silicone-coated polypropylene hollow fiber sampled from group A used for 24-hour experimental venoarterial bypass; there were a few scattered platelet adhesions on the surface. (B) The finding of an uncoated polypropylene hollow fiber sampled from group B used for 18-hour experimental venoarterial bypass; there were scattered aggregated platelet adhesions on the surface. (C) The finding of a silicone-coated polypropylene hollow fiber sampled from group A used for 24-hour experimental venoarterial bypass; no damage of the silicone coating of the polypropylene hollow fiber was noted. (A, B 31,000, C 35,000; all before 53% reduction.)

The results of this study suggest that the silicone-coated hollow-fiber oxygenator allows for good gas transfer and durability. It showed a marked improvement over the previous generation of oxygenators. Previously, we developed a silicone hollow-fiber homogeneous membrane oxygenator composed of a silicone hollow fiber with an inner diameter of 200 mm, an outer diameter of 400 mm, and a wall thickness of 100 mm [6]. This oxygenator showed good durability. However, the pressure loss of this oxygenator was quite high because blood flowed through rather than outside the fibers, and its gas transfer ability was not adequate because of the thick homogeneous membrane of the silicone fiber. However, the blood contact surface of the polypropylene fiber of the Mera Excelung Binding Prim membrane oxygenator is coated with a 0.2-mm ultrathin silicone layer to retain good gas permeability of the polypropylene fibers. The technology of this silicone layer coating is based on the IVOX fiber technology (Cardiopulmonics, Inc) [7], and cyclosiloxane is coated by a plasma polymerization process (Surface Engineering Technologies, Division of Innerdyne, Inc; Salt Lake City, UT; US Patent 5463010) [8]. Durability has been a problem with microporous polypropylene hollow-fiber oxygenators with or without heparin coating because plasma leakage occurs with prolonged use of this type of oxygenator [4, 9]. Stolar and colleagues [5] have reported an aggregate experience for all categories (neonatal, pediatric, and cardiac) of ECMO from 1976 to 1993. They determined that oxygenator failures and cannula problems were the most frequent mechanical complications in cardiac ECMO. Recently, Muehrcke and colleagues [9] reported their experience with heparin-coated ECMO circuits with a microporous

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Table 1. Preoperative Patient Characteristics and Types of Proceduresa Variable Age (y) Sex Weight (kg) BSA (m2) CPB duration (min) Aortic cross-clamp time (min) Bypass flow (L/min) Bypass flow/BSA (L z min21 z m22) V/Q ratio Procedures

a

Group A (n 5 6)

Group B (n 5 8)

49.3 6 12.6 (range, 28 to 64) Male 2, female 4 50.1 6 3.9 (range, 44 to 55) 1.52 6 0.05 (range, 1.46 to 1.58) 101.3 6 36.8 (range, 78 to 173) 54.8 6 23.1 (range, 33 to 94) 3.8 6 0.2 (range, 3.6 to 4.2) 2.5 6 0.1 (range, 2.4 to 2.7) 0.82:1 to 0.55:1 ASD closure 3 MVR 1 AVR 1 CABG 1

56.2 6 8.1 (range, 43 to 68) Male 7, female 1 60.8 6 9.1 (range, 45 to 68) 1.65 6 0.15 (range, 1.43 to 1.85) 156.1 6 64.3 (range, 67 to 289) 82.0 6 43.2 (range, 22 to 132) 4.1 6 0.3 (range, 3.6 to 4.5) 2.5 6 0.1 (range, 2.4 to 2.8) 0.89:1 to 0.55:1 CABG 8

Where applicable, data are shown as the mean 6 the standard deviation.

ASD 5 atrial septal defect; cardiopulmonary bypass;

AVR 5 aortic valve replacement; MVR 5 mitral valve replacement;

BSA 5 body surface area; CABG 5 coronary artery bypass grafting; V/Q ratio 5 gas flow/blood flow of oxygenator.

CPB 5

polypropylene hollow-fiber oxygenator in 30 patients with cardiogenic shock. They demonstrated that oxygenator failure requiring oxygenator replacement occurred in 13 patients (43%); the mean number of oxygenator changes was 2.25 per patient.

Plasma leakage from the blood phase to the gas phase through the micropore of the fibers causes loss of the hydrophobic property of the membrane and leads to rapid deterioration of the gas transfer ability of the oxygenators. In this study, a significant amount of leakage occurred after 12.2 hours of perfusion using the conventional polypropylene hollow-fiber oxygenators. However, no plasma leakage was noted from any oxygenators employing the silicone-coated fiber during 24 hours of bypass. The oxygen transfer rate and the carbon dioxide transfer rate of the silicone-coated oxygenator were significantly better than the previous generation of silicone hollow-fiber membrane oxygenators. The exact mechanism responsible for plasma leakage is still not clear. Mottaghy and associates [10] assume that condensation of the slowly evaporating fluid fills the pores of a membrane and leads to a capillary effect that causes a continuous passage of plasma. Tamari and colleagues [11] suggest that albumin may alter the mi-

Fig 9. Changes in O2 and CO2 tension levels during clinical cardiopulmonary bypass (Pa 5 arterial tension; Pv 5 venous tension.)

Fig 10. Pressure loss through the oxygenators during clinical cardiopulmonary bypass.

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croporous membrane by acting as a wetting agent for the micropores, thus allowing plasma to leak. On the other hand, Montoya and co-workers [12] indicated that the absorption of phospholipids on the surface of microporous membranes is associated with the development of plasma leakage. Although it is controversial how the hydrophobic property of the membrane diminishes in clinical prolonged CPB or ECMO, it is obvious that the passage of liquid through micropores of the membrane causes plasma leakage and oxygenator failure. The scanning electron microscopic evaluation showed that the ultrathin silicone-coated layer of the Mera Excelung Binding Prim oxygenator was not destroyed after 24 hours of bypass. The thin silicone layer of this oxygenator completely prevented the passage of the plasma through the micropores, and the oxygenator maintained good gas permeability over a 24-hour period. The pressure loss of the HPO 15 H-C and the 25 H-C were around 150 mm Hg and 130 mm Hg against blood flow of 4 L/min, respectively. These values are relatively high due to the high pressure loss through the heat exchangers, compared with the values of previous microporous polypropylene oxygenators [13]. However, the pressure loss of this oxygenator is acceptable for clinical use because the hemolytic data of plasma free hemoglobin was maintained at low levels in both groups. A next model oxygenator with an improved heat exchanger is now under development. Some authors have reported that a heparin-coated extracorporeal circuit improved antithrombogenicity, platelet activation, and hemostasis [1–3, 14, 15]. Muehrcke and colleagues [9], however, have reported thrombus formation in the heart during ECMO using heparinbound surfaces. Silicone shows low platelet activation in in vitro experiments [16]. From findings using a scanning electron microscope, it appears that silicone coating reduces platelet adhesion on the surface of the hollow fibers, but the effects of this oxygenator on platelet activation, the coagulation system, and the complement system were not evaluated in this study. Theoretically the silicone layer could reduce the contact activation of the oxygenator because of its good biocompatibility and complete prevention of contact between blood and gas. Further evaluation of the biocompatibility of this oxygenator will be necessary. We conclude that this oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.

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5. 6. 7. 8. 9.

10. 11. 12. 13. 14.

15.

16.

long-term extracorporeal circulation using bioactive surfaces. ASAIO Trans 1989;35:635–7. Magovern GJ, Magovern JA, Benckart DH, et al. Extracorporeal membrane oxygenation: preliminary results in patients with postcardiotomy cardiogenic shock. Ann Thorac Surg 1994;57:1462–71. Nasu M, Miyamura K, Shikano K, et al. Evaluation of membrane oxygenator during long term ECMO: silicone hollow fiber and polypropylene hollow fiber membrane oxygenator. Jpn J Artif Organs 1984;13:586– 8. Stolar CJH, Delosh T, Bartlett RH. Extracorporeal life support organization 1993. ASAIO J 1993;39:976–9. Morimoto T. Development of a hollow fiber membrane oxygenator for long term extracorporeal membrane oxygenation. Nippon Kyobu Geka Gakkai Zasshi 1982;30:1351– 66. Bagley B, Bagley A, Henrie J, et al. Quantitative gas transfer into and out of circulating venous blood by means of an intravenacaval oxygenator. ASAIO Trans 1991;37:M413–5. Nakanishi H, Nishitani Y, Kuwana K, et al. Development of new oxygenator with cyclosiloxane coated polypropylene hollow fiber. Jpn J Artif Organs 1996;25:329–32. Muehrcke DD, McCarthy PM, Stewart RW, et al. Complications of extracorporeal life support systems using heparinbound surfaces: the risk of intracardiac clot formation. J Thorac Cardiovasc Surg 1995;110:843–51. Mottaghy K, Oedekoven B, Starmans H, et al. Technical aspects of plasma leakage prevention in microporous capillary membrane oxygenators. ASAIO Trans 1989;35:640–3. Tamari Y, Tortolani AJ, Lee-Sensiba KJ. Bloodless testing for microporous membrane oxygenator failure: a preliminary study. Int J Artif Organs 1991;14:154– 60. Montoya JP, Shanley CJ, Merz SI, Bartlett RH. Plasma leakage through microporous membranes: role of phospholipids. ASAIO J 1992;38:M399 – 405. Fried DW, DeBenedetto BN, Zombolas TL, Leo JJ. Clinical evaluation of the Medtronic Maxima Plus membrane oxygenator. Perfusion 1994;9:363–72. Nakajima T, Osawa S, Ogawa M, et al. Clinical study of platelet function and coagulation/fibrinolysis with Duraflo II heparin coated cardiopulmonary bypass equipment. ASAIO J 1996;42:301–5. Boonstra PW, Gu YJ, Akkerman C, Haan J, Huyzen R, van Oeveren W. Heparin coating of an extracorporeal circuit partly improves hemostasis after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1994;107:289–92. Gemmell CH, Ramirez SM, Yeo EL, Sefton MV. Platelet activation in whole blood by artificial surfaces: identification of platelet-derived microparticles and activated platelet binding to leukocytes as material-induced activation events. J Lab Clin Med 1995;125:276 – 87

Appendix 1. Gas Transfer Calculations Gas transfer was calculated using the following formulas:

Co2 5 ~1.36 3 Hb 3 %Sat/100! 1 ~0.0031 3 Po2! To2 5 Qc 3 ~Co2~pre!-Co2~post!!/100 3 1/MA Tco2 5 Qc 3 ~Cco2~pre!-Cco2~post!!/100 3 1/MA

This study was supported in part by grant from Senko Medical Instrument Mfg Co, Ltd, Tokyo, Japan.

References 1. Bindslev L, Gouda I, Inacio J, et al. Extracorporeal elimination of carbon dioxide using a surface-heparinized venovenous bypass system. ASAIO Trans 1986;32:530–2. 2. Mottaghy K, Oedekoven B, Poppel K, et al. Heparin free

Co2 5 oxygen content (mL/100 mL blood) To2 5 oxygen transfer (mL z min21 z m22) Tco2 5 carbon dioxide transfer (mL z min21 z m22) Hb 5 hemoglobin concentration (mg/dL) %Sat 5 oxyhemoglobin saturation (%) Po2 5 partial pressure of oxygen (mm Hg) Qc 5 extracorporeal blood flow (mL/min) Cco2 5 carbon dioxide content (mL/100 mL blood) MA 5 membrane area of oxygenator