- Email: [email protected]
Development of a membrane oxygenator: Overcoming blood diffusion limitation
Development of a membrane oxygenator: Overcoming blood diffusion limitation Robert H. Bartlett, M.D. (by invitation), Diane Kittredge, A.B. (by invitation), Bertram S. Noyes, Jr., S.M. (by invitation), Ralph H. Willard, III, A.B. (by invitation), and Philip A. Drinker, Ph.D. (by invitation), Boston, Mass. Sponsored by Dwight E. Harken, M.D., Boston, Mass.
JLrolonged extracorporeal oxygenation has potential application for respiratory sup port, organ preservation, and as an adjunct to lung transplantation. The adverse side effects produced by most current oxygenators, especially those which expose the blood directly to gas, limit their use to short periods, and have thus prevented full in vestigation of these concepts. Many of these problems, such as red cell damage or hemolysis, enzyme alteration, toxic plasma fac tors, and lung injury1 can be eliminated by interposing a gas permeable membrane be tween the blood and the gas phases.2 As experience was gained with experi mental membrane oxygenators, and im proved membranes of silicone rubber were developed, it became apparent that the limiting factor was not the gas transfer propFrom the Department of Surgery, Harvard Medical School at the Peter Bent Brigham Hospital, Boston, Mass. 02115, and the Department of Mechanical Engineer ing, Massachusetts Institute of Technology, Cambridge, Mass. This study was supported by the National Science Founda tion, the John A. Hartford Foundation, Inc., the U. S. Army Medical Research and Development Command, and a National Institutes of Health Re search Training Grant. Read at the Forty-ninth Annual Meeting of The American Association for Thoracic Surgery, San Francisco, Calif., Mar. 31, April 1 and 2, 1969.
erty of the membrane, but, rather, the diffusivity of oxygen in plasma.' In a gasto-gas diffusion system oxygen passes through 1 mil silicone rubber membrane at a rate of 1,210 c.c. per square meter per minute when the gradient is one atmos phere.1 ■ ■' However, when a film of deoxygenated blood as thin as 100 /x is intro duced on one side of the membrane, the transfer rate actually achieved falls ten fold.6 This dramatic reduction in gas trans fer capacity is due to the low diffusivity of oxygen in plasma. The plasma and red cells adjacent to the membrane become satu rated with oxygen rapidly, but the oxygen diffuses slowly through the rest of the blood. This film resistance imposed by a stable boundary layer has been a major limitation to development of membrane oxygenators. It has also inhibited interest in fabrication of very thin fabric-supported membranes, because, in gas-membrane-blood systems, essentially the same transfer rates can be achieved with the thicker and more dur able membranes which are now readily available.7 Two main approaches to the diffusion limitation have been taken. The first is to thin the blood film as much as possible by passage through narrow blood paths— 795
Journal of
796
Bartlett et al.
Thoracic and Cardiovascular Surgery
whether by forcing it through closely spaced flat membranes, 8 by pulsing oxygen on the gas side to periodically collapse the mem branes," or by directing it through bundles of capillary tubes.10 Functioning oxygenators achieving 10 to 30 per cent of theoret ical oxygen transfer rates have been de signed on these principles. However, the narrow blood passages have led to high perfusion pressure requirements, which can cause leakage or internal shunting, and large surface areas have produced problems of manifold design and flow distribution, resulting in stagnation areas and high anti coagulant requirements. The second main approach is to modify the flow pattern of the blood in such a way as to induce convective mixing, so that the plasma and cells at the membrane surface are constantly replaced. Most promising in this regard has been the work of Weissman and Mockros, 11 who demonstrated im proved gas transfer due to the secondary flows induced in blood flowing through a helically coiled silicone rubber tube. The effectiveness of such hydrodynamically in duced mixing is far greater than that which can be achieved by simple agitation of the membrane structure in a system in which the flow is laminar and inherently stable. 12 - 13 Fluid mechanics experiments in our lab oratory demonstrated a type of secondary flow which can greatly augment convective mixing and gas transfer in a tubular mem brane. This report presents the develop ment of an oxygenator, based on this prin ciple, and initial in vivo studies. Background We have previously described the sec ondary flows induced when a torus or end less loop of Tygon tubing undergoes torsional oscillation about its axis14 (Fig. 1). The motion of the tubing wall relative to the fluid creates a double set of helicoidal flows which are similar, but of opposite rotation to those seen when fluid flows through a curved conduit. These induced flows increase with tube wall velocity, which
Fig. 1. Secondary flows induced in an oscillating torus. (From Drinker et al. 1J )
is in turn related to the radius of the torus and the frequency and amplitude of oscilla tion. In spite of the vigorous convective mixing produced in blood, hemolysis was insignificant as long as any gas exposure was meticulously avoided. To gain access to this system with a con tinuous through-flow, a helix was substituted for the toroidal chamber. Ten-foot lengths of silicone membrane tubing, 5 mils wall thickness and VA in. internal diameter, were used. Each tube had a surface area of y1G square meter and a priming volume of 100 c.c. The membrane was supported by encasing it in a sleeve made from mosquito netting. The tubing was wrapped around a perforated cylinder to form a helix (Fig. 2 ) , with the inflow and outflow lines led to the center. The system was enclosed by a plastic cover, permitting control of the gas surrounding the membrane tubing. The
Volume 58 Number 6
Development of membrane oxygenator
797
December, 1969
Fig. 2. The oscillating helix of silicone membrane tubing. The plastic cover is not shown. (From Drinker et al. 11 )
cylinder was driven at different frequencies of oscillation by a variable speed motor, and it was possible to produce different ampli tudes by adjusting the position of the crank arm. In vitro testing was carried out with hu man blood which drained, by gravity, at controlled rates from a reservoir into the oxygenator. A roller pump returned the blood to the reservoir or into a collecting bag. Venous conditions were attained by recirculating the blood with 95 per cent N 2 -5 per cent C 0 2 in the oxygenator. For each test run, 100 per cent oxygen (humid ified at 37° C.) was supplied to the mem brane and the outflow blood was diverted to the collecting bag which created a single pass test system. Oxygen transfer was cal culated as the difference between the inflow and outflow oxygen content times the flow. The gas transfer results were the same over a wide variation of blood flow rates. The effect of the induced convective mixing is shown by relating the gas transfer to the wall velocity of the oscillating helix (Fig. 3). Gas transfer increases as tube wall ve locity increases, to the level of membrane capacity, which is 205 c.c. per square meter per minute for 5 mil silicone rubber, with a 670 mm. Hg gradient.4' 5
Methods and materials A series of in vivo experiments were then undertaken in order to allow simple and practical testing of the gas transfer properties of the device under continuous flow condi tions. These experiments were designed to test the oxygenator system, with no attempt to provide extracorporeal respiratory sup port. Anesthetized mongrel dogs (10 to 15 kilograms) were heparinized and placed on venovenous (femoral-jugular) or arteriovenous (femoral-femoral) partial bypass at flow rates ranging from 200 to 500 c.c. per minute. During the test periods, the animals were made hypoxic by 5 per cent oxygen breathing, or by rebreathing into a bag. The oxygenator was identical to that used in the in vitro tests, as were the measure ments and calculations. Several test runs were made on each animal over periods of 2 to 7 hours. Between tests the animal was kept on partial bypass through the oxygena tor, but allowed to breath room air. Results Fifty-one determinations were made on 8 dogs during venovenous partial bypass. The results are shown in Fig. 4. As before, oxygen transfer increased with tube wall velocity, approaching the level of membrane
Journal of
7 9 8 Bartlett et al.
Thoracic and Cardiovascular Surgery
205 200
OXYGEN TRANSFER (cc02/MVmin)
-5 mil Membrane Limitation-
100
50-
100 150 200 TUBE WALL VELOCITY (cm/sec)
Fig. 3. Effects of induced mixing on gas transfer. Results of in vitro testing (40 determinations, mean ± S.E.). (After Drinker et al. 14 )
tos 200
-5 mil Membrane Limitation-
1 \ it OXYGEN TRANSFER (cc02/M2/min)
100-
100 150 200 TUBE WALL VELOCITY (cm/sec)
Fig. 4. Effects of induced mixing on gas transfer. Results of in vivo testing (51 determinations, venovenous bypass, mean ± S.E.).
limitation, and indicating elimination of the boundary layer phenomenon in the in vivo situation. Similar results were obtained dur ing arteriovenous bypass. The dogs toler ated this small bypass well, and showed no gross pathologic changes when sacrificed. Oxygen transfer characteristics of the mem brane did not change with time, or from
animal to animal. The major problem in these experiments was mechanical failure of the membrane tubing after several hours of continuous operation. Discussion These studies have demonstrated that in duced convective mixing can overcome the
Volume 58 Number 6
Development of membrane oxygenator
7 99
December, 1969
blood diffusion limitation, and have led to the design of a system which appears feasi ble for extracorporeal oxygenation. The ad ditional mechanical energy necessary to gen erate the secondary flow pattern has minimal effect on blood components as long as a blood-gas interface is avoided. Clot ting was not a problem, up to 7 hours after a single heparin dose (2 mg./Kg.), indi cating that the rapid flow through the large bore tubing decreases the tendency to thrombus formation. The problems of handling very thin mem branes, and their disappointing performance in blood-diffusion limited systems, has tended to discourage serious efforts at mem brane improvement. We hope that the demonstration of a workable solution to the latter problem will stimulate renewed interest in the development of thinner, stronger membranes of silicone rubber or other polymer materials. Experiments are currently in progress to evaluate heparin requirements and possible adverse effects arising from prolonged use of the apparatus. Preliminary results are en couraging, with dogs maintained up to 5 days, without gas exchange, on partial by pass through a similar oxygenator system. Studies in many laboratories are demon strating that prolonged bypass through membrane systems is within reach.15-1G Routine survival is an essential objective to be realized before the efficacy of prolonged extracorporeal respiratory support can be established. Summary The gas transfer efficiency of membrane oxygenators can be improved by the super position of secondary flow patterns which create convective mixing within the blood. A membrane oxygenator has been devel oped in which the diffusion limitation is overcome by the secondary flows induced in a torsionally oscillating helical or toroidal chamber. These experiments have demon strated gas transfer rates which are limited only by the transfer capacity of the mem brane material. A prototype model tested
in vivo has shown that the design is prac tical and short periods of bypass are well tolerated. We are grateful for the assistance in these ex periments of Miss Lois C. Beveridge and Miss Virginia H. Vilnis. REFERENCES 1 Veith, F. J., Deysine, M., Nehlsen, S. L., Panossian, A., and Hagstrom, W. C : Pulmo nary Changes Common to Isolated Lung Perfusion, Venovenous Bypass, and Total Cardiopulmonary Bypass, Surg., Gynec. & Obst. 125: 1047-1057, 1967. 2 Dobell, A. R. C , Mitri, M., Galva, R., Sarkozy, E., and Murphy, D. R.: Biologic Evalu ation of Blood After Prolonged Recirculation Through Film and Membrane Oxygenators, Ann. Surg. 161: 617, 1965. 3 Galletti, P. M., and Brecher, G. A.: HeartLung Bypass, New York, 1962, Grune & Stratton, Inc., chapt. VII. 4 Robb, W. L.: Thin Silicone Membranes—Their Permeation Properties and Some Applications, General Electric Research and Development Center, Report N o . 65-C-031, Schenectady, New York, 1965. 5 Galletti, P. M., Sinder, M. T., and SilbertAidan, D.: Gas Permeability of Plastic Mem branes for Artificial Lungs, Med. Res. Engin. 5: 20, 1966. 6 Pierce, E. C , II, and Dibelius, N . R.: The Membrane Lung: Studies With a New High Permeability Co-polymer Membrane, Tr. Amer. Soc. Artif. Int. Organs. 14: 220-226, 1968. 7 Buckles, R. G., Merrill, E. W., and Gilliland, E. R.: An Analysis of Oxygen Absorption in a Tubular Membrane Oxygenator, Am. Inst. Chemical Eng. J. 14: 703-708, 1968. 8 Bramson, M. L., Osborn, J. J., Main, F . B., O'Brien, M. F., Wright, J. S., and Gerbode, F.: A New Disposable Oxygenator With Integral Heat
Exchange,
SURG. 50:
391,
J.
THORACIC
& CARDIOVAS.
1965.
9 Crescenzi, A. A., Hofstra, P. C , Sze, K. C , Foster, B. H., Claff, C. L., and Cooper, P.: Development of a Simplified Disposable Mem brane Oxygenator, Surg. Forum 10: 610, 1959. 10 De Filippi, R. P., Tompkins, F . C , Porter, J. H., Timmins, R. S., and Buckley, M. J.: T h e Capillary Membrane Oxygenator: in vitro and in vivo Gas Exchange Measurements, Tr. Amer. Soc. Artif. Int. Organs. 14: 236-241, 1968. 11 Weissman, M. H., and Mockros, L. F.: Gas Transfer to Blood Flowing in Coiled Circular
Journal of
8 0 0 Bartlett et al.
Thoracic and Cardiovascular Surgery
12
13
14
15
Tubes, J. Eng. Mechanics Div., Am. Soc. Civil Eng. 94: 857, 1968. Day, S. W., Crystal, D. K., Wagner, C. L., and Konnz, J. M.: Properties of Synthetic Mem branes in Extracorporeal Circuits, Am. J. Surg. 114: 214, 1967. Katsuhara, K., Yokosuka, T., and Sakakibara, S.: The Swing-Type Membrane Oxygenator: Gas Exchange Performance of the Swing Mo tion System, J. Surg. Res. 8: 245-252, 1968. Drinker, P. A., Bartlett, R. H., Bialer, R. M., and Noyes, B. S., Jr.: Augmentation of Mem brane Gas Transfer by Induced Secondary Flows, Surgery 66: 775, 1969. Kolobow, T., Zapol, W., Pierce, J. E., Keeley,
A. F., Replogle, R. L., and Haller, A.: Partial Extracorporeal Gas Exchange in Alert New born Lambs With a Membrane Artificial Lung Perfused Via an A-V Shunt for Periods up to 96 Hours, Tr. Amer. Soc. Artif. Int. Organs 14: 328-334, 1968. 16 Hill, J. D., Bramson, M. L., Hackel, A., Deal, C. W., Sanchez, P. A., Osborn, J. J., and Gerbode, F.: Laboratory and Clinical Studies During Prolonged Partial Extracorporeal Cir culation Using the Bramson Membrane Lung, Circulation 37: 139-145, 1968 (Suppl. 2). (For Discussion, see page 816)
JLrolonged extracorporeal oxygenation has potential application for respiratory sup port, organ preservation, and as an adjunct to lung transplantation. The adverse side effects produced by most current oxygenators, especially those which expose the blood directly to gas, limit their use to short periods, and have thus prevented full in vestigation of these concepts. Many of these problems, such as red cell damage or hemolysis, enzyme alteration, toxic plasma fac tors, and lung injury1 can be eliminated by interposing a gas permeable membrane be tween the blood and the gas phases.2 As experience was gained with experi mental membrane oxygenators, and im proved membranes of silicone rubber were developed, it became apparent that the limiting factor was not the gas transfer propFrom the Department of Surgery, Harvard Medical School at the Peter Bent Brigham Hospital, Boston, Mass. 02115, and the Department of Mechanical Engineer ing, Massachusetts Institute of Technology, Cambridge, Mass. This study was supported by the National Science Founda tion, the John A. Hartford Foundation, Inc., the U. S. Army Medical Research and Development Command, and a National Institutes of Health Re search Training Grant. Read at the Forty-ninth Annual Meeting of The American Association for Thoracic Surgery, San Francisco, Calif., Mar. 31, April 1 and 2, 1969.
erty of the membrane, but, rather, the diffusivity of oxygen in plasma.' In a gasto-gas diffusion system oxygen passes through 1 mil silicone rubber membrane at a rate of 1,210 c.c. per square meter per minute when the gradient is one atmos phere.1 ■ ■' However, when a film of deoxygenated blood as thin as 100 /x is intro duced on one side of the membrane, the transfer rate actually achieved falls ten fold.6 This dramatic reduction in gas trans fer capacity is due to the low diffusivity of oxygen in plasma. The plasma and red cells adjacent to the membrane become satu rated with oxygen rapidly, but the oxygen diffuses slowly through the rest of the blood. This film resistance imposed by a stable boundary layer has been a major limitation to development of membrane oxygenators. It has also inhibited interest in fabrication of very thin fabric-supported membranes, because, in gas-membrane-blood systems, essentially the same transfer rates can be achieved with the thicker and more dur able membranes which are now readily available.7 Two main approaches to the diffusion limitation have been taken. The first is to thin the blood film as much as possible by passage through narrow blood paths— 795
Journal of
796
Bartlett et al.
Thoracic and Cardiovascular Surgery
whether by forcing it through closely spaced flat membranes, 8 by pulsing oxygen on the gas side to periodically collapse the mem branes," or by directing it through bundles of capillary tubes.10 Functioning oxygenators achieving 10 to 30 per cent of theoret ical oxygen transfer rates have been de signed on these principles. However, the narrow blood passages have led to high perfusion pressure requirements, which can cause leakage or internal shunting, and large surface areas have produced problems of manifold design and flow distribution, resulting in stagnation areas and high anti coagulant requirements. The second main approach is to modify the flow pattern of the blood in such a way as to induce convective mixing, so that the plasma and cells at the membrane surface are constantly replaced. Most promising in this regard has been the work of Weissman and Mockros, 11 who demonstrated im proved gas transfer due to the secondary flows induced in blood flowing through a helically coiled silicone rubber tube. The effectiveness of such hydrodynamically in duced mixing is far greater than that which can be achieved by simple agitation of the membrane structure in a system in which the flow is laminar and inherently stable. 12 - 13 Fluid mechanics experiments in our lab oratory demonstrated a type of secondary flow which can greatly augment convective mixing and gas transfer in a tubular mem brane. This report presents the develop ment of an oxygenator, based on this prin ciple, and initial in vivo studies. Background We have previously described the sec ondary flows induced when a torus or end less loop of Tygon tubing undergoes torsional oscillation about its axis14 (Fig. 1). The motion of the tubing wall relative to the fluid creates a double set of helicoidal flows which are similar, but of opposite rotation to those seen when fluid flows through a curved conduit. These induced flows increase with tube wall velocity, which
Fig. 1. Secondary flows induced in an oscillating torus. (From Drinker et al. 1J )
is in turn related to the radius of the torus and the frequency and amplitude of oscilla tion. In spite of the vigorous convective mixing produced in blood, hemolysis was insignificant as long as any gas exposure was meticulously avoided. To gain access to this system with a con tinuous through-flow, a helix was substituted for the toroidal chamber. Ten-foot lengths of silicone membrane tubing, 5 mils wall thickness and VA in. internal diameter, were used. Each tube had a surface area of y1G square meter and a priming volume of 100 c.c. The membrane was supported by encasing it in a sleeve made from mosquito netting. The tubing was wrapped around a perforated cylinder to form a helix (Fig. 2 ) , with the inflow and outflow lines led to the center. The system was enclosed by a plastic cover, permitting control of the gas surrounding the membrane tubing. The
Volume 58 Number 6
Development of membrane oxygenator
797
December, 1969
Fig. 2. The oscillating helix of silicone membrane tubing. The plastic cover is not shown. (From Drinker et al. 11 )
cylinder was driven at different frequencies of oscillation by a variable speed motor, and it was possible to produce different ampli tudes by adjusting the position of the crank arm. In vitro testing was carried out with hu man blood which drained, by gravity, at controlled rates from a reservoir into the oxygenator. A roller pump returned the blood to the reservoir or into a collecting bag. Venous conditions were attained by recirculating the blood with 95 per cent N 2 -5 per cent C 0 2 in the oxygenator. For each test run, 100 per cent oxygen (humid ified at 37° C.) was supplied to the mem brane and the outflow blood was diverted to the collecting bag which created a single pass test system. Oxygen transfer was cal culated as the difference between the inflow and outflow oxygen content times the flow. The gas transfer results were the same over a wide variation of blood flow rates. The effect of the induced convective mixing is shown by relating the gas transfer to the wall velocity of the oscillating helix (Fig. 3). Gas transfer increases as tube wall ve locity increases, to the level of membrane capacity, which is 205 c.c. per square meter per minute for 5 mil silicone rubber, with a 670 mm. Hg gradient.4' 5
Methods and materials A series of in vivo experiments were then undertaken in order to allow simple and practical testing of the gas transfer properties of the device under continuous flow condi tions. These experiments were designed to test the oxygenator system, with no attempt to provide extracorporeal respiratory sup port. Anesthetized mongrel dogs (10 to 15 kilograms) were heparinized and placed on venovenous (femoral-jugular) or arteriovenous (femoral-femoral) partial bypass at flow rates ranging from 200 to 500 c.c. per minute. During the test periods, the animals were made hypoxic by 5 per cent oxygen breathing, or by rebreathing into a bag. The oxygenator was identical to that used in the in vitro tests, as were the measure ments and calculations. Several test runs were made on each animal over periods of 2 to 7 hours. Between tests the animal was kept on partial bypass through the oxygena tor, but allowed to breath room air. Results Fifty-one determinations were made on 8 dogs during venovenous partial bypass. The results are shown in Fig. 4. As before, oxygen transfer increased with tube wall velocity, approaching the level of membrane
Journal of
7 9 8 Bartlett et al.
Thoracic and Cardiovascular Surgery
205 200
OXYGEN TRANSFER (cc02/MVmin)
-5 mil Membrane Limitation-
100
50-
100 150 200 TUBE WALL VELOCITY (cm/sec)
Fig. 3. Effects of induced mixing on gas transfer. Results of in vitro testing (40 determinations, mean ± S.E.). (After Drinker et al. 14 )
tos 200
-5 mil Membrane Limitation-
1 \ it OXYGEN TRANSFER (cc02/M2/min)
100-
100 150 200 TUBE WALL VELOCITY (cm/sec)
Fig. 4. Effects of induced mixing on gas transfer. Results of in vivo testing (51 determinations, venovenous bypass, mean ± S.E.).
limitation, and indicating elimination of the boundary layer phenomenon in the in vivo situation. Similar results were obtained dur ing arteriovenous bypass. The dogs toler ated this small bypass well, and showed no gross pathologic changes when sacrificed. Oxygen transfer characteristics of the mem brane did not change with time, or from
animal to animal. The major problem in these experiments was mechanical failure of the membrane tubing after several hours of continuous operation. Discussion These studies have demonstrated that in duced convective mixing can overcome the
Volume 58 Number 6
Development of membrane oxygenator
7 99
December, 1969
blood diffusion limitation, and have led to the design of a system which appears feasi ble for extracorporeal oxygenation. The ad ditional mechanical energy necessary to gen erate the secondary flow pattern has minimal effect on blood components as long as a blood-gas interface is avoided. Clot ting was not a problem, up to 7 hours after a single heparin dose (2 mg./Kg.), indi cating that the rapid flow through the large bore tubing decreases the tendency to thrombus formation. The problems of handling very thin mem branes, and their disappointing performance in blood-diffusion limited systems, has tended to discourage serious efforts at mem brane improvement. We hope that the demonstration of a workable solution to the latter problem will stimulate renewed interest in the development of thinner, stronger membranes of silicone rubber or other polymer materials. Experiments are currently in progress to evaluate heparin requirements and possible adverse effects arising from prolonged use of the apparatus. Preliminary results are en couraging, with dogs maintained up to 5 days, without gas exchange, on partial by pass through a similar oxygenator system. Studies in many laboratories are demon strating that prolonged bypass through membrane systems is within reach.15-1G Routine survival is an essential objective to be realized before the efficacy of prolonged extracorporeal respiratory support can be established. Summary The gas transfer efficiency of membrane oxygenators can be improved by the super position of secondary flow patterns which create convective mixing within the blood. A membrane oxygenator has been devel oped in which the diffusion limitation is overcome by the secondary flows induced in a torsionally oscillating helical or toroidal chamber. These experiments have demon strated gas transfer rates which are limited only by the transfer capacity of the mem brane material. A prototype model tested
in vivo has shown that the design is prac tical and short periods of bypass are well tolerated. We are grateful for the assistance in these ex periments of Miss Lois C. Beveridge and Miss Virginia H. Vilnis. REFERENCES 1 Veith, F. J., Deysine, M., Nehlsen, S. L., Panossian, A., and Hagstrom, W. C : Pulmo nary Changes Common to Isolated Lung Perfusion, Venovenous Bypass, and Total Cardiopulmonary Bypass, Surg., Gynec. & Obst. 125: 1047-1057, 1967. 2 Dobell, A. R. C , Mitri, M., Galva, R., Sarkozy, E., and Murphy, D. R.: Biologic Evalu ation of Blood After Prolonged Recirculation Through Film and Membrane Oxygenators, Ann. Surg. 161: 617, 1965. 3 Galletti, P. M., and Brecher, G. A.: HeartLung Bypass, New York, 1962, Grune & Stratton, Inc., chapt. VII. 4 Robb, W. L.: Thin Silicone Membranes—Their Permeation Properties and Some Applications, General Electric Research and Development Center, Report N o . 65-C-031, Schenectady, New York, 1965. 5 Galletti, P. M., Sinder, M. T., and SilbertAidan, D.: Gas Permeability of Plastic Mem branes for Artificial Lungs, Med. Res. Engin. 5: 20, 1966. 6 Pierce, E. C , II, and Dibelius, N . R.: The Membrane Lung: Studies With a New High Permeability Co-polymer Membrane, Tr. Amer. Soc. Artif. Int. Organs. 14: 220-226, 1968. 7 Buckles, R. G., Merrill, E. W., and Gilliland, E. R.: An Analysis of Oxygen Absorption in a Tubular Membrane Oxygenator, Am. Inst. Chemical Eng. J. 14: 703-708, 1968. 8 Bramson, M. L., Osborn, J. J., Main, F . B., O'Brien, M. F., Wright, J. S., and Gerbode, F.: A New Disposable Oxygenator With Integral Heat
Exchange,
SURG. 50:
391,
J.
THORACIC
& CARDIOVAS.
1965.
9 Crescenzi, A. A., Hofstra, P. C , Sze, K. C , Foster, B. H., Claff, C. L., and Cooper, P.: Development of a Simplified Disposable Mem brane Oxygenator, Surg. Forum 10: 610, 1959. 10 De Filippi, R. P., Tompkins, F . C , Porter, J. H., Timmins, R. S., and Buckley, M. J.: T h e Capillary Membrane Oxygenator: in vitro and in vivo Gas Exchange Measurements, Tr. Amer. Soc. Artif. Int. Organs. 14: 236-241, 1968. 11 Weissman, M. H., and Mockros, L. F.: Gas Transfer to Blood Flowing in Coiled Circular
Journal of
8 0 0 Bartlett et al.
Thoracic and Cardiovascular Surgery
12
13
14
15
Tubes, J. Eng. Mechanics Div., Am. Soc. Civil Eng. 94: 857, 1968. Day, S. W., Crystal, D. K., Wagner, C. L., and Konnz, J. M.: Properties of Synthetic Mem branes in Extracorporeal Circuits, Am. J. Surg. 114: 214, 1967. Katsuhara, K., Yokosuka, T., and Sakakibara, S.: The Swing-Type Membrane Oxygenator: Gas Exchange Performance of the Swing Mo tion System, J. Surg. Res. 8: 245-252, 1968. Drinker, P. A., Bartlett, R. H., Bialer, R. M., and Noyes, B. S., Jr.: Augmentation of Mem brane Gas Transfer by Induced Secondary Flows, Surgery 66: 775, 1969. Kolobow, T., Zapol, W., Pierce, J. E., Keeley,
A. F., Replogle, R. L., and Haller, A.: Partial Extracorporeal Gas Exchange in Alert New born Lambs With a Membrane Artificial Lung Perfused Via an A-V Shunt for Periods up to 96 Hours, Tr. Amer. Soc. Artif. Int. Organs 14: 328-334, 1968. 16 Hill, J. D., Bramson, M. L., Hackel, A., Deal, C. W., Sanchez, P. A., Osborn, J. J., and Gerbode, F.: Laboratory and Clinical Studies During Prolonged Partial Extracorporeal Cir culation Using the Bramson Membrane Lung, Circulation 37: 139-145, 1968 (Suppl. 2). (For Discussion, see page 816)