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Cortiva BioActive Surface

Biocompatible Surface for Cardiopulmonary Bypass Devices

  • cortiva-bioactive-surface

Overview

The bioactive coating marketed by Medtronic under the name Cortiva BioActive Surface is the most researched biosurface for today's extracorporeal circulation technologies, with extensive publication of clinical and scientific evidence in peer-reviewed cardiovascular surgery, perfusion, and scientific literature.

THROMBORESISTANCE AND ENHANCED BLOOD COMPATIBILITY

Cortiva BioActive Surface is a durable, non-leaching End Point Attached heparin coating technology that enhances blood compatibility and provides thromboresistant blood-contacting surfaces for cardiopulmonary bypass circuit devices. This heparin coating has the largest body of peer-reviewed clinical and scientific evidence of any biocompatible surface used for cardiopulmonary bypass devices today. From pediatric patients to adults, Cortiva BioActive Surface is an important component of routine as well as complex extracorporeal circulation procedures.

End Point Attached Heparin Technology

1. Prime Coat

Alternating layers of cationic and anionic polymers are deposited on the device surface via electrostatic adsorption to provide a consistent substrate that allows the Cortiva BioActive Surface to be applied to a variety of device materials, including plastics and metals.

2a. End Point Attachment Bonding Process

Heparin is bonded to the surface using End Point Attachment. End Point Attached heparin molecules are oriented to the blood in a manner similar to that of heparan sulfate naturally found on the vascular endothelium. The heparin molecules protrude into the blood, allowing their active sequences to interact with the blood. End Point Attachment of heparin results in a strong, covalent bond so that heparin does not leach from the surface during extracorporeal circulation in the presence of blood or albumin.

2b. Potent Surface Anticoagulant Activity

The End Point Attached heparin active sequence binds to antithrombin (AT) in the blood, resulting in a heparin-AT complex that has a much higher affinity for blood coagulation factors than AT alone. Attachment of activated blood coagulation factors to AT forms harmless inactive complexes that are no longer available to participate in or trigger other events in the coagulation cascade. For example, the activated blood coagulation factor II (thrombin) binds to the heparin-AT complex and subsequently becomes inactivated.

2c. Intact End Point Attached Heparin Molecule

The End Point Attached heparin molecule is not consumed by this cycle and remains bonded, intact, to the material surface. Its anticoagulant active sequence is then free to attach to another AT molecule.

2c. Neutral AT-Thrombin Complex

AT-coagulation factor complexes are then released from the immobilized heparin and are swept away from the surface by the flowing blood. These complexes are eventually metabolized by the body.

Extensive Peer-reviewed Clinical and Scientific Evidence

cortiva-surface-flowchart

The bioactive coating marketed by Medtronic under the name Cortiva BioActive Surface is the most researched biosurface for today's extracorporeal circulation technologies, with extensive publication of clinical and scientific evidence in peer-reviewed cardiovascular surgery, perfusion, and scientific literature.

  • Less blood product use1,2,3,4,5,6,7
  • Less perioperative blood loss5,6,7,8,9,10,11,12
  • Shorter ventilator time3,6,9,13,14
  • Shorter hospital length of stay2,3,9
  • Less postoperative body temperature rise9,15
  • Significantly greater urine output during CPB13
  • Lower costs, as related to improved clinical outcomes3
  • Less negative impact on the body's defense systems, including the:
    • contact system16,17,18,19,20,21
    • coagulation system11,17,22,23,24,25,26,27,28,29,30,31
    • fibrinolytic system6,23,32,33
    • complement system10,12,14,22,29,33,34,35,36,37,38,39,40
    • cytokine proteins14,26,33,35,39,40
  • Reduced impact on the blood's formed elements, including:
    • platelets10,17,26,29,30,37,39,41
    • red blood cells11,16,20,25,32,35,42
    • leukocytes14,20,26,29,30,33,36,37,38

Note: Citations with bold font represent clinical studies. Citations with standard font represent experimental in vitro and in vivo studies.

Why Use Biocompatible Surfaces for Extracorporeal Circulation Circuits?

Blood is naturally compatible with vascular endothelium, not artificial surfaces.

  • Blood is compatible with the healthy vascular endothelium, a single layer of cells that lines all blood vessels and the heart.
  • The endothelium plays an active biological role in maintaining homeostasis, or a balance, among the various body defense systems in a manner that simultaneously provides a state of readiness and avoids the trigger of adverse responses.43, 44
  • The blood-contacting surfaces of endothelial cells are highly negatively charged, a characteristic that may repel the negatively charged platelets and be important in limiting the hemostatic reaction.45

Blood recognizes the extracorporeal circuit surfaces as “foreign”, triggering coagulation and inflammatory events that may lead to adverse patient outcomes.

cardiopulm-prods-whyuse

Responses to Blood-Material Contact

  • Within seconds of blood exposure to artificial, non-endothelial surfaces, there is a rapid adsorption of proteins from the blood onto the surface of the foreign material.46
  • Adsorption onto a surface may result in protein denaturation, such as the denaturation of adsorbed fibrinogen, and ultimately lead to activation of the plasma proteolytic systems.43 Subsequent events, including cell adhesion, are mediated by the adsorbed protein layer.43
  • The blood’s formed elements and other specific protein groups in the blood that are associated with the body’s defense systems may then interact with the material and its new protein layer.43, 44
  • Ultimately, the biological reactions associated with the defense systems may affect the heart, lungs, brain and other organs, causing conditions that have been described as the “systemic inflammatory response syndrome.” 47

Biocompatible surfaces for Medtronic extracorporeal circulation technologies mimic critical characteristics of the vascular endothelium.

  • These coatings mitigate the foreign body response that occurs when blood comes in contact with non-endothelial surfaces.
  • Around the world, leading cardiovascular surgery teams adopt coatings surfaces offered by Medtronic as a critical component of comprehensive, multi-modal strategies to achieve the best possible outcomes for their patients undergoing extracorporeal circulation.

Warnings: A strict anticoagulation protocol should be followed and anticoagulation should be routinely monitored during all procedures. The benefits of extracorporeal support must be weighed against the risk of systematic anticoagulation and must be assessed by the prescribing physician.

Caution: Federal law (USA) restricts devices coated with Cortiva BioActive Surface, Trillium Biosurface and Balance Biosurface to sale by or on the order of a physician. For a complete listing of indications, contraindications, precautions and warnings, please refer to the Instructions for Use which accompany each product.

Trillium Biosurface technology is licensed under agreement from BioInteractions, Limited.

1

Kreisler KR, Vance RA , Cruzzavala J, Mahnken JD. Heparin-bonded cardiopulmonary bypass circuits reduce the rate of red blood cell transfusion during elective coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2005;19(5):608-611.

2

Mahoney CB , Lemole GM. Transfusion after coronary artery bypass surgery: the impact of heparin bonded circuits. Eur J Cardiothorac Surg. 1999;16(2):206-210.

3

Mahoney CB . Heparin-bonded circuits: clinical outcomes and costs. Perfusion. 1998;13(3):192-204.

4

Mahoney CB . Blood use: The impact of coated circuits in routine cardiac surgery. Heart Surg Forum. 2004;7(6):E619.

5

Svenmarker S, Sandstrom E, Karlsson T, et al. Neurological and general outcome in low-risk coronary artery bypass patients using heparin coated circuits. Eur J Cardiothorac Surg. 2001;19(1):47-53.

6

Saenz A, Larranaga G, Alvarez L, et al. Heparin-coated circuit in coronary surgery. A clinical study. Eur J Cardiothorac Surg. 1996;10(1):48-53.

7

Belboul A, al-Khaja N. Does heparin coating improve biocompatibility? A study on complement, blood cells and postoperative morbidity during cardiac surgery. Perfusion. 1997;12(6):385-391.

8

Svenmarker S, Haggmark S, Jansson E, et al. Use of heparin-bonded circuits in cardiopulmonary bypass improves clinical outcome. Scand Cardiovasc J. 2002;36(4):241-246.

9

Svenmarker S, Sandstrom E, Karlsson T, et al. Clinical effects of the heparin coated surface in cardiopulmonary bypass. Eur J Cardiothorac Surg. 1997;11(5):957-964.

10

Fukutomi M, Kobayashi S, Niwaya K, Hamada Y, Kitamura S. Changes in platelet, granulocyte, and complement activation during cardiopulmonary bypass using heparin-coated equipment. Artif Organs. 1996;20(7):767-776.

11

Borowiec J, Thelin S, Bagge L, Hultman J, Hansson HE. Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose. Scand J Thorac Cardiovasc Surg. 1992;26(3):177-185.

12

Videm V, Svennevig JL, Fosse E, Semb G, Osterud A, Mollnes TE .Reduced complement activation with heparin-coated oxygenator and tubings in coronary bypass operations. J Thorac Cardiovasc Surg. 1992;103(4):806-813.

13

Miyaji K, Hannan RL, Ojito J, Jacobs JP, White JA, Burke RP. Heparin coated cardiopulmonary bypass circuit: clinical effects in pediatric cardiac surgery. J Card Surg. 2000;15(3):194-198.

14

Ashraf S, Tian Y, Cowan D, Entress A, Martin PG, Watterson KG. Release of proinflammatory cytokines during pediatric cardiopulmonary bypass: heparin-bonded versus nonbonded oxygenators. Ann Thorac Surg. 1997;64(6):1790-1794.

15

Schreurs HH, Wijers MJ, Gu YJ, et al. Heparin-coated bypass circuits: effects on inflammatory response in pediatric cardiac operations. Ann Thorac Surg. 1998;66(1):166-171.

16

Wendel HP, Scheule AM , Eckstein FS , Ziemer G. Haemocompatibility of paediatric membrane oxygenators with heparin-coated surfaces. Perfusion. 1999;14(1):21-28.

17

Wendel HP, Weber N, Ziemer G. Increased adsorption of high molecular weight kininogen to heparin-coated artificial surfaces and correlation to hemocompatibility. Immunopharmacology. 1999;43(2-3):149-

18

Sanchez J, Elgue G, Riesenfeld J, Olsson P. Control of contact activation on end-point immobilized heparin: the role of antithrombin and the specific antithrombin-binding sequence. J Biomed Mater Res. 1995;29(5):655-661.

19

Wendel HP, Heller W, Gallimore MJ. Heparin-coated devices and high-dose aprotinin optimally inhibit contact system activation in an in vitro cardiopulmonary bypass model. Immunopharmacology. 1996;32 (1-3):128-130.

20

Wendel HP, Heller W, Gallimore MJ, Hoffmeister HE. Heparin-coated oxygenators significantly reduce contact system activation in an in vitro cardiopulmonary bypass model. Blood Coagul Fibrinolysis. 1994;5(5):673-678.

21

Elgue G, Sanchez J, Egberg N, Olsson P, Riesenfeld J. Effect of surface immobilized heparin on the activation of adsorbed factor XII. Artif Organs. 1993;17(8):721-726.

22

Heyer EJ, Lee KS, Manspeizer HE, et al. Heparin-bonded cardiopulmonary bypass circuits reduce cognitive dysfunction. J Cardiothorac Vasc Anesth. 2002;16(1):37-42.

23

Eisses MJ, Seidel K, Aldea GS, Chandler WL. Reducing hemostatic activation during cardiopulmonary bypass: a combined approach. Anesth Analg. 2004;98(5):1208-1216, table.

24

Mueller XM, Tevaearai HT, Jegger D, Augstburger M, Goddar G, von Segesser LK. Antithrombotic properties of Trillium coated connectors. ASAIO J. 2002;48(5):483-486.

25

Shigemitsu O, Hadama T, Takasaki H, et al. Biocompatibility of a heparin bonded membrane oxygenator ([the bioactive surface currently offered by Medtronic as Cortiva]MAXIMA) during the first 90 minutes of cardiopulmonary bypass: clinical comparison with the conventional system. Artif Organs. 94;18(12):936-941.

26

Weber N, Wendel HP, Ziemer G. Hemocompatibility of heparin coated surfaces and the role of selective plasma protein adsorption. Biomaterials. 2002;23(2):429-439.

27

Weerwind PW, van der Veen V, Lindhout T, de Jong DS , Cahalan PT. Ex vivo testing of heparin-coated extracorporeal circuits: bovine experiments. Int J Artif Organs. 1998;21(5):291-298.

28

Videm V, Mollnes TE , Garred P, Svennevig JL. Biocompatibility of extracorporeal circulation. In vitro comparison of heparin-coated and uncoated oxygenator circuits. J Thorac Cardiovasc Surg. 1991;101(4):654-660.

29

Munch K, Wolf MF , Gruffaz P, et al. Use of simple and complex in vitro models for multiparameter characterization of human blood-material/device interactions. J Biomater Sci Polym Ed. 2000;11(11):1147-1163.

30

Bannan S, Danby A, Cowan D, Ashraf S, Gesinde M, Martin P. Cell activation and thrombin generation in heparin bonded cardiopulmonary bypass circuits using a novel in vitro model. Eur J Cardiothorac Surg. 1997;12(2):268-275.

31

Elgue G, Blomback M, Olsson P, Riesenfeld J. On the mechanism of coagulation inhibition on surfaces with end point immobilized heparin. Thromb Haemost. 1993;70(2):289-293.

32

Jensen E, Andreasson S, Bengtsson A, et al. Changes in hemostasis during pediatric heart surgery: impact of a biocompatible heparincoated perfusion system. Ann Thorac Surg. 2004;77(3):962-967.

33

Lindholm L, Westerberg M, Bengtsson A, Ekroth R, Jensen E, Jeppsson A. A closed perfusion system with heparin coating and centrifugal pump improves cardiopulmonary bypass biocompatibility in elderly patients. Ann Thorac Surg. 2004;78(6):2131-2138.

34

Baufreton C, Allain P, Chevailler A, et al. Brain injury and neuropsychological outcome after coronary artery surgery are affected by complement activation. Ann Thorac Surg. 2005;79(5):1597-1605.

35

Olsson C, Siegbahn A, Henze A, et al. Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in pediatric heart surgery. Scand Cardiovasc J. 2000;34(1):33-40.

36

van den Goor J, Nieuwland R, van den Brink A, et al. Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response. Eur J CardiothoracSurg. 2004;26(5):926-931.

37

Moen O, Fosse E, Dregelid E, et al. Centrifugal pump and heparin coating improves Cardiopulmonary bypass biocompatibility. Ann Thorac Surg. 1996;62(4):1134-1140.

38

Jensen E, Andreasson S, Bengtsson A, et al. Influence of two different perfusion system on Inflammatory response in pediatric heart surgery. Ann Thorac Surg. 2003;75(3):919-925.

39

Kagisaki K, Masai T, Kadoba K, et al. Biocompatibility of heparin coated circuits in pediatric cardiopulmonary bypass. Artif Organs. 1997;21(7):836-840.

40

Grossi EA , Kallenbach K, Chau S, Derivaux CC , Aguinaga MG, Steinberg BM , Kim D, Iyer S, Tayyarah M, Artman M, Galloway AC , Colvin SB . Impact of heparin bonding on pediatric cardiopulmonary bypass: a prospective randomized study. Ann Thorac Surg. 2000;70(1):191-196.

41

Mollnes TE , Videm V, Christiansen D, Bergseth G, Riesenfeld J, Hovig T. Platelet compatibility of an artificial surface modified with functionally active heparin. Thromb Haemost. 1999;82(3):1132-1136.

42

Belboul A, al-Khaja N, Gudmundsson M, et al. The influence of heparin coated and uncoated extracorporeal circuits on blood rheology during cardiac surgery. J Extra Corpor Technol. 1993;25(2):40-46.

43

Lamba NMK, Cooper SL. Interaction of blood with artificial surfaces. In: Coleman RW, Clowes AW, George JN, Hirsh J, Marder V, eds. Hemostasis and thrombosis: Basic principles and practice, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001:661-672.

44

Edmunds LH, Stenach N. Blood-surface interface. In: Gravlee GP, Davis RF , Jurusz M, Utley JR, eds. Cardiopulmonary bypass: Principles and practice, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2000:149-166.

45

Coleman RW, Clowes AW, George JN, Hirsh J, Marder V. Overview of Hemostasis. In: Coleman RW, Clowes AW, George JN, Hirsh J, Marder V, eds. Hemostasis and thrombosis: Basic principles and practice, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001:3-16.

46

Baier RE , Dutton RC . Initial events in interactions of blood with a foreign surface. J Biomed Mater Res. 1969;3(1):191-206.

47

Paparella D, Yau TM , Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg. 2002 ;21(2):232-244.

Medtronic Italia S.p.A. Società a socio unico soggetta ad attività di direzione e coordinamento da parte di Medtronic PLC.
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