Coating-techniques to improve the hemocompatibility of artificial devices used for extracorporeal circulation.

OBJECTIVE Extracorporeal circulation procedures have been shown to induce complement and leukocyte activation, release of endotoxin and inflammatory mediators, including cytokines, nitric oxide, oxygen free radicals, and platelet activating factors. The contact between the blood and the various artificial surfaces of the extracorporeal system results in an unspecific post-perfusion syndrome. For diminishing these negative side effects several coating-techniques have been developed to create devices with improved hemocompatibility. METHODS This review deals with the current knowledge of heparin-coated and otherwise surface-modified perfusion systems. The pathway how heparin-coated surfaces work is discussed and techniques for surface-coatings, both clinically introduced as well as newly developed are presented. RESULTS Numerous clinical studies compared heparin-coated versus non-coated circuits. Heparin-bonded devices showed lessened humoral and cellular activation, in particular a reduced complement activation with a reduced inflammatory post-perfusion syndrome. Also platelet protection and more favorable post-operative lung function are of particular note. Recent clinical trials demonstrated shortened hospital stays, less drainage bleeding, and reduced cerebral complications using heparin-coated oxygenation systems. The diminished expression of the leukocyte adhesion molecules CD 11b/c in CBAS devices points to a decreased activation of neutrophils. In addition, one research group found a reduced production of oxygen radicals. Heparin-bonding minimizes oxygenator failure by a significant reduced pressure gradient across the oxygenator, probably caused by decreased fibrin and platelet deposition at the hollow fiber surfaces. A meta analysis examined the impact of heparin-bonded systems on clinical outcomes and resulting costs. Using heparin-bonded circuits led to total cost savings from US $1000 to 3000. Several authors demonstrated reduced blood loss and better clinical outcome by reduction of systemic heparinization and the employment of heparin-coated devices. CONCLUSION Above and beyond the long-term applications, routine heart operations have also markedly begun to utilize heparin-coated devices. This trend will assuredly continue in the coming years and is an important step toward higher hemocompatibility of blood-contacting surfaces in the ECC device. Heparin-coatings are merely the beginning of improved hemocompatibility for all materials that come into contact with human blood or tissues. Intelligent materials with almost completely physiological surfaces will be at the surgeon's disposal within the next few years.

[1]  A. Galloway,et al.  Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass. , 1995 .

[2]  P. Venge,et al.  Effects of heparin coating of cardiopulmonary bypass circuits on in vitro oxygen free radical production during coronary bypass surgery. , 1996, Artificial organs.

[3]  S. Bannan,et al.  Low heparinization with heparin-bonded bypass circuits: is it a safe strategy? , 1997, The Annals of thoracic surgery.

[4]  E. Fosse,et al.  Endothelin-1 and neutrophil activation during heparin-coated cardiopulmonary bypass. , 1997, The Annals of thoracic surgery.

[5]  Peter J. Quinn,et al.  Structural and dynamic properties of lipids and membranes , 1992 .

[6]  E. Fosse,et al.  Complement and granulocyte activation in two different types of heparinized extracorporeal circuits. , 1995, The Journal of thoracic and cardiovascular surgery.

[7]  G. Tangen,et al.  Completely heparinized cardiopulmonary bypass and reduced systemic heparin: clinical and hemostatic effects. , 1995, The Annals of thoracic surgery.

[8]  R. P. Cochran,et al.  Heparin-coated bypass circuits (Carmeda) suppress the release of tissue plasminogen activator during normothermic coronary artery bypass graft surgery. , 1998, Journal of cardiothoracic and vascular anesthesia.

[9]  M. Voorhees,et al.  Surface modifying additives for improved device-blood compatibility. , 1994, ASAIO journal.

[10]  T. Saldeen,et al.  Biocompatibility Reflected by Haemostasis Variables during Cardiopulmonary Bypass Using Heparin-Coated Circuits , 1997, The thoracic and cardiovascular surgeon.

[11]  D. Kuik,et al.  Clinical evaluation of Duraflo II heparin treated extracorporeal circulation circuits (2nd version). The European Working Group on heparin coated extracorporeal circulation circuits. , 1997, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[12]  E. Fosse,et al.  Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes : a European multicentre study. , 1997, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[13]  E. Fosse,et al.  Attenuation of changes in leukocyte surface markers and complement activation with heparin-coated cardiopulmonary bypass. , 1997, The Annals of thoracic surgery.

[14]  A. Usui,et al.  A clinical study for the durability of oxygenators on cardiopulmonary support. , 1997, Artificial organs.

[15]  A. Belboul,et al.  Does heparin coating improve biocompatibility? A study on complement, blood cells and postoperative morbidity during cardiac surgery , 1997, Perfusion.

[16]  C. B. Mahoney Heparin-bonded circuits: clinical outcomes and costs , 1998, Perfusion.

[17]  K. Taylor,et al.  SIRS--the systemic inflammatory response syndrome after cardiac operations. , 1996, The Annals of thoracic surgery.

[18]  E. Greco,et al.  Heparin-coated circuit in coronary surgery. A clinical study. , 1996, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[19]  T. Karlsson,et al.  Clinical effects of the heparin coated surface in cardiopulmonary bypass. , 1997, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[20]  H. Harasaki,et al.  Biocompatibility of heparin-coated extracorporeal bypass circuits: a randomized, masked clinical trial. , 1996, The Journal of thoracic and cardiovascular surgery.

[21]  T. Kazui,et al.  Experimental studies on three types of heparin-coated cardiopulmonary bypass circuits. , 1997, Artificial organs.

[22]  A. Siegbahn,et al.  Thrombin generation during cardiopulmonary bypass using heparin-coated or standard circuits. , 1995, Scandinavian journal of thoracic and cardiovascular surgery.

[23]  J. van der Linden,et al.  Heparin-coated cardiopulmonary bypass circuits and 25% reduction of heparin dose in coronary artery surgery--a clinical study. , 1992, Upsala journal of medical sciences.

[24]  T. Tötterman,et al.  Circulating cytokines and granulocyte-derived enzymes during complex heart surgery. A clinical study with special reference to heparin-coating of cardiopulmonary bypass circuits. , 1995, Scandinavian journal of thoracic and cardiovascular surgery.

[25]  A. Schmaier,et al.  Initiation of Blood Coagulation at Artificial Surfaces , 1987, Annals of the New York Academy of Sciences.

[26]  L. Hsu Biocompatibility in cardiopulmonary bypass. , 1997, Journal of cardiothoracic and vascular anesthesia.

[27]  R. Colman,et al.  Surface-bound heparin fails to reduce thrombin formation during clinical cardiopulmonary bypass. , 1996, The Journal of thoracic and cardiovascular surgery.

[28]  R. Shemin,et al.  Heparin-bonded circuits with a reduced anticoagulation protocol in primary CABG: a prospective, randomized study. , 1996, The Annals of thoracic surgery.

[29]  P. Martin,et al.  Aprotinin complements heparin bonding in an in vitro model of cardiopulmonary bypass , 1998, British journal of haematology.

[30]  E. Fosse,et al.  Effects of heparin coating on the expression of CD11b, CD11c and CD62L by leucocytes in extracorporeal circulation in vitro , 1997, Perfusion.

[31]  C. Hack,et al.  Heparin coating of extracorporeal circuits inhibits contact activation during cardiac operations. , 1997, The Journal of thoracic and cardiovascular surgery.

[32]  R. Stephens,et al.  Induction of monocyte tissue factor procoagulant activity during coronary artery bypass surgery is reduced with heparin‐coated extracorporeal circuit , 1996, British journal of haematology.

[33]  H. Hansson,et al.  Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose. , 1992, Scandinavian journal of thoracic and cardiovascular surgery.

[34]  E. Fosse,et al.  Complete heparin-coated cardiopulmonary bypass and low heparin dose reduce complement and granulocyte activation. , 1996, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[35]  G. Gravlee Heparin-coated cardiopulmonary bypass circuits. , 1994, Journal of cardiothoracic and vascular anesthesia.

[36]  R. Larsson,et al.  The Search for Thromboresistance Using Immobilized Heparin , 1987, Annals of the New York Academy of Sciences.

[37]  P. Venge,et al.  Biocompatibility of heparin-coated circuits used in cardiopulmonary bypass. , 1994, Scandinavian journal of thoracic and cardiovascular surgery.

[38]  R. Shemin,et al.  Enhanced Blood Conservation in Primary Coronary Artery Bypass Surgery Using Heparin‐Bonded Circuits with Lower Anticoagulation , 1996, Journal of cardiac surgery.

[39]  J. Vincent,et al.  Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. , 1997, Chest.

[40]  M. Tönz,et al.  Evaluation of Phospholipidic Surface Coatings ex-vivo , 1994, The International journal of artificial organs.

[41]  H. Philippou,et al.  Mechanisms of thrombin generation during surgery and cardiopulmonary bypass [see comments] , 1993 .

[42]  A. Siegbahn,et al.  Monocyte tissue factor expression, cell activation, and thrombin formation during cardiopulmonary bypass: a clinical study. , 1997, The Journal of thoracic and cardiovascular surgery.

[43]  C. Baufreton,et al.  Heparin coating with aprotinin reduces blood activation during coronary artery operations. , 1997, The Annals of thoracic surgery.

[44]  W. Flameng,et al.  The Use of a Heparin Removal Device: A Valid Alternative to Protamine , 1997, The International journal of artificial organs.

[45]  P. McCarthy,et al.  Complications of extracorporeal life support systems using heparin-bound surfaces. The risk of intracardiac clot formation. , 1995, The Journal of thoracic and cardiovascular surgery.

[46]  G. Tangen,et al.  Complete heparin-coated (CBAS) cardiopulmonary bypass and reduced systemic heparin dose; effects on coagulation and fibrinolysis. , 1996, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[47]  E. Fosse,et al.  High and low heparin dose with heparin-coated cardiopulmonary bypass: activation of complement and granulocytes. , 1995, The Annals of thoracic surgery.

[48]  M. Özbaran,et al.  Complement consumption during cardiopulmonary bypass: comparison of Duraflo II heparin-coated and uncoated circuits in fully heparinized patients , 1996, Perfusion.

[49]  W. Wagner,et al.  Heparin-coated cardiopulmonary bypass circuits: hemostatic alterations and postoperative blood loss. , 1994, The Annals of thoracic surgery.

[50]  L. Menicanti,et al.  Beneficial effects of Duraflo II heparin-coated circuits on postperfusion lung dysfunction. , 1996, The Annals of thoracic surgery.

[51]  R. Shemin,et al.  Effect of anticoagulation protocol on outcome in patients undergoing CABG with heparin-bonded cardiopulmonary bypass circuits. , 1998, The Annals of thoracic surgery.

[52]  G. Elgue,et al.  On the Mechanism of Coagulation Inhibition on Surfaces with End Point Immobilized Heparin , 1993, Thrombosis and Haemostasis.

[53]  R. Dutton,et al.  Heparin Bonding on Colloidal Graphite Surfaces , 1963, Science.

[54]  R. Colman Hemostatic complications of cardiopulmonary bypass , 1995, American journal of hematology.

[55]  P. Stratford,et al.  Biocompatible surfaces using methacryloylphosphorylcholine laurylmethacrylate copolymer. , 1994, ASAIO journal.

[56]  M. Pasic,et al.  Risk and benefit of low systemic heparinization during open heart operations. , 1994, The Annals of thoracic surgery.

[57]  G. Rakhorst,et al.  Blood Interaction with a Bioline Heparin Coated HIA-VAD: A Study on Calves , 1997, The International journal of artificial organs.

[58]  I. Kudoh,et al.  Heparin-coated circuits reduce the formation of TNF alpha during cardiopulmonary bypass. , 1996, Acta anaesthesiologica Scandinavica.

[59]  G. Sfakianakis,et al.  Platelet preservation during cardiopulmonary bypass with iloprost and Duraflo-II heparin-coated surfaces. , 1991, ASAIO Transactions.

[60]  L. Deenen,et al.  Membrane asymmetry and blood coagulation , 1977, Nature.

[61]  C. Hack,et al.  Specific complement inhibition with heparin-coated extracorporeal circuits. , 1996, The Annals of thoracic surgery.

[62]  H. Matsuda,et al.  Biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass. , 1997, Artificial organs.

[63]  R. Larsson,et al.  A new non-thrombogenic surface prepared by selective covalent binding of heparin via a modified reducing terminal residue. , 1983, Biomaterials, medical devices, and artificial organs.

[64]  G Janvier,et al.  Extracorporeal circulation, hemocompatibility, and biomaterials. , 1996, The Annals of thoracic surgery.

[65]  K. Asada,et al.  Heparin-coated cardiopulmonary bypass circuits in coronary bypass surgery. , 1996, Artificial organs.

[66]  V. Jeevanandam,et al.  The effects of Carmeda Bioactive Surface on human blood components during simulated extracorporeal circulation. , 1996, The Journal of thoracic and cardiovascular surgery.

[67]  M. Turina,et al.  Reduction and elimination of systemic heparinization during cardiopulmonary bypass. , 1992, The Journal of thoracic and cardiovascular surgery.

[68]  B. Seifert,et al.  Perioperative course and recovery after heparin-coated cardiopulmonary bypass: low-dose versus high-dose heparin management. , 1996, Journal of cardiothoracic and vascular anesthesia.

[69]  A. Kuitunen,et al.  Cardiopulmonary bypass with heparin-coated circuits and reduced systemic anticoagulation. , 1997, The Annals of thoracic surgery.

[70]  L. Vroman The life of an artificial device in contact with blood: initial events and their effect on its final state. , 1988, Bulletin of the New York Academy of Medicine.

[71]  M. Meyerhoff,et al.  A novel electrochemical heparin sensor. , 1993, ASAIO journal.

[72]  I. Kudoh,et al.  Heparin‐coated circuits reduce the formation of TNFα during cardiopulmonary bypass , 1996 .

[73]  E. Fosse,et al.  Disparity in blood activation by two different heparin-coated cardiopulmonary bypass systems. , 1995, The Annals of thoracic surgery.

[74]  K. Niwaya,et al.  Changes in platelet, granulocyte, and complement activation during cardiopulmonary bypass using heparin-coated equipment. , 1996, Artificial organs.

[75]  P. Bezemer,et al.  Reduced complement activation and improved postoperative performance after cardiopulmonary bypass with heparin-coated circuits. , 1995, The Journal of thoracic and cardiovascular surgery.

[76]  W. van Oeveren,et al.  Cardiopulmonary bypass circuit treated with surface-modifying additives: a clinical evaluation of blood compatibility. , 1998, The Annals of thoracic surgery.

[77]  D. Birnbaum,et al.  Heparin-coated equipment reduces the risk of oxygenator failure. , 1998, The Annals of thoracic surgery.

[78]  E. Fosse,et al.  Centrifugal pump and heparin coating improves cardiopulmonary bypass biocompatibility. , 1996, The Annals of thoracic surgery.

[79]  G. Gravlee,et al.  Heparin-coated cBypass circuits , 1994 .

[80]  G. Tangen,et al.  Effects on coagulation and fibrinolysis with reduced versus full systemic heparinization and heparin-coated cardiopulmonary bypass. , 1995, Circulation.