aprotinin

Summary

Summary: A single-chain polypeptide derived from bovine tissues consisting of 58 amino-acid residues. It is an inhibitor of proteolytic enzymes including CHYMOTRYPSIN; KALLIKREIN; PLASMIN; and TRYPSIN. It is used in the treatment of HEMORRHAGE associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with EXTRACORPOREAL CIRCULATION. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)

Top Publications

  1. Schneeweiss S, Seeger J, Landon J, Walker A. Aprotinin during coronary-artery bypass grafting and risk of death. N Engl J Med. 2008;358:771-83 pubmed publisher
    b>Aprotinin (Trasylol) is used to mitigate bleeding during coronary-artery bypass grafting (CABG). Accumulating evidence suggests that this practice increases mortality...
  2. Khurana A, Guha A, Saxena N, Pugh S, Ahuja S. Comparison of aprotinin and tranexamic acid in adult scoliosis correction surgery. Eur Spine J. 2012;21:1121-6 pubmed publisher
    ..of consecutive adult patients undergoing scoliosis correction surgery was performed to compare the effects of aprotinin and tranexamic acid in blood conservation and to define a comprehensive blood conservation strategy for such ..
  3. Wang X, Zheng Z, Ao H, Zhang S, Wang Y, Zhang H, et al. Effects of aprotinin on short-term and long-term outcomes after coronary artery bypass grafting surgery. Ann Thorac Surg. 2010;89:1489-95 pubmed publisher
    Recent studies demonstrated that aprotinin use would increase the short-term and long-term mortality and complications after coronary artery bypass grafting (CABG)...
  4. Du L, Zhou J, Tang J, An Q, Lin K, Wu X, et al. Aprotinin combined with nitric oxide and prostaglandin E1 protects the canine kidney from cardiopulmonary bypass-induced injury. Eur J Cardiothorac Surg. 2010;38:98-103 pubmed publisher
    b>Aprotinin is frequently used to reduce blood loss during cardiac surgery; however, it also causes renal injury...
  5. Dietrich W. Aprotinin: 1 year on. Curr Opin Anaesthesiol. 2009;22:121-7 pubmed publisher
    The nonspecific protease inhibitor aprotinin has been used successfully to reduce bleeding in cardiac surgery...
  6. Orchard J, Massey A, Brown R, Cardon Dunbar A, Hofmann J. Successful management of tendinopathy with injections of the MMP-inhibitor aprotinin. Clin Orthop Relat Res. 2008;466:1625-32 pubmed publisher
    b>Aprotinin is a broad spectrum proteinase inhibitor (including matrix metalloproteinase [MMP] inhibitor) used for treating patellar and Achilles tendinopathies...
  7. Del Duca D, Sheth S, Clarke A, Lachapelle K, Ergina P. Use of methylene blue for catecholamine-refractory vasoplegia from protamine and aprotinin. Ann Thorac Surg. 2009;87:640-2 pubmed publisher
    ..One case was related to the administration of protamine and the other case to the administration of aprotinin. Both cases were successfully managed using intravenous methylene blue...
  8. Bojan M, Boulat C, Peperstraete H, Pouard P. High-dose aprotinin, blood product transfusions, and short-term outcome in neonates and infants: a pediatric cardiac surgery center experience. Paediatr Anaesth. 2012;22:818-25 pubmed publisher
    The efficacy of aprotinin, the most popular antifibrinolytic agent in congenital cardiac surgery, was still uncertain in small infants when its prophylactic use was suspended for safety reasons...
  9. Muedra V, Delas F, Villalonga V, Gomez M, Sanchez F, Llopis J. [Transfusion requirements, morbidity and mortality in cardiac surgery and the use of antifibrinolytic agents: a comparison of aprotinin and tranexamic acid]. Rev Esp Anestesiol Reanim. 2011;58:140-6 pubmed
    To evaluate transfusion requirements, morbidity and mortality when 2 antifibrinolytic agents (aprotinin and tranexamic acid) were used in patients undergoing cardiac surgery.

More Information

Publications62

  1. Colomina M, Bagó J, Vidal X, Mora L, Pellisé F. Antifibrinolytic therapy in complex spine surgery: a case-control study comparing aprotinin and tranexamic acid. Orthopedics. 2009;32:91 pubmed
    A case-control study was performed to determine the impact of aprotinin or tranexamic acid use on reducing intraoperative blood loss and transfusion needs in complex spine surgery...
  2. Flight S, Johnson L, Du Q, Warner R, Trabi M, Gaffney P, et al. Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss. Br J Haematol. 2009;145:207-11 pubmed publisher
    b>Aprotinin has been used widely in surgery as an anti-bleeding agent but is associated with a number of side effects...
  3. Smith M, Kocher H, Hunt B. Aprotinin in severe acute pancreatitis. Int J Clin Pract. 2010;64:84-92 pubmed publisher
    b>Aprotinin, a Kunitz protease inhibitor, has a wide inhibitory action with particular activity against trypsin, chymotrypsin and kallikrein, making it theoretically attractive in ameliorating the effects of acute pancreatitis...
  4. Badri M, Rivard D, Coenen K, Michaud D. Unintended molecular interactions in transgenic plants expressing clinically useful proteins: the case of bovine aprotinin traveling the potato leaf cell secretory pathway. Proteomics. 2009;9:746-56 pubmed publisher
    ..impact of subcellular targeting on the heterologous expression of a clinically useful protease inhibitor, bovine aprotinin, in leaves of potato, Solanum tuberosum...
  5. Dietrich W, Ebell A, Busley R, Boulesteix A. Aprotinin and anaphylaxis: analysis of 12,403 exposures to aprotinin in cardiac surgery. Ann Thorac Surg. 2007;84:1144-50 pubmed
    Hypersensitivity reactions to the nonspecific proteinase inhibitor aprotinin may occur. The present study evaluates the incidence of hypersensitivity reactions to aprotinin...
  6. Dietrich W, Busley R, Boulesteix A. Effects of aprotinin dosage on renal function: an analysis of 8,548 cardiac surgical patients treated with different dosages of aprotinin. Anesthesiology. 2008;108:189-98 pubmed publisher
    The nonspecific serine protease inhibitor aprotinin is widely used in cardiac surgery to limit bleeding. Recently, concerns about the safety of this drug were raised, especially regarding impaired renal outcome...
  7. Pogue G, Vojdani F, Palmer K, Hiatt E, Hume S, Phelps J, et al. Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant Biotechnol J. 2010;8:638-54 pubmed
    ..One transient plant system case study illustrates the properties of greenhouse and field-produced recombinant aprotinin compared with an US Food and Drug Administration-approved pharmaceutical product and found them to be highly ..
  8. Carter J, Buerke U, Rossner E, Russ M, Schubert S, Schmidt H, et al. Anti-inflammatory actions of aprotinin provide dose-dependent cardioprotection from reperfusion injury. Br J Pharmacol. 2008;155:93-102 pubmed publisher
    ..We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R)...
  9. Sniecinski R, Chen E, Makadia S, Kikura M, Bolliger D, Tanaka K. Changing from aprotinin to tranexamic acid results in increased use of blood products and recombinant factor VIIa for aortic surgery requiring hypothermic arrest. J Cardiothorac Vasc Anesth. 2010;24:959-63 pubmed publisher
    b>Aprotinin, once used to reduce allogeneic blood product transfusion during cardiac surgery, was withdrawn from the market in late 2007 over concerns of causing increased mortality...
  10. Strouch Z, Drum M, Chaney M. Aprotinin use during cardiac surgery: recent alterations and effects on blood product utilization. J Clin Anesth. 2009;21:502-7 pubmed publisher
    To investigate a single institution's changing use of aprotinin and subsequent effects on intraoperative blood product utilization (red blood cells/fresh frozen plasma) and postoperative clinical bleeding requiring reoperation...
  11. Myles P. Aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;359:1181; author reply 1181-2 pubmed
  12. Stamou S, Reames M, Skipper E, Stiegel R, Nussbaum M, Geller R, et al. Aprotinin in cardiac surgery patients: is the risk worth the benefit?. Eur J Cardiothorac Surg. 2009;36:869-75 pubmed publisher
    b>Aprotinin is the only Food and Drug Administration-approved agent to reduce haemorrhage related to cardiac surgery and its safety and efficacy has been extensively studied...
  13. Jakobsen C, Søndergaard F, Hjortdal V, Johnsen S. Use of aprotinin in cardiac surgery: effectiveness and safety in a population-based study. Eur J Cardiothorac Surg. 2009;36:863-8 pubmed publisher
    The effectiveness and safety of aprotinin use in cardiac surgery have been questioned. More data reflecting everyday clinical practice from large-scale, unselected populations are needed...
  14. Breuer T, Martin K, Wilhelm M, Wiesner G, Schreiber C, Hess J, et al. The blood sparing effect and the safety of aprotinin compared to tranexamic acid in paediatric cardiac surgery. Eur J Cardiothorac Surg. 2009;35:167-71; author reply 171 pubmed publisher
    Recently, the safety of aprotinin administration during open-heart surgery has been debated...
  15. Paesen G, Siebold C, Dallas M, Peers C, Harlos K, Nuttall P, et al. An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. J Mol Biol. 2009;389:734-47 pubmed publisher
  16. Zhirnov O, Matrosovich T, Matrosovich M, Klenk H. Aprotinin, a protease inhibitor, suppresses proteolytic activation of pandemic H1N1v influenza virus. Antivir Chem Chemother. 2011;21:169-74 pubmed publisher
    ..Host proteases responsible for viral haemagglutinin (HA) cleavage are attractive targets for such drugs. Aprotinin, a natural 58-amino-acid polypeptide from bovine lungs, was chosen for this purpose because it is a drug already ..
  17. Avlonitis V, Wigfield C, Kirby J, Dark J. Treatment of the brain-dead lung donor with aprotinin and nitric oxide. J Heart Lung Transplant. 2010;29:1177-84 pubmed publisher
    It has been previously shown that donor treatment with aprotinin or inhaled nitric oxide reduces reperfusion injury after lung transplantation in animals. These studies used living donors with normal lungs...
  18. Lima C, Torquato R, Sasaki S, Justo G, Tanaka A. Biochemical characterization of a Kunitz type inhibitor similar to dendrotoxins produced by Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) hemocytes. Vet Parasitol. 2010;167:279-87 pubmed publisher
    ..In conclusion, we demonstrated that rBmCI is cytotoxic against mammalian cells and obtained evidence that this growth inhibition is caused by an apoptosis-inducing activity. ..
  19. Polat K, Aydinli B, Polat O, Aydin U, Yazici P, Ozturk G, et al. The protective effect of aprotinin and alpha-tocopherol on ischemia-reperfusion injury of the rat liver. Transplant Proc. 2008;40:63-8 pubmed publisher
    ..In this study, we investigated whether aprotinin provided protection against the adverse effects of I/R injury in liver tissue...
  20. Buerke M, Pruefer D, Sankat D, Carter J, Buerke U, Russ M, et al. Effects of aprotinin on gene expression and protein synthesis after ischemia and reperfusion in rats. Circulation. 2007;116:I121-6 pubmed
    ..Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown...
  21. Ngaage D, Cale A, Cowen M, Griffin S, Guvendik L. Aprotinin in primary cardiac surgery: operative outcome of propensity score-matched study. Ann Thorac Surg. 2008;86:1195-202 pubmed publisher
    Some recent multicenter series have questioned the safety of aprotinin in primary cardiac operations...
  22. Dietrich W, Spannagl M, Boehm J, Hauner K, Braun S, Schuster T, et al. Tranexamic acid and aprotinin in primary cardiac operations: an analysis of 220 cardiac surgical patients treated with tranexamic acid or aprotinin. Anesth Analg. 2008;107:1469-78 pubmed publisher
    ..In the present study we evaluated the impact of tranexamic acid compared to aprotinin on the transfusion incidence in cardiac surgical patients with low risk of bleeding...
  23. Koster A, Buz S, Krabatsch T, Dehmel F, Kuppe H, Hetzer R, et al. High-dose aprotinin effectively reduces blood loss during on-pump coronary artery bypass grafting with bivalirudin anticoagulation. J Thorac Cardiovasc Surg. 2008;135:685-7 pubmed publisher
  24. Han S, Chong V, Murray T, McDonagh T, Hunter J, Poon F, et al. Preliminary experience of 99mTc-Aprotinin scintigraphy in amyloidosis. Eur J Haematol. 2007;79:494-500 pubmed
    Radio-labelled Aprotinin has been shown to bind with amyloid fibrils in vitro as well as in vivo. The aim was to test the usefulness of 99mTc-Aprotinin imaging in systemic amyloidosis...
  25. Liu C, Chen J, Wang X. Requirements for transfusion and postoperative outcomes in orthotopic liver transplantation: a meta-analysis on aprotinin. World J Gastroenterol. 2008;14:1425-9 pubmed
    To study the effect of aprotinin used in orthotopic liver transplantation (OLT) on the intraoperative requirement for blood products and on the incidence of laparotomy for bleeding, thrombotic events and mortality...
  26. Lindvall G, Sartipy U, Ivert T, van der Linden J. Aprotinin is not associated with postoperative renal impairment after primary coronary surgery. Ann Thorac Surg. 2008;86:13-9 pubmed publisher
    Studies on the safety of aprotinin in coronary artery surgery have given conflicting results...
  27. Later A, Maas J, Engbers F, Versteegh M, Bruggemans E, Dion R, et al. Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery: a non-sponsored, double-blind, randomised, placebo-controlled trial. Eur J Cardiothorac Surg. 2009;36:322-9 pubmed publisher
    Tranexamic acid has been suggested to be as effective as aprotinin in reducing blood loss and transfusion requirements after cardiac surgery...
  28. Mouton R, Finch D, Davies I, Binks A, Zacharowski K. Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: a retrospective observational study. Lancet. 2008;371:475-82 pubmed publisher
    b>Aprotinin is used during cardiac surgery for its blood-saving effects. However, reports suggest a possible association between use of this drug and increased renal dysfunction and mortality...
  29. Martin K, Wiesner G, Breuer T, Lange R, Tassani P. The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesth Analg. 2008;107:1783-90 pubmed publisher
    Our aim was to investigate postoperative complications and mortality after administration of aprotinin compared to tranexamic acid in an unselected, consecutive cohort...
  30. Turut H, Ciralik H, Kilinc M, Ozbag D, Imrek S. Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin on inflammatory and oxidant-antioxidant status after lung contusion in rats. Injury. 2009;40:521-7 pubmed publisher
    ..We intended to determine the effects of dexamethasone (DXM), N-acetylcysteine (NAC) and aprotinin (APR) in terms of their ability to diminish the consequences of acute lung injury due to PC...
  31. Christy L, Arvinth S, Saravanakumar M, Kanchana M, Mukunthan N, Srikanth J, et al. Engineering sugarcane cultivars with bovine pancreatic trypsin inhibitor (aprotinin) gene for protection against top borer (Scirpophaga excerptalis Walker). Plant Cell Rep. 2009;28:175-84 pubmed publisher
    The inhibitory activity of bovine pancreatic trypsin inhibitor (aprotinin), a natural polypeptide and a proteinase inhibitor, was demonstrated on gut proteinases of three lepidopteran borers of sugarcane using commercially available ..
  32. Karkouti K, Wijeysundera D, Yau T, McCluskey S, Tait G, Beattie W. The risk-benefit profile of aprotinin versus tranexamic acid in cardiac surgery. Anesth Analg. 2010;110:21-9 pubmed publisher
    b>Aprotinin is superior to other antifibrinolytic drugs for preventing major blood loss after cardiac surgery but may also increase perioperative mortality...
  33. Sander M, Spies C, Martiny V, Rosenthal C, Wernecke K, von Heymann C. Mortality associated with administration of high-dose tranexamic acid and aprotinin in primary open-heart procedures: a retrospective analysis. Crit Care. 2010;14:R148 pubmed publisher
    ..Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding. Because of safety concerns, aprotinin was withdrawn from the market in 2007...
  34. Szekely A, Sápi E, Breuer T, Kertai M, Bodor G, Vargha P, et al. Aprotinin and renal dysfunction after pediatric cardiac surgery. Paediatr Anaesth. 2008;18:151-9 pubmed publisher
    b>Aprotinin is a potent antifibrinolytic drug, which reduces postoperative bleeding and transfusion requirements. Recently, two observational studies reported increased incidence of renal dysfunction after aprotinin use in adults...
  35. Olenchock S, Lee P, Yehoshua T, Murphy S, Symes J, Tolis G. Impact of aprotinin on adverse clinical outcomes and mortality up to 12 years in a registry of 3,337 patients. Ann Thorac Surg. 2008;86:560-6; discussion 566-7 pubmed publisher
    Recent studies have suggested increased renal complications and long-term mortality with aprotinin use in coronary artery bypass grafting (CABG) patients...
  36. Kempaiah P, Danielson L, Barry M, Kisiel W. Comparative effects of aprotinin and human recombinant R24K KD1 on temporal renal function in Long-Evans rats. J Pharmacol Exp Ther. 2009;331:940-5 pubmed publisher
    Bovine aprotinin, a reversible inhibitor of plasmin and kallikrein, has been clinically approved for over two decades to prevent perioperative blood loss during cardiac surgery...
  37. Murkin J. Lessons learned in antifibrinolytic therapy: The BART trial. Semin Cardiothorac Vasc Anesth. 2009;13:127-31 pubmed publisher
    ..nearly 2 decades of published reports and clinical trials demonstrating the relative safety and efficacy of aprotinin in adult cardiac surgical patients at increased risk of bleeding-culminating in an official endorsement of the ..
  38. Guzzetta N, Evans F, Rosenberg E, Fazlollah T, Baker M, Wilson E, et al. The impact of aprotinin on postoperative renal dysfunction in neonates undergoing cardiopulmonary bypass: a retrospective analysis. Anesth Analg. 2009;108:448-55 pubmed publisher
    Recent concern about the safety of aprotinin administration to adults has led to its suspension from worldwide markets. However, few studies have examined its safety in pediatric patients...
  39. Henry D, Carless P, Fergusson D, Laupacis A. The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. CMAJ. 2009;180:183-93 pubmed publisher
    Because of recent concerns about the safety of aprotinin, we updated our 2007 Cochrane review that compared the relative benefits and risks of aprotinin and the lysine analogues tranexamic acid and epsilon aminocaproic acid...
  40. Immer F, Jent P, Englberger L, Stalder M, Gygax E, Carrel T, et al. Aprotinin in cardiac surgery: a different point of view. Heart Surg Forum. 2008;11:E9-12 pubmed publisher
    b>Aprotinin is widely used in cardiac surgery to reduce postoperative bleeding and the need for blood transfusion...
  41. Pietruska M, Pietruski J, Skurska A, Bernaczyk A, Zak J, Zelazowska B, et al. Assessment of aprotinin influence on periodontal clinical status and matrix metalloproteinases 1, 2 and their tissue inhibitors saliva concentrations in patients with chronic periodontitis. Adv Med Sci. 2009;54:239-46 pubmed publisher
    Assessment of the effect of treatment with aprotinin-containing drug on the clinical status of the periodontal tissue and on the concentrations of metalloproteinases released in the course of periodontitis (MMP-1, MMP-2) as well as their ..
  42. Zhirnov O, Klenk H, Wright P. Aprotinin and similar protease inhibitors as drugs against influenza. Antiviral Res. 2011;92:27-36 pubmed publisher
    ..b>Aprotinin, a 58 amino acid polypeptide purified from bovine lung that is one of a family of host-targeted antivirals that ..
  43. Wagener G, Lee H. Aprotinin and urinary neutrophil gelatinase-associated lipocalin after cardiac surgery. Anesth Analg. 2008;106:1593 pubmed publisher
  44. Kristeller J, Roslund B, Stahl R. Benefits and risks of aprotinin use during cardiac surgery. Pharmacotherapy. 2008;28:112-24 pubmed
    b>Aprotinin is a serine protease inhibitor with antithrombotic, antifibrinolytic, and antiinflammatory effects. It is effective in reducing bleeding and the need for blood transfusions after cardiac surgery with cardiopulmonary bypass...
  45. Ray W, Stein C. The aprotinin story--is BART the final chapter?. N Engl J Med. 2008;358:2398-400 pubmed publisher
  46. Pagano D, Howell N, Freemantle N, Cunningham D, Bonser R, Graham T, et al. Bleeding in cardiac surgery: the use of aprotinin does not affect survival. J Thorac Cardiovasc Surg. 2008;135:495-502 pubmed publisher
    The antifibrinolytic drug aprotinin has been the most widely used agent to reduce bleeding and its complications in cardiac surgery. Several randomized trials and meta-analyses have demonstrated it to be effective and safe...
  47. Greilich P, Jessen M, Satyanarayana N, Whitten C, Nuttall G, Beckham J, et al. The effect of epsilon-aminocaproic acid and aprotinin on fibrinolysis and blood loss in patients undergoing primary, isolated coronary artery bypass surgery: a randomized, double-blind, placebo-controlled, noninferiority trial. Anesth Analg. 2009;109:15-24 pubmed publisher
    Until recently, aprotinin was the only antifibrinolytic drug with a licensed indication in cardiac surgery in the United States...
  48. Edmunds L. Managing fibrinolysis without aprotinin. Ann Thorac Surg. 2010;89:324-31 pubmed publisher
    ..Neither aprotinin nor lysine analogs successfully control bleeding in many complex procedures, reoperations, aortic resections, or ..
  49. Baldus C, Bridwell K, Lenke L, Okubadejo G. Can we safely reduce blood loss during lumbar pedicle subtraction osteotomy procedures using tranexamic acid or aprotinin? A comparative study with controls. Spine (Phila Pa 1976). 2010;35:235-9 pubmed publisher
    ..To compare the safety and efficacy of 2 pharmaceutical antifibrinolytic agents, aprotinin and tranexamic acid, in controlling blood loss during lumbar pedicle subtraction osteotomy (PSO) in adults...
  50. Werle M, Takeuchi H. Chitosan-aprotinin coated liposomes for oral peptide delivery: Development, characterisation and in vivo evaluation. Int J Pharm. 2009;370:26-32 pubmed publisher
    ..of therapeutic peptides/proteins after oral administration, the polymer-protease inhibitor conjugate chitosan-aprotinin was synthesised and polyelectrolyte complexes between negatively charged multilamellar vesicles (MLV) and ..
  51. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee H. Increased incidence of acute kidney injury with aprotinin use during cardiac surgery detected with urinary NGAL. Am J Nephrol. 2008;28:576-82 pubmed publisher
    Use of aprotinin has been associated with acute kidney injury after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel, very sensitive marker for renal injury...
  52. Balasubramanian N, Toubarro D, Simoes N. Biochemical study and in vitro insect immune suppression by a trypsin-like secreted protease from the nematode Steinernema carpocapsae. Parasite Immunol. 2010;32:165-75 pubmed publisher
    ..high activity with trypsin-specific substrate N-Ben-Phe-Val-Arg-p-nitroanilide and was highly sensitive to aprotinin and benzamidine...
  53. DeSantis S, Toole J, Kratz J, Uber W, Wheat M, Stroud M, et al. Early postoperative outcomes and blood product utilization in adult cardiac surgery: the post-aprotinin era. Circulation. 2011;124:S62-9 pubmed publisher
    b>Aprotinin was a commonly used pharmacological agent for homeostasis in cardiac surgery but was discontinued, resulting in the extensive use of lysine analogues...