{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:16:25Z","timestamp":1792718185276,"version":"4.5.0"},"reference-count":35,"publisher":"IMR Press","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HSF"],"abstract":"<jats:p>&lt;p&gt;&lt;b&gt;Objective:&lt;\/b&gt; To investigate the effect of ulinastatin and tranexamic acid administered alone or in combination on inflammatory cytokines and fibrinolytic system in patients undergoing heart valve replacement surgery during cardiopulmonary bypass (CPB).&lt;\/p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;\/b&gt; CPB-induced fibrinolytic hyperfunction and systemic inflammatory response syndrome (SIRS) are the leading causes responsible for the occurrence of postsurgical complications such as postsurgical cardiac insufficiency and lung injury, which may lead to an increase in postsurgical bleeding, prolongation of hospital stay, and increased costs.&lt;\/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;\/b&gt; One hundred twenty patients undergoing heart valve replacement surgery during CPB were randomly assigned into 4 groups of 30 patients each: blank control group (Group C), tranexamic acid group (Group T), ulinastatin group (Group U), and tranexamic acid-ulinastatin combination group (Group D). Physiological saline, tranexamic acid, ulinastatin, and a combination of tranexamic acid and ulinastatin were given to each group, respectively. Arterial blood was collected from the radial artery at 4 time points: after induction of anesthesia (T1), unclamping the ascending aorta (T2), and at 1 hour (T3) and 24 hours (T4) after CPB. The levels of plasma tumor necrosis factor alpha (TNF-), interleukin 6 (IL-6), neutrophil elastase (NE), and the concentrations of tissue plasminogen activator (t-PA) and 2-antiplasmin (2-AP) were detected. The changes in the volume of pericardial mediastinal drainage after surgery were observed and recorded.&lt;\/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;\/b&gt; The plasma TNF-, IL-6, and NE levels significantly increased in patients from all 4 groups at time points of T2, T3, and T4 in comparison to those before CPB (&lt;i&gt;P&lt;\/i&gt; &lt; .05), and the plasma TNF- and IL-6 levels in groups U and D were significantly lower than those in the other 2 groups (&lt;i&gt;P&lt;\/i&gt; &lt; .05). The plasma t-PA, ?2-AP, and D-dimer concentrations significantly increased in patients from all 4 groups at T2 and T3 compared with those before CPB (&lt;i&gt;P&lt;\/i&gt; &lt; .05), and the plasma t-PA and D-dimer concentrations were significantly lower in groups T and D than those in groups U and C (&lt;i&gt;P&lt;\/i&gt; &lt; .05) at T2 and T3. The plasma ?2-AP concentrations in groups T and D were significantly higher than those in Group C at T3 (&lt;i&gt;P&lt;\/i&gt; &lt; .05). The volumes of pericardial mediastinal drainage per body surface area were significantly lower in groups T and D than those in Group C 6 hours after the surgery (&lt;i&gt;P&lt;\/i&gt; &lt; .05).&lt;\/p&gt;&lt;p&gt;Conclusions: Ulinastatin inhibits the release of inflammatory medium and reduces the inflammatory response during CPB. Tranexamic acid can effectively inhibit the fibrinolytic hyperfunction caused by CPB and thus decreases postsurgical bleeding. In addition, it exhibits a minor anti-inflammatory response. As a consequence, a combined treatment of ulinastatin and tranexamic acid reduces postsurgical bleeding and shortens postoperative hospital stay in patients undergoing heart valve replacement surgery.&lt;\/p&gt;<\/jats:p>","DOI":"10.1532\/hsf98.20121072","type":"journal-article","created":{"date-parts":[[2013,2,25]],"date-time":"2013-02-25T21:04:12Z","timestamp":1361826252000},"page":"38","source":"Crossref","is-referenced-by-count":22,"title":["Combined Treatment of Ulinastatin and Tranexamic Acid Provides Beneficial Effects by Inhibiting Inflammatory and Fibrinolytic Response in Patients Undergoing Heart Valve Replacement Surgery"],"prefix":"10.31083","volume":"16","author":[{"given":"Ting-ting","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. M.","family":"Jiandong-Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-li","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-bing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-qing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2013,2,25]]},"reference":[{"key":"1","doi-asserted-by":"crossref","first-page":"3732","DOI":"10.1016\/S0041-1345(98)01214-7","article-title":"Ulinastatin, a protease inhibitor, attenuates hepatic ischemia\/reperfusion injury by downregulating TNF-alpha in the liver","volume":"30","author":"T. Aihara","year":"1998","journal-title":"Transplant Proc"},{"key":"2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/00024382-200115020-00004","article-title":"Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor alpha production of monocytes","volume":"15","author":"S. Aosasa","year":"2001","journal-title":"Shock"},{"key":"3","first-page":"497","article-title":"Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. Effect of ulinastatin on inflammatory response","volume":"48","author":"J. Bingyang","year":"2007","journal-title":"J Cardiovasc Surg"},{"key":"4","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0003-4975(99)01433-2","article-title":"Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart","volume":"69","author":"Z. Cao","year":"2000","journal-title":"Ann Thorac Surg"},{"key":"5","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1055\/s-0038-1649929","article-title":"Individual variations in the fibrinolytic response during and after cardiopulmonary bypass","volume":"74","author":"W. Chandler","year":"1995","journal-title":"Thromb Haemost"},{"key":"6","first-page":"583","article-title":"Plasmin generation and D-dimer formation during cardiopulmonary bypass","volume":"15","author":"W. Chandler","year":"2004","journal-title":"Blood Coagul Fibrinolysis"},{"key":"7","doi-asserted-by":"crossref","DOI":"10.1016\/S0003-4975(01)03211-8","article-title":"Mechanisms and attenuation of hemostatic activation during extracorporeal circulation","volume":"72","author":"G. Despotis","year":"2001","journal-title":"Ann Thorac Surg"},{"key":"8","first-page":"27","article-title":"The inhibitory actions of protease inhibitors on the production of polymorphonuclear leukocyte elastase and interleukin 8","volume":"82","author":"S. Endo","year":"1993","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0003-4975(03)00194-2","article-title":"Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10","volume":"76","author":"P. Giomarelli","year":"2003","journal-title":"Ann Thorac Surg"},{"key":"10","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/S0022-5223(03)00946-2","article-title":"Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of epsilon-aminocaproic acid and aprotinin","volume":"126","author":"P. Greilich","year":"2003","journal-title":"J Thorac Cardiovasc Surg"},{"key":"11","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S0967-2109(01)00129-6","article-title":"Hemorrhage related reexploration following open heart surgery: the impact of pre-operative and postoperative coagulation testing","volume":"10","author":"T. Hall","year":"2002","journal-title":"Cardiovasc Surg"},{"key":"12","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/S0022-5223(19)36612-7","article-title":"The effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation","volume":"101","author":"M. Havel","year":"1991","journal-title":"J Thorac Cardiovasc Surg"},{"key":"13","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1248\/bpb.21.651","article-title":"Human neutrophil elastase degrades inter-alpha-trypsin inhibitor to liberate urinary trypsin inhibitor related proteins","volume":"21","author":"J. Hirose","year":"1998","journal-title":"Biol Pharm Bull"},{"key":"14","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S0003-4975(97)01345-3","article-title":"Activation of coagulation and fibrinolysis during cardiothoracic operations","volume":"65","author":"B. Hunt","year":"1998","journal-title":"Ann Thorac Surg"},{"key":"15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1749-8090-2-17","article-title":"Factors associated with excessive bleeding in cardiopulmonary bypass patients: a nested case-control study","volume":"2","author":"J. Jimenez Rivera","year":"2007","journal-title":"J Cardiothorac Surg"},{"key":"16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1213\/ANE.0b013e3181c0ea6d","article-title":"The risk-benefit profile of aprotinin versus tranexamic acid in cardiac surgery","volume":"110","author":"K. Karkouti","year":"2010","journal-title":"Anesth Analg"},{"key":"17","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1111\/j.1537-2995.2004.04144.x","article-title":"The independent association of massive blood loss with mortality in cardiac surgery","volume":"44","author":"K. Karkouti","year":"2004","journal-title":"Transfusion"},{"key":"18","first-page":"305","article-title":"Fibrinolysis and extracorporeal circulation","volume":"38","author":"C. Kluft","year":"1992","journal-title":"Agents Actions Suppl"},{"key":"19","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.athoracsur.2005.12.037","article-title":"Transfusion in coronary artery bypass grafting is associated with reduced long-term survival","volume":"81","author":"C. Koch","year":"2006","journal-title":"Ann Thorac Surg"},{"key":"20","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/01.shk.0000074483.07619.4b","article-title":"Urinary trypsin inhibitor improves peripheral microcirculation and bronchospasm associated with systemic anaphylaxis in rabbits in vivo","volume":"20","author":"M. Komori","year":"2003","journal-title":"Shock"},{"key":"21","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1111\/j.1399-6576.2005.00809.x","article-title":"The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery","volume":"49","author":"A. Kuitunen","year":"2005","journal-title":"Acta Anaesthesiol Scand"},{"key":"22","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/S1010-7940(03)00137-4","article-title":"Risk factors for sternal wound infection and mid-term survival following coronary artery bypass surgery","volume":"23","author":"J. Lu","year":"2003","journal-title":"Eur J Cardiothorac Surg"},{"key":"23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1378\/chest.119.1.31","article-title":"Evidence for inflammatory responses of the lungs during coronary artery bypass grafting with cardiopulmonary bypass","volume":"119","author":"P. Massoudy","year":"2001","journal-title":"Chest"},{"key":"24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1161\/01.CIR.99.1.81","article-title":"Is epsilon-aminocaproic acid as effective as apotinin in reducing bleeding with cardiac surgery? A meta-analysis","volume":"99","author":"J. Munoz","year":"1999","journal-title":"Circulation"},{"key":"25","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3109\/08860229609047715","article-title":"Ulinastatin ameliorates acute ischemic renal injury in rats","volume":"18","author":"H. Nakahama","year":"1996","journal-title":"Ren Fail"},{"key":"26","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1097\/01.CCM.0000215110.55899.AE","article-title":"Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction","volume":"34","author":"K. Nakanishi","year":"2006","journal-title":"Crit Care Med"},{"key":"27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1189\/jlb.69.2.241","article-title":"Inhibitory effect of serine protease inhibitors on neutrophil-mediated endothelial cell injury","volume":"69","author":"K. Nakatani","year":"2001","journal-title":"J Leukoc Biol"},{"key":"28","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1016\/j.transproceed.2006.08.166","article-title":"Ulinastatin attenuates lung ischemia-reperfusion injury in rats by inhibiting tumor necrosis factor alpha","volume":"38","author":"B. Ren","year":"2006","journal-title":"Transplant Proc"},{"key":"29","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1191\/0267659102pf543oa","article-title":"The systemic inflammatory response syndrome following cardiac surgery: different expression of proinflammatory cytokines and procalcitonin in patients with and without multiorgan dysfunctions","volume":"17","author":"A. Sablotzki","year":"2002","journal-title":"Perfusion"},{"key":"30","first-page":"549","article-title":"Antifibrinolytics and cardiac surgery with cardiopulmonary bypass [in Portuguese]","volume":"57","author":"A. Santos","year":"2007","journal-title":"Rev Bras Anestesiol"},{"key":"31","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/BF03218170","article-title":"Induction of acute-phase reactive substances during open-heart surgery and efficacy of ulinastatin. Inhibiting cytokines and postoperative organ injury","volume":"48","author":"Y. Sato","year":"2000","journal-title":"Jpn J Thorac Cardiovasc Surg"},{"key":"32","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1213\/00000539-199712000-00008","article-title":"The effects of epislon-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery","volume":"85","author":"T. Slaughter","year":"1997","journal-title":"Anesth Analg"},{"key":"33","first-page":"437","article-title":"Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass","volume":"43","author":"T. Sugita","year":"2002","journal-title":"J Cardiovasc Surg"},{"key":"34","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1161\/01.CIR.0000157737.92938.D8","article-title":"Relationship between race and mortality and morbidity after valve replacement surgery","volume":"111","author":"N. Taylor","year":"2005","journal-title":"Circulation"},{"key":"35","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1378\/chest.112.3.676","article-title":"Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies","volume":"112","author":"S. Wan","year":"1997","journal-title":"Chest"}],"container-title":["The Heart Surgery Forum"],"original-title":[],"link":[{"URL":"http:\/\/journal.hsforum.com\/index.php\/HSF\/article\/viewFile\/528\/532","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T18:22:53Z","timestamp":1759429373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/HSF\/16\/1\/10.1532\/HSF98.20121072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,25]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,2,1]]}},"URL":"https:\/\/doi.org\/10.1532\/hsf98.20121072","relation":{},"ISSN":["1522-6662","1098-3511"],"issn-type":[{"value":"1522-6662","type":"electronic"},{"value":"1098-3511","type":"print"}],"subject":[],"published":{"date-parts":[[2013,2,25]]}}}