Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of ϵ-aminocaproic acid and aprotinin
Aprotinin is a broad-spectrum serine protease inhibitor that has been shown to attenuate the systemic inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass. Although ϵ-aminocaproic acid is similar to aprotinin in its ability to inhibit excessive fibrinolysis (ie, p...
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| Veröffentlicht in: | The Journal of thoracic and cardiovascular surgery 2003-11, Vol.126 (5), p.1498-1503 |
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| creator | Greilich, Philip E Brouse, Chad F Whitten, Charles W Chi, Lei DiMaio, J.Michael Jessen, Michael E |
| description | Aprotinin is a broad-spectrum serine protease inhibitor that has been shown to attenuate the systemic inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass. Although ϵ-aminocaproic acid is similar to aprotinin in its ability to inhibit excessive fibrinolysis (ie, plasmin activity and D-dimer formation), its ability to influence proinflammatory cytokine production remains unclear. This study was designed to compare the effects of ϵ-aminocaproic acid and aprotinin on plasma levels of interleukin-6 and interleukin-8 during and after cardiopulmonary bypass.
Sixty patients were randomized in a double-blind fashion to receive ϵ-aminocaproic acid, aprotinin, or saline (placebo) in similar dosing regimens (loading dose, pump prime, and infusion). Arterial blood samples were collected before, during, and after cardiopulmonary bypass, and plasma levels of D-dimer, interleukin-6, and interleukin-8 were measured. Data were analyzed using repeated measures analysis of variance.
Both ϵ-aminocaproic acid and aprotinin administration resulted in significant (
P < .05) reductions in D-dimer and interleukin-8 levels compared with saline. These reductions in D-dimer and interleukin-8 levels did not differ between the 2 drug-treated groups. The effect of these two antifibrinolytic agents on interleukin-6 was qualitatively similar to that noted with interleukin-8 but did not reach statistical significance.
When dosed in a similar manner, ϵ-aminocaproic acid seems to be as effective as aprotinin at reducing interleukin-6 and interleukin-8 levels in patients undergoing primary coronary artery bypass graft surgery. These data indicate that suppression of excessive plasmin activity or D-dimer formation or both may play an important role in the generation of proinflammatory cytokines during and after cardiopulmonary bypass. |
| doi_str_mv | 10.1016/S0022-5223(03)00946-2 |
| format | Article |
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Sixty patients were randomized in a double-blind fashion to receive ϵ-aminocaproic acid, aprotinin, or saline (placebo) in similar dosing regimens (loading dose, pump prime, and infusion). Arterial blood samples were collected before, during, and after cardiopulmonary bypass, and plasma levels of D-dimer, interleukin-6, and interleukin-8 were measured. Data were analyzed using repeated measures analysis of variance.
Both ϵ-aminocaproic acid and aprotinin administration resulted in significant (
P < .05) reductions in D-dimer and interleukin-8 levels compared with saline. These reductions in D-dimer and interleukin-8 levels did not differ between the 2 drug-treated groups. The effect of these two antifibrinolytic agents on interleukin-6 was qualitatively similar to that noted with interleukin-8 but did not reach statistical significance.
When dosed in a similar manner, ϵ-aminocaproic acid seems to be as effective as aprotinin at reducing interleukin-6 and interleukin-8 levels in patients undergoing primary coronary artery bypass graft surgery. These data indicate that suppression of excessive plasmin activity or D-dimer formation or both may play an important role in the generation of proinflammatory cytokines during and after cardiopulmonary bypass.</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1016/S0022-5223(03)00946-2</identifier><identifier>PMID: 14666025</identifier><language>eng</language><publisher>United States: Mosby, Inc</publisher><subject>Aged ; Aminocaproic Acid - administration & dosage ; Antifibrinolytic Agents - administration & dosage ; Aprotinin - administration & dosage ; Cardiopulmonary Bypass - adverse effects ; Cardiopulmonary Bypass - methods ; Coronary Artery Bypass - adverse effects ; Coronary Artery Bypass - methods ; Coronary Disease - surgery ; Cytokines - blood ; Cytokines - drug effects ; Double-Blind Method ; Female ; Fibrin Fibrinogen Degradation Products - analysis ; Follow-Up Studies ; Humans ; Inflammation Mediators - blood ; Infusions, Intravenous ; Interleukin-6 - analysis ; Interleukin-8 - analysis ; Intraoperative Complications - prevention & control ; Male ; Middle Aged ; Postoperative Complications - prevention & control ; Probability ; Reference Values ; Risk Assessment ; Treatment Outcome</subject><ispartof>The Journal of thoracic and cardiovascular surgery, 2003-11, Vol.126 (5), p.1498-1503</ispartof><rights>2003 The American Association for Thoracic Surgery</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-42f23b9777fdb864d4326d4f1de1585e8f6a0f6035c92422fdd8cf4bd78135e73</citedby><cites>FETCH-LOGICAL-c408t-42f23b9777fdb864d4326d4f1de1585e8f6a0f6035c92422fdd8cf4bd78135e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0022-5223(03)00946-2$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14666025$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Greilich, Philip E</creatorcontrib><creatorcontrib>Brouse, Chad F</creatorcontrib><creatorcontrib>Whitten, Charles W</creatorcontrib><creatorcontrib>Chi, Lei</creatorcontrib><creatorcontrib>DiMaio, J.Michael</creatorcontrib><creatorcontrib>Jessen, Michael E</creatorcontrib><title>Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of ϵ-aminocaproic acid and aprotinin</title><title>The Journal of thoracic and cardiovascular surgery</title><addtitle>J Thorac Cardiovasc Surg</addtitle><description>Aprotinin is a broad-spectrum serine protease inhibitor that has been shown to attenuate the systemic inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass. Although ϵ-aminocaproic acid is similar to aprotinin in its ability to inhibit excessive fibrinolysis (ie, plasmin activity and D-dimer formation), its ability to influence proinflammatory cytokine production remains unclear. This study was designed to compare the effects of ϵ-aminocaproic acid and aprotinin on plasma levels of interleukin-6 and interleukin-8 during and after cardiopulmonary bypass.
Sixty patients were randomized in a double-blind fashion to receive ϵ-aminocaproic acid, aprotinin, or saline (placebo) in similar dosing regimens (loading dose, pump prime, and infusion). Arterial blood samples were collected before, during, and after cardiopulmonary bypass, and plasma levels of D-dimer, interleukin-6, and interleukin-8 were measured. Data were analyzed using repeated measures analysis of variance.
Both ϵ-aminocaproic acid and aprotinin administration resulted in significant (
P < .05) reductions in D-dimer and interleukin-8 levels compared with saline. These reductions in D-dimer and interleukin-8 levels did not differ between the 2 drug-treated groups. The effect of these two antifibrinolytic agents on interleukin-6 was qualitatively similar to that noted with interleukin-8 but did not reach statistical significance.
When dosed in a similar manner, ϵ-aminocaproic acid seems to be as effective as aprotinin at reducing interleukin-6 and interleukin-8 levels in patients undergoing primary coronary artery bypass graft surgery. These data indicate that suppression of excessive plasmin activity or D-dimer formation or both may play an important role in the generation of proinflammatory cytokines during and after cardiopulmonary bypass.</description><subject>Aged</subject><subject>Aminocaproic Acid - administration & dosage</subject><subject>Antifibrinolytic Agents - administration & dosage</subject><subject>Aprotinin - administration & dosage</subject><subject>Cardiopulmonary Bypass - adverse effects</subject><subject>Cardiopulmonary Bypass - methods</subject><subject>Coronary Artery Bypass - adverse effects</subject><subject>Coronary Artery Bypass - methods</subject><subject>Coronary Disease - surgery</subject><subject>Cytokines - blood</subject><subject>Cytokines - drug effects</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Fibrin Fibrinogen Degradation Products - analysis</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Inflammation Mediators - blood</subject><subject>Infusions, Intravenous</subject><subject>Interleukin-6 - analysis</subject><subject>Interleukin-8 - analysis</subject><subject>Intraoperative Complications - prevention & control</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Postoperative Complications - prevention & control</subject><subject>Probability</subject><subject>Reference Values</subject><subject>Risk Assessment</subject><subject>Treatment Outcome</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd-K1TAQxoMo7tnVR1ByJS5YTdI07fFGlsV_sOCFCt6FNJloNE26SbpQ38sbX8JXMvUc9FIYGGbym_nCfAg9oOQpJVQ8e08IY03HWPuYtOeE7Llo2C20o2TfN2LoPt1Gu7_ICTrN-SshpCd0fxedUC6EIKzboZ8XoTjrxuRC9GtxGpcvkNS8YrPU3mesVTIuzoufYlBpxeM6q5xxArNoyHhO0QXr1TSpEuuzXkv85gJgDzfg83OscFLBxMl9B_MEm7iMHprRu1Cr2SsNY2x0DCVF78HgXBaz4mjxrx-NmuqntNokNFbaGVw34a0uLrhwD92xyme4f8xn6OOrlx8u3zRX716_vby4ajQnQ2k4s6wd933fWzMOghveMmG4pQZoN3QwWKGIFaTt9J5xxqwxg7Z8NP1A2w769gw9OuytwtcL5CInlzV4rwLEJcueci46zirYHUCdYs4JrJyTm-rRJCVyM03-MU1ujkhSYzNNbnMPjwLLOIH5N3V0qQIvDkC9KNw4SDJrB0GDcQl0kSa6_0j8BgXVrXY</recordid><startdate>20031101</startdate><enddate>20031101</enddate><creator>Greilich, Philip E</creator><creator>Brouse, Chad F</creator><creator>Whitten, Charles W</creator><creator>Chi, Lei</creator><creator>DiMaio, J.Michael</creator><creator>Jessen, Michael E</creator><general>Mosby, Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20031101</creationdate><title>Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of ϵ-aminocaproic acid and aprotinin</title><author>Greilich, Philip E ; Brouse, Chad F ; Whitten, Charles W ; Chi, Lei ; DiMaio, J.Michael ; Jessen, Michael E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-42f23b9777fdb864d4326d4f1de1585e8f6a0f6035c92422fdd8cf4bd78135e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aged</topic><topic>Aminocaproic Acid - administration & dosage</topic><topic>Antifibrinolytic Agents - administration & dosage</topic><topic>Aprotinin - administration & dosage</topic><topic>Cardiopulmonary Bypass - adverse effects</topic><topic>Cardiopulmonary Bypass - methods</topic><topic>Coronary Artery Bypass - adverse effects</topic><topic>Coronary Artery Bypass - methods</topic><topic>Coronary Disease - surgery</topic><topic>Cytokines - blood</topic><topic>Cytokines - drug effects</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Fibrin Fibrinogen Degradation Products - analysis</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Inflammation Mediators - blood</topic><topic>Infusions, Intravenous</topic><topic>Interleukin-6 - analysis</topic><topic>Interleukin-8 - analysis</topic><topic>Intraoperative Complications - prevention & control</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Postoperative Complications - prevention & control</topic><topic>Probability</topic><topic>Reference Values</topic><topic>Risk Assessment</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Greilich, Philip E</creatorcontrib><creatorcontrib>Brouse, Chad F</creatorcontrib><creatorcontrib>Whitten, Charles W</creatorcontrib><creatorcontrib>Chi, Lei</creatorcontrib><creatorcontrib>DiMaio, J.Michael</creatorcontrib><creatorcontrib>Jessen, Michael E</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Greilich, Philip E</au><au>Brouse, Chad F</au><au>Whitten, Charles W</au><au>Chi, Lei</au><au>DiMaio, J.Michael</au><au>Jessen, Michael E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of ϵ-aminocaproic acid and aprotinin</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2003-11-01</date><risdate>2003</risdate><volume>126</volume><issue>5</issue><spage>1498</spage><epage>1503</epage><pages>1498-1503</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><abstract>Aprotinin is a broad-spectrum serine protease inhibitor that has been shown to attenuate the systemic inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass. Although ϵ-aminocaproic acid is similar to aprotinin in its ability to inhibit excessive fibrinolysis (ie, plasmin activity and D-dimer formation), its ability to influence proinflammatory cytokine production remains unclear. This study was designed to compare the effects of ϵ-aminocaproic acid and aprotinin on plasma levels of interleukin-6 and interleukin-8 during and after cardiopulmonary bypass.
Sixty patients were randomized in a double-blind fashion to receive ϵ-aminocaproic acid, aprotinin, or saline (placebo) in similar dosing regimens (loading dose, pump prime, and infusion). Arterial blood samples were collected before, during, and after cardiopulmonary bypass, and plasma levels of D-dimer, interleukin-6, and interleukin-8 were measured. Data were analyzed using repeated measures analysis of variance.
Both ϵ-aminocaproic acid and aprotinin administration resulted in significant (
P < .05) reductions in D-dimer and interleukin-8 levels compared with saline. These reductions in D-dimer and interleukin-8 levels did not differ between the 2 drug-treated groups. The effect of these two antifibrinolytic agents on interleukin-6 was qualitatively similar to that noted with interleukin-8 but did not reach statistical significance.
When dosed in a similar manner, ϵ-aminocaproic acid seems to be as effective as aprotinin at reducing interleukin-6 and interleukin-8 levels in patients undergoing primary coronary artery bypass graft surgery. These data indicate that suppression of excessive plasmin activity or D-dimer formation or both may play an important role in the generation of proinflammatory cytokines during and after cardiopulmonary bypass.</abstract><cop>United States</cop><pub>Mosby, Inc</pub><pmid>14666025</pmid><doi>10.1016/S0022-5223(03)00946-2</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
| subjects | Aged Aminocaproic Acid - administration & dosage Antifibrinolytic Agents - administration & dosage Aprotinin - administration & dosage Cardiopulmonary Bypass - adverse effects Cardiopulmonary Bypass - methods Coronary Artery Bypass - adverse effects Coronary Artery Bypass - methods Coronary Disease - surgery Cytokines - blood Cytokines - drug effects Double-Blind Method Female Fibrin Fibrinogen Degradation Products - analysis Follow-Up Studies Humans Inflammation Mediators - blood Infusions, Intravenous Interleukin-6 - analysis Interleukin-8 - analysis Intraoperative Complications - prevention & control Male Middle Aged Postoperative Complications - prevention & control Probability Reference Values Risk Assessment Treatment Outcome |
| title | Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of ϵ-aminocaproic acid and aprotinin |
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