Leukocyte elastase inhibition and t-PA-induced coronary artery thrombolysis in dogs: Beneficial effects on myocardial histology
Leukocyte-derived elastase is released following coronary artery occlusion and reperfusion and may contribute to reperfusion-related myocardial injury. Leukocyte infiltration into the reperfused myocardium may also contribute to ischemic injury following reflow. In the present study, we examined the...
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| Veröffentlicht in: | The American heart journal 1991-11, Vol.122 (5), p.1245-1251 |
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| container_title | The American heart journal |
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| creator | Nicolini, F.A. Mehta, J.L. Nichols, W.W. Donnelly, W.H. Luostarinen, R. Saldeen, T.G.P. |
| description | Leukocyte-derived elastase is released following coronary artery occlusion and reperfusion and may contribute to reperfusion-related myocardial injury. Leukocyte infiltration into the reperfused myocardium may also contribute to ischemic injury following reflow. In the present study, we examined the effects of tissue-plasminogen activator (t-PA, 1 mg/kg over 20 minutes) given intravenously with either saline or a leukocyte elastase inhibitor (ICI 200,880, 5 mg/kg) in dogs with electrically-induced coronary artery thrombosis. ICI 200,880 administration increased elastase inhibitory activity without affecting t-PA and plasminogen activator inhibitor (PAI-1) activities. Time to reflow, magnitude of peak coronary blood flow, and duration of reflow were not different in dogs given t-PA with saline or with the elastase inhibitor. However, administration of the elastase inhibitor decreased the histologically-determined leukocyte infiltration and severity of myocardial injury in dogs subjected to coronary artery thrombosis and subsequent thrombolysis. These early observations suggest that elastase release during reperfusion may be an important mediator of anoxia-reoxygenation-mediated tissue injury. |
| doi_str_mv | 10.1016/0002-8703(91)90562-V |
| format | Article |
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Leukocyte infiltration into the reperfused myocardium may also contribute to ischemic injury following reflow. In the present study, we examined the effects of tissue-plasminogen activator (t-PA, 1 mg/kg over 20 minutes) given intravenously with either saline or a leukocyte elastase inhibitor (ICI 200,880, 5 mg/kg) in dogs with electrically-induced coronary artery thrombosis. ICI 200,880 administration increased elastase inhibitory activity without affecting t-PA and plasminogen activator inhibitor (PAI-1) activities. Time to reflow, magnitude of peak coronary blood flow, and duration of reflow were not different in dogs given t-PA with saline or with the elastase inhibitor. However, administration of the elastase inhibitor decreased the histologically-determined leukocyte infiltration and severity of myocardial injury in dogs subjected to coronary artery thrombosis and subsequent thrombolysis. These early observations suggest that elastase release during reperfusion may be an important mediator of anoxia-reoxygenation-mediated tissue injury.</description><identifier>ISSN: 0002-8703</identifier><identifier>EISSN: 1097-6744</identifier><identifier>DOI: 10.1016/0002-8703(91)90562-V</identifier><identifier>PMID: 1950986</identifier><identifier>CODEN: AHJOA2</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Animals ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Coronary Thrombosis - blood ; Coronary Thrombosis - drug therapy ; Coronary Thrombosis - pathology ; Dogs ; Drug Evaluation, Preclinical ; Drug Therapy, Combination ; Heart - drug effects ; Leukocytes - drug effects ; Leukocytes - enzymology ; Medical sciences ; Myocardium - pathology ; Oligopeptides - therapeutic use ; Pancreatic Elastase - antagonists & inhibitors ; Pharmacology. Drug treatments ; Plasminogen Inactivators - blood ; Thrombolytic Therapy ; Tissue Plasminogen Activator - blood ; Tissue Plasminogen Activator - therapeutic use</subject><ispartof>The American heart journal, 1991-11, Vol.122 (5), p.1245-1251</ispartof><rights>1991</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-e42b52023e250876dede12ccebd479e958407b73617507698cfdb52b001546033</citedby><cites>FETCH-LOGICAL-c386t-e42b52023e250876dede12ccebd479e958407b73617507698cfdb52b001546033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/000287039190562V$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5018517$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1950986$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nicolini, F.A.</creatorcontrib><creatorcontrib>Mehta, J.L.</creatorcontrib><creatorcontrib>Nichols, W.W.</creatorcontrib><creatorcontrib>Donnelly, W.H.</creatorcontrib><creatorcontrib>Luostarinen, R.</creatorcontrib><creatorcontrib>Saldeen, T.G.P.</creatorcontrib><title>Leukocyte elastase inhibition and t-PA-induced coronary artery thrombolysis in dogs: Beneficial effects on myocardial histology</title><title>The American heart journal</title><addtitle>Am Heart J</addtitle><description>Leukocyte-derived elastase is released following coronary artery occlusion and reperfusion and may contribute to reperfusion-related myocardial injury. Leukocyte infiltration into the reperfused myocardium may also contribute to ischemic injury following reflow. In the present study, we examined the effects of tissue-plasminogen activator (t-PA, 1 mg/kg over 20 minutes) given intravenously with either saline or a leukocyte elastase inhibitor (ICI 200,880, 5 mg/kg) in dogs with electrically-induced coronary artery thrombosis. ICI 200,880 administration increased elastase inhibitory activity without affecting t-PA and plasminogen activator inhibitor (PAI-1) activities. Time to reflow, magnitude of peak coronary blood flow, and duration of reflow were not different in dogs given t-PA with saline or with the elastase inhibitor. However, administration of the elastase inhibitor decreased the histologically-determined leukocyte infiltration and severity of myocardial injury in dogs subjected to coronary artery thrombosis and subsequent thrombolysis. These early observations suggest that elastase release during reperfusion may be an important mediator of anoxia-reoxygenation-mediated tissue injury.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Coronary Thrombosis - blood</subject><subject>Coronary Thrombosis - drug therapy</subject><subject>Coronary Thrombosis - pathology</subject><subject>Dogs</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Therapy, Combination</subject><subject>Heart - drug effects</subject><subject>Leukocytes - drug effects</subject><subject>Leukocytes - enzymology</subject><subject>Medical sciences</subject><subject>Myocardium - pathology</subject><subject>Oligopeptides - therapeutic use</subject><subject>Pancreatic Elastase - antagonists & inhibitors</subject><subject>Pharmacology. Drug treatments</subject><subject>Plasminogen Inactivators - blood</subject><subject>Thrombolytic Therapy</subject><subject>Tissue Plasminogen Activator - blood</subject><subject>Tissue Plasminogen Activator - therapeutic use</subject><issn>0002-8703</issn><issn>1097-6744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAURS1EVYbCH4DkBUKwCDw7iZ2wQCoV0EojwQK6tRz7pWNI7GI7SFn11_Ewo7Jj9WS_c6_sQ8gzBm8YMPEWAHjVSahf9ex1D63g1fUDsmHQy0rIpnlINvfII_I4pR_lKHgnTskp61voO7Ehd1tcfgazZqQ46ZR1Qur8zg0uu-Cp9pbm6ut55bxdDFpqQgxex5XqmLGMvIthHsK0JpdKkNpwk97RD-hxdMbpieI4osmJlrJ5DUZHu7_duZTDFG7WJ-Rk1FPCp8d5Rr5_-vjt4rLafvl8dXG-rUzdiVxhw4eWA6-Rt9BJYdEi48bgYBvZY992DchB1oLJFqToOzPaEhgAWNsIqOsz8vLQexvDrwVTVrNLBqdJewxLUpI3HUiAAjYH0MSQUsRR3UY3lx8rBmrvXe2lqr1U1TP117u6LrHnx_5lmNH-Cx1El_2L414no6cxam9cusdaYF3LZMHeHzAsLn47jCoZh76Yd7FoVDa4_7_jDynsoCI</recordid><startdate>19911101</startdate><enddate>19911101</enddate><creator>Nicolini, F.A.</creator><creator>Mehta, J.L.</creator><creator>Nichols, W.W.</creator><creator>Donnelly, W.H.</creator><creator>Luostarinen, R.</creator><creator>Saldeen, T.G.P.</creator><general>Mosby, Inc</general><general>Elsevier</general><scope>IQODW</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>19911101</creationdate><title>Leukocyte elastase inhibition and t-PA-induced coronary artery thrombolysis in dogs: Beneficial effects on myocardial histology</title><author>Nicolini, F.A. ; Mehta, J.L. ; Nichols, W.W. ; Donnelly, W.H. ; Luostarinen, R. ; Saldeen, T.G.P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-e42b52023e250876dede12ccebd479e958407b73617507698cfdb52b001546033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Coronary Thrombosis - blood</topic><topic>Coronary Thrombosis - drug therapy</topic><topic>Coronary Thrombosis - pathology</topic><topic>Dogs</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug Therapy, Combination</topic><topic>Heart - drug effects</topic><topic>Leukocytes - drug effects</topic><topic>Leukocytes - enzymology</topic><topic>Medical sciences</topic><topic>Myocardium - pathology</topic><topic>Oligopeptides - therapeutic use</topic><topic>Pancreatic Elastase - antagonists & inhibitors</topic><topic>Pharmacology. 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Leukocyte infiltration into the reperfused myocardium may also contribute to ischemic injury following reflow. In the present study, we examined the effects of tissue-plasminogen activator (t-PA, 1 mg/kg over 20 minutes) given intravenously with either saline or a leukocyte elastase inhibitor (ICI 200,880, 5 mg/kg) in dogs with electrically-induced coronary artery thrombosis. ICI 200,880 administration increased elastase inhibitory activity without affecting t-PA and plasminogen activator inhibitor (PAI-1) activities. Time to reflow, magnitude of peak coronary blood flow, and duration of reflow were not different in dogs given t-PA with saline or with the elastase inhibitor. However, administration of the elastase inhibitor decreased the histologically-determined leukocyte infiltration and severity of myocardial injury in dogs subjected to coronary artery thrombosis and subsequent thrombolysis. These early observations suggest that elastase release during reperfusion may be an important mediator of anoxia-reoxygenation-mediated tissue injury.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>1950986</pmid><doi>10.1016/0002-8703(91)90562-V</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Coronary Thrombosis - blood Coronary Thrombosis - drug therapy Coronary Thrombosis - pathology Dogs Drug Evaluation, Preclinical Drug Therapy, Combination Heart - drug effects Leukocytes - drug effects Leukocytes - enzymology Medical sciences Myocardium - pathology Oligopeptides - therapeutic use Pancreatic Elastase - antagonists & inhibitors Pharmacology. Drug treatments Plasminogen Inactivators - blood Thrombolytic Therapy Tissue Plasminogen Activator - blood Tissue Plasminogen Activator - therapeutic use |
| title | Leukocyte elastase inhibition and t-PA-induced coronary artery thrombolysis in dogs: Beneficial effects on myocardial histology |
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