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Differential Effects of Thromboxane A2 Synthase Inhibition, Singly or Combined With Thromboxane A2/Prostaglandin Endoperoxide Receptor Antagonism, on Occlusive Thrombosis Elicited by Endothelial Cell Injury or by Deep Vascular Damage in Canine Coronary Arteries
In open-chest dogs, cyclic flow reductions (CFRs, 5.1-6.6/hr in controls; n=24) caused by platelet deposition/dislodgment at sites of endothelial cell injury in critically stenosed left anterior descending coronary arteries (59% flow reduction) were attenuated to the same extent either by single thr...
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| Published in: | Circulation research 1991-08, Vol.69 (2), p.313-324 |
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| container_start_page | 313 |
| container_title | Circulation research |
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| creator | Vandeplassche, Godelieve Hermans, Carlo de Water, Andre Van Xhonneux, Raymond Wouters, Luc Ammel, Karel Van De Clerck, Fred |
| description | In open-chest dogs, cyclic flow reductions (CFRs, 5.1-6.6/hr in controls; n=24) caused by platelet deposition/dislodgment at sites of endothelial cell injury in critically stenosed left anterior descending coronary arteries (59% flow reduction) were attenuated to the same extent either by single thromboxane A2 (TXA2) synthase inhibition (0.31 mg/kg i.v. ridogrel; CFR, 0.16±0.16/hr; n=6; p |
| doi_str_mv | 10.1161/01.RES.69.2.313 |
| format | article |
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By contrast, occlusive thrombosis on deep vascular damage elicited by intraluminal stimulation (150-μA anodal constant current) in nonpreconstricted canine coronary arteries (time to occlusion, 237.1±13.9 minutes; n=7; incidence of occlusion within 300 minutes, six of seven experiments) was not affected by platelet cyclooxygenase inhibition (5 mg/kg i.v. acetylsalicylic acid; n=7), single TXA2 synthase inhibition (1.25 mg/kg i.v. ridogrel; n=7), or single TXA2/prostaglandin endoperoxide receptor antagonism (10 mg/kg+10 mg/kg/hr i.v. sulotroban for 300 minutes; n=5). However, such an occlusive thrombus formation was significantly reduced by combined TXA2 synthase/prostaglandin endoperoxide receptor inhibition (5 mg/kg i.v. ridogrel; time to occlusion >300 minutes, n=7; incidence of occlusion within 300 minutes, one of seven experiments; p<0.05). This study reveals 1) a differential efficacy of TXA2 synthase inhibition, singly or combined with TXA2/prostaglandin endoperoxide receptor antagonism, depending on the extent of the vessel wall lesion triggering thrombosis and the size of the thrombus required to obstruct the vascular lumen and 2) a significant synergism in preventing occlusive thrombosis of extensively damaged coronary arteries between strong TXA2 synthase inhibition and comparatively modest TXA2/prostaglandin endoperoxide receptor antagonism with ridogrel. (Circulation Research 1991;69:313-324)</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.RES.69.2.313</identifier><identifier>PMID: 1830517</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Animals ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Coronary Thrombosis - etiology ; Coronary Thrombosis - pathology ; Coronary Vessels - pathology ; Dogs ; Endothelium, Vascular - pathology ; Female ; Hemodynamics ; In Vitro Techniques ; Male ; Medical sciences ; Pentanoic Acids - pharmacology ; Pharmacology. Drug treatments ; Pyridines - pharmacology ; Receptors, Prostaglandin - antagonists & inhibitors ; Receptors, Thromboxane ; Sulfonamides - pharmacology ; Thromboxane A2 ; Thromboxane-A Synthase - antagonists & inhibitors</subject><ispartof>Circulation research, 1991-08, Vol.69 (2), p.313-324</ispartof><rights>1991 American Heart Association, Inc.</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4436-267b3df5f85fe406f3e9aaf9882525a8d139917bf44fe499d29c1c2e9c3aaeee3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5123068$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1830517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vandeplassche, Godelieve</creatorcontrib><creatorcontrib>Hermans, Carlo</creatorcontrib><creatorcontrib>de Water, Andre Van</creatorcontrib><creatorcontrib>Xhonneux, Raymond</creatorcontrib><creatorcontrib>Wouters, Luc</creatorcontrib><creatorcontrib>Ammel, Karel Van</creatorcontrib><creatorcontrib>De Clerck, Fred</creatorcontrib><title>Differential Effects of Thromboxane A2 Synthase Inhibition, Singly or Combined With Thromboxane A2/Prostaglandin Endoperoxide Receptor Antagonism, on Occlusive Thrombosis Elicited by Endothelial Cell Injury or by Deep Vascular Damage in Canine Coronary Arteries</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>In open-chest dogs, cyclic flow reductions (CFRs, 5.1-6.6/hr in controls; n=24) caused by platelet deposition/dislodgment at sites of endothelial cell injury in critically stenosed left anterior descending coronary arteries (59% flow reduction) were attenuated to the same extent either by single thromboxane A2 (TXA2) synthase inhibition (0.31 mg/kg i.v. ridogrel; CFR, 0.16±0.16/hr; n=6; p<0.05) or by a comparatively modest degree of TXA2/prostaglandin endoperoxide receptor antagonism on top of TXA2 synthase inhibition (5 mg/kg i.v. ridogrel; CFR, 0.22±0.1/hr; n=10; p<0.05). By contrast, occlusive thrombosis on deep vascular damage elicited by intraluminal stimulation (150-μA anodal constant current) in nonpreconstricted canine coronary arteries (time to occlusion, 237.1±13.9 minutes; n=7; incidence of occlusion within 300 minutes, six of seven experiments) was not affected by platelet cyclooxygenase inhibition (5 mg/kg i.v. acetylsalicylic acid; n=7), single TXA2 synthase inhibition (1.25 mg/kg i.v. ridogrel; n=7), or single TXA2/prostaglandin endoperoxide receptor antagonism (10 mg/kg+10 mg/kg/hr i.v. sulotroban for 300 minutes; n=5). However, such an occlusive thrombus formation was significantly reduced by combined TXA2 synthase/prostaglandin endoperoxide receptor inhibition (5 mg/kg i.v. ridogrel; time to occlusion >300 minutes, n=7; incidence of occlusion within 300 minutes, one of seven experiments; p<0.05). This study reveals 1) a differential efficacy of TXA2 synthase inhibition, singly or combined with TXA2/prostaglandin endoperoxide receptor antagonism, depending on the extent of the vessel wall lesion triggering thrombosis and the size of the thrombus required to obstruct the vascular lumen and 2) a significant synergism in preventing occlusive thrombosis of extensively damaged coronary arteries between strong TXA2 synthase inhibition and comparatively modest TXA2/prostaglandin endoperoxide receptor antagonism with ridogrel. (Circulation Research 1991;69:313-324)</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Coronary Thrombosis - etiology</subject><subject>Coronary Thrombosis - pathology</subject><subject>Coronary Vessels - pathology</subject><subject>Dogs</subject><subject>Endothelium, Vascular - pathology</subject><subject>Female</subject><subject>Hemodynamics</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pentanoic Acids - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyridines - pharmacology</subject><subject>Receptors, Prostaglandin - antagonists & inhibitors</subject><subject>Receptors, Thromboxane</subject><subject>Sulfonamides - pharmacology</subject><subject>Thromboxane A2</subject><subject>Thromboxane-A Synthase - antagonists & inhibitors</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><recordid>eNpdkstvEzEQxhdEVULhzAnJB8Spm_ixLx-jJEClSkVNgePK653Nujh2sHdp898zaQJInPyY33zzecZJ8pbRKWMFm1E2vV2tp4Wc8qlg4nkyYTnP0iwv2YtkQimVaSkEfZm8ivGeUpYJLs-Tc1YJmrNy8uxsaboOArjBKEtWuNdDJL4jd33w28Y_Kgdkzsl674ZeRSBXrjeNGYx3l2Rt3MbuiQ9kgaxx0JLvZuj_y519CT4OamOVa40jK9f6HQT_aFogt6BhN6DA3CHhnYnbS-IdudHajtH8gj9a0USyskabAYs0-yeVoQd7cL0Aa9HX_RievGB0CbAj31TUo1WBLNVWbYBg7YVy6BLdBu8U0vMwQDAQXydnnbIR3pzWi-Trx9Xd4nN6ffPpajG_TnWWiSLlRdmItsu7Ku8go0UnQCrVyariOc9V1TIhJSubLsswLmXLpWaag9RCKQAQF8mHo-4u-J8jxKHemqjRPnbKj7GuaEkloxLB2RHU2LsYoKt3wWzRcs1ofRh8TVmNg68LWfMaB48Z707SY7OF9h9_nDTG35_i2BZlu6CcNvEvljMuaFEhlh2xB2-xN_GHHR8g1D0oO_Q1_icqKOMpw3fSCk_p4aoQvwHUnspc</recordid><startdate>199108</startdate><enddate>199108</enddate><creator>Vandeplassche, Godelieve</creator><creator>Hermans, Carlo</creator><creator>de Water, Andre Van</creator><creator>Xhonneux, Raymond</creator><creator>Wouters, Luc</creator><creator>Ammel, Karel Van</creator><creator>De Clerck, Fred</creator><general>American Heart Association, Inc</general><general>Lippincott</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>199108</creationdate><title>Differential Effects of Thromboxane A2 Synthase Inhibition, Singly or Combined With Thromboxane A2/Prostaglandin Endoperoxide Receptor Antagonism, on Occlusive Thrombosis Elicited by Endothelial Cell Injury or by Deep Vascular Damage in Canine Coronary Arteries</title><author>Vandeplassche, Godelieve ; Hermans, Carlo ; de Water, Andre Van ; Xhonneux, Raymond ; Wouters, Luc ; Ammel, Karel Van ; De Clerck, Fred</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4436-267b3df5f85fe406f3e9aaf9882525a8d139917bf44fe499d29c1c2e9c3aaeee3</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 - etiology</topic><topic>Coronary Thrombosis - pathology</topic><topic>Coronary Vessels - pathology</topic><topic>Dogs</topic><topic>Endothelium, Vascular - pathology</topic><topic>Female</topic><topic>Hemodynamics</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pentanoic Acids - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyridines - pharmacology</topic><topic>Receptors, Prostaglandin - antagonists & inhibitors</topic><topic>Receptors, Thromboxane</topic><topic>Sulfonamides - pharmacology</topic><topic>Thromboxane A2</topic><topic>Thromboxane-A Synthase - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vandeplassche, Godelieve</creatorcontrib><creatorcontrib>Hermans, Carlo</creatorcontrib><creatorcontrib>de Water, Andre Van</creatorcontrib><creatorcontrib>Xhonneux, Raymond</creatorcontrib><creatorcontrib>Wouters, Luc</creatorcontrib><creatorcontrib>Ammel, Karel Van</creatorcontrib><creatorcontrib>De Clerck, Fred</creatorcontrib><collection>Pascal-Francis</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>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vandeplassche, Godelieve</au><au>Hermans, Carlo</au><au>de Water, Andre Van</au><au>Xhonneux, Raymond</au><au>Wouters, Luc</au><au>Ammel, Karel Van</au><au>De Clerck, Fred</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential Effects of Thromboxane A2 Synthase Inhibition, Singly or Combined With Thromboxane A2/Prostaglandin Endoperoxide Receptor Antagonism, on Occlusive Thrombosis Elicited by Endothelial Cell Injury or by Deep Vascular Damage in Canine Coronary Arteries</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>1991-08</date><risdate>1991</risdate><volume>69</volume><issue>2</issue><spage>313</spage><epage>324</epage><pages>313-324</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>In open-chest dogs, cyclic flow reductions (CFRs, 5.1-6.6/hr in controls; n=24) caused by platelet deposition/dislodgment at sites of endothelial cell injury in critically stenosed left anterior descending coronary arteries (59% flow reduction) were attenuated to the same extent either by single thromboxane A2 (TXA2) synthase inhibition (0.31 mg/kg i.v. ridogrel; CFR, 0.16±0.16/hr; n=6; p<0.05) or by a comparatively modest degree of TXA2/prostaglandin endoperoxide receptor antagonism on top of TXA2 synthase inhibition (5 mg/kg i.v. ridogrel; CFR, 0.22±0.1/hr; n=10; p<0.05). By contrast, occlusive thrombosis on deep vascular damage elicited by intraluminal stimulation (150-μA anodal constant current) in nonpreconstricted canine coronary arteries (time to occlusion, 237.1±13.9 minutes; n=7; incidence of occlusion within 300 minutes, six of seven experiments) was not affected by platelet cyclooxygenase inhibition (5 mg/kg i.v. acetylsalicylic acid; n=7), single TXA2 synthase inhibition (1.25 mg/kg i.v. ridogrel; n=7), or single TXA2/prostaglandin endoperoxide receptor antagonism (10 mg/kg+10 mg/kg/hr i.v. sulotroban for 300 minutes; n=5). However, such an occlusive thrombus formation was significantly reduced by combined TXA2 synthase/prostaglandin endoperoxide receptor inhibition (5 mg/kg i.v. ridogrel; time to occlusion >300 minutes, n=7; incidence of occlusion within 300 minutes, one of seven experiments; p<0.05). This study reveals 1) a differential efficacy of TXA2 synthase inhibition, singly or combined with TXA2/prostaglandin endoperoxide receptor antagonism, depending on the extent of the vessel wall lesion triggering thrombosis and the size of the thrombus required to obstruct the vascular lumen and 2) a significant synergism in preventing occlusive thrombosis of extensively damaged coronary arteries between strong TXA2 synthase inhibition and comparatively modest TXA2/prostaglandin endoperoxide receptor antagonism with ridogrel. (Circulation Research 1991;69:313-324)</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>1830517</pmid><doi>10.1161/01.RES.69.2.313</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation research, 1991-08, Vol.69 (2), p.313-324 |
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| language | eng |
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| source | Freely Accessible Science Journals |
| subjects | Animals Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Coronary Thrombosis - etiology Coronary Thrombosis - pathology Coronary Vessels - pathology Dogs Endothelium, Vascular - pathology Female Hemodynamics In Vitro Techniques Male Medical sciences Pentanoic Acids - pharmacology Pharmacology. Drug treatments Pyridines - pharmacology Receptors, Prostaglandin - antagonists & inhibitors Receptors, Thromboxane Sulfonamides - pharmacology Thromboxane A2 Thromboxane-A Synthase - antagonists & inhibitors |
| title | Differential Effects of Thromboxane A2 Synthase Inhibition, Singly or Combined With Thromboxane A2/Prostaglandin Endoperoxide Receptor Antagonism, on Occlusive Thrombosis Elicited by Endothelial Cell Injury or by Deep Vascular Damage in Canine Coronary Arteries |
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