Effect of aspirin on local prostaglandin production and serotonin accumulation in a canine model with coronary cyclic flow variations or thrombosis
We have reported that thromboxane A 2 and serotonin are two important mediators of coronary cyclic flow variations (CFVs) caused by recurrent platelet aggregation and dislodgement on a stenosed coronary arterial wall with endothelial injury. To test the hypothesis that blocking the synthesis of thro...
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Veröffentlicht in: | Journal of molecular and cellular cardiology 1991-04, Vol.23 (4), p.473-482 |
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creator | Yao, Sheng-Kun Benedict, Claude R. Rosolowsky, Mark McNatt, Janice Falinska, Barbara Campbell, William B. Buja, L.Maximilian Willerson, James T. |
description | We have reported that thromboxane
A
2 and serotonin are two important mediators of coronary cyclic flow variations (CFVs) caused by recurrent platelet aggregation and dislodgement on a stenosed coronary arterial wall with endothelial injury. To test the hypothesis that blocking the synthesis of thromboxane
A
2 would not prevent serotonin release, 1.1, 4.6, and 9.2 mg/kg of aspirin were administered through the left atrium to 27 dogs with CFVs. The CFV elimination rate was 70% in the aspirin-treated dogs. Thromboxane
B
2 and serotonin concentrations were measured in different coronary arterial segments. There were significantly lower thromboxane
B
2 and 6-keto-PFG
1a levels in the stenosed left arterior descending (LAD) segments with increasing dosage of aspirin-208 ± 36, 24 ± 31, 50 ± 6 ng/g (
P |
doi_str_mv | 10.1016/0022-2828(91)90171-H |
format | Article |
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A
2 and serotonin are two important mediators of coronary cyclic flow variations (CFVs) caused by recurrent platelet aggregation and dislodgement on a stenosed coronary arterial wall with endothelial injury. To test the hypothesis that blocking the synthesis of thromboxane
A
2 would not prevent serotonin release, 1.1, 4.6, and 9.2 mg/kg of aspirin were administered through the left atrium to 27 dogs with CFVs. The CFV elimination rate was 70% in the aspirin-treated dogs. Thromboxane
B
2 and serotonin concentrations were measured in different coronary arterial segments. There were significantly lower thromboxane
B
2 and 6-keto-PFG
1a levels in the stenosed left arterior descending (LAD) segments with increasing dosage of aspirin-208 ± 36, 24 ± 31, 50 ± 6 ng/g (
P<0.0001) and 125 ± 27, 58 ± 38, 25 ± 5 ng/g (
P<0.0001), respectively. Serotonin levels were significantly higher in stenosd LAD (265.7 ± 131.2 ng/g) than in LAD segments proximal or distal to the stenosis and in corresponding circumflex coronary artery segments, 17.1 ± 3.7, 18.6 ± 3.7, and 19.2 ± 5.1 ng/g, respectively (
P<0.05) following the highest dose of aspirin. In 41 additional dogs, electrical injury was used to initiate thrombosis in the circumflex artery and in those receiving aspirin (15mg/kg) (
n=5), occlusive thrombus formation was inhibited. However, the local accumulation of serotonin was not significantly different between the control (194 ± 27 ng/g) (
n=36) and the aspirin-treated group (167 ± 19 ng/g) (
n=5).
In vitro platelet aggregation induced by arachidonic acid was inhibited by the
in vivo adminstration of 1.1 mg/kg of aspirin and abolished by 4.6 + 1.1 and 9.2 + 4.6 + 1.1 mg/kg of aspirin. However, serotonin-induced platelet aggregation was not affected following all doses of aspirin. Thus, aspirin eliminates CFVs in 70% of dogs, and markedly diminishes thromboxane
A
2 and prostacyclin concentrations in stenosed canine coronary arteries, but it does not prevent local serotonin accumulation. Similarly, aspirin prevents occlusive coronary thrombosis in dogs with electrically-induced endothelial injury, but it did not prevent local assumulation of serotonin. These experimental findings suggest that cyclo-oxygenese inhibition does not prevent serotonin accumulation at sites of coronary artery endothelial injury, and they thereby help provide a potential explanation of the lack of complete protection provided by aspirin in eliminating CFVs in this experimental model.</description><identifier>ISSN: 0022-2828</identifier><identifier>EISSN: 1095-8584</identifier><identifier>DOI: 10.1016/0022-2828(91)90171-H</identifier><identifier>PMID: 1942081</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>6-Ketoprostaglandin F1 alpha - biosynthesis ; Animals ; Aspirin ; Aspirin - pharmacology ; Coronary Circulation - drug effects ; Coronary Disease - metabolism ; Coronary stenosis ; Coronary Thrombosis - metabolism ; Dogs ; Electricity ; Female ; Male ; Platelet Aggregation ; Prostaglandin ; Serotonin ; Serotonin - metabolism ; Thromboxane B2 - biosynthesis</subject><ispartof>Journal of molecular and cellular cardiology, 1991-04, Vol.23 (4), p.473-482</ispartof><rights>1991</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-42190434b055a6422325025d868b93183b30a8cbb43f614db18f5e2fef6997b13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0022-2828(91)90171-H$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1942081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yao, Sheng-Kun</creatorcontrib><creatorcontrib>Benedict, Claude R.</creatorcontrib><creatorcontrib>Rosolowsky, Mark</creatorcontrib><creatorcontrib>McNatt, Janice</creatorcontrib><creatorcontrib>Falinska, Barbara</creatorcontrib><creatorcontrib>Campbell, William B.</creatorcontrib><creatorcontrib>Buja, L.Maximilian</creatorcontrib><creatorcontrib>Willerson, James T.</creatorcontrib><title>Effect of aspirin on local prostaglandin production and serotonin accumulation in a canine model with coronary cyclic flow variations or thrombosis</title><title>Journal of molecular and cellular cardiology</title><addtitle>J Mol Cell Cardiol</addtitle><description>We have reported that thromboxane
A
2 and serotonin are two important mediators of coronary cyclic flow variations (CFVs) caused by recurrent platelet aggregation and dislodgement on a stenosed coronary arterial wall with endothelial injury. To test the hypothesis that blocking the synthesis of thromboxane
A
2 would not prevent serotonin release, 1.1, 4.6, and 9.2 mg/kg of aspirin were administered through the left atrium to 27 dogs with CFVs. The CFV elimination rate was 70% in the aspirin-treated dogs. Thromboxane
B
2 and serotonin concentrations were measured in different coronary arterial segments. There were significantly lower thromboxane
B
2 and 6-keto-PFG
1a levels in the stenosed left arterior descending (LAD) segments with increasing dosage of aspirin-208 ± 36, 24 ± 31, 50 ± 6 ng/g (
P<0.0001) and 125 ± 27, 58 ± 38, 25 ± 5 ng/g (
P<0.0001), respectively. Serotonin levels were significantly higher in stenosd LAD (265.7 ± 131.2 ng/g) than in LAD segments proximal or distal to the stenosis and in corresponding circumflex coronary artery segments, 17.1 ± 3.7, 18.6 ± 3.7, and 19.2 ± 5.1 ng/g, respectively (
P<0.05) following the highest dose of aspirin. In 41 additional dogs, electrical injury was used to initiate thrombosis in the circumflex artery and in those receiving aspirin (15mg/kg) (
n=5), occlusive thrombus formation was inhibited. However, the local accumulation of serotonin was not significantly different between the control (194 ± 27 ng/g) (
n=36) and the aspirin-treated group (167 ± 19 ng/g) (
n=5).
In vitro platelet aggregation induced by arachidonic acid was inhibited by the
in vivo adminstration of 1.1 mg/kg of aspirin and abolished by 4.6 + 1.1 and 9.2 + 4.6 + 1.1 mg/kg of aspirin. However, serotonin-induced platelet aggregation was not affected following all doses of aspirin. Thus, aspirin eliminates CFVs in 70% of dogs, and markedly diminishes thromboxane
A
2 and prostacyclin concentrations in stenosed canine coronary arteries, but it does not prevent local serotonin accumulation. Similarly, aspirin prevents occlusive coronary thrombosis in dogs with electrically-induced endothelial injury, but it did not prevent local assumulation of serotonin. These experimental findings suggest that cyclo-oxygenese inhibition does not prevent serotonin accumulation at sites of coronary artery endothelial injury, and they thereby help provide a potential explanation of the lack of complete protection provided by aspirin in eliminating CFVs in this experimental model.</description><subject>6-Ketoprostaglandin F1 alpha - biosynthesis</subject><subject>Animals</subject><subject>Aspirin</subject><subject>Aspirin - pharmacology</subject><subject>Coronary Circulation - drug effects</subject><subject>Coronary Disease - metabolism</subject><subject>Coronary stenosis</subject><subject>Coronary Thrombosis - metabolism</subject><subject>Dogs</subject><subject>Electricity</subject><subject>Female</subject><subject>Male</subject><subject>Platelet Aggregation</subject><subject>Prostaglandin</subject><subject>Serotonin</subject><subject>Serotonin - metabolism</subject><subject>Thromboxane B2 - biosynthesis</subject><issn>0022-2828</issn><issn>1095-8584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uc1KJDEYDOKi488bKOQk66HX_PYkF0EGdRYG9rKeQ5JONJLujEm34nP4wpuZEb3tKXxfVX2hqgA4w-gXRri9QoiQhggifkp8KRGe42a5B2YYSd4ILtg-mH1RDsFRKc8IIckoPQAHWDKCBJ6Bj1vvnR1h8lCXdchhgGmAMVkd4TqnMurHqIeuruvUTXYMFa4LWFxOYxoqoK2d-inqLbSZodV172CfOhfhWxifoE05DTq_Q_tuY7DQx_QGX3UOW1WBKcPxKafepBLKCfjhdSzu9PM9Bg93t38Xy2b15_734mbVWMrnY8MIlohRZhDnumWEUMIR4Z1ohZEUC2oo0sIaw6hvMesMFp474p1vpZwbTI_Bxe5utfYyuTKqPhTrYjXs0lTUnDDOpWwrke2ItiZSsvNqnUNf7SiM1KYLtQlabYJWEqttF2pZZeef9yfTu-5btAu_4tc73FWTr8FlVWxwg3VdyLUT1aXw_w_-AWz2myc</recordid><startdate>19910401</startdate><enddate>19910401</enddate><creator>Yao, Sheng-Kun</creator><creator>Benedict, Claude R.</creator><creator>Rosolowsky, Mark</creator><creator>McNatt, Janice</creator><creator>Falinska, Barbara</creator><creator>Campbell, William B.</creator><creator>Buja, L.Maximilian</creator><creator>Willerson, James T.</creator><general>Elsevier Ltd</general><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>19910401</creationdate><title>Effect of aspirin on local prostaglandin production and serotonin accumulation in a canine model with coronary cyclic flow variations or thrombosis</title><author>Yao, Sheng-Kun ; Benedict, Claude R. ; Rosolowsky, Mark ; McNatt, Janice ; Falinska, Barbara ; Campbell, William B. ; Buja, L.Maximilian ; Willerson, James T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-42190434b055a6422325025d868b93183b30a8cbb43f614db18f5e2fef6997b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>6-Ketoprostaglandin F1 alpha - biosynthesis</topic><topic>Animals</topic><topic>Aspirin</topic><topic>Aspirin - pharmacology</topic><topic>Coronary Circulation - drug effects</topic><topic>Coronary Disease - metabolism</topic><topic>Coronary stenosis</topic><topic>Coronary Thrombosis - metabolism</topic><topic>Dogs</topic><topic>Electricity</topic><topic>Female</topic><topic>Male</topic><topic>Platelet Aggregation</topic><topic>Prostaglandin</topic><topic>Serotonin</topic><topic>Serotonin - metabolism</topic><topic>Thromboxane B2 - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yao, Sheng-Kun</creatorcontrib><creatorcontrib>Benedict, Claude R.</creatorcontrib><creatorcontrib>Rosolowsky, Mark</creatorcontrib><creatorcontrib>McNatt, Janice</creatorcontrib><creatorcontrib>Falinska, Barbara</creatorcontrib><creatorcontrib>Campbell, William B.</creatorcontrib><creatorcontrib>Buja, L.Maximilian</creatorcontrib><creatorcontrib>Willerson, James T.</creatorcontrib><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>Journal of molecular and cellular cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yao, Sheng-Kun</au><au>Benedict, Claude R.</au><au>Rosolowsky, Mark</au><au>McNatt, Janice</au><au>Falinska, Barbara</au><au>Campbell, William B.</au><au>Buja, L.Maximilian</au><au>Willerson, James T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of aspirin on local prostaglandin production and serotonin accumulation in a canine model with coronary cyclic flow variations or thrombosis</atitle><jtitle>Journal of molecular and cellular cardiology</jtitle><addtitle>J Mol Cell Cardiol</addtitle><date>1991-04-01</date><risdate>1991</risdate><volume>23</volume><issue>4</issue><spage>473</spage><epage>482</epage><pages>473-482</pages><issn>0022-2828</issn><eissn>1095-8584</eissn><abstract>We have reported that thromboxane
A
2 and serotonin are two important mediators of coronary cyclic flow variations (CFVs) caused by recurrent platelet aggregation and dislodgement on a stenosed coronary arterial wall with endothelial injury. To test the hypothesis that blocking the synthesis of thromboxane
A
2 would not prevent serotonin release, 1.1, 4.6, and 9.2 mg/kg of aspirin were administered through the left atrium to 27 dogs with CFVs. The CFV elimination rate was 70% in the aspirin-treated dogs. Thromboxane
B
2 and serotonin concentrations were measured in different coronary arterial segments. There were significantly lower thromboxane
B
2 and 6-keto-PFG
1a levels in the stenosed left arterior descending (LAD) segments with increasing dosage of aspirin-208 ± 36, 24 ± 31, 50 ± 6 ng/g (
P<0.0001) and 125 ± 27, 58 ± 38, 25 ± 5 ng/g (
P<0.0001), respectively. Serotonin levels were significantly higher in stenosd LAD (265.7 ± 131.2 ng/g) than in LAD segments proximal or distal to the stenosis and in corresponding circumflex coronary artery segments, 17.1 ± 3.7, 18.6 ± 3.7, and 19.2 ± 5.1 ng/g, respectively (
P<0.05) following the highest dose of aspirin. In 41 additional dogs, electrical injury was used to initiate thrombosis in the circumflex artery and in those receiving aspirin (15mg/kg) (
n=5), occlusive thrombus formation was inhibited. However, the local accumulation of serotonin was not significantly different between the control (194 ± 27 ng/g) (
n=36) and the aspirin-treated group (167 ± 19 ng/g) (
n=5).
In vitro platelet aggregation induced by arachidonic acid was inhibited by the
in vivo adminstration of 1.1 mg/kg of aspirin and abolished by 4.6 + 1.1 and 9.2 + 4.6 + 1.1 mg/kg of aspirin. However, serotonin-induced platelet aggregation was not affected following all doses of aspirin. Thus, aspirin eliminates CFVs in 70% of dogs, and markedly diminishes thromboxane
A
2 and prostacyclin concentrations in stenosed canine coronary arteries, but it does not prevent local serotonin accumulation. Similarly, aspirin prevents occlusive coronary thrombosis in dogs with electrically-induced endothelial injury, but it did not prevent local assumulation of serotonin. These experimental findings suggest that cyclo-oxygenese inhibition does not prevent serotonin accumulation at sites of coronary artery endothelial injury, and they thereby help provide a potential explanation of the lack of complete protection provided by aspirin in eliminating CFVs in this experimental model.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>1942081</pmid><doi>10.1016/0022-2828(91)90171-H</doi><tpages>10</tpages></addata></record> |
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source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | 6-Ketoprostaglandin F1 alpha - biosynthesis Animals Aspirin Aspirin - pharmacology Coronary Circulation - drug effects Coronary Disease - metabolism Coronary stenosis Coronary Thrombosis - metabolism Dogs Electricity Female Male Platelet Aggregation Prostaglandin Serotonin Serotonin - metabolism Thromboxane B2 - biosynthesis |
title | Effect of aspirin on local prostaglandin production and serotonin accumulation in a canine model with coronary cyclic flow variations or thrombosis |
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