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
Hauptverfasser: Yao, Sheng-Kun, Benedict, Claude R., Rosolowsky, Mark, McNatt, Janice, Falinska, Barbara, Campbell, William B., Buja, L.Maximilian, Willerson, James T.
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container_end_page 482
container_issue 4
container_start_page 473
container_title Journal of molecular and cellular cardiology
container_volume 23
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
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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&lt;0.0001) and 125 ± 27, 58 ± 38, 25 ± 5 ng/g ( P&lt;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&lt;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&lt;0.0001) and 125 ± 27, 58 ± 38, 25 ± 5 ng/g ( P&lt;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&lt;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 ; 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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&lt;0.0001) and 125 ± 27, 58 ± 38, 25 ± 5 ng/g ( P&lt;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&lt;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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ispartof Journal of molecular and cellular cardiology, 1991-04, Vol.23 (4), p.473-482
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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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