Failure of Calcium Channel Blockade to Reduce Platelet-Mediated Cyclic Flow Variations in Dogs with Coronary Stenosis and Endothelial Injury
Experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in blood flow to almost zero values followed by abrupt restorations to original levels. Cyclic flow variations (CFVs) are the consequence o...
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| Veröffentlicht in: | Journal of cardiovascular pharmacology 1995-10, Vol.26 (4), p.577-583 |
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| creator | Beaughard, Michéle Brasset, Maxime John, Gareth Massingham, Roy |
| description | Experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in blood flow to almost zero values followed by abrupt restorations to original levels. Cyclic flow variations (CFVs) are the consequence of recurrent platelet aggregation at the site of the stenosis and subsequent dislodge-ment of the thrombus. The present study was designed to test the efficacy of diltiazem, nifedipine, and verapamil in inhibiting in vivo platelet aggregation as compared with that of aspirin and ketanserin, two potent reference compounds effective in this model. Except for aspirin, compounds were given as a slow intravenous infusion (i.v.) for 60 min to avoid hemodynamic changes. Diltiazem (0.01 mg/kg/min), nifedipine (3 μg/kg/min), and verapamil (0.01 mg/kg/min) were totally inactive against CFVs. A higher dose of verapamil (0.02 mg/kg/min) abolished CFVs in 3 of 4 dogs, but serious side effects were observed [atrioventricular (AV) block and death of 2 animals]. Aspirin (10 mg/kg bolus) caused complete inhibition of CFVs in 4 of 4 dogs, and ketanserin (0.01 mg/kg/ min) abolished CFVs in 4 of 5 dogs. These data suggest that calcium channel blockade alone in contrast to cyclo-oxygenase inhibition or 5-HT2 antagonism cannot inhibit thrombus formation in this model. |
| doi_str_mv | 10.1097/00005344-199510000-00011 |
| format | Article |
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Cyclic flow variations (CFVs) are the consequence of recurrent platelet aggregation at the site of the stenosis and subsequent dislodge-ment of the thrombus. The present study was designed to test the efficacy of diltiazem, nifedipine, and verapamil in inhibiting in vivo platelet aggregation as compared with that of aspirin and ketanserin, two potent reference compounds effective in this model. Except for aspirin, compounds were given as a slow intravenous infusion (i.v.) for 60 min to avoid hemodynamic changes. Diltiazem (0.01 mg/kg/min), nifedipine (3 μg/kg/min), and verapamil (0.01 mg/kg/min) were totally inactive against CFVs. A higher dose of verapamil (0.02 mg/kg/min) abolished CFVs in 3 of 4 dogs, but serious side effects were observed [atrioventricular (AV) block and death of 2 animals]. Aspirin (10 mg/kg bolus) caused complete inhibition of CFVs in 4 of 4 dogs, and ketanserin (0.01 mg/kg/ min) abolished CFVs in 4 of 5 dogs. These data suggest that calcium channel blockade alone in contrast to cyclo-oxygenase inhibition or 5-HT2 antagonism cannot inhibit thrombus formation in this model.</description><identifier>ISSN: 0160-2446</identifier><identifier>EISSN: 1533-4023</identifier><identifier>DOI: 10.1097/00005344-199510000-00011</identifier><identifier>PMID: 8569218</identifier><identifier>CODEN: JCPCDT</identifier><language>eng</language><publisher>Philadelphia, PA: Lippincott-Raven Publishers</publisher><subject><![CDATA[Animals ; Aspirin - administration & dosage ; Aspirin - pharmacology ; Aspirin - therapeutic use ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Calcium Channel Blockers - administration & dosage ; Calcium Channel Blockers - pharmacology ; Calcium Channel Blockers - therapeutic use ; Coronary Circulation - drug effects ; Coronary Circulation - physiology ; Coronary Disease - drug therapy ; Coronary Disease - physiopathology ; Diltiazem - administration & dosage ; Diltiazem - pharmacology ; Diltiazem - therapeutic use ; Disease Models, Animal ; Dogs ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - injuries ; Female ; Heart Block - drug therapy ; Heart Block - mortality ; Infusions, Intravenous ; Ketanserin - administration & dosage ; Ketanserin - pharmacology ; Ketanserin - therapeutic use ; Male ; Medical sciences ; Nifedipine - administration & dosage ; Nifedipine - pharmacology ; Nifedipine - therapeutic use ; Pharmacology. Drug treatments ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - administration & dosage ; Platelet Aggregation Inhibitors - pharmacology ; Platelet Aggregation Inhibitors - therapeutic use ; Thrombosis - drug therapy ; Vasodilator Agents - administration & dosage ; Vasodilator Agents - pharmacology ; Vasodilator Agents - therapeutic use ; Verapamil - administration & dosage ; Verapamil - pharmacology ; Verapamil - therapeutic use]]></subject><ispartof>Journal of cardiovascular pharmacology, 1995-10, Vol.26 (4), p.577-583</ispartof><rights>Lippincott-Raven Publishers.</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4031-52f26041457cc3351b5afa95c91ad941c8a7071448b1b73bf45ace9b293706663</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00005344-199510000-00011$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>314,778,782,4597,27907,27908,65214</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3674162$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8569218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beaughard, Michéle</creatorcontrib><creatorcontrib>Brasset, Maxime</creatorcontrib><creatorcontrib>John, Gareth</creatorcontrib><creatorcontrib>Massingham, Roy</creatorcontrib><title>Failure of Calcium Channel Blockade to Reduce Platelet-Mediated Cyclic Flow Variations in Dogs with Coronary Stenosis and Endothelial Injury</title><title>Journal of cardiovascular pharmacology</title><addtitle>J Cardiovasc Pharmacol</addtitle><description>Experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in blood flow to almost zero values followed by abrupt restorations to original levels. Cyclic flow variations (CFVs) are the consequence of recurrent platelet aggregation at the site of the stenosis and subsequent dislodge-ment of the thrombus. The present study was designed to test the efficacy of diltiazem, nifedipine, and verapamil in inhibiting in vivo platelet aggregation as compared with that of aspirin and ketanserin, two potent reference compounds effective in this model. Except for aspirin, compounds were given as a slow intravenous infusion (i.v.) for 60 min to avoid hemodynamic changes. Diltiazem (0.01 mg/kg/min), nifedipine (3 μg/kg/min), and verapamil (0.01 mg/kg/min) were totally inactive against CFVs. A higher dose of verapamil (0.02 mg/kg/min) abolished CFVs in 3 of 4 dogs, but serious side effects were observed [atrioventricular (AV) block and death of 2 animals]. Aspirin (10 mg/kg bolus) caused complete inhibition of CFVs in 4 of 4 dogs, and ketanserin (0.01 mg/kg/ min) abolished CFVs in 4 of 5 dogs. These data suggest that calcium channel blockade alone in contrast to cyclo-oxygenase inhibition or 5-HT2 antagonism cannot inhibit thrombus formation in this model.</description><subject>Animals</subject><subject>Aspirin - administration & dosage</subject><subject>Aspirin - pharmacology</subject><subject>Aspirin - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Calcium Channel Blockers - administration & dosage</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channel Blockers - therapeutic use</subject><subject>Coronary Circulation - drug effects</subject><subject>Coronary Circulation - physiology</subject><subject>Coronary Disease - drug therapy</subject><subject>Coronary Disease - physiopathology</subject><subject>Diltiazem - administration & dosage</subject><subject>Diltiazem - pharmacology</subject><subject>Diltiazem - therapeutic use</subject><subject>Disease Models, Animal</subject><subject>Dogs</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - injuries</subject><subject>Female</subject><subject>Heart Block - drug therapy</subject><subject>Heart Block - mortality</subject><subject>Infusions, Intravenous</subject><subject>Ketanserin - administration & dosage</subject><subject>Ketanserin - pharmacology</subject><subject>Ketanserin - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nifedipine - administration & dosage</subject><subject>Nifedipine - pharmacology</subject><subject>Nifedipine - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation Inhibitors - administration & dosage</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Platelet Aggregation Inhibitors - therapeutic use</subject><subject>Thrombosis - drug therapy</subject><subject>Vasodilator Agents - administration & dosage</subject><subject>Vasodilator Agents - pharmacology</subject><subject>Vasodilator Agents - therapeutic use</subject><subject>Verapamil - administration & dosage</subject><subject>Verapamil - pharmacology</subject><subject>Verapamil - therapeutic use</subject><issn>0160-2446</issn><issn>1533-4023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kdtu1DAQhi0EKtvCIyDNBbcBOz4kuYTQhUpFVOVwG00ch7j12pWdaLXv0Ieut7vsHSNZY8_8v2V_Qwgw-oHRpvpIc0guRMGaRrL9qciLsRdkxSTnhaAlf0lWlClalEKo1-Q8pbusELJSZ-SslqopWb0ij2u0bokGwggtOm2XDbQTem8cfHZB3-NgYA5wa4ZFG7hxOBtn5uK7GWzeDtDutLMa1i5s4Q_GXLTBJ7AevoS_CbZ2nqANMXiMO_g5Gx-STYB-gEs_hHkyzqKDK3-3xN0b8mpEl8zbY74gv9eXv9pvxfWPr1ftp-tCC8pZIcuxVFTs_6I155L1EkdspG4YDo1gusaKVkyIumd9xftRSNSm6cuGV1QpxS9IfbhXx5BSNGP3EO0mP7BjtNvz7f7x7U58u2e-2fruYH1Y-o0ZTsYj0Nx_f-xj0ujGiF7bdJJxVQmmyiwTB9k2uNnEdO-WrYndZNDNU_e_6fInOFeSdw</recordid><startdate>199510</startdate><enddate>199510</enddate><creator>Beaughard, Michéle</creator><creator>Brasset, Maxime</creator><creator>John, Gareth</creator><creator>Massingham, Roy</creator><general>Lippincott-Raven Publishers</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></search><sort><creationdate>199510</creationdate><title>Failure of Calcium Channel Blockade to Reduce Platelet-Mediated Cyclic Flow Variations in Dogs with Coronary Stenosis and Endothelial Injury</title><author>Beaughard, Michéle ; Brasset, Maxime ; John, Gareth ; Massingham, Roy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4031-52f26041457cc3351b5afa95c91ad941c8a7071448b1b73bf45ace9b293706663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Aspirin - administration & dosage</topic><topic>Aspirin - pharmacology</topic><topic>Aspirin - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Calcium Channel Blockers - administration & dosage</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channel Blockers - therapeutic use</topic><topic>Coronary Circulation - drug effects</topic><topic>Coronary Circulation - physiology</topic><topic>Coronary Disease - drug therapy</topic><topic>Coronary Disease - physiopathology</topic><topic>Diltiazem - administration & dosage</topic><topic>Diltiazem - pharmacology</topic><topic>Diltiazem - therapeutic use</topic><topic>Disease Models, Animal</topic><topic>Dogs</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - injuries</topic><topic>Female</topic><topic>Heart Block - drug therapy</topic><topic>Heart Block - mortality</topic><topic>Infusions, Intravenous</topic><topic>Ketanserin - administration & dosage</topic><topic>Ketanserin - pharmacology</topic><topic>Ketanserin - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nifedipine - administration & dosage</topic><topic>Nifedipine - pharmacology</topic><topic>Nifedipine - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Aggregation Inhibitors - administration & dosage</topic><topic>Platelet Aggregation Inhibitors - pharmacology</topic><topic>Platelet Aggregation Inhibitors - therapeutic use</topic><topic>Thrombosis - drug therapy</topic><topic>Vasodilator Agents - administration & dosage</topic><topic>Vasodilator Agents - pharmacology</topic><topic>Vasodilator Agents - therapeutic use</topic><topic>Verapamil - administration & dosage</topic><topic>Verapamil - pharmacology</topic><topic>Verapamil - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beaughard, Michéle</creatorcontrib><creatorcontrib>Brasset, Maxime</creatorcontrib><creatorcontrib>John, Gareth</creatorcontrib><creatorcontrib>Massingham, Roy</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><jtitle>Journal of cardiovascular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beaughard, Michéle</au><au>Brasset, Maxime</au><au>John, Gareth</au><au>Massingham, Roy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Failure of Calcium Channel Blockade to Reduce Platelet-Mediated Cyclic Flow Variations in Dogs with Coronary Stenosis and Endothelial Injury</atitle><jtitle>Journal of cardiovascular pharmacology</jtitle><addtitle>J Cardiovasc Pharmacol</addtitle><date>1995-10</date><risdate>1995</risdate><volume>26</volume><issue>4</issue><spage>577</spage><epage>583</epage><pages>577-583</pages><issn>0160-2446</issn><eissn>1533-4023</eissn><coden>JCPCDT</coden><abstract>Experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in blood flow to almost zero values followed by abrupt restorations to original levels. Cyclic flow variations (CFVs) are the consequence of recurrent platelet aggregation at the site of the stenosis and subsequent dislodge-ment of the thrombus. The present study was designed to test the efficacy of diltiazem, nifedipine, and verapamil in inhibiting in vivo platelet aggregation as compared with that of aspirin and ketanserin, two potent reference compounds effective in this model. Except for aspirin, compounds were given as a slow intravenous infusion (i.v.) for 60 min to avoid hemodynamic changes. Diltiazem (0.01 mg/kg/min), nifedipine (3 μg/kg/min), and verapamil (0.01 mg/kg/min) were totally inactive against CFVs. A higher dose of verapamil (0.02 mg/kg/min) abolished CFVs in 3 of 4 dogs, but serious side effects were observed [atrioventricular (AV) block and death of 2 animals]. Aspirin (10 mg/kg bolus) caused complete inhibition of CFVs in 4 of 4 dogs, and ketanserin (0.01 mg/kg/ min) abolished CFVs in 4 of 5 dogs. These data suggest that calcium channel blockade alone in contrast to cyclo-oxygenase inhibition or 5-HT2 antagonism cannot inhibit thrombus formation in this model.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>Lippincott-Raven Publishers</pub><pmid>8569218</pmid><doi>10.1097/00005344-199510000-00011</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0160-2446 |
| ispartof | Journal of cardiovascular pharmacology, 1995-10, Vol.26 (4), p.577-583 |
| issn | 0160-2446 1533-4023 |
| language | eng |
| recordid | cdi_crossref_primary_10_1097_00005344_199510000_00011 |
| source | MEDLINE; Journals@Ovid LWW Legacy Archive; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Animals Aspirin - administration & dosage Aspirin - pharmacology Aspirin - therapeutic use Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Calcium Channel Blockers - administration & dosage Calcium Channel Blockers - pharmacology Calcium Channel Blockers - therapeutic use Coronary Circulation - drug effects Coronary Circulation - physiology Coronary Disease - drug therapy Coronary Disease - physiopathology Diltiazem - administration & dosage Diltiazem - pharmacology Diltiazem - therapeutic use Disease Models, Animal Dogs Endothelium, Vascular - drug effects Endothelium, Vascular - injuries Female Heart Block - drug therapy Heart Block - mortality Infusions, Intravenous Ketanserin - administration & dosage Ketanserin - pharmacology Ketanserin - therapeutic use Male Medical sciences Nifedipine - administration & dosage Nifedipine - pharmacology Nifedipine - therapeutic use Pharmacology. Drug treatments Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - administration & dosage Platelet Aggregation Inhibitors - pharmacology Platelet Aggregation Inhibitors - therapeutic use Thrombosis - drug therapy Vasodilator Agents - administration & dosage Vasodilator Agents - pharmacology Vasodilator Agents - therapeutic use Verapamil - administration & dosage Verapamil - pharmacology Verapamil - therapeutic use |
| title | Failure of Calcium Channel Blockade to Reduce Platelet-Mediated Cyclic Flow Variations in Dogs with Coronary Stenosis and Endothelial Injury |
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