Inhibition of acute stent thrombosis under high-shear flow conditions by a nitric oxide donor, DMHD/NO : An ex vivo porcine arteriovenous shunt study
Coronary stenting is limited by subacute thrombosis, especially in smaller-diameter vessels, in which shear rates are high. The objective of the present study was to determine whether local delivery of a new type of NO donor, the NO adduct of N,N'-dimethylhexanediamine (DMHD/NO), inhibits acute...
Gespeichert in:
| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 1996-11, Vol.94 (9), p.2228-2234 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2234 |
|---|---|
| container_issue | 9 |
| container_start_page | 2228 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 94 |
| creator | KAUL, S MAKKAR, R. R NAKAMURA, M LITVACK, F. I SHAH, P. K FORRESTER, J. S HUTSELL, T. C EIGLER, N. L |
| description | Coronary stenting is limited by subacute thrombosis, especially in smaller-diameter vessels, in which shear rates are high. The objective of the present study was to determine whether local delivery of a new type of NO donor, the NO adduct of N,N'-dimethylhexanediamine (DMHD/NO), inhibits acute stent thrombosis (ST) at high-shear flow.
Effects of local infusion of DMHD/NO; intravenous aspirin, and heparin on ST were evaluated in an ex vivo porcine AV shunt model. Nitinol stents (2 mum in diameter, n = 120) were placed in a tubular chamber and perfused with blood from pigs (n = 13) at a shear rate of 2100s-1 for 20 minutes. ST was quantified by measurement of dry thrombus weight(TW). Effects on platelet aggregation (PA), blood pressure, bleeding time, and activated clotting time (ACT) were also examined. There was a dose-dependent inhibition of ST and PA by DMHD/NO. TW was reduced by 95% (1 +/- 2 versus 16 +/- 4 mg control, mean +/- SD, P < .001), and PA was reduced by 75% (4 +/- 3 versus 14 +/- 9 omega/min control, P < .05) at the highest dose of 10 mumol/L. DMHD/NO had no effects on bleeding time, ACT, or blood pressure. In contrast, aspirin (10 mg/kg), despite inhibiting PA, had no effects on TW (12 +/- 5 versus 16 +/- 8 mg control, P = .3). Heparin (200 U/kg) reduced TW by 33% (14 +/- 4 versus 21 +/- 3 mg control, P < .05) and prolonged ACT.
Local delivery of DMHD/NO produced a 15-fold inhibition of acute ST at high-shear flow without producing adverse systemic hemostatic or hemodynamic effects. Thus, treatment with DMHD/NO may be an effective strategy for prevention of stent thrombosis. |
| doi_str_mv | 10.1161/01.CIR.94.9.2228 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_78500576</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>18783285</sourcerecordid><originalsourceid>FETCH-LOGICAL-c344t-6a87445791a1d49e84838ba2b884ee52f624f4b0b2141cab2b5c505fe97236af3</originalsourceid><addsrcrecordid>eNpdkUFv1DAQhS0EKkvhzgVphBAnktqOHcfcqi3QlQqVEJwt23GIq6y9tZ2l-0P4v6R01QOn0Wi-9-ZJD6HXBNeEtOQMk3q9-V5LVsuaUto9QSvCKasYb-RTtMIYy0o0lD5HL3K-Wda2EfwEnXQSk1a0K_RnE0ZvfPExQBxA27k4yMWFAmVMcWti9hnm0LsEo_81Vnl0OsEwxd9gY-j_KTOYA2gIviRvId753kEfQ0wf4OLr5cXZt2v4COcB3B3s_T7CLibrgwOdiks-7l2Ic4Y8zsvXXOb-8BI9G_SU3avjPEU_P3_6sb6srq6_bNbnV5VtGCtVqzvBGBeSaNIz6TrWNZ3R1HQdc47ToaVsYAYbShix2lDDLcd8cFLQptVDc4reP_juUrydXS5q67N106SDWyIp0XGMuWgX8O1_4E2cU1iyKUqoIAITsUD4AbIp5pzcoHbJb3U6KILVfV0KE7XUpSRTUt3XtUjeHH1ns3X9o-DYz3J_d7zrbPU0JB2sz48YZR3BUjZ_AX6BndQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>212717017</pqid></control><display><type>article</type><title>Inhibition of acute stent thrombosis under high-shear flow conditions by a nitric oxide donor, DMHD/NO : An ex vivo porcine arteriovenous shunt study</title><source>MEDLINE</source><source>American Heart Association Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Complete</source><creator>KAUL, S ; MAKKAR, R. R ; NAKAMURA, M ; LITVACK, F. I ; SHAH, P. K ; FORRESTER, J. S ; HUTSELL, T. C ; EIGLER, N. L</creator><creatorcontrib>KAUL, S ; MAKKAR, R. R ; NAKAMURA, M ; LITVACK, F. I ; SHAH, P. K ; FORRESTER, J. S ; HUTSELL, T. C ; EIGLER, N. L</creatorcontrib><description>Coronary stenting is limited by subacute thrombosis, especially in smaller-diameter vessels, in which shear rates are high. The objective of the present study was to determine whether local delivery of a new type of NO donor, the NO adduct of N,N'-dimethylhexanediamine (DMHD/NO), inhibits acute stent thrombosis (ST) at high-shear flow.
Effects of local infusion of DMHD/NO; intravenous aspirin, and heparin on ST were evaluated in an ex vivo porcine AV shunt model. Nitinol stents (2 mum in diameter, n = 120) were placed in a tubular chamber and perfused with blood from pigs (n = 13) at a shear rate of 2100s-1 for 20 minutes. ST was quantified by measurement of dry thrombus weight(TW). Effects on platelet aggregation (PA), blood pressure, bleeding time, and activated clotting time (ACT) were also examined. There was a dose-dependent inhibition of ST and PA by DMHD/NO. TW was reduced by 95% (1 +/- 2 versus 16 +/- 4 mg control, mean +/- SD, P < .001), and PA was reduced by 75% (4 +/- 3 versus 14 +/- 9 omega/min control, P < .05) at the highest dose of 10 mumol/L. DMHD/NO had no effects on bleeding time, ACT, or blood pressure. In contrast, aspirin (10 mg/kg), despite inhibiting PA, had no effects on TW (12 +/- 5 versus 16 +/- 8 mg control, P = .3). Heparin (200 U/kg) reduced TW by 33% (14 +/- 4 versus 21 +/- 3 mg control, P < .05) and prolonged ACT.
Local delivery of DMHD/NO produced a 15-fold inhibition of acute ST at high-shear flow without producing adverse systemic hemostatic or hemodynamic effects. Thus, treatment with DMHD/NO may be an effective strategy for prevention of stent thrombosis.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.94.9.2228</identifier><identifier>PMID: 8901676</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Anticoagulants - pharmacology ; Arteriovenous Shunt, Surgical ; Aspirin - pharmacology ; Biological and medical sciences ; Bleeding Time ; Blood Coagulation - drug effects ; Blood Platelets - drug effects ; Blood Platelets - physiology ; Cyclic GMP - metabolism ; Diseases of the digestive system ; Hemodynamics - drug effects ; Heparin - pharmacology ; Hexanones - pharmacology ; Medical sciences ; Nitric Oxide - metabolism ; Platelet Aggregation - drug effects ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Stents ; Swine ; Thrombosis - prevention & control ; Whole Blood Coagulation Time</subject><ispartof>Circulation (New York, N.Y.), 1996-11, Vol.94 (9), p.2228-2234</ispartof><rights>1997 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Nov 1, 1996</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c344t-6a87445791a1d49e84838ba2b884ee52f624f4b0b2141cab2b5c505fe97236af3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2481099$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8901676$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KAUL, S</creatorcontrib><creatorcontrib>MAKKAR, R. R</creatorcontrib><creatorcontrib>NAKAMURA, M</creatorcontrib><creatorcontrib>LITVACK, F. I</creatorcontrib><creatorcontrib>SHAH, P. K</creatorcontrib><creatorcontrib>FORRESTER, J. S</creatorcontrib><creatorcontrib>HUTSELL, T. C</creatorcontrib><creatorcontrib>EIGLER, N. L</creatorcontrib><title>Inhibition of acute stent thrombosis under high-shear flow conditions by a nitric oxide donor, DMHD/NO : An ex vivo porcine arteriovenous shunt study</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Coronary stenting is limited by subacute thrombosis, especially in smaller-diameter vessels, in which shear rates are high. The objective of the present study was to determine whether local delivery of a new type of NO donor, the NO adduct of N,N'-dimethylhexanediamine (DMHD/NO), inhibits acute stent thrombosis (ST) at high-shear flow.
Effects of local infusion of DMHD/NO; intravenous aspirin, and heparin on ST were evaluated in an ex vivo porcine AV shunt model. Nitinol stents (2 mum in diameter, n = 120) were placed in a tubular chamber and perfused with blood from pigs (n = 13) at a shear rate of 2100s-1 for 20 minutes. ST was quantified by measurement of dry thrombus weight(TW). Effects on platelet aggregation (PA), blood pressure, bleeding time, and activated clotting time (ACT) were also examined. There was a dose-dependent inhibition of ST and PA by DMHD/NO. TW was reduced by 95% (1 +/- 2 versus 16 +/- 4 mg control, mean +/- SD, P < .001), and PA was reduced by 75% (4 +/- 3 versus 14 +/- 9 omega/min control, P < .05) at the highest dose of 10 mumol/L. DMHD/NO had no effects on bleeding time, ACT, or blood pressure. In contrast, aspirin (10 mg/kg), despite inhibiting PA, had no effects on TW (12 +/- 5 versus 16 +/- 8 mg control, P = .3). Heparin (200 U/kg) reduced TW by 33% (14 +/- 4 versus 21 +/- 3 mg control, P < .05) and prolonged ACT.
Local delivery of DMHD/NO produced a 15-fold inhibition of acute ST at high-shear flow without producing adverse systemic hemostatic or hemodynamic effects. Thus, treatment with DMHD/NO may be an effective strategy for prevention of stent thrombosis.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Anticoagulants - pharmacology</subject><subject>Arteriovenous Shunt, Surgical</subject><subject>Aspirin - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Bleeding Time</subject><subject>Blood Coagulation - drug effects</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - physiology</subject><subject>Cyclic GMP - metabolism</subject><subject>Diseases of the digestive system</subject><subject>Hemodynamics - drug effects</subject><subject>Heparin - pharmacology</subject><subject>Hexanones - pharmacology</subject><subject>Medical sciences</subject><subject>Nitric Oxide - metabolism</subject><subject>Platelet Aggregation - drug effects</subject><subject>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</subject><subject>Stents</subject><subject>Swine</subject><subject>Thrombosis - prevention & control</subject><subject>Whole Blood Coagulation Time</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUFv1DAQhS0EKkvhzgVphBAnktqOHcfcqi3QlQqVEJwt23GIq6y9tZ2l-0P4v6R01QOn0Wi-9-ZJD6HXBNeEtOQMk3q9-V5LVsuaUto9QSvCKasYb-RTtMIYy0o0lD5HL3K-Wda2EfwEnXQSk1a0K_RnE0ZvfPExQBxA27k4yMWFAmVMcWti9hnm0LsEo_81Vnl0OsEwxd9gY-j_KTOYA2gIviRvId753kEfQ0wf4OLr5cXZt2v4COcB3B3s_T7CLibrgwOdiks-7l2Ic4Y8zsvXXOb-8BI9G_SU3avjPEU_P3_6sb6srq6_bNbnV5VtGCtVqzvBGBeSaNIz6TrWNZ3R1HQdc47ToaVsYAYbShix2lDDLcd8cFLQptVDc4reP_juUrydXS5q67N106SDWyIp0XGMuWgX8O1_4E2cU1iyKUqoIAITsUD4AbIp5pzcoHbJb3U6KILVfV0KE7XUpSRTUt3XtUjeHH1ns3X9o-DYz3J_d7zrbPU0JB2sz48YZR3BUjZ_AX6BndQ</recordid><startdate>19961101</startdate><enddate>19961101</enddate><creator>KAUL, S</creator><creator>MAKKAR, R. R</creator><creator>NAKAMURA, M</creator><creator>LITVACK, F. I</creator><creator>SHAH, P. K</creator><creator>FORRESTER, J. S</creator><creator>HUTSELL, T. C</creator><creator>EIGLER, N. L</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>19961101</creationdate><title>Inhibition of acute stent thrombosis under high-shear flow conditions by a nitric oxide donor, DMHD/NO : An ex vivo porcine arteriovenous shunt study</title><author>KAUL, S ; MAKKAR, R. R ; NAKAMURA, M ; LITVACK, F. I ; SHAH, P. K ; FORRESTER, J. S ; HUTSELL, T. C ; EIGLER, N. L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-6a87445791a1d49e84838ba2b884ee52f624f4b0b2141cab2b5c505fe97236af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Anticoagulants - pharmacology</topic><topic>Arteriovenous Shunt, Surgical</topic><topic>Aspirin - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Bleeding Time</topic><topic>Blood Coagulation - drug effects</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - physiology</topic><topic>Cyclic GMP - metabolism</topic><topic>Diseases of the digestive system</topic><topic>Hemodynamics - drug effects</topic><topic>Heparin - pharmacology</topic><topic>Hexanones - pharmacology</topic><topic>Medical sciences</topic><topic>Nitric Oxide - metabolism</topic><topic>Platelet Aggregation - drug effects</topic><topic>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</topic><topic>Stents</topic><topic>Swine</topic><topic>Thrombosis - prevention & control</topic><topic>Whole Blood Coagulation Time</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KAUL, S</creatorcontrib><creatorcontrib>MAKKAR, R. R</creatorcontrib><creatorcontrib>NAKAMURA, M</creatorcontrib><creatorcontrib>LITVACK, F. I</creatorcontrib><creatorcontrib>SHAH, P. K</creatorcontrib><creatorcontrib>FORRESTER, J. S</creatorcontrib><creatorcontrib>HUTSELL, T. C</creatorcontrib><creatorcontrib>EIGLER, N. L</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KAUL, S</au><au>MAKKAR, R. R</au><au>NAKAMURA, M</au><au>LITVACK, F. I</au><au>SHAH, P. K</au><au>FORRESTER, J. S</au><au>HUTSELL, T. C</au><au>EIGLER, N. L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of acute stent thrombosis under high-shear flow conditions by a nitric oxide donor, DMHD/NO : An ex vivo porcine arteriovenous shunt study</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1996-11-01</date><risdate>1996</risdate><volume>94</volume><issue>9</issue><spage>2228</spage><epage>2234</epage><pages>2228-2234</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Coronary stenting is limited by subacute thrombosis, especially in smaller-diameter vessels, in which shear rates are high. The objective of the present study was to determine whether local delivery of a new type of NO donor, the NO adduct of N,N'-dimethylhexanediamine (DMHD/NO), inhibits acute stent thrombosis (ST) at high-shear flow.
Effects of local infusion of DMHD/NO; intravenous aspirin, and heparin on ST were evaluated in an ex vivo porcine AV shunt model. Nitinol stents (2 mum in diameter, n = 120) were placed in a tubular chamber and perfused with blood from pigs (n = 13) at a shear rate of 2100s-1 for 20 minutes. ST was quantified by measurement of dry thrombus weight(TW). Effects on platelet aggregation (PA), blood pressure, bleeding time, and activated clotting time (ACT) were also examined. There was a dose-dependent inhibition of ST and PA by DMHD/NO. TW was reduced by 95% (1 +/- 2 versus 16 +/- 4 mg control, mean +/- SD, P < .001), and PA was reduced by 75% (4 +/- 3 versus 14 +/- 9 omega/min control, P < .05) at the highest dose of 10 mumol/L. DMHD/NO had no effects on bleeding time, ACT, or blood pressure. In contrast, aspirin (10 mg/kg), despite inhibiting PA, had no effects on TW (12 +/- 5 versus 16 +/- 8 mg control, P = .3). Heparin (200 U/kg) reduced TW by 33% (14 +/- 4 versus 21 +/- 3 mg control, P < .05) and prolonged ACT.
Local delivery of DMHD/NO produced a 15-fold inhibition of acute ST at high-shear flow without producing adverse systemic hemostatic or hemodynamic effects. Thus, treatment with DMHD/NO may be an effective strategy for prevention of stent thrombosis.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>8901676</pmid><doi>10.1161/01.CIR.94.9.2228</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 1996-11, Vol.94 (9), p.2228-2234 |
| issn | 0009-7322 1524-4539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_78500576 |
| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Anticoagulants - pharmacology Arteriovenous Shunt, Surgical Aspirin - pharmacology Biological and medical sciences Bleeding Time Blood Coagulation - drug effects Blood Platelets - drug effects Blood Platelets - physiology Cyclic GMP - metabolism Diseases of the digestive system Hemodynamics - drug effects Heparin - pharmacology Hexanones - pharmacology Medical sciences Nitric Oxide - metabolism Platelet Aggregation - drug effects Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Stents Swine Thrombosis - prevention & control Whole Blood Coagulation Time |
| title | Inhibition of acute stent thrombosis under high-shear flow conditions by a nitric oxide donor, DMHD/NO : An ex vivo porcine arteriovenous shunt study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T16%3A00%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20acute%20stent%20thrombosis%20under%20high-shear%20flow%20conditions%20by%20a%20nitric%20oxide%20donor,%20DMHD/NO%20:%20An%20ex%20vivo%20porcine%20arteriovenous%20shunt%20study&rft.jtitle=Circulation%20(New%20York,%20N.Y.)&rft.au=KAUL,%20S&rft.date=1996-11-01&rft.volume=94&rft.issue=9&rft.spage=2228&rft.epage=2234&rft.pages=2228-2234&rft.issn=0009-7322&rft.eissn=1524-4539&rft.coden=CIRCAZ&rft_id=info:doi/10.1161/01.CIR.94.9.2228&rft_dat=%3Cproquest_cross%3E18783285%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=212717017&rft_id=info:pmid/8901676&rfr_iscdi=true |