Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase
Summary The present study compares the efficacy of two formulations of encapsulated streptokinase to streptokinase in a rabbit model of carotid artery thrombosis. Arterial thrombosis followed the injection of thrombin mixed with autologous whole blood into a carotid artery of New Zealand white rabbi...
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| Veröffentlicht in: | Thrombosis and haemostasis 2003-07, Vol.90 (1), p.64-70 |
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| creator | Leach, J. Kent O’Rear, Edgar A. Patterson, Eugene Miao, Yiwei Johnson, Arthur E. |
| description | Summary
The present study compares the efficacy of two formulations of encapsulated streptokinase to streptokinase in a rabbit model of carotid artery thrombosis. Arterial thrombosis followed the injection of thrombin mixed with autologous whole blood into a carotid artery of New Zealand white rabbits. Thirty minutes after the confirmation of an occlusive thrombus, one of four streptokinase formulations was infused at a dosage of 6,000 IU/kg into the jugular vein. Free streptokinase (FREE SK) was compared to identical dosages of streptokinase encapsulated in a liposome (LESK), streptokinase entrapped in a water-soluble polymer (MESK), and free streptokinase admixed with blank microparticles (FREE SK + BLANK). Carotid arterial blood flow was determined by pulsed Doppler flowmetry to confirm clot formation and reperfusion. Two hours after drug infusion, the rabbits were killed and the residual thrombus mass was determined.
Compared to FREE SK (74.5 ± 16.9 min; mean ± SEM), LESK demonstrated significantly reduced reperfusion times (19.3 ± 4.6 min) while MESK exhibited even greater improvement (7.3 ± 1.6 min). FREE SK + BLANK showed no statistical improvement versus FREE SK. LESK and MESK also resulted in reduced residual clot mass and greater return of arterial blood flow. These studies suggest that encapsulation of streptokinase offers a potential method of improved fibrinolytic treatment for patients with clot-based disorders. MESK performed slightly better than LESK with improved production and storage characteristics. |
| doi_str_mv | 10.1055/s-0037-1613600 |
| format | Article |
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The present study compares the efficacy of two formulations of encapsulated streptokinase to streptokinase in a rabbit model of carotid artery thrombosis. Arterial thrombosis followed the injection of thrombin mixed with autologous whole blood into a carotid artery of New Zealand white rabbits. Thirty minutes after the confirmation of an occlusive thrombus, one of four streptokinase formulations was infused at a dosage of 6,000 IU/kg into the jugular vein. Free streptokinase (FREE SK) was compared to identical dosages of streptokinase encapsulated in a liposome (LESK), streptokinase entrapped in a water-soluble polymer (MESK), and free streptokinase admixed with blank microparticles (FREE SK + BLANK). Carotid arterial blood flow was determined by pulsed Doppler flowmetry to confirm clot formation and reperfusion. Two hours after drug infusion, the rabbits were killed and the residual thrombus mass was determined.
Compared to FREE SK (74.5 ± 16.9 min; mean ± SEM), LESK demonstrated significantly reduced reperfusion times (19.3 ± 4.6 min) while MESK exhibited even greater improvement (7.3 ± 1.6 min). FREE SK + BLANK showed no statistical improvement versus FREE SK. LESK and MESK also resulted in reduced residual clot mass and greater return of arterial blood flow. These studies suggest that encapsulation of streptokinase offers a potential method of improved fibrinolytic treatment for patients with clot-based disorders. MESK performed slightly better than LESK with improved production and storage characteristics.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1055/s-0037-1613600</identifier><identifier>PMID: 12876627</identifier><identifier>CODEN: THHADQ</identifier><language>eng</language><publisher>Stuttgart: Schattauer Verlag für Medizin und Naturwissenschaften</publisher><subject>Animals ; Biological and medical sciences ; Blood Coagulation, Fibrinolysis and Cellular Haemostasis ; Blood. Blood coagulation. Reticuloendothelial system ; Carotid Artery Thrombosis - drug therapy ; Drug Carriers ; Drug Compounding ; Drug Evaluation, Preclinical ; Female ; Fibrinolytic Agents - administration & dosage ; Fibrinolytic Agents - therapeutic use ; Liposomes ; Male ; Medical sciences ; Microspheres ; Models, Animal ; Pharmacology. Drug treatments ; Polyethylene Glycols ; Rabbits ; Recurrence ; Streptokinase - administration & dosage ; Streptokinase - therapeutic use ; Thrombin - toxicity ; Thrombolytic Therapy</subject><ispartof>Thrombosis and haemostasis, 2003-07, Vol.90 (1), p.64-70</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c549t-4f57ee69d5ef3b2cd58181e4d15228cbc793e910e6913d843401fe410afa3853</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0037-1613600.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1055/s-0037-1613600$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,776,780,3004,3005,27901,27902,54534,54535</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14905893$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12876627$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leach, J. Kent</creatorcontrib><creatorcontrib>O’Rear, Edgar A.</creatorcontrib><creatorcontrib>Patterson, Eugene</creatorcontrib><creatorcontrib>Miao, Yiwei</creatorcontrib><creatorcontrib>Johnson, Arthur E.</creatorcontrib><title>Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
The present study compares the efficacy of two formulations of encapsulated streptokinase to streptokinase in a rabbit model of carotid artery thrombosis. Arterial thrombosis followed the injection of thrombin mixed with autologous whole blood into a carotid artery of New Zealand white rabbits. Thirty minutes after the confirmation of an occlusive thrombus, one of four streptokinase formulations was infused at a dosage of 6,000 IU/kg into the jugular vein. Free streptokinase (FREE SK) was compared to identical dosages of streptokinase encapsulated in a liposome (LESK), streptokinase entrapped in a water-soluble polymer (MESK), and free streptokinase admixed with blank microparticles (FREE SK + BLANK). Carotid arterial blood flow was determined by pulsed Doppler flowmetry to confirm clot formation and reperfusion. Two hours after drug infusion, the rabbits were killed and the residual thrombus mass was determined.
Compared to FREE SK (74.5 ± 16.9 min; mean ± SEM), LESK demonstrated significantly reduced reperfusion times (19.3 ± 4.6 min) while MESK exhibited even greater improvement (7.3 ± 1.6 min). FREE SK + BLANK showed no statistical improvement versus FREE SK. LESK and MESK also resulted in reduced residual clot mass and greater return of arterial blood flow. These studies suggest that encapsulation of streptokinase offers a potential method of improved fibrinolytic treatment for patients with clot-based disorders. MESK performed slightly better than LESK with improved production and storage characteristics.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Coagulation, Fibrinolysis and Cellular Haemostasis</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Carotid Artery Thrombosis - drug therapy</subject><subject>Drug Carriers</subject><subject>Drug Compounding</subject><subject>Drug Evaluation, Preclinical</subject><subject>Female</subject><subject>Fibrinolytic Agents - administration & dosage</subject><subject>Fibrinolytic Agents - therapeutic use</subject><subject>Liposomes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microspheres</subject><subject>Models, Animal</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyethylene Glycols</subject><subject>Rabbits</subject><subject>Recurrence</subject><subject>Streptokinase - administration & dosage</subject><subject>Streptokinase - therapeutic use</subject><subject>Thrombin - toxicity</subject><subject>Thrombolytic Therapy</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqtkEtv1DAUhS0EokNhyxJ5wzLFjh9JllXFS6rEpgt21o1zo7gkceTrUM0f4Hc3wwyMQGLHyrL9nXPuPYy9luJKCmPeUSGEqgpppbJCPGG70tiqsHXz9SnbCaVFYUttLtgLonshpNWNec4uZFlX1pbVjv249h5HTJCx43lIcWrjuKdAPMwceIK2DZlPscORx557SDGHjkPKmPa_BAf8IeSBj2GJFCcscPaw0Dr-tIW541PwKf7xSjnhkuO3MAPhS_ash5Hw1em8ZHcf3t_dfCpuv3z8fHN9W3ijm1zo3lSItukM9qotfWdqWUvUnTRlWfvWV43CRooNkaqr9ba_7FFLAT2o2qhLdnW03YYhSti7JYUJ0t5J4Q59OnKHPt2pz03w5ihY1nbC7oyfCtyAtycAyMPYJ5h9oDOnG2HqRm1cceTyEHBCdx_XNG-b_js4HHnyA-QMK6bfpufW3VatGwCnSBkOdx_njHPePpIfwnd0gWhFVzXaTTCv5FNYslPaWkdDfHBDnsYty__HLFrQBxj_zlOPl3rgwg</recordid><startdate>20030701</startdate><enddate>20030701</enddate><creator>Leach, J. Kent</creator><creator>O’Rear, Edgar A.</creator><creator>Patterson, Eugene</creator><creator>Miao, Yiwei</creator><creator>Johnson, Arthur E.</creator><general>Schattauer Verlag für Medizin und Naturwissenschaften</general><general>Schattauer GmbH</general><general>Schattauer</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>20030701</creationdate><title>Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase</title><author>Leach, J. Kent ; O’Rear, Edgar A. ; Patterson, Eugene ; Miao, Yiwei ; Johnson, Arthur E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c549t-4f57ee69d5ef3b2cd58181e4d15228cbc793e910e6913d843401fe410afa3853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Coagulation, Fibrinolysis and Cellular Haemostasis</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Carotid Artery Thrombosis - drug therapy</topic><topic>Drug Carriers</topic><topic>Drug Compounding</topic><topic>Drug Evaluation, Preclinical</topic><topic>Female</topic><topic>Fibrinolytic Agents - administration & dosage</topic><topic>Fibrinolytic Agents - therapeutic use</topic><topic>Liposomes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microspheres</topic><topic>Models, Animal</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyethylene Glycols</topic><topic>Rabbits</topic><topic>Recurrence</topic><topic>Streptokinase - administration & dosage</topic><topic>Streptokinase - therapeutic use</topic><topic>Thrombin - toxicity</topic><topic>Thrombolytic Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leach, J. Kent</creatorcontrib><creatorcontrib>O’Rear, Edgar A.</creatorcontrib><creatorcontrib>Patterson, Eugene</creatorcontrib><creatorcontrib>Miao, Yiwei</creatorcontrib><creatorcontrib>Johnson, Arthur E.</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>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leach, J. Kent</au><au>O’Rear, Edgar A.</au><au>Patterson, Eugene</au><au>Miao, Yiwei</au><au>Johnson, Arthur E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2003-07-01</date><risdate>2003</risdate><volume>90</volume><issue>1</issue><spage>64</spage><epage>70</epage><pages>64-70</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><coden>THHADQ</coden><abstract>Summary
The present study compares the efficacy of two formulations of encapsulated streptokinase to streptokinase in a rabbit model of carotid artery thrombosis. Arterial thrombosis followed the injection of thrombin mixed with autologous whole blood into a carotid artery of New Zealand white rabbits. Thirty minutes after the confirmation of an occlusive thrombus, one of four streptokinase formulations was infused at a dosage of 6,000 IU/kg into the jugular vein. Free streptokinase (FREE SK) was compared to identical dosages of streptokinase encapsulated in a liposome (LESK), streptokinase entrapped in a water-soluble polymer (MESK), and free streptokinase admixed with blank microparticles (FREE SK + BLANK). Carotid arterial blood flow was determined by pulsed Doppler flowmetry to confirm clot formation and reperfusion. Two hours after drug infusion, the rabbits were killed and the residual thrombus mass was determined.
Compared to FREE SK (74.5 ± 16.9 min; mean ± SEM), LESK demonstrated significantly reduced reperfusion times (19.3 ± 4.6 min) while MESK exhibited even greater improvement (7.3 ± 1.6 min). FREE SK + BLANK showed no statistical improvement versus FREE SK. LESK and MESK also resulted in reduced residual clot mass and greater return of arterial blood flow. These studies suggest that encapsulation of streptokinase offers a potential method of improved fibrinolytic treatment for patients with clot-based disorders. MESK performed slightly better than LESK with improved production and storage characteristics.</abstract><cop>Stuttgart</cop><pub>Schattauer Verlag für Medizin und Naturwissenschaften</pub><pmid>12876627</pmid><doi>10.1055/s-0037-1613600</doi><tpages>7</tpages></addata></record> |
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| ispartof | Thrombosis and haemostasis, 2003-07, Vol.90 (1), p.64-70 |
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| language | eng |
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| source | MEDLINE; Thieme Connect Journals |
| subjects | Animals Biological and medical sciences Blood Coagulation, Fibrinolysis and Cellular Haemostasis Blood. Blood coagulation. Reticuloendothelial system Carotid Artery Thrombosis - drug therapy Drug Carriers Drug Compounding Drug Evaluation, Preclinical Female Fibrinolytic Agents - administration & dosage Fibrinolytic Agents - therapeutic use Liposomes Male Medical sciences Microspheres Models, Animal Pharmacology. Drug treatments Polyethylene Glycols Rabbits Recurrence Streptokinase - administration & dosage Streptokinase - therapeutic use Thrombin - toxicity Thrombolytic Therapy |
| title | Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase |
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