Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase

Jonathan K Leach, Edgar A. O'Rear, Eugene Patterson, Yiwei Miao, Arthur E. Johnson

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)64-70
Number of pages7
JournalThrombosis and Haemostasis
Volume90
Issue number1
StatePublished - Jul 1 2003
Externally publishedYes

Fingerprint

Carotid Artery Thrombosis
Streptokinase
Liposomes
Rabbits
Thrombosis
Reperfusion
Rheology
Jugular Veins
Carotid Arteries
Thrombin

Keywords

  • Liposomes
  • Microencapsulation
  • Streptokinase
  • Thrombolytic therapy
  • Thrombus

ASJC Scopus subject areas

  • Hematology

Cite this

Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase. / Leach, Jonathan K; O'Rear, Edgar A.; Patterson, Eugene; Miao, Yiwei; Johnson, Arthur E.

In: Thrombosis and Haemostasis, Vol. 90, No. 1, 01.07.2003, p. 64-70.

Research output: Contribution to journalArticle

Leach, Jonathan K ; O'Rear, Edgar A. ; Patterson, Eugene ; Miao, Yiwei ; Johnson, Arthur E. / Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase. In: Thrombosis and Haemostasis. 2003 ; Vol. 90, No. 1. pp. 64-70.
@article{1b4eb996df5c4862b502ee4ab5e8fbf4,
title = "Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase",
abstract = "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.",
keywords = "Liposomes, Microencapsulation, Streptokinase, Thrombolytic therapy, Thrombus",
author = "Leach, {Jonathan K} and O'Rear, {Edgar A.} and Eugene Patterson and Yiwei Miao and Johnson, {Arthur E.}",
year = "2003",
month = "7",
day = "1",
language = "English (US)",
volume = "90",
pages = "64--70",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "1",

}

TY - JOUR

T1 - Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase

AU - Leach, Jonathan K

AU - O'Rear, Edgar A.

AU - Patterson, Eugene

AU - Miao, Yiwei

AU - Johnson, Arthur E.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

KW - Liposomes

KW - Microencapsulation

KW - Streptokinase

KW - Thrombolytic therapy

KW - Thrombus

UR - http://www.scopus.com/inward/record.url?scp=0037961999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037961999&partnerID=8YFLogxK

M3 - Article

C2 - 12876627

AN - SCOPUS:0037961999

VL - 90

SP - 64

EP - 70

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 1

ER -