Abstract
To evaluate the effect of thrombin on the dynamics of thrombolysis, we infused rabbits with heparin or hirudin alone or in conjunction with tissue-type plasminogen activator (t-PA) and monitored the kinetics of fibrinolysis and changes in ex vivo platelet aggregation responses over time. Both heparin and hirudin enhanced total fibrinolysis in an ex vivo arteriovenous shunt preparation: 82±2% and 79±2%, respectively, compared with 51±8% for t-PA alone (p<0.05) and 50±4% for t-PA plus aspirin (p<0.05). Heparin coadministered with t-PA significantly reduced the half-time for clot lysis compared with t-PA alone (p<0.05), whereas hirudin coadministered with t-PA significantly reduced the half-time for clot lysis compared with that for t-PA alone, t-PA plus aspirin, and t-PA plus heparin (5.5±0.6 versus 12.1±2.0 versus 12.6±2.2 versus 10.0±0.8 minutes, respectively; p<0.05). Both heparin and hirudin prevented the increase in ADP-induced platelet aggregation normally seen with t-PA alone (p<0.01 by t test; p<0.05 by two-way analysis of variance). These data demonstrate that selective, antithrombin III-independent thrombin inhibitors can enhance the efficacy of thrombolysis by modulating the dynamics of the process and preventing platelet activation associated with plasminogen activator therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 829-834 |
| Number of pages | 6 |
| Journal | Circulation Research |
| Volume | 70 |
| Issue number | 4 |
| State | Published - 1990 |
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Keywords
- Heparin
- Hirudin
- Platelet aggregation
- Thrombolysis
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy. / Rudd, M. Audrey; George, Dorinda; Johnstone, Michael T.; Moore, Richard T.; Collins, Laura; Rabbani, LeRoy E.; Loscalzo, Joseph.
In: Circulation Research, Vol. 70, No. 4, 1990, p. 829-834.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy
AU - Rudd, M. Audrey
AU - George, Dorinda
AU - Johnstone, Michael T.
AU - Moore, Richard T.
AU - Collins, Laura
AU - Rabbani, LeRoy E.
AU - Loscalzo, Joseph
PY - 1990
Y1 - 1990
N2 - To evaluate the effect of thrombin on the dynamics of thrombolysis, we infused rabbits with heparin or hirudin alone or in conjunction with tissue-type plasminogen activator (t-PA) and monitored the kinetics of fibrinolysis and changes in ex vivo platelet aggregation responses over time. Both heparin and hirudin enhanced total fibrinolysis in an ex vivo arteriovenous shunt preparation: 82±2% and 79±2%, respectively, compared with 51±8% for t-PA alone (p<0.05) and 50±4% for t-PA plus aspirin (p<0.05). Heparin coadministered with t-PA significantly reduced the half-time for clot lysis compared with t-PA alone (p<0.05), whereas hirudin coadministered with t-PA significantly reduced the half-time for clot lysis compared with that for t-PA alone, t-PA plus aspirin, and t-PA plus heparin (5.5±0.6 versus 12.1±2.0 versus 12.6±2.2 versus 10.0±0.8 minutes, respectively; p<0.05). Both heparin and hirudin prevented the increase in ADP-induced platelet aggregation normally seen with t-PA alone (p<0.01 by t test; p<0.05 by two-way analysis of variance). These data demonstrate that selective, antithrombin III-independent thrombin inhibitors can enhance the efficacy of thrombolysis by modulating the dynamics of the process and preventing platelet activation associated with plasminogen activator therapy.
AB - To evaluate the effect of thrombin on the dynamics of thrombolysis, we infused rabbits with heparin or hirudin alone or in conjunction with tissue-type plasminogen activator (t-PA) and monitored the kinetics of fibrinolysis and changes in ex vivo platelet aggregation responses over time. Both heparin and hirudin enhanced total fibrinolysis in an ex vivo arteriovenous shunt preparation: 82±2% and 79±2%, respectively, compared with 51±8% for t-PA alone (p<0.05) and 50±4% for t-PA plus aspirin (p<0.05). Heparin coadministered with t-PA significantly reduced the half-time for clot lysis compared with t-PA alone (p<0.05), whereas hirudin coadministered with t-PA significantly reduced the half-time for clot lysis compared with that for t-PA alone, t-PA plus aspirin, and t-PA plus heparin (5.5±0.6 versus 12.1±2.0 versus 12.6±2.2 versus 10.0±0.8 minutes, respectively; p<0.05). Both heparin and hirudin prevented the increase in ADP-induced platelet aggregation normally seen with t-PA alone (p<0.01 by t test; p<0.05 by two-way analysis of variance). These data demonstrate that selective, antithrombin III-independent thrombin inhibitors can enhance the efficacy of thrombolysis by modulating the dynamics of the process and preventing platelet activation associated with plasminogen activator therapy.
KW - Heparin
KW - Hirudin
KW - Platelet aggregation
KW - Thrombolysis
UR - http://www.scopus.com/inward/record.url?scp=0026514409&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026514409&partnerID=8YFLogxK
M3 - Article
C2 - 1551206
AN - SCOPUS:0026514409
VL - 70
SP - 829
EP - 834
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 4
ER -