Related Experiment Videos
Inhibition of coronary artery reocclusion after thrombolysis with an RGD-containing peptide with no significant
J F Tschopp1, E M Driscoll, D X Mu
1Department of Pharmacology, University of Michigan Medical School, Ann Arbor.
Insights
TP9201, a peptide targeting platelet receptors, significantly prolonged vessel patency and prevented reocclusion after thrombolysis in a canine model. This peptide offers a promising approach to prevent re-thrombosis without compromising hemostasis.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Thrombosis and Hemostasis
Background:
- A synthetic RGD-containing cyclic peptide, TP9201, targets the platelet alpha IIb beta 3 receptor complex.
- Investigated for its potential to accelerate thrombolysis and prevent reocclusion in coronary artery thrombosis.
Purpose of the Study:
- To evaluate the efficacy of TP9201 in preventing reocclusion after thrombolytic therapy.
- To assess the impact of TP9201 on thrombolysis, vessel patency, and hemostasis in a canine model of coronary artery thrombosis.
Main Methods:
- Open-chest dogs with induced coronary artery thrombi received tissue plasminogen activator with either TP9201 or a saline control.
- Ex-vivo platelet aggregation and bleeding times were measured.
Main Results:
- TP9201 significantly increased vessel patency duration (2.8-fold) and reduced occlusion duration (2.4-fold).
- Persistent patency was observed in 4/7 treated dogs versus 0/9 controls (P < 0.05).
- TP9201 inhibited platelet aggregation ex-vivo but did not affect bleeding time or hemodynamics.
Conclusions:
- TP9201 demonstrated effectiveness in preventing re-thrombosis after thrombolytic therapy.
- The peptide showed a favorable safety profile, with no adverse effects on hemostasis or hemodynamics.
- TP9201 may be a valuable therapeutic agent for preventing re-thrombosis post-thrombolysis.
Background:
A synthetic RGD-containing cyclic peptide, TP9201, specific for the platelet alpha IIb beta 3 receptor complex, was tested for its ability to accelerate thrombolysis and prevent reocclusion in experimentally induced coronary artery thrombosis.
Methods:
Anesthetized, open-chest dogs with occlusive thrombi received tissue plasminogen activator with TP9201 (113 micrograms/kg bolus; 2.7 micrograms/kg/min infusion, n = 7) or saline control (n = 9).
Results:
A 2.8-fold increase in the duration of vessel patency from 52.7 +/- 63.7 min to 149.1 +/- 63.7 min (P < 0.05) was observed with TP9201 treatment. The mean duration of vessel occlusion was reduced 2.4-fold from 172.4 +/- 81.1 min to 71.7 +/- 63.7 min (P < 0.05). Administration of TP9201 reduced the mean time to lysis from 76.6 +/- 42.9 min to 54.4 +/- 42.9 min, but thrombolysis was not significantly accelerated. Persistent patency was observed in four out of seven of the treated dogs compared with none of the nine in the control group (P < 0.05). Administration of TP9201 inhibited ex-vivo platelet aggregation stimulated by ADP (30 microM) or collagen (10 micrograms/ml). No thrombocytopenia or changes in hemodynamic parameters were observed in the treated group compared with the control group. Peptide TP9201 had no effect on bleeding time and the inhibitory effect on ex-vivo platelet aggregation was rapid and reversible. The pharmacodynamic half-life of TP9201 was approximately 1 h with ex-vivo platelet activity returning to baseline within 2 h of discontinuation of treatment.
Conclusions:
TP9201 may be an effective therapy for the prevention of re-thrombosis after thrombolytic therapy without adversely affecting hemostasis.