Mediation of reocclusion by thromboxane A2 and serotonin after thrombolysis with tissue-type plasminogen activator in a canine preparation of coronary thrombosis.

Golino, Paolo; Ashton, J; Glas-Greenwalt, Pia; McNatt, J; Buja, L. Maximilian; Willerson, J. T.

doi:10.1161/01.cir.77.3.678

Cited by 154 publications

(48 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 We have also shown that this phenomenon is primarily caused by intracoronary platelet activation and that TXA2 and serotonin cooperatively mediate reocclusion.6 SQ29548 and LY53857, given at the moment of reperfusion, were able to prevent this exclude the possibility that the interaction between SQ29548 and LY53857 observed in the present study may be pharmacokinetic and not pharmacodynamic (i.e., one antagonist had increased the plasma concentration of the other). However, this possibility seems very unlikely because LY53857 at half of the dose used in the present study35 and SQ29548 at a dose comparable to that used in the present study33'34 elicit a complete blockade of their respective receptors.…”

Section: Discussionsupporting

confidence: 48%

Simultaneous administration of thromboxane A2- and serotonin S2-receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis.

et al. 1989

Self Cite

View full text Add to dashboard Cite

Dynamic changes of the thrombus after its formation due to platelet activation may affect the speed of thrombolysis. In the present study, we wanted to evaluate the role played by thromboxane A2 (TXA2) and serotonin (5HT) in (LAD). LAD blood flow was monitored throughout the experiment by means of a Doppler flow probe placed proximally to the coil. Presence of the thrombus was documented for 30 minutes. The dogs were then assigned to one of four groups as follows: group 1 dogs (n=8), serving as controls, received a bolus of heparin (200 units/kg) and a bolus of t-PA (80 ,ug/kg) followed by a continuous infusion (8 ,ug/kg/min) for up to 90 minutes or until reperfusion was achieved; group 2 dogs (n = 10) received, immediately before heparin and t-PA, an intravenous bolus of SQ29548 (SQ) (0.4 mg/kg, a selective TXA2-receptor antagonist) and LY53857 (LY) (0.2 mg/kg, a selective serotonin S2-receptor antagonist); group 3 dogs (n=7) received, before heparin and t-PA, an intravenous bolus of SQ alone (0.4 mg/kg); and group 4 dogs (n=7) received, before heparin and t-PA, an intravenous bolus of LY alone (0.2 mg/kg). After thrombolysis, all dogs were monitored for 90 minutes or until a persistent reocclusion occurred. Treatment with the combination of SQ and LY markedly shortened the time required to lyse the thrombus, 46±7 compared with 15±3 minutes in groups 1 and 2, respectively, p<0.01; whereas either antagonist alone was not effective in accelerating the lysis, 38+8 and 43+4 minutes in groups 3 and 4, respectively,p=NS compared with group 1. In group 1 dogs, after discontinuation of t-PA, repeated cycles of gradual occlusions followed by spontaneous restorations of flow (cyclic flow variations, CFVs) were observed before a persistent reocclusion occurred. The administration of both SQ and LY immediately before heparin and t-PA completely prevented CFVs and reocclusion in all the group 2 dogs that were successfully reperfused. Neither SQ nor LY alone was effective in preventing CFVs and reocclusion. We conclude that SQ and LY in combination markedly enhance the thrombolytic efect of t-PA, probably by preventing further platelet activation and their incorporation into the thrombus during lysis. Furthermore, the combination of the two drugs is very efective in preventing reocclusion after discontinuation of t-PA. (Circulation

show abstract

Section: Discussionsupporting

confidence: 48%

Simultaneous administration of thromboxane A2- and serotonin S2-receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis.

et al. 1989

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similarly, after rt-PA induced thrombolysis, platelet activation and thromboxane are important mediators of vasomotor instability and reocclusion. 7,41 Although neither heparin7 nor aspirin'2 completely prevented reocclusion, intravenous aspirin did appear to facilitate reperfusion.…”

Section: Discussionmentioning

confidence: 92%

Antiplatelet antibody [7E3 F(ab')2] prevents rethrombosis after recombinant tissue-type plasminogen activator-induced coronary artery thrombolysis in a canine model.

et al. 1990

View full text Add to dashboard Cite

Coronary artery rethrombosis can complicate initially effective thrombolytic therapy. Platelets interacting with injured vascular endothelium in a region along the coronary artery with reduced luminal cross-sectional area contribute to rethrombosis. The purpose of this study was to investigate the potential of the F(ab')2 fragment of the murine monoclonal antibody 7E3 [7E3 F(ab')2] to prevent rethrombosis after intracoronary clot lysis with recombinant tissue-type plasminogen activator (rt-PA) in an experimental model. The 7E3 F(ab')2 binds to the platelet glycoprotein lIb/llla complex (GPIIb/IIIa), thereby preventing platelet-fibrinogen interaction and intravascular thrombus formation. Experimental coronary artery thrombosis was produced in the anesthetized dog by application of direct anodal current to the intimal surface of the left circumflex coronary artery in the region of an external stenosis. Lysis of the established intracoronary thrombus was achieved with the intravenous administration of rt-PA (25 mg) after which the animals were randomized into two groups. Group 1 (n=10) served as the control, receiving the saline diluent, and group 2 (n =9) received 7E3 F(ab')2, given as a single intravenous injection (0.8 mg/kg). The times required for occlusive thrombus formation, rt-PA-induced thrombolysis, and rethrombosis (if it occurred) were similar in the animals treated with saline and those treated with 7E3 F(ab')2. The initial left circumflex coronary artery blood flow was similar in both groups but decreased to a negligible level in group 1. In group 2, left circumflex coronary artery blood flow declined modestly (24±+2 to 10±2 ml/min).Rethrombosis occurred in all animals in group 1 but in only two of nine animals in group 2 (p

show abstract

“…Indeed, antagonists to the thromboxane A 2 or serotonin S 2 receptors led to facilitated thrombolysis or avoidance of reocclusion of the infarct vessel in experimental models. 30,31 Although these studies can, in retrospect, be viewed as classic, the pivotal role of platelets in this clinical setting and the potent pharmacological interventions were not fully appreciated or available until more than a decade later.…”

Section: Classic Studiesmentioning

confidence: 99%

Toward a New Frontier in Myocardial Reperfusion Therapy

1998

View full text Add to dashboard Cite

Mediation of reocclusion by thromboxane A2 and serotonin after thrombolysis with tissue-type plasminogen activator in a canine preparation of coronary thrombosis.

Cited by 154 publications

References 25 publications

Simultaneous administration of thromboxane A2- and serotonin S2-receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis.

Simultaneous administration of thromboxane A2- and serotonin S2-receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis.

Antiplatelet antibody [7E3 F(ab')2] prevents rethrombosis after recombinant tissue-type plasminogen activator-induced coronary artery thrombolysis in a canine model.

Toward a New Frontier in Myocardial Reperfusion Therapy

Contact Info

Product

Resources

About