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The effect of exogenous plasminogen activator inhibitor - 1 in a canine model of occlusive thrombus formation

Fibrinolysis, ISSN: 0268-9499, Vol: 5, Issue: 2, Page: 99-104
1991
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  • Citations
    4
    • Citation Indexes
      4

Article Description

The effects of exogenous plasminogen activator inhibitor - 1 (PAI-1) were evaluated in a canine coronary artery model of occlusive thrombus formation. Activated PAI-1 was delivered as a bolus (b) loading dose followed by a constant infusion (i) to 2 groups of 5 dogs (PAI-1-A, b = 5 ug/kg, i = 3.5 ug/kg/h; PAI-1-B, b = 25 ug/kg, i = 17.5 ug/kg/h) while control animals (n = 11) received vehicle only. The administration of PAI-I resulted in dose-dependent increases in the steady state levels of PAJ-1 antigen (PAI-1-A, 32 ± 3 ng/ml; PAI-1-B, 204 ± 19 ng/ml) relative to the basal levels present in the circulation (4.9 ± 1.3 ng/ml). PAI-1 infusion was accompanied by the dose-dependent inhibition of circulating plasminogen activator activity (PAI-1-A, 37% inhibition; PAI-1-B, 78% inhibition). Thrombus formation was initiated by applying continuous 150 μA anodal current to the isolated left circumflex coronary artery in the presence of a flow limiting stenosis. PAI-1 administration decreased the time required to form occlusive thrombi relative to control animals by approximately 13 as determined by the cessation of blood flow through the artery (vehicle, 65.6 ± 6.6 min; PAI-1-A, 43.8 ± 3.4 min; PAI-1-B, 43.4 ± 11.6 min). The differences in occlusion times were significant at the p < 0.1 level (PAI-1-A, p = 0.057, PAI-1-B, p = 0.062). The data suggest that elevated levels of circulating PAI-1 may facilitate the formation of rapidly evolving arterial thrombi.

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