摘要:

The antithrombotic effects of four compounds structurally related to aspirin (acetylsalicylic acid, ASA) were examined in a rat model of arterial thrombosis and compared to ASA. ASA had antithrombotic activity, but only at high doses (200 mg/kg), when carotid artery thrombosis was induced 15 min after intravenous drug administration. Lower doses were associated with augmented thrombus formation in some animals. 2-Propionyloxybenzoic acid, which has in vitro activities similar to ASA, caused similar in vivo effects, but was antithrombotic at 100 mg/kg. 3-Propionyloxybenzoic acid, which augments platelet function in vitro, and 3-methylphthalide, which inhibits biphasic adenosine diphosphate-induced platelet aggregation, had no statistically significant effects. 2-Acetoxybenzoic acid, which is a weak platelet aggregation and prostaglandin biosynthesis inhibitor, had antithrombotic activity at 100 and 200 mg/kg and was not associated with augmented thrombosis at lower doses as found with ASA. The pattern of antithrombotic activity of this series of compounds does not reflect in vitro effects on prostaglandin biosynthesis and indicates alternative mechanisms of antithrombotic activity.

ISSN:1424-8832    

DOI:10.1159/000215087

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Uptake of radioiodinated Lys-plasminogen (125I-PLG), albumin (125I-ALB), and tritiated water (3H-H2O) by in vitro thrombi and interchange of these molecules with blood in an in vitro perfusion system were investigated. The radioisotopes were taken up by thrombi either by incorporation during formation in radiolabelled blood or by perfusion of preformed nonradioactive thrombi in radiolabelled blood. Release of the radioisotopes into a perfusion medium of nonradiolabelled blood was then monitored over a 120-min period. The small molecules of 3H-H2O were rapidly released from the thrombi and achieved equilibrium with the perfusion medium by 120 min in that the specific radioactivity (cpm/mg) of the thrombi equalled that of the medium. The larger molecules of 125I-PLG and 125I-ALB were more slowly released and did not reach equilibrium with the perfusion medium over the period studied. Release of 125I-ALB was intermediate between that of 3H-H2O and 125I-PLG. The greater retention of 125I-PLG by the thrombi was consistent with the high binding affinity of plasminogen for fibrin. The demonstrated movement of these radioisotopes between medium and thrombus suggests that thrombi exist in blood in a dynamic state of flux, exhibiting a fluid exchange of molecules between the interstitial compartment of the thrombus and blood.

ISSN:1424-8832    

DOI:10.1159/000215088

出版商:S. Karger AG    

年代:1984

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000215089

出版商:S. Karger AG    

年代:1984

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000215090

出版商:S. Karger AG    

年代:1984

数据来源: Karger