Formation and Embolization of Thrombi after Electrical Stimulation

1973 ◽  
Vol 30 (02) ◽  
pp. 352-362
Author(s):  
B. A Spilker ◽  
H van Balken

SummaryCharacteristics of thrombi produced upon electrical stimulation of mesentery and brain vessels were studied in five species. Parameters for measuring drug effects were also evaluated to determine which were sensitive to platelet aggregation inhibitors. The current required to cause vasoconstriction in 50% of the rat mesentery arteries stimulated was increased by vasodilators, but not by inhibitors of platelet aggregation. The threshold of current necessary to cause thrombus formation was increased by Imipramine in both acute and chronic experiments and by aspirin and papaverine in chronic experiments. Since these were the only agents tested which inhibit platelet aggregation there appears to be a relationship between this property and the threshold of current necessary to cause thrombus formation. This parameter may possibly be used to differentiate between platelet aggregation inhibitors and streptokinase-like or heparin-like agents. Changes in mean embolization time under present conditions were not related to activity in inhibiting platelet aggregation.

1977 ◽  
Author(s):  
R. Zimmermann ◽  
K. Andrassy ◽  
C. Zeltsch ◽  
D. Lange ◽  
F. Hof

Previous studies documented an impairment of haemostasis by synthetic penicillins (Thromb. Haem. 34: 115, 1976) and penicillin (Lancet II : 1039, 1976). Therefore the antithrombotic activity of synthetic penicillin. (carbenicillin)(C) was compared with that of aspirin (ASA), dipyridamole (DIPY) and heparin in 150 rabbits. Thrombus formation was induced by standardized endothelial lesions. The dose of C was adjusted to a 4.2 fold prolongation of bleeding time, similar to that seen in clinical patients. Analysis and composition of thrombi was done by measurement of incorporation of labeled blood elements (51cr labeled platelets, 125J-fibrinogen and 59Fe labeled red cells). The ‘specific thrombus/blood ratio’ with values of 19.1 and 50.9 (51cr) in venous and arterial thrombi evidenced the significance of platelets in this model. In the venous system C reduced formation of thrombi by 43%, ASA by 34%, ASA and DIPY by 55% and heparin by 90%. In the arterial system C inhibited thrombus formation by 89%, ASA by 15%, ASA and DIPY by 46% and heparin by 60%. It is concluded, that C effectively prevents thrombus formation in the arterial system and to lower extent in the venous system. The results prove the importance of platelets in arterial thrombogenesis and the efficacy of platelet aggregation inhibitors in preventing thrombi in the arterial system. In comparison with other known antiplatelet drugs it seems, that C is the most effective platelet aggregation inhibitor to date.


1997 ◽  
Vol 17 (01) ◽  
pp. 43-48 ◽  
Author(s):  
R. Verhaeghe ◽  
J. Vermylen

1993 ◽  
Vol 41 (9) ◽  
pp. 1604-1607 ◽  
Author(s):  
Kiyomi KAGAWA ◽  
Katsuya TOKURA ◽  
Kiyohisa UCHIDA ◽  
Hisato KAKUSHI ◽  
Tsutomu SHIKE ◽  
...  

2014 ◽  
Vol 10 (38) ◽  
pp. 111 ◽  
Author(s):  
Jing Liao ◽  
Yingzhan Tang ◽  
Chengyu Tan ◽  
Hui Ni ◽  
Xueqin Wu ◽  
...  

2020 ◽  
Vol 21 (11) ◽  
pp. 3932 ◽  
Author(s):  
Preeti Kumari Chaudhary ◽  
Sanggu Kim ◽  
Youngheun Jee ◽  
Seung-Hun Lee ◽  
Kyung-Mee Park ◽  
...  

Platelet G protein-coupled receptors (GPCRs) regulate platelet function by mediating the response to various agonists, including adenosine diphosphate (ADP), thromboxane A2, and thrombin. Although GPCR kinases (GRKs) are considered to have the crucial roles in most GPCR functions, little is known regarding the regulation of GPCR signaling and mechanisms of GPCR desensitization by GRKs in platelets. In this study, we investigated the functional role of GRK6 and the molecular basis for regulation of specific GPCR desensitization by GRK6 in platelets. We used GRK6 knockout mice to evaluate the functional role of GRK6 in platelet activation. Platelet aggregation, dense- and α-granule secretion, and fibrinogen receptor activation induced by 2-MeSADP, U46619, thrombin, and AYPGKF were significantly potentiated in GRK6−/− platelets compared to the wild-type (WT) platelets. However, collagen-related peptide (CRP)-induced platelet aggregation and secretion were not affected in GRK6−/− platelets. Interestingly, platelet aggregation induced by co-stimulation of serotonin and epinephrine which activate Gq-coupled 5HT2A and Gz-coupled α2A adrenergic receptors, respectively, was not affected in GRK6−/− platelets, suggesting that GRK6 was involved in specific GPCR regulation. In addition, platelet aggregation in response to the second challenge of ADP and AYPGKF was restored in GRK6−/− platelets whereas re-stimulation of the agonist failed to induce aggregation in WT platelets, indicating that GRK6 contributed to P2Y1, P2Y12, and PAR4 receptor desensitization. Furthermore, 2-MeSADP-induced Akt phosphorylation and AYPGKF-induced Akt, extracellular signal-related kinase (ERK), and protein kinase Cδ (PKCδ) phosphorylation were significantly potentiated in GRK6−/− platelets. Finally, GRK6−/− mice exhibited an enhanced and stable thrombus formation after FeCl3 injury to the carotid artery and shorter tail bleeding times, indicating that GRK6−/− mice were more susceptible to thrombosis and hemostasis. We conclude that GRK6 plays an important role in regulating platelet functional responses and thrombus formation through selective GPCR desensitization.


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