A new rat model of arterial thrombosis with a platelet-rich head and an erythrocyte-rich tail: thrombolysis experiments with specific thrombin inhibition
Animal model paper published in Blood Coagulation and Fibrinolysis (1993)
Abstract
A model for thrombolysis in rats was developed. Repeated, focal external heating was applied to the carotid artery which leads to the development of a cyclic blood flow with slow, steady decreases followed by abrupt increases. When this cyclic blood flow stops spontaneously, the entire arterial segment (approximately 10 mm) can be demarcated with snares to create an arterial thrombus of fixed size, with a platelet-rich head and an erythrocyte-rich tail. The usefulness of the model was tested by evaluating the thrombolysis induced by a low dose of recombinant tissue-type plasminogen activator (rt-PA) alone and rt-PA in combination with standard heparin and recombinant hirudin. Re-canalization of the artery was measured as blood flow and as the residual 125I-radioactivity in the artery at the end of the experiment, resulting from 125I-fibrinogen incorporated during the formation of the thrombus. Both blood flow and 125I-activity measurements show that hirudin, but not heparin in combination with rt-PA, significantly improves thrombolysis, which is in accordance with previous experimental findings. It is concluded that the model, with a thrombus resembling the thrombus found in man after coronary occlusion, enables complicated experiments with thrombolysis frequently performed only in large animals to be performed in rats.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Novel rat carotid artery thrombosis model with platelet-rich head and erythrocyte-rich tail; recombinant hirudin combined with rt-PA significantly improved thrombolysis vs heparin/rt-PA combination, demonstrating in a rat model what was previously seen in larger animals.
Warum dies für die Hirudotherapie relevant ist
Diese Studie entwickelte ein Ratten-Karotis-Thrombosemodell mittels wiederholter fokaler Hitzeverletzung, das einen Thrombus mit einem plättchenreichen Kopf und einem erythrozytenreichen Schwanz erzeugt, welcher dem menschlichen Koronarokklusionsthrombus ähnelt. Das Modell wurde getestet, indem Thrombolyse mit rt-PA allein, rt-PA plus Heparin und rt-PA plus rekombinantem Hirudin verglichen wurden. Sowohl die Messungen des Blutflusses als auch der residualen 125I-Fibrinogen-Radioaktivität zeigten, dass Hirudin kombiniert mit rt-PA die Rekanalisierung signifikant verbesserte, während Heparin kombiniert mit rt-PA die Thrombolyse nicht signifikant verbesserte. Die Relevanz für das Fachgebiet der ASH ist indirekt: Die Studie verwendet rekombinantes Hirudin, erwähnt jedoch weder Blutegel noch Hirudotherapie. Die Studie ist durch ihr Kleintiermodell (Ratte) und ihren primären Fokus auf die Modellentwicklung limitiert.
Zitation
A new rat model of arterial thrombosis with a platelet-rich head and an erythrocyte-rich tail: thrombolysis experiments with specific thrombin inhibition.
Lenfors S et al. · Blood Coagulation and Fibrinolysis, 1993
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