American Society of Hirudotherapy

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)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Preclinical (animal)Drug DevelopmentClinical LiteratureLenfors S et al. · 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.

Publication typeJournal Article
Indexed MeSH termsAnimalsBlood PlateletsCarotid ArteriesDisease Models, AnimalDrug CombinationsErythrocytesHirudinsHot TemperatureIodine RadioisotopesMaleRatsRats, Sprague-DawleyRecombinant ProteinsThrombosisTissue Plasminogen Activator

Summary

A new rat carotid artery thrombosis model produces a thrombus with a platelet-rich head and erythrocyte-rich tail; hirudin combined with rt-PA significantly improved thrombolysis, while heparin combined with rt-PA did not, consistent with prior experimental findings.

Why This Matters for Hirudotherapy

This study developed a rat carotid artery thrombosis model using repeated focal heat injury, producing a thrombus with a platelet-rich head and erythrocyte-rich tail resembling human coronary occlusion thrombus. The model was tested by comparing thrombolysis with rt-PA alone, rt-PA plus heparin, and rt-PA plus recombinant hirudin. Both blood flow and residual 125I-fibrinogen radioactivity measurements showed that hirudin combined with rt-PA significantly improved recanalization, whereas heparin combined with rt-PA did not significantly improve thrombolysis. The study is limited by its small-animal (rat) model and its primary focus on model development. Recombinant hirudin is produced in microorganisms from the gene of hirudin, the anticoagulant of the medicinal leech (Märki et al., 1991); this paper studies the drug, not leech therapy.

Citation

Reference (Vancouver style)

Lenfors S, Marberg L, Wikström S, Jonsson U, Eriksson AW, Gustafsson D. A new rat model of arterial thrombosis with a platelet-rich head and an erythrocyte-rich tail: thrombolysis experiments with specific thrombin inhibition. Blood Coagul Fibrinolysis. 1993;4(2):263-271. doi:10.1097/00001721-199304000-00008. PMID: 8499564

Bibliographic details (authors, volume, pages, DOI) are taken from the PubMed record.

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