Radiolabeled r-hirudin as a measure of thrombin activity at or within the rabbit aorta wall in vitro and in vivo
Research article published in Thrombosis and haemostasis (1994)
Abstract
The behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound > 95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of 125I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p < 0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p < 0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endothelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (+/- 2.5) and 25.6 (+/- 18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Radiolabeled r-hirudin as a measure of thrombin activity at or within the rabbit aorta wall in vitro and in vivo.
Por qué esto importa para la hirudoterapia
Este estudio examinó hirudina recombinante marcada con 125I como indicador de la actividad de trombina asociada a la pared de la aorta de conejo, tanto in vitro como in vivo. En tejido desendotelizado pretatado con trombina y lesionado con balón, la unión de 125I-r-hirudina se correlacionó positivamente con la trombina unida (p < 0,01 in vitro) y con la trombina activa liberada (p < 0,001 in vivo); la captación in vivo también fue paralela a la captación de 131I-fibrinógeno. Tras 30 minutos en circulación, la unión específica correspondió a aproximadamente 3,4 fmol de trombina/cm² en aorta no lesionada y a 25,6 fmol/cm² en aorta desendotelizada. Para el ámbito de ASH, la relevancia es indirecta: la hirudina es el inhibidor de trombina originalmente caracterizado a partir de la sanguijuela medicinal, y el estudio aprovecha su alta especificidad de unión por la trombina en superficies vasculares. No obstante, se trata de un estudio en animales (conejos) que utiliza hirudina recombinante como sonda de investigación, no de una investigación de hirudoterapia terapéutica, y los autores señalan que podría detectar únicamente la trombina unida a glucosaminoglucanos y accesible a la hirudina.
Citación
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026