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Modelo de sangrado por transyección de la vena de la cola en ratones con hemofilia A totalmente a...
Modelo de sangrado por transyección de la vena de la cola en ratones con hemofilia A totalmente a...
JoVE Journal
Biology
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JoVE Journal Biology
Tail Vein Transection Bleeding Model in Fully Anesthetized Hemophilia A Mice

Modelo de sangrado por transyección de la vena de la cola en ratones con hemofilia A totalmente anestesiada

Full Text
7,667 Views
08:13 min
September 30, 2021

DOI: 10.3791/62952-v

Ariadna Carol Illa1,2, Sarah Baumgarten1, Dennis Danielsen1, Karin Larsen3, Torben Elm1, Peter B. Johansen4, Tom Knudsen5, Brian Lauritzen1, Mikael Tranholm6, Carsten D. Ley1

1Global Drug Discovery,Novo Nordisk A/S, 2Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences,University of Copenhagen, 3Department of Biomedical Sciences, Faculty of Health and Medical Sciences,University of Copenhagen, 4Independent consultant, 5Catalyst Biosciences, 6Værløse Dyreklinik

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Overview

The refined tail vein transection (TVT) bleeding model provides a sensitive in vivo method for assessing hemophilic bleeding in anesthetized mice. This optimized model utilizes blood loss and bleeding time as key endpoints, refining previous models and eliminating death as an endpoint.

Key Study Components

Research Area

  • Hemophilia
  • Coagulation disorders
  • In vivo pharmacological assessment

Background

  • Importance of reliable bleeding models for pharmacological studies
  • Use of anesthesia to minimize animal distress
  • Need for models that accurately measure blood coagulation

Methods Used

  • Tail vein transection bleeding model
  • Hemophilia A mice as biological system
  • Measurement of bleeding time and blood loss as endpoints

Main Results

  • Significant reduction in blood loss observed with recombinant factor VIII treatment
  • Bleeding time normalized in treated groups
  • Strong correlation between blood loss and bleeding time across experiments

Conclusions

  • The study confirms the effectiveness of the refined TVT model for evaluating hemostatic therapies
  • Demonstrates the relevance of optimized animal models in preclinical hemophilia research

Frequently Asked Questions

What are the endpoints measured in the TVT bleeding model?
The model measures blood loss and bleeding time as endpoints.
Why is anesthesia used in this model?
Anesthesia minimizes pain and distress for the mice during the experiment.
What type of mice are primarily used in this study?
The study primarily uses hemophilia A mice.
How does the model assess the effectiveness of treatments?
Effectiveness is assessed by analyzing reductions in bleeding time and blood loss after treatment with hemophilia therapies.
What factors were analyzed in the study's results?
Blood loss and bleeding time were analyzed, with attention to treatment dose and gender effects.
What conclusion can be drawn about the reliability of the results?
The study demonstrates that precise method execution and proper animal handling result in reliable and reproducible data.
Can this model be used for other bleeding disorders?
Yes, the model may be adapted for studying other coagulation disorders beyond hemophilia.

El modelo de sangrado de transección refinada de la vena de la cola (TVT) en ratones anestesiados es un método sensible in vivo para la evaluación del sangrado hemofílico. Este modelo optimizado de sangrado TVT utiliza la pérdida de sangre y el tiempo de sangrado como puntos finales, refinando otros modelos y evitando la muerte como punto final.

Los modelos de sangrado de cola pueden ser herramientas importantes para evaluar los efectos farmacológicos de los compuestos hemostáticos in vivo para garantizar la reproducibilidad entre experimentos. En comparación con otros modelos de sangrado sensible, nuestro modelo utiliza la pérdida de sangre y el tiempo de sangrado como puntos finales en lugar de supervivencia. Además, el modelo se realiza bajo anestesia, reduciendo así el dolor y la angustia de los animales.

Esta técnica es especialmente útil para el estudio preclínico de la hemofilia y otros trastornos de la coagulación, ya que mide la capacidad de la sangre para coagularse y detener una hemorragia después de una lesión. Hemos utilizado este modelo ampliamente, probando compuestos procoagulantes en nuestro trabajo para desarrollar nuevas terapias de hemofilia utilizando ratones con hemofilia A. Sin embargo, también se pueden usar otras cepas hemofílicas de ratón, o ratones en los que se induce hemofilia con un anticuerpo antifactor VIII.

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