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Related Experiment Videos

Defibrotide normalizes cardiovascular function hampered by established atherosclerosis in the rabbit.

G Rossoni1, F Berti, F Trento

  • 1Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy. giuseppe.rossoni@unimi.it

Thrombosis Research
|February 25, 2000
PubMed
Summary

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Defibrotide demonstrates significant cardiovascular benefits even after atherosclerosis is established. This drug improves aortic relaxation, prostaglandin generation, and heart function in diseased rabbits, suggesting a cardioprotective role.

Area of Science:

  • Cardiovascular Science
  • Pharmacology
  • Atherosclerosis Research

Background:

  • Previous research indicated defibrotide's efficacy in preventing atherosclerosis.
  • Established atherosclerosis significantly impairs cardiovascular function, including vascular reactivity and cardiac hemodynamics.

Purpose of the Study:

  • To investigate the therapeutic potential of defibrotide in established atherosclerosis.
  • To evaluate defibrotide's effects on specific cardiovascular parameters compromised by atherosclerosis.

Main Methods:

  • Defibrotide infusion was administered to rabbits with established atherosclerosis.
  • Key cardiovascular functions were assessed, including aorta relaxation, prostaglandin generation (PGE2, 6-keto-PGF1α), and cardiac pressures (LVEDP, CPP, LVDP).
  • The vasopressor activity of acetylcholine and endothelin-1 was also evaluated.

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Main Results:

  • Defibrotide significantly improved rabbit aorta relaxation in response to acetylcholine.
  • Increased generation of prostaglandin E2 and 6-keto-prostaglandin F1α was observed in both aortas and hearts.
  • Cardiac function markers, including left ventricular end-diastolic pressure, coronary perfusion pressure, and left ventricular developed pressure, showed significant amelioration.

Conclusions:

  • Defibrotide exerts beneficial cardiovascular effects even when atherosclerosis is established.
  • The cardioprotective activity of defibrotide may be linked to increased prostacyclin and prostaglandin E2 levels.
  • Defibrotide holds potential as a therapeutic agent for managing established cardiovascular disease.