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PULMONARY ARTERIAL HYPERTENSION

CorDynamics has expertise in multiple 'gold-standard' methods to study the pathology of pulmonary arterial hypertension (PAH) and investigate potential therapies.

Monocrotaline-Induced PAH Model
Using the in vivo rat model, responses to compounds can be evaluated in both prevention and reversal modes.

  • Toxic alkaloid that is activated by the liver and selectively affects the pulmonary vasculature without producing systemic hypertension.
  • Accompanying right ventricular hypertrophy and pulmonary edema are apparent by three weeks.
  • Increase in pulmonary vessel wall medial thickness correlates with an elevated pulmonary arterial pressure.

Hypoxia + VEGF-Antagonist Induced PAH Model
Using the rat model, test articles can be interrogated in the most robust small animal preclinical model available.

  • The co-exposure to both chronic hypoxia and VEGF antagonism results in pulmonary arterial wall thickening and occlusion of arterioles due to endothelial cell overgrowth.
  • Accompanying right ventricular hypertrophy and pulmonary edema are apparent by three weeks.
  • Pathology similar to human PAH.

Hypoxia-Induced Pulmonary
Vasoconstriction Model
Because pulmonary arteries constrict in response to hypoxia in order to divert blood to more ventilated areas of the lungs, this physiologic phenomenon can be exploited to assess selectivity of test articles on pulmonary versus systemic arteries.

  • Subjects exposed to low oxygen conditions (i.e. 10% O2).
  • Manifestations of pulmonary vasoconstriction revert toward baseline levels once animals are exposed to normoxia.
  • Performed in a variety of species.

CorDynamics collaborates with clients on all their drug discovery steps, with an eye on eventual regulatory compliance.