IPST employs four preclinical models of induced pulmonary arterial hypertension. Each is characterized by defined underlying phenomena, and is best suited to specific pathologies and associated treatments.
Following MCT and CH-induced models, other models of PAH were developed at IPST to meet the needs of our clients.
The more recent model of Sugen5416 combined with chronic hypoxia SU/CH is associated with tissue restructuration involving formation of occlusive neointimal (plexiform) lesions in small pulmonary arteries and arterioles often seen in human with severe pulmonary hypertension. The progression of the disease continues and worsens even after the animals had been removed from hypoxic stimulus.
The absence of endothelial damage in chronic hypoxia PAH is a limitation of the model, as pertains to its direct relevance to adult pulmonary arterial hypertension. A model was developed using Sugen reagent SU5416, which is injected once (rodent) or repeatedly (other species) over three weeks combined with chronic hypoxia.
This results in endothelial damage and inflammation, along with the expected hypertrophy/hyperplasia of the smooth muscle layer to cause pulmonary arterial hypertension with both inflammation and vasoconstriction.
As for the chronic hypoxia model above, physiological parameters are monitored to ascribe various functional changes to the correct anatomical systems of the animal. The functional parameter assessment is complemented by histopathological examination and morphometric analysis of the vasculature.
IPST’s chronic hypoxia systems are used for the Sugen Model and allow simultaneous treatment of approximately 100 animals at a time. Typical experimental group size is 10 animals.