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.
Monocrotaline (MCT) is a toxin injected once which causes a remodeling of the pulmonary vasculature through a combination of endothelial damage, tissue inflammation, cytokine migration, and resulting increased vasoconstriction. Morphometric analysis of MCT-exposed pulmonary vasculature conducted in this lab and elsewhere reveals a decreased lumen size due to increased muscular layer thickening, hyperplasia of the endothelium, infiltration of monocytes and various signs of inflammation.
MCT causes an irreversible decline of the animal’s pulmonary vasculature, which becomes practical to work with at Day 21 (post-injection) and critical at Day 28, with 65-75% death by Day 30. Physiologically, saturation goes down, gas-exchanges become inefficient, and pulmonary arterial pressure goes up by more than 15 mmHg. Contrary to some literature reports, the condition is irreversible, and treatment with test articles can only slow down the rate of decline of the vascular/respiratory parameters. iPST’s MCT study designs allow simultaneous treatment of approximately 100 animals at a time. Typical experimental group size is 10 animals.