Pulmonary Arterial Hypertension in Non Human Primates
My team and I are returning from the 2009 Safety Pharmacology Society meeting in Strasbourg, France. With us was our lead veterinary technician, Ms. Melissa Fisher, who was awarded a Junior Investigator Travel Award for her work with her colleagues developing a model of hypoxic pulmonary vasoconstriction / pulmonary arterial hypertension (PAH) in the cynomolgus monkey.
After conducting more than 18 experiments interrogating the intertwining roles of anesthesia, arterial oxygen tension, and surgical plane in the stability of the model, our labs are now providing clients with a paradigm that defines a compound’s ability to selectively reduce pulmonary artery pressure in the presence of existing PAH using non-human primates. Building on our previous work in the dog and rat, Melissa rose to the challenge and coordinated the experiments to bolster the disheartening lack of scientific literature in this arena. There are no reliable publications describing PAH in the monkey; only a few aged papers detail measurement of arterial oxygen tension or other tangential parameters having a relationship to pulmonary function in this species.
Looking at the graphs below, we’ve defined the selectivity for prostacyclin (a well-characterized vasodilator) in this model. The experiments could not have gone any better. We previously demonstrated that 10% inhaled oxygen is sufficient to induce a greater than 30% increase in pulmonary artery pressure. At the lowest studied dose of prostacyclin (1.5 μg/kg/min), there was no appreciable reduction in either pulmonary artery pressure or systemic arterial pressure during the hypoxic vasoconstriction.
However, at 15 μg/kg/min, our labs uncovered the differential vasoactivity of prostacyclin on the pulmonary architecture.
As a result of these data, we are highly confident that we can uncover similar properties in proprietary molecules; improvements would likely involve either an augmented differential response or via longer pharmacodynamic action than prostacyclin.
Melissa was excited to accept the award and present the team’s research in France. We believe these paradigms can be of tremendous value as the industry looks toward meeting patient needs in the area of pulmonary hypertension.
Regards,
Dr. Michael R. Gralinski, CorDynamics CEO