Time Course of Hypoxia/Sugen-Induced PAH
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Additional data demonstrates the time course of pulmonary arterial hypertension (PAH) development in our most relevant preclinical model. This is important information in the effort to guide reversal therapy.
Time Course of Hypoxia/Sugen-Induced PAH
- 1. Time Course of Hypoxia/ Sugen-Induced PAH
- 2. Additional data demonstrating time course of PAH development in most relevant preclinical model Hypoxia + SU5416 - rat develops thickening of arterioles AND occlusion of endothelial lumen (as human PAH) We previously validated model with sildenafil, bosentan, riociguat 0 50 100 150 SystolicPulmonaryArterial Pressure(mmHg) Vehicle Sildenafil 60 mg/kg Riociguat 10 mg/kg 0.000 0.200 0.400 0.600 0.800Fulton'sIndexRV/(LV+S) Vehicle Sildenafil 60 mg/kg Riociguat 10 mg/kg
- 3. - Rats administered DMSO/normoxia or SU5416/hypoxia - Serial measurements at Days 2, 4, 8, 15, 22, and 29 - Pulmonary arterial pressures and RV hypertrophy obtained 0 10 20 30 40 50 60 70 SPAP(mmHg) Systolic Pulmonary Arterial Pressure (SPAP) G1 2 Days (Normoxia) G2 4 Days (Normoxia) G3 8 Days (Normoxia) G4 15 Days (Normoxia) G5 22 Days (Normoxia) G6 29 Days (Normoxia) G7 2 Days (Hypoxia) G8 4 Days (Hypoxia) G9 8 Days (Hypoxia) G10 15 Days (Hypoxia) G11 22 Days (Hypoxia) G12 29 Days (Hypoxia)
- 4. - Statistically significant increases are observed as early as 8 days into hypoxia - Important information to guide reversal therapy 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 Fulton's Index (RV/LV+S) G1 2 Days (Normoxia) G2 4 Days (Normoxia) G3 8 Days (Normoxia) G4 15 Days (Normoxia) G5 22 Days (Normoxia) G6 29 Days (Normoxia) G7 2 Days (Hypoxia) G8 4 Days (Hypoxia) G9 8 Days (Hypoxia) G10 15 Days (Hypoxia) G11 22 Days (Hypoxia) G12 29 Days (Hypoxia)