Time Course of Hypoxia/Sugen-Induced PAH

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

RAT PULMONARY ARTERIAL HYPERTENSION

0

20

40

60

80

100

120

Vehicle_x000d_Sildenafil 60 mg/kgRiociguat 10 mg/kg

Syst

olic

Pulm

onar

y Ar

teria

l Pr

essu

re (m

m H

g)

0.0000.1000.2000.3000.4000.5000.6000.700

Vehicle_x000d_Sildenafil 60 mg/kgRiociguat 10 mg/kg

Fulto

n's I

ndex

RV/

(LV+

S)

- 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

RAT PULMONARY ARTERIAL HYPERTENSION

- Statistically significant increases are observed as early as 8 days into hypoxia- Important information to guide reversal therapy

RAT PULMONARY ARTERIAL HYPERTENSION