Fig. 1.
Sugen/hypoxic rat haemodynamic and cardiac characteristics after ASK1 inhibition. The impact of ASK1 inhibitor GS-44217 in reversing established pulmonary hypertension (PH) was investigated in the Sugen/hypoxic (SuHx) rat model. Four groups of animals were investigated; SuHx animals treated with vehicle (SuHx + V) or the ASK1 inhibitor GS-444217 (SuHx + GS) for three weeks post disease establishment (at five weeks) or age-matched normoxic controls treated with vehicle (Norm + V) or drug (Norm + GS). Parameters investigated were (a) right ventricular systolic pressure (RVSP), (b) body weight, (c) systemic arterial pressure (SAP), (d) heart rate, (e) cardiac output, (f) right ventricular hypertrophy, (g–j) representative images of transverse heart histological sections stained with haematoxylin (double arrows highlight RV free wall thickening), (k) cardiomyocyte cross-sectional area determined from high-powered magnification images of haematoxylin-stained transverse whole heart sections and (l) quantification by post hoc ImageJ analysis, (m) collagen content determined in heart sections stained with Picro-sirius red stain and (n) quantification by post hoc ImageJ analysis. Data are (a, c, d and f) n = 6 animals per group (b) n = 7/8 animals per group, (e) n = 4 animals per group, displayed as individual data points and mean; (l and n) n = 6 animals (mean of four sections per heart) displayed as individual data points and mean (l) or mean ± SEM (n). Statistical analysis is by two-way ANOVA with Turkey's post hoc analysis *p ≤ 0.05 and **p ≤ 0.01, ***p ≤ 0.001.
RV: right ventricle; LV: left ventricle.