Remodeling and Oxidative Damage in RV Tissue of Patients With Dilated Cardiomyopathy Before Heart Transplantation
Patients with dilated cardiomyopathy were divided into 2 groups with normal systolic right ventricular function (nRVF) and severely impaired right ventricular function (iRVF), exhibiting significant differences in (A) TAPSE (n = 9/10), (B) fractional area change (FAC) (n = 11/10), (D) mean pulmonary arterial (PA) pressure (n = 11/10), and (E) pulmonary artery wedge pressure (PAWP) (n = 11/10). (C) Systolic LV ejection fraction was reduced without differences between the 2 groups (n = 8/9). (F) Pulmonary vascular resistance (PVR) was markedly increased in iRVF patients (n = 11/10). (G) RV-PA coupling reflected by the ratio of TAPSE to systolic pulmonary artery pressure (sPAP) was significantly impaired in iRVF patients (n = 9/9). (H) Percentage of fibrotic area as assessed from picrosirius red staining (scale bar = 100 μm) was not different in RV of nRVF and iRVF patients (n = 11/10). (I) Representative images of RV sections stained for cardiomyocyte cross-sectional area analysis using wheat germ agglutinin (WGA) and capillary density using isolectin of griffonia simplicifolia (GSI-B4). Scale bar = 50 μm. (J) Cross-sectional area of cardiomyocytes was not different in RV of nRVF and iRVF patients (n = 11/10). (K) Capillary density was not different in RV of nRVF and iRVF patients (n = 11/10). (L) Oxidative DNA modifications as reflected by immunoreactivity for 8-hydroxydeoxyguanosin (8-OHdG) were significantly more abundant in nuclei of RV sections of patients with iRVF compared with nRVF (n = 11/10). Representative images, with purple nuclei indicating immunoreactivity for 8-OHdG (raw) and light blue color (hue threshold) indicates 8-OHdG immunoreactivity marked with ImageJ hue threshold analysis. Scale bar = 100 μm. Statistical significance was calculated with unpaired Student's t-test for A to G and L and with Mann-Whitney U test for J and K. ∗∗P < 0.01; ∗∗∗P < 0.001. Variation of n from nRVF/iRVF = 11/10 was caused by impossibility of assessment during echocardiography or catheterization for some of the parameters. Abbreviations as in Figure 1.