Pulmonary vascular remodeling.

<p>At 8 weeks, lungs were harvested, processed, and stained with Masson’s trichrome to examine pulmonary vascular remodeling. Representative images from A) sham and B-D) embolization models with similar patterns of remodeling, including luminal encroachment and hypertrophic intimal and medial remodeling, were observed for the D-Embo (B, D) and P+D-Embo pigs (C). In selected images (D), microspheres are present in the vessel lumen. There is also extensive perivascular collagen deposition. The distal pulmonary arteries were examined in the periphery of the lung in vessels that were not occluded by beads in sections stained with hematoxylin and eosin. Representative vessels from E) sham, F) D-Embo, and G) P+D-Embo animals are shown. H) Vessel media thickness as an indicator of pulmonary artery remodeling was assessed. P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group. Scale bars for A, B, C, and D are 60 μm, 100 μm, 60 μm, and 60 μm, respectively. *p<0.05 vs. D-Embo, **p<0.01 vs. sham by ANOVA.</p

The combination proximal coiling and distal embolization protocol results in occlusion of pulmonary arteries.

<p>Explanted segments from the right inferior pulmonary artery showing silk coil and fibrin clusters obstructing the vessel lumen with dilation of the vessel. (<i>left</i>) Whole vessel segment explant; (<i>right</i>) cross-section through vessel showing silk suture and fibrin clusters occluding the lumen.</p

Comparison between studies utilizing embolization techniques to create large animal pulmonary hypertension models.

<p>Data expressed as mean (SD) unless stated otherwise. SB: spontaneous breathing.</p><p>^a Per protocol.</p><p>^bCompared with baseline (vs. control group).</p><p>^cOnly reported in 2/5 cases.</p><p>^dIndexed (BSA).</p><p>^eMedians (IQR) reported.</p><p>NR = not reported. RHC, right heart catheterization; mPAP, mean pulmonary artery pressure; Δ mPAP, change in mean pulmonary artery pressure; PVR, pulmonary vascular resistance; Δ PVR, change in pulmonary vascular resistance; RV/(LV+S), right ventricular weight divided by left ventricular + septum weight (Fulton index); Δ RV/(LV+S), change in right ventricular weight divided by left ventricular + septum weight (Fulton index); RV, right ventricle.</p><p>Comparison between studies utilizing embolization techniques to create large animal pulmonary hypertension models.</p

Echocardiographic RV function and structural remodeling.

<p>D-Embo, distal embolization model; P+D-Embo, proximal + distal embolization model; EDV, end-diastolic volume; ESV, end-systolic volume; RVEF, right ventricular ejection fraction; MPI, myocardial performance index; TDI peak S, tissue Doppler imaging peak systolic myocardial velocity; TAPSE, tricuspid annular plane systolic excursion; RV, right ventricle; LV, left ventricle.</p><p>^ap<0.05 <i>post-hoc</i> comparison: Sham vs. P+D-Embo.</p><p>^bp<0.05 <i>post-hoc</i> comparison: P+D-Embo vs. D-Embo.</p><p>Echocardiographic RV function and structural remodeling.</p

Infusion of dextran microspheres (100–300 μm) acutely obstructs pulmonary arteries.

<p>Representative still images from pulmonary artery angiographies obtained at (A) baseline or (B) immediately after embolization of microspheres.</p

Acute changes in mPA pressure at the time of consecutive weekly embolization procedures.

<p>Hemodynamic assessments were made by right heart catheterization immediately before and after each weekly infusion of dextran microspheres. Animals in the D-Embo group (n = 6) underwent 6 embolization procedures (top) while pigs in the P+D-Embo group (n = 6) underwent 4 procedures (bottom). Changes for individual animals are plotted with the mean for the group shown as a blue line. mPA, mean pulmonary artery, P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group.</p

Temporal changes in mPA pressure and PVR index.

<p>The change over time in mPA pressure (<i>top</i>) and PVR index (<i>bottom</i>) measured at each embolization procedure and at the 8 week follow-up examination was evaluated in the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4). mPA, mean pulmonary artery; PVR, pulmonary vascular resistance; P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group. Data are reported as mean ± SD, *p<0.05 vs. sham, D-Embo by ANOVA.</p

Right ventricular fibrosis and hypertrophy.

<p>Myocardial fibrosis was examined in RV sections from the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4) stained with Masson’s trichrome and quantified as % area fibrosis (<i>top</i>). Cardiomyocyte hypertrophy was evaluated by staining RV sections with wheat germ agglutinin and co-staining with phalloidin to assess cardiomyocyte cross-sectional area (<i>bottom</i>). Representative images are shown for each group. P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group; RV, right ventricular. *p<0.05 vs. sham, D-Embo by ANOVA.</p