Pulmonary microvascular lesions regress in reperfused chronic thromboembolic pulmonary hypertension

BACKGROUND: Pulmonary microvascular disease (PMD) develops in both occluded and non-occluded territories in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and may cause persistent pulmonary hypertension after pulmonary endarterectomy. Endothelin-1 (ET-1) and interleukin-6 (IL-6) are potential PMD severity biomarkers, but it remains unknown whether they are related to occluded or non-occluded territories. We assessed PMD and ET-1/IL-6 gene expression profiles in occluded and non-occluded territories with and without chronic lung reperfusion in an animal CTEPH model. METHODS: Chronic PH was induced in 10 piglets by left pulmonary artery (PA) ligation followed by weekly embolization of right lower lobe arteries with enbucrilate tissue adhesive for 5 weeks. At Week 6, 5 of 10 animals underwent left PA reperfusion. At Week 12, animals with and without reperfusion were compared with sham animals (n = 5). Hemodynamics, lung morphometry and ET-1/IL-6 gene expression profiles were assessed in the left lung (LL, occluded territories) and right upper lobe (RUL, non-occluded territories). RESULTS: At Week 12, mean PA pressure remained elevated without reperfusion (29.0 +/- 2.8 vs 27.0 +/- 1.1 mm Hg, p = 0.502), but decreased after reperfusion (30.0 +/- 1.5 vs 20.5 +/- 1.7 mm Hg, p = 0.013). Distal media thickness in the LL and RUL PAs and systemic vasculature to the LL were significantly lower in the reperfused and sham groups compared with the non-reperfused group. PMD progression was related to ET-1 and IL-6 gene expression in the RUL and to the ET-A/ET-B gene expression ratio in the LL. CONCLUSIONS: PMD regressed in occluded and non-occluded territories after lung reperfusion. Changes in ET-1 and IL-6 gene expression were associated with PMD in non-occluded territories. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.