Abstract
Purpose: Pulmonary endarterectomy is treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricular (RV) dysfunction remains the main cause of early postoperative mortality. We aimed to investigate mechanisms of RV response to effective CTEPH surgical treatment in an experimental model. Methods and Materials: CTEPH was induced in piglets by ligation of the left pulmonary artery followed by weekly injections under fluoroscopic control of n-butyl-2-cyanoacrylate to progressively occlude right lower lobe arteries for 5 weeks. Studies were performed 5 weeks later (CTEPH group, n 5) or 5 weeks after left lung reperfusion into the main pulmonary artery (Reperfusion group, n 5). Changes in pulmonary vascular resistances (PVR), RV myocardial performance index (RVMPI), RV stoke work (RVSW), RV end-diastolic tricuspid annulus diameter (RV base) and RV base to apex lenght (RV long) were recorded in both groups at 5 and 10 weeks using echocardiography and conductance catheterization. Cardiomyocytes size and beta-myosin heavy chain (beta-MHC) gene expression within RV myocardium were quantified at 10 weeks. Results: At 10 weeks, PVR (769 42 vs. 551 75 dynes.s.cm-5, p 0.034), RVMPI (0.61 0.07 vs. 0.26 0.02, p 0.012) and RVSW (2474 345 vs. 1745 210 ml.mmHg-1, p 0.011) were significantly lower in Reperfusion group when compared to CTEPH group. Similarly RV long and RV base were significantly lower in Reperfusion group at 10 weeks (44.5 2.1 vs. 56.4 2.9 mm, p 0.007 and 25.1 1.1 vs. 31.1 0.1 mm, p 0.007, respectively). Cardiomycytes size (5.8 0.4 vs. 15.5 1.6 m, p 0.001) and beta-MHC expression (1.31 0.29 vs. 2.10 0.06, p 0.03) were lower in the Reperfusion group. Conclusions: For the first time we reproduced hemodynamic and RV functional benefits of pulmonary hypertension surgical treatment in a porcine CTEPH model. RV functional improvement after CTEPH surgical treatment results in significant changes in contractile protein isoform expression and cardiomyocytes diameter in RV myocardium.
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