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Swine Model of Chronic Postcapillary Pulmonary Hypertension with Right Ventricular Remodeling: Long-Term Characterization by Cardiac Catheterization, Magnetic Resonance, and Pathology

Abstract

Pulmonary hypertension (PH) is prevalent and carries high morbidity and mortality, mostly due to right ventricular (RV) dysfunction. Postcapillary PH is the most frequent form but there are no large-animal models available. We developed and characterized a porcine model of postcapillary PH by non-restrictive banding of the confluent of both inferior pulmonary veins (n = 10; sham controls n = 3). Right heart catheterization and magnetic resonance were performed before the procedure and monthly during 4 months. All banded animals developed PH. Compared to controls, banded animals presented higher mean pulmonary artery pressure [median (first to third quartile) 30 mmHg (25–37) vs. 20 mmHg (18–23); p = 0.018] and higher pulmonary vascular resistance [5.2 WU (3.8–7.1) vs. 2.3 WU (2.1–3.5); p = 0.028] after 2 months. Differences in indexed RV end-systolic volume [42 mL/m2 (36–53) vs. 24 mL/m2 (24–33); p = 0.028] and RV ejection fraction [59 % (54–63) vs. 66 % (64–68); p = 0.028] were also significant after 2 months. Differences remained significant throughout the study. Histopathology revealed increased lung weight and fibrosis but no increase in average water content. Also, remodeling on pulmonary arteries including increased medial and intimal thickness and fibrosis and RV myocardial disarray and fibrosis was demonstrated. Lung remodeling findings were similar in all pulmonary lobes.

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Acknowledgments

Gonzalo J. Lopez and Angel Macias were capital for the high-quality CMR examinations. Tamara Córdoba, Oscar Sanz, and the rest of the people working in the animal facilities and CNIC’s farm were outstanding in animal care and unconditional support. Antonio de Molina helped us with histological analyses in our pilot studies. We want to thank Iñigo Sanz for his great surgical pictures.

Funding

This work has been partially funded by the competitive grant “CNIC-Translational 01-2009” (to BI) and by the ISCIII grant “Fondo de Investigación Sanitaria” PI13 /02339 (to A G-A). A G-A and JM G-R have been supported by a CNIC-Cardiojoven Fellowship, Madrid, Spain.

Conflict of Interest

None of the authors have conflicts of interest to disclose regarding the manuscript submitted or the possible implications of this research.

Author information

Correspondence to Borja Ibáñez.

Additional information

Editor-in-Chief Jennifer L. Hall oversaw the review of this article.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Cine cardiac magnetic resonance imaging. Four-chamber view (upper row) and short-axis view at mid-ventricular level (lower row), from a surgical banding subject (on the left) and a sham control subject (on the right). Note the important right ventricular hypertrophy and dilatation on the banded subject as compared to the sham control. In the former, right ventricular systolic function is reduced and there is deformation of the interventricular septum, which is flattened and shifted towards the left ventricle in systole. Dilatation of the main pulmonary artery on the surgical banding subject can also be seen. (MPG 1244 kb)

Video 1

Cine cardiac magnetic resonance imaging. Four-chamber view (upper row) and short-axis view at mid-ventricular level (lower row), from a surgical banding subject (on the left) and a sham control subject (on the right). Note the important right ventricular hypertrophy and dilatation on the banded subject as compared to the sham control. In the former, right ventricular systolic function is reduced and there is deformation of the interventricular septum, which is flattened and shifted towards the left ventricle in systole. Dilatation of the main pulmonary artery on the surgical banding subject can also be seen. (MPG 1244 kb)

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Pereda, D., García-Alvarez, A., Sánchez-Quintana, D. et al. Swine Model of Chronic Postcapillary Pulmonary Hypertension with Right Ventricular Remodeling: Long-Term Characterization by Cardiac Catheterization, Magnetic Resonance, and Pathology. J. of Cardiovasc. Trans. Res. 7, 494–506 (2014) doi:10.1007/s12265-014-9564-6

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Keywords

  • Pulmonary hypertension
  • Right ventricle
  • Cardiac magnetic resonance
  • Experimental models