{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T21:54:17Z","timestamp":1768600457048,"version":"3.49.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Large animal models are key to translational research. Current models of chronic thromboembolic pulmonary hypertension (CTEPH) are rather complex, impractical and most fail to achieve a severe PH and right ventricular (RV) dysfunction phenotype. Our aim was to develop a plain large animal model of severe CTEPH with RV dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In 3 consecutive weeks, 2-month-old male pigs (\u223c25 kg) randomly underwent either left and right pulmonary artery (PA) injection of 15\u201330 15\u2005cm #0 silk sutures (CTEPH,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099) or sham procedure (Sham,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096). Embolization was interrupted based on mean PA pressure (mPAP) elevation, cardiac output (CO) or systemic blood pressure decline, or complete obstruction on angiography. After 4 weeks of follow-up, we assessed echocardiography, biventricular pressure-volume (PV) hemodynamics, RV skinned cardiomyocyte, lung and RV histology, and RV gene expression and protein levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At terminal evaluation, mPAP was consistently higher in CTEPH compared with Sham (51\u2009\u00b1\u20093 vs. 20\u2009\u00b1\u20091\u2005mmHg, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001) with reduced CO (4.2\u2009\u00b1\u20090.2 vs. 6.6\u2009\u00b1\u20090.9\u2005L.min\n                      <jats:sup>\u22121<\/jats:sup>\n                      ;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.042). On angiography, most of the PA territory was obstructed, with cephalad redirection of flow. RV hypertrophy was clear on morphology, echocardiography and histology. CTEPH showed decreased RV ejection fraction (35\u2009\u00b1\u20092 vs. 51\u2009\u00b1\u20093%;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), delayed relaxation, and end-diastolic stiffening but preserved ventricle-vascular coupling. Although fibrosis was not observed on histology and collagen chain expression was not upregulated in RV myocardium, skinned RV cardiomyocytes from CTEPH did show passive stiffening as well as higher active tension development. CTEPH RV showed altered gene expression of myosin heavy chains and B-type natriuretic peptide as well as decreased sarcoendoplasmic reticulum Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -ATPase (SERCA2a) expression. Both SERCA2a and phosphorylated phospholamban protein levels were decreased as well. Medial hypertrophy was observed in distal arteries from the unobstructed right cranial lobe of CTEPH denoting flow-induced vasculopathy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We developed a new and straightforward swine model of severe CTEPH with RV dysfunction by repeated injection of long sutures into the PA without the need for additional hits which may be valuable for preclinical research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2025.1736958","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T10:11:50Z","timestamp":1768558310000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A swine model of severe chronic thromboembolic pulmonary hypertension induced by repeated pulmonary artery long suture 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Portugal"]},{"name":"S\u00e3o Jo\u00e3o Local Health Unit, Department of Cardiothoracic Surgery","place":["Porto, Portugal"]}]},{"given":"Francisca C.","family":"Correia","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto","place":["Porto, Portugal"]}]},{"given":"St\u00e9phanie","family":"Chanon","sequence":"additional","affiliation":[{"name":"Laboratoire CarMeN, UMR INSERM U1060\/INRA U1397, University of Lyon, Universit\u00e9 Claude Bernard Lyon 1","place":["Pierre-B\u00e9nite, France"]}]},{"given":"Aur\u00e9lie","family":"Vieille-Marchiset","sequence":"additional","affiliation":[{"name":"Laboratoire CarMeN, UMR INSERM U1060\/INRA U1397, University of Lyon, Universit\u00e9 Claude Bernard Lyon 1","place":["Pierre-B\u00e9nite, France"]}]},{"given":"Fr\u00e9d\u00e9ric","family":"Perros","sequence":"additional","affiliation":[{"name":"Laboratoire CarMeN, UMR INSERM U1060\/INRA U1397, University of Lyon, Universit\u00e9 Claude Bernard Lyon 1","place":["Pierre-B\u00e9nite, France"]},{"name":"Paris-Porto Pulmonary Hypertension Collaborative Laboratory (3PH), INSERM UMR_S 999, Universit\u00e9 Paris-Saclay","place":["Le Kremlin-Bic\u00eatre, France"]}]},{"given":"Adelino F.","family":"Leite-Moreira","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto","place":["Porto, Portugal"]},{"name":"S\u00e3o Jo\u00e3o Local Health Unit, Department of Cardiothoracic Surgery","place":["Porto, Portugal"]}]},{"given":"Andr\u00e9 P.","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto","place":["Porto, Portugal"]},{"name":"S\u00e3o Jo\u00e3o Local Health Unit, Department of Anesthesiology","place":["Porto, 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