Exercise Response in a New Porcine Model of Chronic Embolic Pulmonary Hypertension

• Published in: The FASEB journal 2015-04, Vol.29 (S1)
• Main Authors: Stam, Kelly, de Wijs‐ Meijler, Daphne, Verzijl, Annemarie, van Duin, Richard, Reiss, Irwin, Duncker, Dirk, Merkus, Daphne
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.29.1_supplement.lb597

Abstract only Chronic Thromboembolic Pulmonary hypertension (CTEPH) is a deadly disease initiated by thrombo‐embolisms persisting in the pulmonary vasculature, followed by remodelling of the pulmonary vascular bed, resulting in a sustained increase in afterload of the right ventricle (RV). Although the response of the pulmonary vasculature to the initiating thromboembolic events as well as the response of the RV to the increased afterload are known to be the most important determinants of patient outcome, the factors that underlie these processes are incompletely understood. In the present study, we developed a novel chronically instrumented swine model of CTEPH. CTEPH was induced by up to 5 weekly injections of polyethylene beads of 700 μm in combination with induction of endothelial dysfunction by eNOS‐inhibition. Swine were followed up to one month after the last embolization. Changes in mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were used as indices of RV afterload and pulmonary vascular remodeling. and assessed at rest and during treadmill exercise (EX) . Repeated embolization resulted in increases in PAP and PVR. Control After first embolization Prior to sacrifice rest EX rest Ex Rest Ex PAP (mmHg) 16±1 33±3* 29±3† 61±7*† 47±15† 72±16*† PVR (mmHg.min.kg.L‐1) 86±13 98±16 160±42† 197±23† 510±237† 633±344† * P