title: Development and Characterization of an Inducible Rat Model of Chronic Thromboembolic Pulmonary Hypertension.
abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is an entity of PH that not only limits patients quality of life but also causes significant morbidity and mortality. The treatment of choice is pulmonary endarterectomy. However numerous patients do not qualify for pulmonary endarterectomy or present with residual vasculopathy post pulmonary endarterectomy and require specific vasodilator treatment. Currently, there is no available specific small animal model of CTEPH that could serve as tool to identify targetable molecular pathways and to test new treatment options. Thus, we generated and standardized a rat model that not only resembles functional and histological features of CTEPH but also emulates thrombi fibrosis. The pulmonary embolism protocol consisted of 3 sequential tail vein injections of fibrinogen/collagen-covered polystyrene microspheres combined with thrombin and administered to 10-week-old male Wistar rats. After the third embolism, rats developed characteristic features of CTEPH including elevated right ventricular systolic pressure, right ventricular cardiomyocyte hypertrophy, pulmonary artery remodeling, increased serum brain natriuretic peptide levels, thrombi fibrosis, and formation of pulmonary cellular-fibrotic lesions. The current animal model seems suitable for detailed study of CTEPH pathophysiology and permits preclinical testing of new pharmacological therapies against CTEPH.
authors.affiliation: From the Department of Internal Medicine I, University Clinic of Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., P.J., S.U., T.W., S.F., T.P.); Comprehensive Heart Failure Center Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., S.U., T.W., T.P.); Institute of Physiology, University Wuerzburg, Wuerzburg, Germany (M.A., K.S.); and University Clinic and Polyclinic for Internal Medicine III, University Clinic Halle, Halle, Germany (S.F.).
authors.forename: Paula-Anahi
authors.initials: PA
authors.lastname: Arias-Loza
authors.affiliation: From the Department of Internal Medicine I, University Clinic of Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., P.J., S.U., T.W., S.F., T.P.); Comprehensive Heart Failure Center Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., S.U., T.W., T.P.); Institute of Physiology, University Wuerzburg, Wuerzburg, Germany (M.A., K.S.); and University Clinic and Polyclinic for Internal Medicine III, University Clinic Halle, Halle, Germany (S.F.).
authors.forename: Pius
authors.initials: P
authors.lastname: Jung
authors.affiliation: From the Department of Internal Medicine I, University Clinic of Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., P.J., S.U., T.W., S.F., T.P.); Comprehensive Heart Failure Center Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., S.U., T.W., T.P.); Institute of Physiology, University Wuerzburg, Wuerzburg, Germany (M.A., K.S.); and University Clinic and Polyclinic for Internal Medicine III, University Clinic Halle, Halle, Germany (S.F.).
authors.forename: Marco
authors.initials: M
authors.lastname: Abeßer
authors.affiliation: From the Department of Internal Medicine I, University Clinic of Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., P.J., S.U., T.W., S.F., T.P.); Comprehensive Heart Failure Center Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., S.U., T.W., T.P.); Institute of Physiology, University Wuerzburg, Wuerzburg, Germany (M.A., K.S.); and University Clinic and Polyclinic for Internal Medicine III, University Clinic Halle, Halle, Germany (S.F.).
authors.forename: Sandra
authors.initials: S
authors.lastname: Umbenhauer
authors.affiliation: From the Department of Internal Medicine I, University Clinic of Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., P.J., S.U., T.W., S.F., T.P.); Comprehensive Heart Failure Center Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., S.U., T.W., T.P.); Institute of Physiology, University Wuerzburg, Wuerzburg, Germany (M.A., K.S.); and University Clinic and Polyclinic for Internal Medicine III, University Clinic Halle, Halle, Germany (S.F.).
authors.forename: Tatjana
authors.initials: T
authors.lastname: Williams
authors.affiliation: From the Department of Internal Medicine I, University Clinic of Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., P.J., S.U., T.W., S.F., T.P.); Comprehensive Heart Failure Center Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., S.U., T.W., T.P.); Institute of Physiology, University Wuerzburg, Wuerzburg, Germany (M.A., K.S.); and University Clinic and Polyclinic for Internal Medicine III, University Clinic Halle, Halle, Germany (S.F.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.affiliation: From the Department of Internal Medicine I, University Clinic of Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., P.J., S.U., T.W., S.F., T.P.); Comprehensive Heart Failure Center Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., S.U., T.W., T.P.); Institute of Physiology, University Wuerzburg, Wuerzburg, Germany (M.A., K.S.); and University Clinic and Polyclinic for Internal Medicine III, University Clinic Halle, Halle, Germany (S.F.).
authors.forename: Kai
authors.initials: K
authors.lastname: Schuh
authors.affiliation: From the Department of Internal Medicine I, University Clinic of Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., P.J., S.U., T.W., S.F., T.P.); Comprehensive Heart Failure Center Wuerzburg, Wuerzburg, Germany (P.-A.A.-L., S.U., T.W., T.P.); Institute of Physiology, University Wuerzburg, Wuerzburg, Germany (M.A., K.S.); and University Clinic and Polyclinic for Internal Medicine III, University Clinic Halle, Halle, Germany (S.F.). pelzer_t@ukw.de.
authors.forename: Theo
authors.initials: T
authors.lastname: Pelzer
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D002908:Chronic Disease; D004195:Disease Models, Animal; D004691:Endarterectomy / Q000379:methods* / Q000401:mortality; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D011651:Pulmonary Artery / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000502:physiology; D011655:Pulmonary Embolism / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome; D066253:Vascular Remodeling / Q000502:physiology
keywords: endarterectomy; hypertension, pulmonary; pulmonary embolism; rats, Wistar; thrombin