Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine.
Pulmonary hypertension (PH) is associated with aberrant vascular remodeling and right ventricular (RV) dysfunction that contribute to early mortality. Large animal models that recapitulate human PH are essential for mechanistic studies and evaluating novel therapies; however, these models are not readily accessible to the field owing to the need for advanced surgical techniques or hypoxia. In this study, we present a novel swine model that develops cardiopulmonary hemodynamics and structural changes characteristic of chronic PH. This percutaneous model was created in swine (n=6) by combining distal embolization of dextran beads with selective coiling of the lobar pulmonary arteries (2 procedures per lung over 4 weeks). As controls, findings from this model were compared with those from a standard weekly distal embolization model (n=6) and sham animals (n=4). Survival with the combined embolization model was 100%. At 8 weeks after the index procedure, combined embolization procedure animals had increased mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR) compared to the controls with no effect on left heart or systemic pressures. RV remodeling and RV dysfunction were also present with a decrease in the RV ejection fraction, increase in the myocardial performance index, impaired longitudinal function, as well as cardiomyocyte hypertrophy, and interstitial fibrosis, which were not present in the controls. Pulmonary vascular remodeling occurred in both embolization models, although only the combination embolization model had a decrease in pulmonary capacitance. Taken together, these cardiopulmonary hemodynamic and structural findings identify the novel combination embolization swine model as a valuable tool for future studies of chronic PH.
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)- Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain.
Jaume
J
Aguero
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Kiyotake
K
Ishikawa
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Kenneth M
KM
Fish
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Nadjib
N
Hammoudi
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Lahouaria
L
Hadri
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)- Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain.
Ana
A
Garcia-Alvarez
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)- Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain.
Borja
B
Ibanez
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)- Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain; Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Valentin
V
Fuster
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Roger J
RJ
Hajjar
Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Jane A
JA
Leopold
D000818:Animals; D015687:Cell Hypoxia; D004621:Embolization, Therapeutic / Q000009:adverse effects*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D011651:Pulmonary Artery / Q000503:physiopathology* / Q000601:surgery; D013552:Swine; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology; D020257:Ventricular Remodeling