Abstract 18635: Development of a Swine Model of Chronic Postcapillary Pulmonary Hypertension: Long Term Characterization by Cardiac Catheterization, Magnetic Resonance and Pathology
Background: Postcapillary pulmonary hypertension (PH) has high prevalence and morbimortality. There are no large-animal models that fully reproduce postcapillary-PH. We aimed to develop and characterize a model that reproduced chronic postcapillary-PH including typical features in lungs and RV.
Methods: Thirteen (10 banding, 3 sham) 4 week-old pigs underwent non-restrictive banding of the confluent of both inferior pulmonary veins. Chronic PH develops as the animal grows. Right heart catheterization and cardiac magnetic resonance (CMR) were performed immediately before and after the procedure and monthly thereafter during 4 months. Histopathology study of the heart and pulmonary vessels (Masson trichrome and picrosirius red staining) was performed at the end of the study.
Results: All banded animals developed chronic PH. Compared to sham, mPAP in banded subjects was significantly higher after 1 month [median (1st-3rd quartile): 26mmHg (25-31) vs. 21mmHg (14-22), p=0.03], increased progressively and reached a plateau after month 3 [33mmHg (28-40) vs. 35mmHg (32-38) at months 3 and 4 respectively; Figure]. PVR behaved similarly and achieved significance after 2 months [5.2WU (3.8-7.1) vs. 2.3WU (2.1-3.5), p=0.03]. CMR demonstrated significant differences in indexed-RV end-systolic volume [42mL/m2 (36-53) vs. 24mL/m2 (24-33); p=0.03], indexed-RVmass [28g/m2 (27-29) vs.19g/m2 (18-23); p=0.02] and RVEF [59% (54-63) vs.66% (64-68); p=0.03] from the 2nd month and thereafter. Histopathology revealed vascular remodeling of pulmonary arteries including hypertrophy and fibrosis of the media, intimal fibrosis and RV myocardial disarray and fibrosis (Figure).
Conclusions: We have successfully developed a large-animal model that produces chronic PH similar of that found in patients, associated with RV remodeling and typical pathology changes. The stability on PAP between months 3 and 4 makes this period the best to test therapies.
- © 2013 by American Heart Association, Inc.