Authors
Bahram Mirani, John Daniel Dauz, Kana Yazaki, Neda Latifi, Paul Santerre, Michelle P Bendeck, Craig A Simmons, Mark K Friedberg
Publication date
2024
Journal
bioRxiv
Pages
2024.02. 20.581269
Publisher
Cold Spring Harbor Laboratory
Description
Rationale
Coupling between right ventricular function and the pulmonary vasculature determines outcomes in pulmonary arterial hypertension. The mechanics of the main pulmonary artery is an important but understudied determinant of right ventricular-pulmonary artery coupling.
Objectives
To investigate the histology and mechanics of the pulmonary artery in relationship to right ventricular remodeling, mechanics, hemodynamics and coupling in experimental pulmonary arterial hypertension.
Methods
In a sugen+hypoxia rat model of pulmonary arterial hypertension, right ventricular hemodynamics were assessed by conductance catheters. Active tension-strain curves were generated using echocardiography. Main pulmonary artery and right ventricle free-wall were harvested to determine their macro- and micro-structure, composition, and mechanical properties. Comprehensive multivariate analyses elucidated relationships between pulmonary artery and right ventricle mechanics, structure and coupling.
Measurements and Main Results
Pulmonary hypertensive main pulmonary arteries developed fibrosis relative to healthy controls, as did right ventricles, which also hypertrophied, with re-orientation of muscle fibres toward a tri-layer architecture reminiscent of normal left ventricular architecture. Increased glycosaminoglycan deposition and increased collagen-to-elastin ratio in the pulmonary artery; and increased collagen, as well as hypertrophy and reorganization of myofibers in the right ventricle, led to increased stiffness. This increase in stiffness was more pronounced in the longitudinal direction in the high- and low-strain regime for the …