C26-11 Biomechanical Modeling of the Evolving Pulmonary Vascular Tree in Animal Models of Pulmonary Hypertension

Rationale Pulmonary hypertension (PH) is a progressive disorder marked by increased pulmonary vascular resistance, right-ventricular hypertrophy, and high mortality. Despite extensive experimental research, the quantitative mechanisms linking elevated hemodynamic load to structural remodeling remain unclear. The monocrotaline (MCT) rat model reproduces many key features of human PH, including endothelial injury, inflammation, and medial thickening. Mechanistic growth and remodeling (G&R) models can bridge the gap between cellular processes and tissue-level outcomes by coupling biomechanical stimuli with turnover of vascular constituents. This study applies and calibrates a constrained-mixture G&R model to MCT data to quantitatively reproduce and interpret temporal changes in pressure, wall thickness, and stiffness. Methods A multiscale G&R model was implemented to represent pulmonary arterial remodeling across multiple vessel orders, linking wall adaptation to evolving hemodynamic loads throughout the network. Each vessel’s composition (elastin, collagen, and smooth muscle) evolved according to kinetic relations governed by key inflammatory parameters: gain on mass production, rate of disease onset, and increase in passive material stiffness. Model parameters were optimized to align simulated and experimental trajectories of pressure, wall thickness, and stiffness, enabling direct comparison with measured physiological data. Aggregated MCT rat datasets from multiple published studies spanning 0–5 weeks post-injection were used for parameter estimation studies (Figure 1) and to assess model sensitivity across vessel orders. Results Aggregated MCT data demonstrated a ∼2.5-fold increase in pulmonary arterial pressure, a ∼40% rise in wall thickness, and an ∼8-fold increase in stiffness over five weeks. The optimized multiscale G&R model accurately captured these progressive changes (R² > 0.9 for all metrics). Pressure increased nonlinearly with progression (Figure 1B), stiffness amplification reflected collagen accumulation and smooth muscle activation (Figure 1C), and wall thickness showed an exponential rise (Figure 1D). These simulations focused on matching observed increases in pressure, wall thickness, and stiffness by tuning parameters associated with constituent mass production and vessel narrowing within the constrained mixture framework. The model’s consistent agreement with multiple experimental datasets shows its ability to capture key hemodynamic features of disease progression and provides a strong foundation for future studies aimed at quantifying reversibility and therapeutic efficacy. Conclusions This multiscale G&R model captures the progression of MCT-induced pulmonary vascular remodeling by linking cellular activation and matrix turnover to network-level adaptation. These findings highlight the potential of G&R modeling to unify diverse remodeling mechanisms and predict therapeutic outcomes in pulmonary hypertension. This abstract is funded by: None