Plasticity and Enzymatic Degradation Coupled With Volumetric Growth in Pulmonary Hypertension Progression

Abstract

Pulmonary hypertension (PH) is one of the least understood and highly elusive cardiovascular conditions associated with elevated pulmonary arterial pressure. Although the disease mechanisms are not completely understood, evidence has accumulated from human and animal studies that irreversible processes of pulmonary arterial wall damage, compensated by stress-mediated growth, play critical roles in eliciting the mechanisms of disease progression. The aim of this study is to develop a thermodynamic modeling structure of the pulmonary artery to consider coupled plastic-degradation-growth irreversible processes to investigate the mechanical roles of the dissipative phenomena in the disease progression. The proposed model performs a model parameter study of plastic deformation and degradation processes coupled with dissipative growth subjected to elevated pulmonary arterial pressure and computationally generates in silico simulations of PH progression using the clinical features of PH, found in human morphological and mechanical data. The results show that considering plastic deformation can provide a much better fitting of the ex vivo inflation tests than a widely used pure hyperelastic model in higher pressure conditions. In addition, the parameter sensitivity study illustrates that arterial damage and growth cause the increased stiffness, and the full simulation (combining elastic-plastic-degradation-growth models) reveals a key postpathological recovery process of compensating vessel damage by vascular adaptation by reducing the rate of vessel dilation and mediating vascular wall stress. Finally, the simulation results of luminal enlargement, arterial thickening, and arterial stiffness for an anisotropic growth are found to be close to the values from the literature.

Keywords: arterial damage; disease progression; parametric sensitive analysis; pulmonary hypertension; thermodynamic modeling.

Fig. 1

Kinematics of the material

Fig. 2

Model calibration of initial material parameters for elastic–plastic behavior with ex vivo test data: (a) elastic modeling fitting (0–30 mmHg data), (b) elastic model fitting (0–50 mmHg data), (c) elastic modeling fitting (0–100 mmHg data), and (d) elastic–plastic model fitting (0–100 mmHg data)

Fig. 3

Degradation effect on the disease progress: (a) degradation variable change according to the C_d parameter, (b) degradation effect on diameter, (c) degradation effect on thickness, and (d) degradation effect on the linearized stiffness

Fig. 4

Growth effect on the disease progress: (a) growth effect on diameter, (b) growth effect on thickness, (c) growth effect on the linearized stiffness, (d) growth with degradation effect on diameter, and (e) growth with degradation effect on thickness

Fig. 5

Numerical analysis of the disease progress: (a) comparison of five mechanisms for diameter change (elastic, plastic, growth, degradation, and full), (b) comparison of five mechanisms for thickness change (elastic, plastic, growth, degradation, and full), (c) pressure-diameter of three cases for diameter change (elastic, plastic, and degradation), and (d) pressure-diameter of three cases for thickness change (elastic, plastic, and degradation)

Fig. 6

Anisotropic growth effect: (a) anisotropic growth effect on diameter and (b) anisotropic growth effect on thickness

Fig. 7

The ratios of the arterial thickening, luminal enlargement, and arterial stiffening against the initial state that are computed from the generated in silico simulations. For the reference data, the ratios are computed by the values of PH patients against those of healthy subjects obtained from the references.

Fig. 8

Effect of degradation on the plastic behavior: (a) pressure-diameter curves of plastic model according to the degradation variable and (b) pressure-thickness curves of plastic model according to the degradation variable

Fig. 9

Effect of growth on J₂ deviatoric stress invariant