Impact of residual stretch and remodeling on collagen engagement in healthy and pulmonary hypertensive calf pulmonary arteries at physiological pressures

Abstract

Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries' histological changes, in vivo pressure-diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized. To further understand the mechanical behavior of the proximal PAs under physiological conditions, this study computed the residual stretch and the in vivo circumferential stretch state in the main pulmonary arteries in both control and hypertensive calves by using in vitro and in vivo artery geometry data, and modeled the impact of residual stretch and arterial remodeling on the in vivo circumferential stretch distribution and collagen engagement in the main pulmonary artery. We found that the in vivo circumferential stretch distribution in both groups was nonuniform across the vessel wall with the largest stretch at the outer wall, suggesting that collagen at the outer wall would engage first. It was also found that the circumferential stretch was more uniform in the hypertensive group, partially due to arterial remodeling that occurred during their hypoxic treatment, and that their onset of collagen engagement occurred at a higher pressure. It is concluded that the residual stretch and arterial remodeling have strong impact on the in vivo stretch state and the collagen engagement and thus the mechanical behavior of the main pulmonary artery in calves.

FIGURE 1

The cross-sectional representations of arteries (a) at the stress-free state with OA<180°, (b) at the stress-free state with OA>180°, (c) at the no-load state and (d) under physiological conditions: P, blood pressure.

FIGURE 2

Schematic of the direction of two-family collagen fibers at stress-free state.

FIGURE 3

Representative circumferential residual stretch distribution across the vessel wall. Note that the normalized radial position goes from the inner wall (0.0) to the outer wall (1.0).

FIGURE 4

Representative circumferential stretch distributions of calf MPA at end-diastolic and end-systolic pressures and λ_z = 1.1 with and without residual circumferential stretch (open and close rings in the figures, respectively) considered for (a) control and (b) hypertensive calves. Note that the normalized radial position goes from the inner wall (0.0) to the outer wall (1.0). Also note that a less uniform stretch distribution is observed with residual stretch incorporated in the control calf (Fig. 4a).

FIGURE 5

Uniformity index at end diastole and end systole for both groups at different in vivo longitudinal stretches. Standard deviations are provided in the text.

FIGURE 6

Mixed-effect regression analyses between UI and MPA blood pressure (P) for (a) control and (b) hypertensive groups at λ_z = 1.1. Note that UI = 0 indicates uniform stretch distribution across the vessel wall.

FIGURE 7

Mean physiological circumferential stretches at the inner and outer walls of the artery at different longitudinal stretches at (a) end-diastolic and (b) end-systolic pressures for control and hypertensive groups and the critical engagement stretches $({\lambda }_{\theta }^{\mathrm{T}})$ with collagen fiber angles at 40° and 45°. Standard deviations are provided in the text.

FIGURE 8

Mixed-effect regression analyses between in vivo circumferential stretch at outer wall and MPA blood pressure (P) for (a) control and (b) hypertensive groups at λ_z = 1.1. The dashed and dash-dotted lines are the critical engagement stretches $({\lambda }_{\theta }^{\mathrm{T}})$ with collagen fiber angles at 40° and 45°, respectively.

FIGURE 9

Representative optical microscopy images for (a) control and (b) hypertensive calves. Collagen and elastin appear red and black, respectively. Adventitia and intima are at the left and right sides of the images, respectively.