Impact of chronic hypoxia on proximal pulmonary artery wave propagation and mechanical properties in rats

Figures

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  Fig. 1.. Overview of the mechanical testing setup. Uniaxial mechanical testing was performed on isolated artery rings, where two sides of the artery ring (A; schematic sagittal section) corresponding to two vessel wall area (outlined in black) were subjected to a given load simultaneously. B: before mechanical testing, the artery ring segments with a longitudinal length (ll) of 1 mm were mounted on a glass rod and photographed to measure the vessel wall area (outlined in black). C: the artery ring was then mounted around two bent steel hooks, which were connected to a load cell and step motor, respectively (schematic overview), and subjected to a tensile test to rupture (D–F). See Table 1 for abbreviations.

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  Fig. 2.. Representative flow velocity traces from the pulmonary trunk. Noninvasive (transthoracic echocardiography) pulsed-wave Doppler flow traces from the pulmonary trunk are shown for a normoxic rat (A) and a hypoxic rat (B). A midsystolic notch during the flow deceleration phase and shorter pulmonary acceleration time (PAT) were observed in hypoxic animals. Trivial diastolic flow reversal was observed in the majority of the traces (both normoxic and hypoxic animals). C: the corresponding invasive (pulmonary artery catheterization) pressure measurement (top) and Doppler flow trace (bottom) with velocity tracking from the same normoxic rat.

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  Fig. 3.. Invasive versus noninvasive measurements. A−C: lower heart rate (A) and mean and peak pulmonary flow velocities (B and C, respectively) were observed during right heart catheterization (RHC; performed in the open-chested condition) compared with measurements acquired by transthoracic echocardiography (TTE; performed in the close-chested condition). Squares and error bars represent means ± SE. *P < 0.05; **P < 0.01.

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  Fig. 4.. Pulmonary arterial wave propagation. Good quality velocity signals were obtained from 7 normoxic and hypoxic animals during right heart catheterization, and arterial wave analyses were performed. A and B: representative ensemble-averaged pressure (P) and flow velocity profiles from a normoxic and hypoxic rat (same animals as shown in Fig. 3). C and D: wave intensity analysis revealed a forward compression wave (FCW) and forward decompression wave (FDW) related to right ventricular ejection and relaxation, respectively. There were negligible backward waves present. The net wave intensity profile is highlighted in black. E and F: measured pressure [Pm; minus diastolic pressure (Pd)] was separated into forward (Pf) and backward (Pb) pressures. t, time.

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  Fig. 5.. Wave intensities. Invasive wave intensity analysis (WIA) was performed using pressure and velocity data obtained by right heart catheterization, and semiinvasive WIA was performed using invasive pressure data combined with velocity data obtained by transthoracic echocardiography. In 5 normoxic animals and 6 hypoxic animals, both WIA methods were applied and pairwise comparison was performed. The energy densities of the forward compression wave (FCW; A) and forward decompression wave (FDW; B) derived from semiinvasive WIA were higher than their invasive counterparts (data presented as means ± SE). However, there were no significant differences in wave intensities between the two groups of animals, be it invasive or semiinvasive WIA. The same was observed for the peak intensities (not shown). *P < 0.05.

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  Fig. 6.. Representative histological sections were obtained from two normoxic and hypoxic animals. A−L: transverse histological sections of the aorta (A−D) and pulmonary trunk from a normoxic rat (E–H) and pulmonary trunk from a hypoxic rat (I–L). The appearance of the aorta from hypoxic animals (not shown here) was similar to normoxic animals. Images in B, F, and J were stained with hematoxylin and eosin; the rest were stained with resorcin, sirius red, and Weigert’s hematoxylin. Images in C, G, and K were photographed in bright field, wherein collagen fibers appear red and elastin fibers appear dark purple. Images in D, H, and L were photographed with a circular polarization filter, wherein collagen fibers appear yellow/orange/red and elastin fibers appear dark blue. Ad, adventitia; Me, media.

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  Fig. 7.. Force-deformation and stress-strain curves of the pulmonary trunk. A: loading-unloading cycles were performed five times for each artery ring (shown here for a representative ring from each animal group). The hysteresis loop from the last cycle is highlighted. B: a stretch test to rupture was performed on the same artery rings. C and D: the average stress-strain curve for the pulmonary trunk up to the breaking point (data presented as means ± SE; C) and at low-strain regions (with expanded scales; D) differed between the two animal groups.

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  Fig. 8.. Significant changes were observed in the vessel dimensions and mechanical properties in hypoxic animals. A−F: vessel wall thickness (A), unstrained vessel luminal diameter (B), maximum load (C), maximum stiffness (D), maximum elastic modulus (Emax; E), and viscous energy loss (F) of the aorta, pulmonary trunk (PT), and right and left pulmonary arteries (PAs). *P < 0.05; **P ≤ 0.001.

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  Fig. 9.. Mechanical properties at physiological distending pressures. A and B: strain-pressure curves for the aorta and pulmonary arteries (PAs). C and D: elastic modulus (Ep) of the main and right PAs. E and F: empirical pulse wave velocity (PWVMK) was calculated using the Moens-Korteveg equation. Pulse wave velocity derived from the sum of squares (PWVsq) method and Bramwell and Hill equation (PWVBH) are plotted in E. Data are presented as medians (25–75% quartiles). The strain and Ep in PAs at each of the distending pressures (11, 16, and 24 mmHg) were significantly lower, wherease pulse wave velocity was significantly higher (P ≤ 0.01), in hypoxic rats.

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  Fig. 10.. A and B: collagen content normalized to vessel circumference (A) and collagen strength defined as the maximum tensile strength per unit collagen (B) are shown for the aorta, pulmonary trunk (PT), and right and left pulmonary arteries (PAs). *P < 0.05; **P ≤ 0.001.