Biomechanical remodeling of the murine descending thoracic aorta during late-gestation pregnancy

Figures

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  Fig. 1. Literature review on maternal hemodynamics during pregnancy (Robson et al., 1989; Grindheim et al., 2012; Katz et al., 1978; Clapp and Capeless, 1997; Kager et al., 2009; Poppas et al., 1997; Zentner et al., 2012; Rodriguez et al., 2018; Huisman et al., 1987; Oosterhof et al., 1993; Buchan, 1984; Mulder et al., 2022). (A) Systolic blood pressure and (B) pulse pressure remain constant throughout pregnancy. (C) Cardiac output increases (rs = 0.766, P < 0.001*). (D) Blood viscosity decreases and rises to normal levels during late gestation. (E) Vascular resistance decreases during gestation (rs = −0.579, P = 0.005*). (F) The trend on the behavior of arterial compliance during gestation is not consistent (or clear) among different studies. We relied on the Pearson correlation coefficient test to determine the level of correlation between the two variables in a linear manner. The rs values indicate the strength and direction of the correlation, with P <0.05 considered a statistically significant correlation.

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  Fig. 2. Hemodynamics of age-matched control mice (gray circles) and late-gestation pregnant (black diamonds). (A) Cardiac Output (CO), calculated by cardiac echocardiograph readings of heart rate and stroke volume. (B) Systolic blood pressure. While there was an increase in CO, systolic blood pressure did not change between groups, similar to humans throughout gestation (Fig. 1A and B). As such, wildtype mice were deemed as an appropriate model for examining cardiovascular adaptations during pregnancy. Statistical significance was assessed by Mann-Whitney-Wilcoxon unpaired sample test for cardiac output measurements and Student's t-test for pressure measurements, with P ≤ 0.05 considered to be statistically significant.

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  Fig. 3. Experimental average mechanical response of tissues of the DTA, depicted by stress-stretch curves. Data are shown for age-matched control (gray circles, n = 9) and late-gestation pregnant mice (black diamonds, n = 9) in the mean (A) circumferential (Circ.) and (B) axial directions. The pregnant group experienced a rightward expansion of the stress stretch curve in both directions, indicative of global tissue softening. Error bars show SEM from experimental data collected on individual specimens.

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  Fig. 4. Structural and material parameters of the DTA of age-matched nulligravida control mice (gray circles, n = 9) and late-gestation pregnant mice (black diamonds, n = 9). (A) Circumferential (Circ.) stretch. (B) Circumferential stress. (C) Circumferential stiffness. (D) Axial stretch. (E) Axial stress. (F) Axial stiffness. (G) Luminal diameter. (H) Wall thickness. (I) Distensibility. Calculations of stretch, stress, stiffness, luminal diameter and wall thickness were performed at group-specific systolic blood pressure measurements. Distensibility measures for structural stiffness and accounts for diameter and pressure changes between diastole and systole. The thickening of the wall in the late-gestation group, coupled with the increase in luminal diameter and the tissue softening, decreased the intrinsic stiffness in both the axial and circumferential directions. Similarly, the significant thickening of the wall in the pregnant group reduced the wall stress to lower values when compared to the control group, by outpacing the increase in luminal diameter. The asterisk (*) represents a statistically significant difference of P<0.05.

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  Fig. A.5. Law of Laplace Diagram. This law describes the relationship between pressure and wall stress in thin structures when the radius of curvature of the curved surface and its thickness are known. (A) Cross-sectional top view of a cylinder illustrating the pressure (P) acting on the inner wall, and the thickness (h) of the wall. (B) Side view of a cylinder, illustrating the tension produced on the wall when pressure is applied. r denotes the luminal radius of the cylinder. (C) Cross-section side view of a cylinder, illustrating the circumferential wall stress (σcirc) acting on the wall as pressure is applied.