Biaxial Creep Resistance and Structural Remodeling of the Aortic and Mitral Valves in Pregnancy

Abstract

Pregnancy produces rapid, dramatic volume-overload changes to the maternal circulation. This paper examines pregnancy-induced structural-mechanical changes in bovine aortic and mitral heart valve leaflets. Valve leaflets were harvested from non-pregnant heifers and pregnant cows. Dimensions, biaxial extensibility and creep resistance were assessed and related to changes in the collagen network: histological leaflet and anatomic layer thicknesses plus collagen crimp, and biochemical collagen content. Collagen stability and crosslinking were assessed thermomechanically. Pregnancy altered both aortic and mitral valve leaflets. Both valves demonstrated biphasic changes in leaflet stretch, decreasing in early pregnancy and recovering by late pregnancy. Creep in leaflets from both valves was minimal and decreased even further with pregnancy in the mitral valve. There were valve-specific changes in preconditioning areal extension with pregnancy: increasing in the aortic valve and decreasing in the mitral valve. Leaflet area increased dramatically (84% aortic, 56% mitral), with thickening mainly in the fibrosa, accompanied by increases in collagen content (8% aortic, 16% mitral): together suggesting synthesis of new collagen. Collagen crimp was almost completely lost in pregnancy, with the denaturation temperature decreased by approximately 2 °C. Mature and total crosslinking increased, curiously without a significant increase in immature crosslinking. Mature aortic and mitral heart valve leaflets in the maternal cardiovascular system remodel substantially and similarly-despite their different embryological origins.

Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis

“…Note that mass fractions of collagen and elastin were not included in the set of estimated parameters, and were instead prescribed from previous biochemical assay results [5,14]. Mass fraction data were re-analysed to identify potential timedependent trends, and appropriate values for f c and f e were assigned to each specimen accordingly.…”

Pregnancy-induced remodeling of heart valves

“…Many investigations of valve adaptation have focused on physiological development (8,20,(51)(52)(53) or pathological conditions such as left ventricular (LV) dysfunction (10), mitral valve regurgitation (58), myxomatous degeneration (19), or heart failure (17). Recent studies from our laboratory, however, have demonstrated the capacity of maternal heart valve leaflets to remodel under the altered hemodynamics of pregnancy, a nonpathological condition (38,39,60). Pregnancy is accompanied by an increase in blood volume and cardiac output of ϳ50%, as the maternal circulation accommodates the developing fetoplacental unit.…”

“…These changes in geometry then elevate stresses on closed valve leaflets per the Law of Laplace (26). Our studies of the aortic and mitral valves have thus far shown dramatic increases in leaflet size of both valves accompanied by alterations in fiber architecture and composition, a decrease in thermal stability of collagen, a reversible shift in leaflet extensibility, and valve-specific alterations in resistance to creep (38,39,60). Together, these results provide strong evidence of both collagen turnover during pregnancy and unexpected maturation of native leaflet collagen, a complex restructuring of the collagen matrix under the altered cardiovascular loading and hormonal shifts of pregnancy.…”

“…Although remodeling in pregnancy has been described in the aortic and mitral valves (39), it is important to examine all four valves since their responses may differ due to differences in 1) their embryological origin or 2) their mechanical loading conditions. For instance, the inflow valves (mitral and tricuspid) arise solely from tissues of the endocardial cushions in the developing heart tube, whereas the outflow valves (aortic and pulmonary) are also derived from immigrating neural crest cells (5,12,20,22,47).…”

“…To test this hypothesis, we have continued to use our bovine pregnancy model that closely emulates the features of human pregnancy. For the work described herein, we applied the same multidisciplinary combination of dimension measurements, biaxial mechanical testing, histology, thermoelastic studies, and biochemical analysis to the right-side valves that we had used previously in our studies of the left-side valves (38,39,60). We also added new assessments of matrix composition (water, elastin, and sulfated GAG contents), cell counting, and assessment of cell phenotype to samples of all four valves in both nonpregnant and pregnant animals.…”