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Culver, M. A.

Publications and source records attributed to Culver, M. A..

3 recordsLinked to original sources

Structural and Mechanical Analysis of Treated and Untreated Aortic Coarctation in a Growing Porcine Model

Coarctation of the aorta (COA) is a congenital heart disease for which successful intervention can restore flow and reduce the blood pressure gradient, but does not ensure long-term health. Adults with successfully treated COA exhibit significantly higher incidence of hypertension. The objective of this study was to measure differences in the structure and mechanics of proximal and distal aortic tissue from a new, physiologically relevant growing porcine model of COA. This animal model also enabled the evaluation of a cutting-edge serially dilatable stent. Quantitative histologic analysis measured structural changes and the mechanical properties were investigated through uniaxial, shear lap, and peel tests of tissue from sham, control COA, and treated COA animals. Our original hypothesis that proximal aortic tissue from control and treated COA groups would be thicker and have less elastin was false. There were no significant differences in elastin content, collagen content, tissue area, lumen area, or lumen-to-tissue area between groups. Mechanically, distal tissue also exhibited no difference in either uniaxial or shear lap stiffness, failure stress, or failure strain between groups. Distal tissue from the COA control and treated COA groups however, exhibited, a lower circumferential failure peel tension, suggesting interlamellar strength was reduced. When compared with other previously published animal models of COA, a clear distinction was timing - our growing porcine model is the first for which COA was induced and treated at physiologically relevant time points. Our results indicated minimal adverse vascular remodeling in either the COA control or treated COA groups, however, it is unclear if this was due to a lack of severity, if elastinogenesis compensated for damage, or if another unknown mechanism prevented remodeling.

bioengineering↗

A Computational Model of Coarctation of the Aorta in Rabbits: Ventricular and Ascending Aortic Remodeling

Coarctation of the aorta (CoA) is a common congenital cardiovascular lesion that typically presents as a localized narrowing of the proximal descending thoracic aorta just distal to the left subclavian artery. While improvements in surgical and catheter-based techniques have increased short-term survival, there is a high long-term risk of hypertension after CoA correction and a reduced average lifespan despite treatment. Computational models can be used to estimate ventricular and arterial remodeling, potentially serving as key tools in developing a mechanistic understanding of the interplay between pre-correction hemodynamics, post-correction recovery, and long-term hypertension risk. In this study, we developed a lumped parameter model of the heart and circulation to simulate aortic coarctation. We then used the model to estimate changes in ventricular thickness and ascending aortic compliance from imaging and catheterization data collected in rabbits with untreated and corrected CoA that used the current putative clinical treatment threshold ([≥]20 mmHg). Model outputs were compared to reported stroke volume, ejection fraction, systolic and diastolic ascending aortic pressures, peak ascending aortic flow, mean and peak aortic blood pressure gradients, and upper-to-lower body flow split, with all results falling within one standard deviation of the data for control, untreated CoA, and corrected CoA groups. In the untreated CoA and corrected simulations, a decrease in ascending aortic compliance was necessary to match reported hemodynamics, suggesting the rabbits exposed to CoA [≥]20 mmHg underwent vascular remodeling that persisted after repair.

bioengineering↗

CARMIL3 is important for cell migration and morphogenesis during early development in zebrafish

Cell migration is important during early animal embryogenesis. Cell migration and cell shape are controlled by actin assembly and dynamics, which depend on capping proteins, including the barbed-end heterodimeric actin capping protein (CP). CP activity can be regulated by capping-protein-interacting (CPI) motif proteins, including CARMIL (capping protein Arp2/3 myosin-I linker) family proteins. Previous studies of CARMIL3, one of the three highly conserved CARMIL genes in vertebrates, have largely been limited to cells in culture. Towards understanding CARMIL function during embryogenesis in vivo, we analyzed zebrafish lines carrying mutations of carmil3. Maternal-zygotic mutants show impaired endodermal migration during gastrulation, along with defects in dorsal forerunner cell (DFC) cluster formation, affecting the morphogenesis of Kupffers vesicle (KV). Mutant KVs are smaller and display decreased numbers of cilia, leading to defects in left/right (L/R) patterning with variable penetrance and expressivity. The penetrance and expressivity of the KV phenotype in carmil3 mutants correlated well with the L/R heart positioning defect at the end of embryogenesis. This first in vivo animal study of CARMIL3 reveals its new role for CARMIL3 during morphogenesis of the vertebrate embryo. This role involves migration of endodermal cells and DFCs, along with subsequent morphogenesis of the KV and L/R asymmetry.

developmental biology↗