Biology subjects

Witzenburg, C. M.

Publications and source records attributed to Witzenburg, C. M..

3 recordsLinked to original sources

bioRxiv2025

Full-Field Analysis Indicates Late Reperfusion Therapy Broadens and Mechanically Smooths the Borderzone During Post-Infarction Inflammation

Late reperfusion therapy (LRT; [≥] 3 hours post-MI) significantly reduces the risk of ventricular rupture following myocardial infarction (MI), yet the structural and mechanical mechanisms behind this protection remain unclear. We hypothesized that LRT would alter the biomechanical properties of the infarct borderzone and to investigate this, we utilized laser micrometry, planar biaxial testing, and quantitative polarized light imaging (QPLI) to quantify spatial variations in the geometric, mechanical, and structural properties of the left ventricle extracellular matrix (LV ECM) in adult male Sprague-Dawley rats. Rats received permanent occlusion (PO), LRT, or a sham surgery and tissue was collected 1-day post-MI, during the inflammatory phase of healing. LRT generated a larger infarct borderzone (LRT: 31.5 {+/-} 7.6 mm2; PO: 22.5 {+/-} 4.2 mm2; p < 0.05) in comparison to PO. Infarct core and borderzone stiffness was reduced post-MI, and LRT samples exhibited smoother, more consistent stiffness gradients between infarct core and remote regions than PO samples. In general, infarcted LV ECM from were thicker and more spatially variable than sham samples, but less stiff. Additionally, dynamic QPLI revealed decreased collagen fiber alignment in infarct cores relative to borders, though this did not differ between PO and LRT groups. Complementary second harmonic generation imaging revealed more gradual, consistent transitions in collagen fiber alignment throughout LV ECMs subjected to LRT, although this was limited to one sample from each group. Ultimately, these results further justify LRT and may inform future therapeutic strategies aimed at spatially modulating post-MI tissue mechanics to improve patient outcomes.

bioengineering↗

bioRxiv2025

Regional and Temporal Changes in Early Structural Remodeling Following Myocardial Infarction via Semi-Automatic Image Analysis

Reperfusion therapy, the restoration of blood flow following a myocardial infarction (MI), is one of the most effective treatment strategies. Unlike early reperfusion therapy, differences in infarct size or collagen content have not been reported in late reperfusion therapy. To evaluate the spatial-temporal effects of late reperfusion therapy, we conducted multimodal imaging of histologic sections of rat myocardium following permanent coronary artery occlusion or three hours of occlusion. Semi-automatic partitioning identified the infarct core, infarct border, and healthy periphery regions from label-free liquid crystal based polarized light microscopy (PolScope) images taken throughout the first 5 days of healing. Associated brightfield and standard polarized light microscopy images of hematoxylin-eosin or Picrosirius Red stained sections were also used to determine cellular and collagen fiber densities, respectively. Even when we consider multiple definitions for the vulnerable infarct border, its size decreased faster in late reperfusion therapy samples. Temporal patterns in collagen density also indicated late reperfusion led to a more rapid progression through the necrotic phase of healing (when the infarct is vulnerable to rupture) and earlier progression to the fibrotic phase of healing (when the infarct stabilizes). Notably, we also observed a broader region of provisional non-collagenous matrix in late reperfusion samples during the necrotic phase of healing. Together these findings suggest late reperfusion therapy accelerates healing and potentially changes the spatial pattern of provisional matrix deposition during the period the heart is most susceptible to rupture events.

pathology↗

bioRxiv2023

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↗