Full-field analysis indicates late reperfusion therapy broadens and mechanically smooths the borderzone during post-infarction inflammation

Late reperfusion therapy (LRT; ≥ 3 h post-MI) reduces the risk of ventricular rupture following myocardial infarction (MI), yet the mechanisms behind this protection remain unclear. We hypothesized that LRT alters 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 larger infarct borderzones (border-to-core area PO: 0.735 ± 0.3; LRT: 1.15 ± 0.3; p = 0.04). 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 was thicker and more spatially variable than sham, but less stiff. Additionally, QPLI revealed decreased collagen fiber alignment in infarct cores relative to borders, though this did not differ between PO and LRT groups. Exploratory second harmonic generation imaging revealed more gradual, consistent transitions in collagen fiber alignment throughout LRT LV ECM, although this was limited to one sample from each group. Ultimately, these results further justify LRT and may inform future therapies aimed at spatially modulating post-MI tissue mechanics to improve patient outcomes. STATEMENT OF SIGNIFICANCE: Myocardial infarctions (MI) initially weaken the heart wall and, in severe cases, can lead to ventricular rupture, a life-threatening complication. Late reperfusion therapy (LRT), in which blood flow is restored 3+ hours post-MI, reduces rupture risk, but how it protects the heart remains unclear. Here, we combine full-field imaging and mechanical testing to reveal that LRT broadens the infarct borderzone and smooths gradients in stiffness and thickness. This previously unrecognized mechanical "smoothing" likely reduces stress concentrations that drive rupture. By establishing how LRT reshapes regional properties in the heart, our findings not only provide a mechanistic basis for LRT's benefits, but may also inform the design of spatially-conscious biomaterials and therapies to improve patient outcomes post-MI.