There is an increased focus on understanding the microvascular system’s role in healthy and diseased myocardial tissue. Capillary networks facilitate the transport of oxygen and other metabolites between the cardiovascular system and surrounding tissue. Because the myocardium extracts a high percentage (~70-85%) of the available oxygen, reductions in blood flow can lead to decreases in tissue oxygen (hypoxemia) and the production of species triggering arterial vasodilation or capillary remodeling. We have developed a computational framework for microvascular hemodynamics and metabolite transport to simulate the delivery of oxygen in capillary networks and predict the production of vasodilatory or angiogenic signals. Hemodynamics are solved with a 0D model that incorporates empirical laws for red blood cell partitioning at bifurcations and estimates of viscosity based on vessel diameter and local hematocrit. A 1D/3D finite volume transport model includes three tissue regions (vascular space, cardiomyocytes, and extracellular space) with multiple species (dissolved oxygen, hemoglobin-bound oxygen, myoglobin-bound oxygen, and vascular endothelial growth factor). Furthermore, we have integrated the hemodynamic and transport modeling framework with simulations of microvascular growth and remodeling. Empirical laws for capillary sprouting, diameter adaptation, capillary pruning, and tension-based vessel migration [1] are combined with vessel-object avoidance to grow and remodel capillary networks around myocyte fibers. Preliminary results showed that initial networks, generated by random placement of capillaries, created regional patches of ischemia. Conversely, remodeled networks showed efficient oxygenation throughout the tissue and could produce networks that match morphologic experimental data (vessel diameters, lengths, and connectivity) [2]. However, ischemic patches reappear when the system is perturbed in exercise simulations. Future work will explore how hemodynamic alterations impact microvascular transport and capillary network remodeling. REFERENCES [1] J.P. Alberding and T.W. Secomb, Simulation of angiogenesis in three dimensions: Applications to cerebral cortex, PLoS Comput Biol 17(6): e1009164. [2] V. E. Sturgess, N. K. Korovesis, D. E. Uceda, et al., “ Immersion-Based Clearing and Autofluorescence Quenching in Myocardial Tissue,” Microcirculation 32, no. 8 (2025): e70034