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One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient’s bloodstream, which breaks down the thrombi’s fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model’s results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.

Background-Microcirculation is a decisive factor in tissue reperfusion inadequacy following myocardial infarction (MI).Nonetheless, experimental assessment of blood flow in microcirculation remains a bottleneck. We sought to model blood flow properties in coronary microcirculation at different time points after MI and to compare them with healthy conditions to obtain insights into alterations in cardiac tissue perfusion., Methods and Results-We developed an image-based modeling framework that permitted feeding a continuum flow model with anatomical data previously obtained from the pig coronary microvasculature to calculate physiologically meaningful permeability tensors. The tensors encompassed the microvascular conductivity and were also used to estimate the arteriole–venule drop in pressure and myocardial blood flow. Our results indicate that the tensors increased in a bimodal pattern at infarcted areas on days 1 and 7 after MI while a nonphysiological decrease in arteriole–venule drop in pressure was observed; contrary, the tensors and the arteriole–venule drop in pressure on day 3 after MI, and in remote areas, were closer to values for healthy tissue. Myocardial blood flow calculated using the condition-dependent arteriole–venule drop in pressure decreased in infarcted areas. Last, we simulated specific modes of vascular remodeling, such as vasodilation, vasoconstriction, or pruning, and quantified their distinct impact on microvascular conductivity., Conclusions-Our study unravels time- and region-dependent alterations of tissue perfusion related to the structural changes occurring in the coronary microvasculature due to MI. It also paves the way for conducting simulations in new therapeutic interventions in MI and for image-based microvascular modeling by applying continuum flow models in other biomedical scenarios.

Microcirculation is a decisive factor in tissue reperfusion inadequacy following myocardial infarction (MI). Nonetheless, experimental assessment of blood flow in microcirculation remains a bottleneck. We sought to model blood flow properties in coronary microcirculation at different time points after MI and to compare them with healthy conditions to obtain insights into alterations in cardiac tissue perfusion. Methods and Results. We developed an image‐based modeling framework that permitted feeding a continuum flow model with anatomical data previously obtained from the pig coronary microvasculature to calculate physiologically meaningful permeability tensors. The tensors encompassed the microvascular conductivity and were also used to estimate the arteriole–venule drop in pressure and myocardial blood flow. Our results indicate that the tensors increased in a bimodal pattern at infarcted areas on days 1 and 7 after MI while a nonphysiological decrease in arteriole–venule drop in pressure was observed; contrary, the tensors and the arteriole–venule drop in pressure on day 3 after MI, and in remote areas, were closer to values for healthy tissue. Myocardial blood flow calculated using the condition‐dependent arteriole–venule drop in pressure decreased in infarcted areas. Last, we simulated specific modes of vascular remodeling, such as vasodilation, vasoconstriction, or pruning, and quantified their distinct impact on microvascular conductivity. Conclusions. Our study unravels time‐ and region‐dependent alterations of tissue perfusion related to the structural changes occurring in the coronary microvasculature due to MI. It also paves the way for conducting simulations in new therapeutic interventions in MI and for image‐based microvascular modeling by applying continuum flow models in other biomedical scenarios.