Dynamic Changes in Microvascular Flow Conductivity and Perfusion After Myocardial Infarction Shown by Image-Based Modeling

Abstract

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.

Keywords: blood flow; confocal microscopy; coronary microcirculation; mathematical modeling; myocardial infarction.

Figure 1

Overview of the proposed pipeline for the calculation of the permeability tensors and myocardial blood flow from microvascular 3‐dimensional anatomical data.

Figure 2

Permeability tensor elements (k ₁₁, k ₂₂, and k ₃₃) after sorting directions by larger permeability. Calculations have been performed considering constant hematocrit of 0.4 in all vessel segments. *P<0.05. The P values were calculated with Wilcoxon rank‐sum tests and corrected by the Benjamini–Hochberg procedure for multiple testing. The central lines in the boxes stand for the median, whereas the top and bottom edges of the boxes represent the 25th and 75th percentiles, respectively. The whiskers extend to the most extreme data points that are not considered outliers. The latter are represented using a red cross. The same annotations and statistical hypothesis testing approach apply to all figures in this article. MI indicates myocardial infarction.

Figure 3

Altered arteriole–venule (AV) drop in pressure (DP) after myocardial infarction (MI). DP was calculated using the larger element of the permeability tensor and different AV path length. DP for a path length 349 μm (A), 512 μm (B) and 675 μm (C). *P<0.05. **P<0.01.

Figure 4

Myocardial blood flow (MBF) calculated using sorted k ₁₁ (MBF _k11/MBF _k11 ^DP), k ₂₂ (MBF _k22/MBF _k22 ^DP), or k ₃₃ (MBF _k33/MBF _k33 ^DP). A, MBF considering constant arteriole–venule (AV) drop in pressure (DP) of 19.5 mm Hg and a path length of 512 μm independent of the tissue condition. B, MBF considering varying AV DP according to the tissue condition and a path length of 512 μm. The DPs for these simulations are the mean values presented in Table 1. In both cases, calculations have been performed considering constant hematocrit of 0.4 in all vessel segments. *P<0.05. MI indicates myocardial infarction.

Figure 5

Example with modified radii and number of segments used in the study of the effect of vessel dilation, constriction, and pruning on the permeability tensors. A, From left to right, increase by 10%, 20%, and 30% of vessel diameter of all microvessels that compose the microvasculature. B, 30% increase of vessel diameter applied to the 10%, 20%, and 30% of vessels. C, Decrease of vessel diameter of all microvessels. (D) Decrease of vessel diameter by percentage of microvessels: 10%, 20%, and 30% (from left to right). E, Pruning of 10%, 20%, and 30% of the capillaries with the smallest radius. The diagonal permeability tensor elements are provided Below each image. In parentheses, the percentages of decrease (negative sign) or increase (positive sign) with respect to the original values (ie, without any remodeling). Image corresponds to tissue from basal conditions. Some examples of remodeled vessels (B, D) or areas of pruned vessels (E) are highlighted in yellow circles.