Simulation of coronary capillary transit time based on full vascular model of the heart

Capillary transit time (CTT) is a fundamental determinant of gas exchange between blood and tissues in the heart and other organs. Despite advances in experimental techniques, it remains difficult to measure coronary CTT in vivo. Here, we developed a novel computational framework that couples coronary microcirculation with cardiac mechanics in a closed-loop system that enables prediction of hemodynamics in the entire coronary network, including arteries, veins, and capillaries. We also developed a novel "particle-tracking" approach for computing CTT where "virtual tracers" are individually tracked as they traverse the capillary network. Model predictions compare well with blood pressure and flow rate distributions in the arterial network reported in previous studies. Model predictions of transit times in the capillaries (1.21 ± 1.5 s) and entire coronary network (11.8 ± 1.8 s) also agree with measurements. We show that, with increasing coronary artery stenosis (as quantified by fractional flow reserve, FFR), intravascular pressure and flow rate downstream are reduced but remain non-stationary even at 100 % stenosis because some flow (∼3 %) is redistributed from the non-occluded to the occluded territories. Importantly, the model predicts that occlusion of a large artery results in higher CTT. For moderate stenosis (FFR > 0.6), the increase in CTT (from 1.21 s without stenosis to 2.23 s at FFR=0.6) is caused by a decrease in capillary flow rate. In severe stenosis (FFR = 0.1), the increase in CTT to 14.2 s is due to both a decrease in flow rate and an increase in path length taken by "virtual tracers" in the capillary network.