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Introduction Coronary artery bypass graft surgery (CABG) is an intervention in patients with extensive obstructive coronary artery disease diagnosed with invasive coronary angiography. Here we present and test a novel application of non-invasive computational assessment of coronary hemodynamics before and after bypass grafting. Methods and results We tested the computational CABG platform in n = 2 post-CABG patients. The computationally calculated fractional flow reserve showed high agreement with the angiography-based fractional flow reserve. Furthermore, we performed multiscale computational fluid dynamics simulations of pre- and post-CABG under simulated resting and hyperemic conditions in n = 2 patient-specific anatomies 3D reconstructed from coronary computed tomography angiography. We computationally created different degrees of stenosis in the left anterior descending artery, and we showed that increasing severity of native artery stenosis resulted in augmented flow through the graft and improvement of resting and hyperemic flow in the distal part of the grafted native artery. Conclusions We presented a comprehensive patient-specific computational platform that can simulate the hemodynamic conditions before and after CABG and faithfully reproduce the hemodynamic effects of bypass grafting on the native coronary artery flow. Further clinical studies are warranted to validate this preliminary data.

Background This work aims to present a fast, affordable, and reproducible three-cell co-culture system that could represent the different cellular mechanisms of atherosclerosis, extending from atherogenesis to pathological intimal thickening. Methods and results We built four culture models: (i) Culture model #1 (representing normal arterial intima), where human coronary artery endothelial cells were added on top of Matrigel-coated collagen type I matrix, (ii) Culture model #2 (representing atherogenesis), which demonstrated the subendothelial accumulation and oxidative modification of low-density lipoproteins (LDL), (iii) Culture model #3 (representing intimal xanthomas), which demonstrated the monocyte adhesion to the endothelial cell monolayer, transmigration into the subendothelial space, and transformation to lipid-laden macrophages, (iv) Culture model #4 (representing pathological intimal thickening), which incorporated multiple layers of human coronary artery smooth muscle cells within the matrix. Coupling this model with different shear stress conditions revealed the effect of low shear stress on the oxidative modification of LDL and the upregulation of pro-inflammatory molecules and matrix-degrading enzymes. Using electron microscopy, immunofluorescence confocal microscopy, protein and mRNA quantification assays, we showed that the behaviors exhibited by the endothelial cells, macrophages and vascular smooth muscle cells in these models were very similar to those exhibited by these cell types in nascent and intermediate atherosclerotic plaques in humans. The preparation time of the cultures was 24 hours. Conclusion We present three-cell co-culture models of human atherosclerosis. These models have the potential to allow cost- and time-effective investigations of the mechanobiology of atherosclerosis and new anti-atherosclerotic drug therapies.