52Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests 53 that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes 54 remain poorly understood. A biophysical model of human coronary vasculature was 55 used to explain the imaging observations, and highlight causes of coronary BF 56 heterogeneity. 57Post-dialysis CT images from patients under control, pharmacological stress 58 (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate 59 conditions were obtained. The data presented disparate phenotypes. To dissect 60 vascular mechanisms, a 3D human coronary vasculature model was implemented. 61Simulations were performed to investigate the effects of altered aortic pressure and 62 blood vessel diameters on myocardial BF heterogeneity which was quantified using 63 relative dispersion, fractal dimension, and transmural BF distribution. 64Imaging showed that stress and therapy potentially increased mean and total BF, 65 while reducing heterogeneity. BF histograms of one patient showed multi-modality. 66Using the model, it was found that total coronary BF increased as coronary perfusion 67 pressure (CPP) was increased. BF heterogeneity was differentially affected by large 68 or small vessel blocking. BF heterogeneity was found to be inversely related to small 69 blood vessel diameters. Simulation of large artery stenosis indicates that BF became 70 heterogeneous (increase relative dispersion) and gave multi-modal histograms. The 71 total transmural BF as well as transmural BF heterogeneity reduced due to large 72 artery stenosis, generating large patches of very low BF regions downstream. 73Blocking of arteries at various orders showed that blocking larger arteries results in 74 multi-modal BF histograms and large patches of low BF, whereas smaller artery 75 blocking results in augmented relative dispersion and fractal dimension. Transmural 76 heterogeneity was also affected. Finally, the effects of augmented aortic pressure in 77 the presence of blood vessel blocking shows differential effects on BF heterogeneity 78 as well as transmural BF. 79Improved aortic blood pressure may lead to improved BF. Stress and therapy may 80 be effective if they dilate small vessels. A potential cause for the observed complex 81 BF distributions (multi-modal BF histograms) may indicate existing large vessel 82 stenosis. 83The intuitive BF heterogeneity methods used can be readily used in clinical studies. 84Further development of the model and methods will permit personalised assessment 85 of patient BF status. 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 106 107
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