Abstract

Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity. Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human vasculature model based on known experimental coronary morphometry and a space filling algorithm was implemented. Steady state simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity. Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF. Improved aortic blood pressure may improve total BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis. The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalized assessment of patient BF status.

Highlights

  • Dialysis is a life prolonging treatment but significantly reduces quality of life due to its deleterious side effects on the heart

  • A representative 3D myocardial blood flow (BF) map which was reconstructed from thoracic CT images is shown in Figure 2, Row 1 and BF histograms in Figure 2, Row 2

  • The BF histograms were converted to Probability distribution functions (PDFs) of relative flow (Figure 2, row 3)

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Summary

Introduction

Dialysis is a life prolonging treatment but significantly reduces quality of life due to its deleterious side effects on the heart. This mathematical modeling study explores some of the coronary vasculature based causes of myocardial blood flow (BF) heterogeneity. ESRD patients experience significantly reduced coronary blood flow (BF) (Dasselaar et al, 2009). Experimental observations have led to the belief that an increased resistance of blood vessels in the sub-endocardium promotes increased transmural BF heterogeneity (Algranati et al, 2011). Non-invasive interventions may not affect existing large vessel structural defects such as stenosis, it is thought that adenosine stress and dialysate cooling therapy may improve myocardial BF by vasodilation of the smaller blood vessels. Knowledge of the cause-effect relationships may permit design of future clinical trials and augment the precision of medications given to this critically ill group of patients

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