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Computational Analyses of Intravascular Tracer Washout Reveal Altered Capillary‐Level Flow Distributions in Obese Zucker Rats

Intravascular tracer washout data of 125I‐albumin obtained from gastrocnemius muscle of lean Zucker rats (LZR) and obese Zucker rats (OZR) is analyzed to investigate flow distributions in OZR, a model of non‐atherosclerotic peripheral vascular disease. A computer model used to simulate the network washout curves is developed based on experimentally‐observed relative dispersions in large vessels and asymmetrical flow distributions at bifurcations in dichotomous microvascular networks. The model results of simulations are compared to experimental washout data to uncover flow distributions on the arterial‐network and capillary levels. The LZR and OZR demonstrate distinct capillary‐level flow distributions, with higher dispersion and significantly more low‐flow capillaries in the OZR than in the LZR. Targeted pharmacological treatments against identified sites of vascular dysfunction in OZR are shown to improve the capillary‐level flow distributions in treated OZR toward distributions determined in control LZR. Combination therapy with multiple pharmacological interventions resulted in a greater degree of recovery. This study demonstrates that the enhanced perfusion heterogeneity at arteriole bifurcations is a potential mechanism underlying perfusion‐demand mismatching in OZR, and suggests that amelioration of this dysfunction must involve a multi‐faceted interventional approach.