Computational Network Model Prediction of Hemodynamic Alterations Due to Arteriolar Rarefaction and Estimation of Skeletal Muscle Perfusion in Peripheral Arterial Disease

Abstract

Objective To estimate the relative influence of input pressure and arteriole rarefaction on gastrocnemius muscle perfusion in patients with peripheral arterial disease (PAD) after exercise and/or percutaneous interventions. Methods A computational network model of the gastrocnemius muscle microcirculation was adapted to reflect rarefaction based on arteriolar density measurements from PAD patients, with and without exercise. A normalized input pressure was applied at the feeder artery to simulate both reduced and restored ankle-brachial index (ABI) in the PAD condition. Results In simulations of arteriolar rarefaction, resistance increased non-linearly with rarefaction, leading to a disproportionally large drop in perfusion. Additionally, perfusion was less sensitive to changes in input pressure as the degree of rarefaction increased. Reduced arteriolar density was observed in PAD patients and improved 33.8% after 3 months of exercise. In model simulations of PAD, ABI restoration yielded perfusion recovery to only 66% of baseline. When exercise training was simulated by reducing rarefaction, ABI restoration increased perfusion to 80% of baseline. Conclusion Microvascular resistance increases non-linearly with increasing arteriole rarefaction. Therefore, muscle perfusion becomes disproportionally less sensitive to ABI restoration as arteriole rarefaction increases. These results highlight the importance of restoring both microvascular structure and upstream input pressure in PAD therapy.

Impaired skeletal muscle performance as a consequence of random functional capillary rarefaction can be restored with overload‐dependent angiogenesis

“…1989) and reduced muscle blood flow (Heuslein et al . 2015). Placement of femoral artery flow probes distal to the profunda femoris enabled gross hindlimb blood flow to be quantified, but the proportion of flow drawn by EDL was not explicitly measured.…”

“…Computational models predict that the magnitude of vessel rarefaction determines the scale of increased vascular resistance (Greene et al 1989) and reduced muscle blood flow (Heuslein et al 2015). Placement of femoral artery flow probes distal to the profunda femoris enabled gross hindlimb blood flow to be quantified, but the proportion of flow drawn by EDL was not explicitly measured.…”

Exposure of Endothelium to Biomimetic Flow Waveforms Yields Identification of miR-199a-5p as a Potent Regulator of Arteriogenesis

“…Revascularization strategies to stimulate the growth of new capillaries from preexisting vessels (i.e., angiogenesis) or lumenal expansion of pre-existing arteries (i.e., arteriogenesis) remain promising therapeutic options, despite their limited success to date 3 . The stimulation of angiogenesis is important in PAD, as capillary density is reduced in these patients;2, 4, 5 however, it is also imperative to restore the driving pressure to the distal tissue via lumenal expansion (i.e., arteriogenesis) of collateral arteries bypassing the occlusion(s) 6, 7, 8. Arteriogenesis is well known to be stimulated by altered shear stress, 9 though endothelial mechano-signaling in response to this altered shear stress is incompletely understood.…”

Vascular growth responses to chronic arterial occlusion are unaffected by myeloid specific focal adhesion kinase (FAK) deletion

“…The stimulation of angiogenesis is important in PAD as capillary density is reduced in these patients 2 4 5 , however, it is also imperative to restore the driving pressure to the distal tissue via lumenal expansion (i.e. arteriogenesis) of collateral arteries bypassing the occlusion(s) 6 7 8 .…”