Flow‐induced ATP release in patient‐specific arterial geometries – a comparative study of computational models

Abstract

The importance of the endothelium in the local regulation of blood flow is reflected by its influence on vascular tone by means of vasodilatory responses to many physiological stimuli. Regulatory pathways are affected by mass transport and wall shear stress (WSS), via mechanotransduction mechanisms. In the present work, we review the most relevant computational models that have been proposed to date, and introduce a general framework for modelling the responses of the endothelium to alteration in the flow, with a view to understanding the biomechanical processes involved in the pathways to endothelial dysfunction. Simulations are performed on two different patient-specific stenosed carotid artery geometries to investigate the influence of WSS and mass transport phenomena upon the agonist coupling response at the endothelium. In particular, results presented for two different models of WSS-dependent adenosine-5'-triphosphate (ATP) release reveal that existing paradigms may not account for the conditions encountered in vivo and may therefore not be adequate to model the kinetics of ATP at the endothelium.

Wall shear stress exposure time: a Lagrangian measure of near-wall stagnation and concentration in cardiovascular flows

“…The local transport of several substances near and at the vessel wall are known to influence atherosclerosis progression [56]. For example, previous studies have looked into transport of low density lipoproteins (LDL) [17,20,30,14], high density lipoproteins (HDL) [40,24], oxygen [16,27], nitric oxide (NO) [45,35], monocytes [12,14], and adenine triphosphate ATP and adenine diphosphate ADP [13,15,8] as important mass transport processes involved in atherosclerosis.Intravascular thrombosis is another compelling pathology associated with most cardiovascular diseases where near-wall transport becomes important [7,25]. The trajectories of individual platelets and the accumulation and residence time of chemical solutes including ADP, thrombin, and various blood factors control clot formation.…”

Mathematical model for shear stress dependent NO and adenine nucleotide production from endothelial cells

“…(36) and by Boileau et al . (71), based on the John and Barakat (34) model ( Model A ) for ATP release, for which R ATP saturates ~ τ w = 35 dyn/cm 2 . Although Model B has not been investigated, higher ATP values would be generated for simulations at high τ w , which can occur with stenosed blood vessels.…”

Biomedical Technology

“…Presently, no endurance tests have been performed on the in-house alloy LA63. However, for several aluminum containing magnesium alloys, the endurance limit was below 70 MPa for 10 7 cycles [37,38]. Consequently, the superposition of both effects-fatigue and corrosion-can lead to a premature material failure.…”

“…Using adenine nucleotides as the agonist (mostly adenosine-5' triphosphate ATP and adenosine diphosphate ADP), many researchers have tried to characterise flow regulation of ATP-and ADP-Ca 2+ coupling in the concentration boundary-layer, and the effect of enzymatic degradation at the endothelium [29][30][31][32][33][34][35][36][37]. Small changes in the model parameters, such as the rate constants for convection of ATP from the bulk fluid to the cell surface or for the degradation and/or production of ATP significantly influence the pattern of catalytic reactions at the endothelium [38]. As we have shown earlier, and as illustrated in Fig.…”