Panta rhei. (Everything flows). 1C ardiology is about flow. The primary purpose of the cardiovascular system is to drive, control, and maintain blood flow to all parts of the body. Flow dictates the form and function of the heart and blood vessels through ontogenic and phylogenic development, the structural and functional consequence of repair, and in its end stages, remodeling and response to failure. Flow should therefore be a primary focus by which we explain where lesions form, why they degrade and decompensate, and how we grade the extent of restoration of function after vascular intervention. Yet this is not the case. Flow is not a standard part of our clinical lexicon. Few reliable and consistent means of measuring flow exist. Despite early use of surrogate flow markers (eg, TIMI frame count), we do not quantify flow restoration after interventions. Moreover, there is simply no agreement as to the aspect or degree of flow that is most important in lesion development or functional recovery. Article p 2744 Flow and AtherogenesisThe nonhomogeneous nature of atherosclerosis has been appreciated since the earliest days of research in the field. 2 Certain arterial segments develop profound lesions, whereas adjacent regions seem completely spared. Neither properties of blood nor local cellular and molecular biological events can vary significantly on such length scales to explain such spatial heterogeneity. Local flow properties can change on these scales (Figure 1), and alterations in local flow patternfor example, the intricate vectorial description of fluid speed and direction across the entire cross section of the lumenwere invoked as a possible explanation for the observed scatter in pathology. [2][3][4][5] In this context, lesion distribution is not random but aligns with, and accumulates within, areas of flow disturbances such as those that occur around tight curves, bifurcations, and in areas already beset by atherosclerosis. Flow disturbances are therefore ubiquitous; they are a fundamental feature of the vascular system. An entire field of study arose correlating disease with its overlying flow pattern. 6 -9 Several factors, including low shear stress, oscillatory (bidirectional) flow, and regions of eddies and/or boundarylayer separation, have repeatedly been shown by numerous researchers, using both numerical and observational techniques, to be the prime candidates for wreaking havoc on vascular biology. 10 -13 Other workers then simulated these same factors in vitro to show their possible effects on a cellular level. 14 -16 Everything flows and nothing abides, everything gives way and nothing stays fixed. 1 In this issue of Circulation, Cheng et al 17 take this one step further by artificially varying flow conditions in vivo. They show that lesions indeed develop consistent with a priori predictions based on flow patterns. In their elegant experiment, a cast alters vessel geometry to create 3 distinct regions of altered flow in the carotid arteries of apolipoprotein E-knockout mice. Areas were c...

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Although arterial bifurcations are frequent sites for obstructive atherosclerotic lesions, the optimal approach to these lesions remains unresolved. Benchtop models of arterial bifurcations were analyzed for flow disturbances known to correlate with vascular disease. These models possess an adaptable geometry capable of simulating the course of arterial disease and the effects of arterial interventions. Chronic in vivo studies evaluated the effect of flow disturbances on the pattern of neointimal hyperplasia. Acute in vivo studies helped propose a mechanism that bridges the early mechanical stimulus and the late tissue effect. Sidebranch (SB) dilation adversely affected flow patterns in the main branch (MB) and, as a result, the long-term MB patency of stents implanted in pig arteries. Critical to this effect is chronic MB remodeling that seems to compensate for an occluded SB. Acute leukocyte recruitment was directly influenced by the changes in flow patterns, suggesting a link between flow disturbance on the one hand and leukocyte recruitment and intimal hyperplasia on the other. It is often impossible to simultaneously maximize the total cross-sectional area of both branches and to minimize flow disturbance in the MB. The apparent trade-off between these two clinically desirable goals may explain many of the common failure modes of bifurcation stenting.Nonstandard abbreviations used: main branch (MB); poly(ethylene glycol) (PEG); side branch (SB).