It has been well established that wall shear stress is an important determinant of endothelial cell function and gene expression as well as of its structure. There is increasing evidence that low wall shear stress, as pres- ent in artery bifurcations opposite to the flow divider where atherosclerotic lesions preferentially originate, expresses an atherogenic endothelial gene profile. Besides, wall shear stress regulates arterial diameter by modifying the release of vasoactive mediators by endothelial cells. Most of the studies on the influence of wall shear stress on endothelial cell function and structure have been performed in vitro, generally exposing endothelial cells from different vascular regions to an average wall shear stress level calculated according to Poiseuille’s law, which does not hold for the in vivo situation, assuming wall shear stress to be constant along the arterial tree. Also in vivo wall shear stress has been determined based upon theory, assuming the velocity profile in arteries to be parabolic, which is generally not the case. Wall shear stress has been calculated, because of the lack of techniques to assess wall shear stress in vivo. In recent years, techniques have been developed to accurately assess velocity profiles in arterioles, using fluorescently labeled particles as flow tracers, and non-invasively in large arteries by means of ultrasound or magnetic resonance imaging. Wall shear rate is derived from the in vivo recorded velocity profiles and wall shear stress is estimated as the product of wall shear rate and plasma viscosity in arterioles and whole blood viscosity in large arteries. In this review, we will discuss wall shear stress in vivo, paying attention to its assessment and especially to the results obtained in both arterioles and large arteries. The limitations of the methods currently in use are discussed as well. The data obtained in the arterial system in vivo are compared with the theoretically predicted ones, and the consequences of values deviating from theory for in vitro studies are considered. Applications of wall shear stress as in flow-mediated arterial dilation, clinically in use to assess endothelial cell (dys)function, are also addressed. This review starts with some background considerations and some theoretical aspects.

Abstract-A mathematical model (TriSeg model) of ventricular mechanics incorporating mechanical interaction of the left and right ventricular free walls and the interventricular septum is presented. Global left and right ventricular pump mechanics were related to representative myofiber mechanics in the three ventricular walls, satisfying the principle of conservation of energy. The walls were mechanically coupled satisfying tensile force equilibrium in the junction. Wall sizes and masses were rendered by adaptation to normalize mechanical myofiber load to physiological standard levels. The TriSeg model was implemented in the previously published lumped closed-loop CircAdapt model of heart and circulation. Simulation results of cardiac mechanics and hemodynamics during normal ventricular loading, acute pulmonary hypertension, and chronic pulmonary hypertension (including load adaptation) agreed with clinical data as obtained in healthy volunteers and pulmonary hypertension patients. In chronic pulmonary hypertension, the model predicted right ventricular free wall hypertrophy, increased systolic pulmonary flow acceleration, and increased right ventricular isovolumic contraction and relaxation times. Furthermore, septal curvature decreased linearly with its transmural pressure difference. In conclusion, the TriSeg model enables realistic simulation of ventricular mechanics including interaction between left and right ventricular pump mechanics, dynamics of septal geometry, and myofiber mechanics in the three ventricular walls.Keywords-Pulmonary hypertension, Septal motion, Adaptation, Stress, Strain, Myofiber, Cardiac mechanics. NOMENCLATURE General LV

The asynchronous ventricular activation during LBBB leads to redistribution of circumferential shortening and myocardial blood flow and, in the long run, LV remodelling. Septal hypoperfusion during LBBB appears to be primarily determined by reduced septal workload.

Background-Asynchronous electrical activation, induced by ventricular pacing, causes regional differences in workload, which is lower in early-than in late-activated regions. Because the myocardium usually adapts its mass and structure to altered workload, we investigated whether ventricular pacing leads to inhomogeneous hypertrophy and whether such adaptation, if any, affects global left ventricular (LV) pump function. Methods and Results-Eight dogs were paced at physiological heart rate for 6 months (AV sequential, AV interval 25 ms, ventricular electrode at the base of the LV free wall). Five dogs were sham operated and served as controls. Ventricular pacing increased QRS duration from 47.2Ϯ10.6 to 113Ϯ16.5 ms acutely and to 133.8Ϯ25.2 ms after 6 months. Two-dimensional echocardiographic measurements showed that LV cavity and wall volume increased significantly by 27Ϯ15% and 15Ϯ17%, respectively. The early-activated LV free wall became significantly (17Ϯ17%) thinner, whereas the late-activated septum thickened significantly (23Ϯ12%). Calculated sector volume did not change in the LV free wall but increased significantly in the septum by 39Ϯ13%. In paced animals, cardiomyocyte diameter was significantly (18Ϯ7%) larger in septum than in LV free wall, whereas myocardial collagen fraction was unchanged in both areas. LV pressure-volume analysis showed that ventricular pacing reduced LV function to a similar extent after 15 minutes and 6 months of pacing. Conclusions-Asynchronous activation induces asymmetrical hypertrophy and LV dilatation. Cardiac pump function is not affected by the adaptational processes. These data indicate that local cardiac load regulates local cardiac mass of both myocytes and collagen. (Circulation. 1998;98:588-595.)

Hearts of 11 anesthetized open-chest dogs were paced from the right atrium (RA), right ventricular outflow tract (RVOT), and left ventricular apex (LVA). Maps of the sequence of electrical activation (192 electrodes), fiber strain (video technique), and blood flow (microsphere technique) in the epicardial layers were obtained from a 15- to 20-cm2 area of the anterior left ventricular wall. Electrical asynchrony in this area was 10 +/- 5 (RA), 52 +/- 12 (RVOT), and 30 +/- 16 ms (LVA, mean +/- SD, P less than 0.05 for RVOT and LVA compared with RA). Epicardial fiber strain during the ejection phase was uniformly distributed during RA pacing. However, during ventricular pacing it ranged from 13 +/- 33% (RVOT) and 23 +/- 29% (LVA) of the value during RA pacing in early-activated regions to 268 +/- 127% (RVOT) and 250 +/- 130% (LVA) of this value in late-activated regions. Epicardial blood flow ranged from 81 +/- 22% (RVOT) and 79 +/- 23% (LVA) in early-activated regions to 142 +/- 42% (RVOT) and 126 +/- 22% (LVA) in late activated regions. In all above values P less than 0.05 compared with RA. During RVOT pacing, gradients of epicardial electrical activation time, fiber strain, and blood flow pointed in the same direction. Compared with RVOT pacing, during LVA pacing all gradients were opposite in direction, and the gradients of electrical activation time and blood flow appeared to be smaller. These results indicate that timing of electrical activation is an important determinant for the distribution of fiber strain and blood flow in the left ventricular wall.