Mechanical properties of the adventitia are largely determined by the organization of collagen fibers. Measurements on the waviness and orientation of collagen, particularly at the zero-stress state, are necessary to relate the structural organization of collagen to the mechanical response of the adventitia. Using the fluorescence collagen marker CNA38-OG488 and confocal laser scanning microscopy, we imaged collagen fibers in the adventitia of rabbit common carotid arteries ex vivo. The arteries were cut open along their longitudinal axes to get the zero-stress state. We used semi-manual and automatic techniques to measure parameters related to the waviness and orientation of fibers. Our results showed that the straightness parameter (defined as the ratio between the distances of endpoints of a fiber to its length) was distributed with a beta distribution (mean value 0.72, variance 0.028) and did not depend on the mean angle orientation of fibers. Local angular density distributions revealed four axially symmetric families of fibers with mean directions of 0 • , 90 • , 43 • and −43 • , with respect to the axial direction of the artery, and corresponding circular standard deviations of 40 • , 47 • , 37 • and 37 • . The distribution of local orientations was shifted to the circumferential direction when measured in arteries at the zero-load state (intact), as compared to arteries at the zero-stress state (cutopen). Information on collagen fiber waviness and orientation, such as obtained in this study, could be used to develop structural models of the adventitia, providing better means for analyzing and understanding the mechanical properties of vascular wall.

The beating heart creates blood pressure and flow pulsations that propagate as waves through the arterial tree that are reflected at transitions in arterial geometry and elasticity. Waves carry information about the matter in which they propagate. Therefore, modeling of arterial wave propagation extends our knowledge about the functioning of the cardiovascular system and provides a means to diagnose disorders and predict the outcome of medical interventions. In this review we focus on the physical and mathematical modeling of pulse wave propagation, based on general fluid dynamical principles. In addition we present potential applications in cardiovascular research and clinical practice. Models of short-and long-term adaptation of the arterial system and methods that deal with uncertainties in personalized model parameters and boundary conditions are briefly discussed, as they are believed to be major topics for further study and will boost the significance of arterial pulse wave modeling even more.

Background-Guide wire-based simultaneous measurement of fractional flow reserve (FFR) and coronary flow reserve (CFR) is important to understand microvascular disease of the heart. The aim of this study was to investigate the feasibility of simultaneous measurement of FFR and CFR by one pressure-temperature sensor-tipped guide wire with the use of coronary thermodilution and to compare CFR by thermodilution (CFR thermo ) with simultaneously measured Doppler CFR (CFR Doppl ). Methods and Results-In 103 coronary arteries in 50 patients, a pressure-temperature sensor-tipped 0.014-inch floppy guide wire and a 0.014-inch Doppler guide wire were introduced. Both normal vessels and a wide range of stenotic vessels were included. With 3 mL of saline at room temperature used as an indicator, by hand-injection, thermodilution curves in the coronary artery were obtained in triplicate, both at baseline and at intravenous adenosine-induced maximum hyperemia. After adequate curve-fitting, CFR thermo was calculated from the ratio of inverse mean transit times and compared with CFR Doppl calculated by velocities at hyperemia and baseline. Adequate sets of thermodilution curves and corresponding CFR thermo could be obtained in 87% of the arteries versus 91% for Doppler CFR and 100% for FFR. CFR thermo correlated fairly well to CFR Doppl (CFR thermo ϭ0.84 CFR Doppl ϩ0.17; rϭ0.80; PϽ0.001), although individual differences of Ͼ20% between both indexes were seen in a quarter of all arteries. Conclusions-This study shows the feasibility of simultaneous measurement of FFR (by coronary pressure) and CFR (by coronary thermodilution) in humans by one single guide wire in a practical and straightforward way and will facilitate assessment of microvascular disease.

A wave propagation model of blood flow in large vessels using an approximate velocity profile functionLumped-parameter models (zero-dimensional) and wave-propagation models (onedimensional) for pressure and flow in large vessels, as well as fully three-dimensional fluid-structure interaction models for pressure and velocity, can contribute valuably to answering physiological and patho-physiological questions that arise in the diagnostics and treatment of cardiovascular diseases. Lumped-parameter models are of importance mainly for the modelling of the complete cardiovascular system but provide little detail on local pressure and flow wave phenomena. Fully threedimensional fluid-structure interaction models consume a large amount of computer time and must be provided with suitable boundary conditions that are often not known. One-dimensional wave-propagation models in the frequency and time domain are well suited to obtaining clinically relevant information on local pressure and flow waves travelling through the arterial system. They can also be used to provide boundary conditions for fully three-dimensional models, provided that they are defined in, or transferred to, the time domain.Most of the one-dimensional wave propagation models in the time domain described in the literature assume velocity profiles and therefore frictional forces to be in phase with the flow, whereas from exact solutions in the frequency domain a phase difference between the flow and the wall shear stress is known to exist. In this study an approximate velocity profile function more suitable for one-dimensional wave propagation is introduced and evaluated. It will be shown that this profile function provides first-order approximations for the wall shear stress and the nonlinear term in the momentum equation, as a function of local flow and pressure gradient in the time domain. The convective term as well as the approximate friction term are compared to their counterparts obtained from Womersley profiles and show good agreement in the complete range of the Womersley parameter α. In the limiting cases, for Womersley parameters α → 0 and α → ∞, they completely coincide. It is shown that in one-dimensional wave propagation, the friction term based on the newly introduced approximate profile function is important when considering pressure and flow wave propagation in intermediate-sized vessels.

Background-Whether minimal microvascular resistance of the myocardium is affected by the presence of an epicardial stenosis is controversial. Recently, an index of microcirculatory resistance (IMR) was developed that is based on combined measurements of distal coronary pressure and thermodilution-derived mean transit time. In normal coronary arteries, IMR correlates well with true microvascular resistance. However, to be applicable in the case of an epicardial stenosis, IMR should account for collateral flow. We investigated the feasibility of determining IMR in humans and tested the hypothesis that microvascular resistance is independent of epicardial stenosis. Methods and Results-Thirty patients scheduled for percutaneous coronary intervention were studied. The stenosis was stented with a pressure guidewire, and coronary wedge pressure (P w ) was measured during balloon occlusion. After successful stenting, a short compliant balloon with a diameter 1.0 mm smaller than the stent was placed in the stented segment and inflated with increasing pressures, creating a 10%, 50%, and 75% area stenosis. At each of the 3 degrees of stenosis, fractional flow reserve (FFR) and IMR were measured at steady-state maximum hyperemia induced by intravenous adenosine. A total of 90 measurements were performed in 30 patients. When uncorrected for P w , an apparent increase in microvascular resistance was observed with increasing stenosis severity (IMRϭ24, 27, and 37 U for the 3 different degrees of stenosis; PϽ0.001). In contrast, when P w is appropriately accounted for, microvascular resistance did not change with stenosis severity (IMRϭ22, 23, and 23 U, respectively; Pϭ0.28). Conclusions-Minimal microvascular resistance does not change with epicardial stenosis severity, and IMR is a specific index of microvascular resistance when collateral flow is properly taken into account.

Abstract-The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity.

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A larger thrombus in AAA was associated with a higher AAA growth rate, but also with a lower wall stress. Therefore, weakening of the AAA wall, under the influence of thrombus, may play a more imminent role in the process of AAA growth than the stress acting on the wall.