Ventilatory effects of high and pulsatile blood flow in the pulmonary circulation

The mechanism of ventilatory stimulation that accompanies increases in cardiac output is unknown. Previous studies addressing this issue have been inconclusive. However, only steady pulmonary blood flow was used. The effect of flow pulsatility merits consideration, because increasing cardiac output raises not only mean pulmonary arterial pressure but also pulse pressure; mechanoreceptors with an important dynamic component to their responses may cause a response to pulsatile, but not steady, flow. Studies were done on anesthetized cats (n = 4) and dogs (n = 4). The right pulmonary artery was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the right pulmonary artery. The right pulmonary circulation was perfused at different levels of flow, which was either steady or pulsatile. Steady-state flow of up to 150 ml.kg-1.min-1 (270 ml.kg-1.min-1 when corrected for the proportion of lung tissue perfused) did not affect breathing pattern. When high pulmonary flow was made pulsatile (pulse pressure approximately 23 mmHg), breath duration decreased from 3.7 +/- 0.72 to 3.4 +/- 0.81 (SD) s (P less than 0.01), representing a change in frequency of only 9%. There was no change in peak inspiratory activity. It was concluded that pulmonary vascular mechanoreceptors are not likely to contribute significantly to the increase in ventilation in association with increases in cardiac output.     

Pulmonary capillaries are recruited during pulsatile flow.

Capillaries recruit when pulmonary arterial pressure rises. The duration of increased pressure imposed in such experiments is usually on the order of minutes, although recent work shows that the recruitment response can occur in <4 s. In the present study, we investigate whether the brief pressure rise during cardiac systole can also cause recruitment and whether the recruitment is maintained during diastole. To study these basic aspects of pulmonary capillary hemodynamics, isolated dog lungs were pump perfused alternately by steady flow and pulsatile flow with the mean arterial and left atrial pressures held constant. Several direct measurements of capillary recruitment were made with videomicroscopy. The total number and total length of perfused capillaries increased significantly during pulsatile flow by 94 and 105%, respectively. Of the newly recruited capillaries, 92% were perfused by red blood cells throughout the pulsatile cycle. These data provide the first direct account of how the pulmonary capillaries respond to pulsatile flow by showing that capillaries are recruited during the systolic pulse and that, once open, the capillaries remain open throughout the pulsatile cycle.     

The effect of asymmetry in abdominal aortic aneurysms under physiologically realistic pulsatile flow conditions

In the abdominal segment of the human aorta under a patient's average resting conditions, pulsatile blood flow exhibits complex laminar patterns with secondary flows induced by adjacent branches and irregular vessel geometries. The flow dynamics becomes more complex when there is a pathological condition that causes changes in the normal structural composition of the vessel wall, for example, in the presence of an aneurysm. This work examines the hemodynamics of pulsatile blood flow in hypothetical three-dimensional models of abdominal aortic aneurysms (AAAs). Numerical predictions of blood flow patterns and hemodynamic stresses in AAAs are performed in single-aneurysm, asymmetric, rigid wall models using the finite element method. We characterize pulsatile flow dynamics in AAAs for average resting conditions by means of identifying regions of disturbed flow and quantifying the disturbance by evaluating flow-induced stresses at the aneurysm wall, specifically wall pressure and wall shear stress. Physiologically realistic abdominal aortic blood flow is simulated under pulsatile conditions for the range of time-average Reynolds numbers 50 < or = Rem < or = 300, corresponding to a range of peak Reynolds numbers 262.5 < or = Repeak < or = 1575. The vortex dynamics induced by pulsatile flow in AAAs is depicted by a sequence of four different flow phases in one period of the cardiac pulse. Peak wall shear stress and peak wall pressure are reported as a function of the time-average Reynolds number and aneurysm asymmetry. The effect of asymmetry in hypothetically shaped AAAs is to increase the maximum wall shear stress at peak flow and to induce the appearance of secondary flows in late diastole.     

Disturbance of macro- and microcirculation: relations with pulse pressure and cardiac organ damage

Whereas large arteries dampen oscillations resulting from intermittent ventricular ejection, small arteries steadily deliver optimal blood flow to various organs as the heart. The transition from pulsatile to steady pressure is influenced by several factors as wave travel, damping, and reflections, which are mainly determined by the impedance mismatch between large vessels and arteriolar bifurcations. The mechanism(s) behind the dampening of pressure wave in the periphery and the links between central and peripheral pulsatile pressure (PP) may determine cardiac damage. Active pathways participate to pulse widening and changes in pulse amplitude in microvessels. Steady and cyclic stresses operate through different transduction mechanisms, the former being focal adhesion kinase and the latter being free radicals and oxidative stress. Independently of mechanics, calcifications and attachment molecules contribute to enhance vessel wall stiffness through changes in collagen cross-links, proteoglycans, integrins, and fibronectin. Enhanced PP transmission may thus occur and precipitate organ damage at each time that autoregulatory mechanisms, normally protecting the heart from vascular injury, are blunted. Such circumstances, observed in old subjects with systolic hypertension and/or Type 2 diabetes mellitus, particularly under high-sodium diet, cause cardiac damage and explain why increased PP and arterial stiffness are significant predictors of morbidity and mortality in the elderly.     

Numerical simulation of cardiovascular dynamics with different types of VAD assistance

A variety of methods by which mechanical circulatory support (MCS) can be provided have been described. However, the haemodynamic benefits of the different methods have not been adequately quantified. The aim of this paper is to compare the haemodynamic effects of six forms of MCS by numerical simulation. Three types of ventricular assist device (VAD) are studied: positive displacement; impeller and a novel reciprocating-valve design. Similarly, three pumping modes are modelled: constant flow; counterpulsation and copulsation. The cardiovascular system is modelled using an approach developed previously, using the concentrated parameter method by considering flow resistance, vessel elasticity and inertial effects of blood in individual conduit segments. The dynamic modelling of displacement and impeller pumps is represented by VAD inlet/outlet flow-rate changes. The dynamics of the reciprocating-valve pump is modelled with a specified displacement profile. Results show that in each simulation, the physiological variables of mean arterial pressure and systemic flow are adequately maintained. Modulation of the impeller pump flow profile produces a small (5 mmHg) oscillatory component to arterial pressure, whereas the displacement and reciprocating-valve pumps generate substantial arterial pressure and flow pulsatility. The impeller pump requires the least power input, the reciprocating valve pump slightly more, and the displacement pump the most. The in parallel configuration of the impeller and displacement pump designs with respect to the left ventricle provides near complete unloading and can cause the aortic valve to remain closed throughout the entire cardiac cycle with the attendant risk of aortic valve leaflet fusion following prolonged support. The in series configuration of the reciprocating-valve pump avoids this shortcoming but activation must be carefully synchronized to the cardiac cycle to allow adequate coronary perfusion. The reciprocating-valve pump is associated with haemodynamic advantages and a favourable power consumption.     

A data-driven model to study utero-ovarian blood flow physiology during pregnancy

In this paper, we describe a mathematical model of the cardiovascular system in human pregnancy. An automated, closed-loop 1D–0D modelling framework was developed, and we demonstrate its efficacy in (1) reproducing measured multi-variate cardiovascular variables (pulse pressure, total peripheral resistance and cardiac output) and (2) providing automated estimates of variables that have not been measured (uterine arterial and venous blood flow, pulse wave velocity, pulsatility index). This is the first model capable of estimating volumetric blood flow to the uterus via the utero-ovarian communicating arteries. It is also the first model capable of capturing wave propagation phenomena in the utero-ovarian circulation, which are important for the accurate estimation of arterial stiffness in contemporary obstetric practice. The model will provide a basis for future studies aiming to elucidate the physiological mechanisms underlying the dynamic properties (changing shapes) of vascular flow waveforms that are observed with advancing gestation. This in turn will facilitate the development of methods for the earlier detection of pathologies that have an influence on vascular structure and behaviour.

     

A 3D unsteady flow analysis in a doubly constricted arterial vessel

The aim of this study is to examine the interaction between two mild atherosclerotic proliferations spaced apart by a distance S by analyzing their influence on flow structure, pressure drop and stress field in an arterial vessel under pulsatile flow conditions. This has been achieved numerically by employing a time accurate, cell centered finite volume method in solving the Navier-Stokes equations governing the 3D unsteady flow dynamics in a conceptual model of an multiply constricted arterial vessel. In comparison to the pressure drop across a single stenosis, nearly a 50% increase in the late systolic and early diastolic pressure drops has been observed across the two mild constrictions when they are spaced within a distance of S相似文献   

Pulsatile blood flow in the entire coronary arterial tree: theory and experiment

The pulsatility of coronary circulation can be accurately simulated on the basis of the measured branching pattern, vascular geometry, and material properties of the coronary vasculature. A Womersley-type mathematical model is developed to analyze pulsatile blood flow in diastole in the absence of vessel tone in the entire coronary arterial tree on the basis of previously measured morphometric data. The model incorporates a constitutive equation of pressure and cross-section area relation based on our previous experimental data. The formulation enables the prediction of the impedance, the pressure distribution, and the pulsatile flow distribution throughout the entire coronary arterial tree. The model is validated by experimental measurements in six diastolic arrested, vasodilated porcine hearts. The agreement between theory and experiment is excellent. Furthermore, the present pulse wave results at low frequency agree very well with previously published steady-state model. Finally, the phase angle of flow is seen to decrease along the trunk of the major coronary artery and primary branches toward the capillary vessels. This study represents the first, most extensive validated analysis of Womersley-type pulse wave transmission in the entire coronary arterial tree down to the first segment of capillaries. The present model will serve to quantitatively test various hypotheses in the coronary circulation under pulsatile flow conditions.     

Harmonic analysis of perfusion pumps

The controversy over the use of nonpulsatile versus pulsatile pumps for maintenance of normal organ function during ex vivo perfusion has continued for many years, but resolution has been limited by lack of a congruent mathematical definition of pulsatility. We hypothesized that the waveform frequency and amplitude, as well as the underlying mean distending pressure are all key parameters controlling vascular function. Using discrete Fourier Analysis, our data demonstrate the complexity of the pulmonary arterial pressure waveform in vivo and the failure of commonly available perfusion pumps to mimic in vivo dynamics. In addition, our data show that the key harmonic signatures are intrinsic to the perfusion pumps, are similar for flow and pressure waveforms, and are unchanged by characteristics of the downstream perfusion circuit or perfusate viscosity.     

Cells in fluidic environments are sensitive to flow frequency

Virtually all cells accommodate to their mechanical environment. In particular, cells subject to flow respond to rapid changes in fluid shear stress (SS), cyclic stretch (CS), and pressure. Recent studies have focused on the effect of pulsatility on cellular behavior. Since cells of many different tissue beds are constantly exposed to fluid flows over a narrow range of frequencies, we hypothesized that an intrinsic flow frequency that is optimal for determining cell phenotype exists. We report here that cells from various tissue beds (bovine aortic endothelial cells (BAEC), rat small intestine epithelial cells (RSIEC), and rat lung epithelial cells (RLEC)) proliferate maximally when cultured in a perfusion bioreactor under pulsatile conditions at a specific frequency, independent of the applied SS. Vascular endothelial and pulmonary epithelial cell proliferation peaked under 1 Hz pulsatile flow. In contrast, proliferation of gastrointestinal cells, which in their physiological context are subject to no flow or higher wavelength signal, was maximum at 0.125 Hz or under no flow. Moreover, exposure of BAEC to pulsatile flow of varying frequency influenced their nitric oxide synthase activity and prostacyclin production, which reached maximum values at 1 Hz. Notably, the "optimal" frequencies for the cell types examined correspond to the physiologic operating range of the organs from where they were initially derived. These findings suggest that frequency, independent of shear, is an essential determinant of cell response in pulsatile environments.     

Hypoxic pulmonary vasoconstriction during steady and pulsatile flow in ferrets

We examined the effects of hypoxia and pulsatile flow on the pressure-flow relationships in the isolated perfused lungs of Fitch ferrets. When perfused by autologous blood from a pump providing a steady flow of 60 ml/min, the mean pulmonary arterial pressure rose from 14.6 to 31.3 Torr when alveolar PO2 was reduced from 122 to 46 Torr. This hypoxic pressor response was characterized by a 10.1-Torr increase in the pressure-axis intercept of the extrapolated pressure-flow curves and an increase in the slope of these curves from 130 to 240 Torr X l-1 X min. With pulsatile perfusion from a piston-type pump, mean pulmonary arterial pressure increased from 17.5 to 36.3 Torr at the same mean flow. This hypoxic pressor response was also characterized by increases in the intercept pressure and slope of the pressure-flow curves. When airway pressure was raised during hypoxia, the intercept pressure increased further to 25 +/- 1 Torr with a further increase in vascular resistance to 360 Torr X l-1 X min. Thus, in contrast to the dog lung, in the ferret lung pulsatile perfusion does not result in lower perfusion pressures during hypoxia when compared with similar mean levels of steady flow. Since the effects of high airway pressure and hypoxia are additive, they appear to act at or near the same site in elevating perfusion pressure.     

Numerical simulation of pulsatile flow in a compliant curved tube model of a coronary artery

The endothelial cells (ECs) lining a blood vessel wall are exposed to both the wall shear stress (WSS) of blood flow and the circumferential strain (CS) of pulsing artery wall motion. These two forces and their interaction are believed to play a role in determining remodeling of the vessel wall and development of arterial disease (atherosclerosis). This study focused on the WSS and CS dynamic behavior in a compliant model of a coronary artery taking into account the curvature of the bending artery and physiological radial wall motion. A three-dimensional finite element model with transient flow and moving boundaries was set up to simulate pulsatile flow with physiological pressure and flow wave forms characteristic of the coronary arteries. The characteristic coronary artery curvature and flow conditions applied to the simulation were: aspect ratio (lambda) = 10, diameter variation (DV) = 6 percent, mean Reynolds number (Re) = 150, and unsteadiness parameter (alpha) = 3. The results show that mean WSS is about 50 percent lower on the inside wall than the outside wall while WSS oscillation is stronger on the inside wall. The stress phase angle (SPA) between CS and WSS, which characterizes the dynamics of the mechanical force pattern applied to the endothelial cell layer, shows that CS and WSS are more out of phase in the coronaries than in any other region of the circulation (-220 deg on the outside wall, -250 deg on the inside wall). This suggests that in addition to WSS, SPA may play a role in localization of coronary atherosclerosis.     

Blood flow in abdominal aortic aneurysms: pulsatile flow hemodynamics

Numerical predictions of blood flow patterns and hemodynamic stresses in Abdominal Aortic Aneurysms (AAAs) are performed in a two-aneurysm, axisymmetric, rigid wall model using the spectral element method. Physiologically realistic aortic blood flow is simulated under pulsatile conditions for the range of time-averaged Reynolds numbers 50< or =Re(m)< or =300, corresponding to a range of peak Reynolds numbers 262.5< or =Re(peak) < or = 1575. The vortex dynamics induced by pulsatile flow in AAAs is characterized by a sequence of five different flow phases in one period of the flow cycle. Hemodynamic disturbance is evaluated for a modified set of indicator functions, which include wall pressure (p(w)), wall shear stress (tau(w)), and Wall Shear Stress Gradient (WSSG). At peak flow, the highest shear stress and WSSG levels are obtained downstream of both aneurysms, in a pattern similar to that of steady flow. Maximum values of wall shear stresses and wall shear stress gradients obtained at peak flow are evaluated as a function of the time-average Reynolds number resulting in a fourth order polynomial correlation. A comparison between predictions for steady and pulsatile flow is presented, illustrating the importance of considering time-dependent flow for the evaluation of hemodynamic indicators.     

Regulation of vascular smooth muscle cells and mesenchymal stem cells by mechanical strain

Vascular smooth muscle cells (SMCs) populate in the media of the blood vessel, and play an important role in the control of vasoactivity and the remodeling of the vessel wall. Blood vessels are constantly subjected to hemodynamic stresses, and the pulsatile nature of the blood flow results in a cyclic mechanical strain in the vessel walls. Accumulating evidence in the past two decades indicates that mechanical strain regulates vascular SMC phenotype, function and matrix remodeling. Bone marrow mesenchymal stem cell (MSC) is a potential cell source for vascular regeneration therapy, and may be used to generate SMCs to construct tissue-engineered vascular grafts for blood vessel replacements. In this review, we will focus on the effects of mechanical strain on SMCs and MSCs, e.g., cell phenotype, cell morphology, cytoskeleton organization, gene expression, signal transduction and receptor activation. We will compare the responses of SMCs and MSCs to equiaxial strain, uniaxial strain and mechanical strain in three-dimensional culture. Understanding the hemodynamic regulation of SMC and MSC functions will provide a basis for the development of new vascular therapies and for the construction of tissue-engineered vascular grafts.     

Blood flow multiscale phenomena

The cardiovascular disease is one of most frequent cause deaths in modern society. The objective of this work is analyse the effect of dynamic vascular geometry (curvature, torsion, bifurcation) and pulsatile blood nature on secondary flow, wall shear stress and platelet deposition. The problem was examined as multi-scale physical phenomena using perturbation analysis and numerical modelling. The secondary flow determined as influence pulsatile pressure, vascular tube time-dependent bending and torsion on the main axial flow. Bifurcation and branching phenomena are analysed experimentally through, blood-like fluid pulsatile flow across elastic rubber-like Y-model model. The problem complex geometry near branching in platelet deposit modelling is resolved numerically as Falker-Skan flow.     

Computational simulations of hemodynamic changes within thoracic, coronary, and cerebral arteries following early wall remodeling in response to distal aortic coarctation

Mounting evidence suggests that the pulsatile character of blood pressure and flow within large arteries plays a particularly important role as a mechano-biological stimulus for wall growth and remodeling. Nevertheless, understanding better the highly coupled interactions between evolving wall geometry, structure, and properties and the hemodynamics will require significantly more experimental data. Computational fluid–solid-growth models promise to aid in the design and interpretation of such experiments and to identify candidate mechanobiological mechanisms for the observed arterial adaptations. Motivated by recent aortic coarctation models in animals, we used a computational fluid–solid interaction model to study possible local and systemic effects on the hemodynamics within the thoracic aorta and coronary, carotid, and cerebral arteries due to a distal aortic coarctation and subsequent spatial variations in wall adaptation. In particular, we studied an initial stage of acute cardiac compensation (i.e., maintenance of cardiac output) followed by early arterial wall remodeling (i.e., spatially varying wall thickening and stiffening). Results suggested, for example, that while coarctation increased both the mean and pulse pressure in the proximal vessels, the locations nearest to the coarctation experienced the greatest changes in pulse pressure. In addition, after introducing a spatially varying wall adaptation, pressure, left ventricular work, and wave speed all increased. Finally, vessel wall strain similarly experienced spatial variations consistent with the degree of vascular wall adaptation.     

Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells

The pulsatile nature of blood pressure and flow creates hemodynamic stimuli in the forms of cyclic stretch and shear stress, which exert continuous influences on the constituents of the blood vessel wall. Vascular smooth muscle cells (VSMCs) use multiple sensing mechanisms to detect the mechanical stimulus resulting from pulsatile stretch and transduce it into intracellular signals that lead to modulations of gene expression and cellular functions, e.g., proliferation, apoptosis, migration, and remodeling. The cytoskeleton provides a structural framework for the VSMC to transmit mechanical forces between its luminal, abluminal, and junctional surfaces, as well as its interior, including the focal adhesion sites, the cytoplasm, and the nucleus. VSMCs also respond differently to the surrounding structural environment, e.g., two-dimensional versus three-dimensional matrix. In vitro studies have been conducted on cultured VSMCs on deformable substrates to elucidate the molecular mechanisms by which the cells convert mechanical inputs into biochemical events, eventually leading to functional responses. The knowledge gained from research on mechanotransduction in vitro, in conjunction with verifications under in vivo conditions, will advance our understanding of the physiological and pathological processes involved in vascular remodeling and adaptation in health and disease.     

Computation in the rabbit aorta of a new metric – the transverse wall shear stress – to quantify the multidirectional character of disturbed blood flow

Spatial variation of the haemodynamic stresses acting on the arterial wall is commonly assumed to explain the focal development of atherosclerosis. Disturbed flow in particular is thought to play a key role. However, widely-used metrics developed to quantify its extent are unable to distinguish between uniaxial and multidirectional flows. We analysed pulsatile flow fields obtained in idealised and anatomically-realistic arterial geometries using computational fluid dynamics techniques, and in particular investigated the multidirectionality of the flow fields, capturing this aspect of near-wall blood flow with a new metric – the transverse wall shear stress (transWSS) – calculated as the time-average of wall shear stress components perpendicular to the mean flow direction. In the idealised branching geometry, multidirectional flow was observed downstream of the branch ostium, a region of flow stagnation, and to the sides of the ostium. The distribution of the transWSS was different from the pattern of traditional haemodynamic metrics and more dependent on the velocity waveform imposed at the branch outlet. In rabbit aortas, transWSS patterns were again different from patterns of traditional metrics. The near-branch pattern varied between intercostal ostia, as is the case for lesion distribution; for some branches there were striking resemblances to the age-dependent patterns of disease seen in rabbit and human aortas. The new metric may lead to improved understanding of atherogenesis.     

The initiation of blood flow and flow induced events in early vascular development

Within a day of gastrulation, the embryonic heart begins to beat and creates blood flow in the developing cardiovascular system. The onset of blood flow completely changes the environment in which the cardiovascular system is forming. Flow provides physiological feedback such that the developing network adapts to cue provided by the flow. Targeted inactivation of genes that alter early blood fluid dynamics induce secondary defects in the heart and vasculature and therefore proper blood flow is known to be essential for vascular development. Though hemodynamics, or blood fluid dynamics, are known to activate signaling pathways in the mature cardiovascular system in pathologies ranging from artherosclerosis to angiogenesis, the role in development has not been as intensively studied. The question arises how blood vessels in the embryos, which initially lack cells types such as smooth muscle cells, differ in their response to mechanical signals from blood flow as compared to the more mature cardiovascular system. Many genes known to be regulated by hemodynamics in the adult are important for developmental angiogenesis. Therefore the onset of blood flow is of primary importance to vascular development. This review will focus on how blood flow initiates and the effects of the mechanical signals created by blood flow on cardiovascular development.     

Pulsatile flow of Casson's fluid through stenosed arteries with applications to blood flow

The effects of non-Newtonian nature of blood and pulsatility on flow through a stenosed tube have been investigated. A perturbation method is used to analyse the flow. It is of interest to note that the thickness of the viscous flow region is non-uniform (changing with axial distance). An analytic relation between viscous flow region thickness and red cell concentration has been obtained. It is important to mention that some researchers have obtained an approximate solution for the flow rate-pressure gradient equation (assuming the ratio between the yield stress and the wall shear to be very small in comparison to unity); in the present analysis, we have obtained an exact solution for this non-linear equation without making that assumption. The approximate and exact solutions compare well with one of the exact solutions. Another important result is that the mean and steady flow rates decrease as the yield stress theta increases. For the low values of the yield stress, the mean flow rate is higher than the steady flow rate, but for high values of the yield stress, the mean flow rate behaviour is of opposite nature. The critical value of the yield stress at which the flow rate behaviour changes from one type to another has been determined. Further, it seems that there exists a value of the yield stress at which flow stops for both the flows (steady and pulsatile). It is observed that the flow stop yield value for pulsatile flow is lower than the steady flow. The most notable result of pulsatility is the phase lag between the pressure gradient and flow rate, which is further influenced by the yield stress and stenosis. Another important result of pulsatility is the mean resistance to flow is greater than its steady flow value, whereas the mean value of the wall shear for pulsatile flow is equal to steady wall shear. Many standard results regarding Casson and Newtonian fluids flow, uniform tube flow and steady flow can be obtained as the special cases of the present analysis. Finally, some applications of this theoretical analysis have been cited.