On the detection of messages carried in arterial pulse waves

The hypothesis is made that a disturbance in blood flow at one place can be detected in the arterial pulse waves at a distant site. This hypothesis was motivated by the traditional Chinese medicine which uses arterial pulse waves as a principal means of diagnosis. We formulated a test by asking whether a disturbance to the blood flow in a leg can be detected by changes in the pulse waves in the radial arteries. In particular, we ask whether the radial artery can differentiate a disturbance in the right leg from that in the left leg. We put force transducers on the radial arteries, depressed them by a specific amount, and recorded the force waves in response to a 2-min occlusion of the blood flow in the right or left tibial artery. The results show that the radial artery force waves do change in response to the flow disturbance. For a given individual, the force varies with the location of the force transducer on the radial artery, the specific amount of initial depression, and the right or left leg occlusion. Generally, an occlusion in the right leg reduces the force level in both radial arteries, the more so in the right radial artery than in the left. Although the discrimination is not very strong, the phenomenon is novel, and warrants further investigation.     

Radial artery wall shear stress evaluation in patients with arteriovenous fistula for hemodialysis access

It has been extensively documented that changes in blood flow induce vascular remodeling and this phenomenon seems to be correlated to the shear forces imposed on the vessel wall by motion of blood. Wall shear stress, the tractive force that acts on the endothelium, has been shown to influence endothelial cell function. To study changes in wall shear stress that develop on the vessel wall upon changes of blood flow, we set up a technique that allows estimation of shear stress in the radial artery of patients on chronic hemodialysis therapy. The technique is based on color-flow Doppler examination of the radial artery before and after surgical creation of radiocephalic fistula for hemodialysis. Calculation of time function wall shear stress and blood flow rate in the radial artery is performed on the basis of arterial diameter, center-line velocity waveform and blood viscosity, using a numerical method developed according to Womersley's theory for pulsatile flow in tubes. The results presented confirm that the model developed is suitable for calculation of the wall shear stress that develops in the radial artery of patients before and after surgical creation of an arteriovenous fistula for hemodialysis. This methodology was developed for characterization of wall shear stress in the radial artery but may be well applied to other vessels that can be examined by echo-Doppler technique.     

Can the modified Allen's test always detect sufficient collateral flow in the hand? A computational study

Blood flow in the largest arteries of the arm up to the digital arteries is numerically modelled using the one-dimensional equations of pressure and flow wave propagation in compliant vessels. The model can be applied to different anatomies of arterial networks and can simulate compression of arteries, these allowing us to simulate the modified Allen's test (MAT) and to assess its suitability for the detection of sufficient collateral flow in the hand if radial blood supply is interrupted. The test measures blood flow in the superficial palmar arch before and during compression of the radial artery. The absence of reversal flow in the palmar arch with the compression indicates insufficient collateral flow and is referred to as a positive MAT. This study shows that small calibres of the superficial palmar arch and insufficient compression of the radial artery can lead to false-positive results. Measurement of the drop in digital systolic pressures with compression of the radial artery has proved to be a more sensitive test to predict the presence of sufficient ulnar collateral flow in networks with small calibres of the superficial palmar arch. However, this study also shows that digital pressure measurements can fail in detecting enough collateral flow if the radial artery is insufficiently compressed.     

Can the modified Allen's test always detect sufficient collateral flow in the hand? A computational study

Blood flow in the largest arteries of the arm up to the digital arteries is numerically modelled using the one-dimensional equations of pressure and flow wave propagation in compliant vessels. The model can be applied to different anatomies of arterial networks and can simulate compression of arteries, these allowing us to simulate the modified Allen's test (MAT) and to assess its suitability for the detection of sufficient collateral flow in the hand if radial blood supply is interrupted. The test measures blood flow in the superficial palmar arch before and during compression of the radial artery. The absence of reversal flow in the palmar arch with the compression indicates insufficient collateral flow and is referred to as a positive MAT. This study shows that small calibres of the superficial palmar arch and insufficient compression of the radial artery can lead to false-positive results. Measurement of the drop in digital systolic pressures with compression of the radial artery has proved to be a more sensitive test to predict the presence of sufficient ulnar collateral flow in networks with small calibres of the superficial palmar arch. However, this study also shows that digital pressure measurements can fail in detecting enough collateral flow if the radial artery is insufficiently compressed.     

Doppler continuous-wave analysis of grafted mammary artery as a non-invasive technique for static and dynamic assessment of coronary flow in man

In this paper, Doppler continuous-wave analysis of blood velocity in the internal mammary artery, anastomosed to the left coronary vascular bed in humans who have undergone myocardial revascularization, is proposed as a non-invasive technique to study coronary blood flow during physiological procedures which cause it to change. Blood velocity curves obtained in normal and anastomosed internal mammary arteries were compared during hyperventilation and the Valsalva manoeuvre. During hyperventilation, blood velocity increased in the normal mammary but not in the anastomosed artery. During the expiratory effort of the Valsalva manoeuvre, the mean blood velocity decreased in the normal mammary artery but it did not change significantly in the anastomosed artery. Variations in the mean velocity were largely prevented by simultaneous and well-balanced increases and decreases in the diastolic and systolic velocities, respectively.     

Coronary artery flow measurement using navigator echo gated phase contrast magnetic resonance velocity mapping at 3.0 T

A validation study and early results for non-invasive, in vivo measurement of coronary artery blood flow using phase contrast magnetic resonance imaging (PC-MRI) at 3.0T is presented. Accuracy of coronary artery blood flow measurements by phase contrast MRI is limited by heart and respiratory motion as well as the small size of the coronary arteries. In this study, a navigator echo gated, cine phase velocity mapping technique is described to obtain time-resolved velocity and flow waveforms of small diameter vessels at 3.0T. Phantom experiments using steady, laminar flow are presented to validate the technique and show flow rates measured by 3.0T phase contrast MRI to be accurate within 15% of true flow rates. Subsequently, in vivo scans on healthy volunteers yield velocity measurements for blood flow in the right, left anterior descending, and left circumflex arteries. Measurements of average, cross-sectional velocity were obtainable in 224/243 (92%) of the cardiac phases. Time-averaged, cross-sectional velocity of the blood flow was 6.8+/-4.3cm/s in the LAD, 8.0+/-3.8cm/s in the LCX, and 6.0+/-1.6cm/s in the RCA.     

Peripheral vascular decoupling in porcine endotoxic shock

Cardiac output measurement from arterial pressure waveforms presumes a defined relationship between the arterial pulse pressure (PP), vascular compliance (C), and resistance (R). Cardiac output estimates degrade if these assumptions are incorrect. We hypothesized that sepsis would differentially alter central and peripheral vasomotor tone, decoupling the usual pressure wave propagation from central to peripheral sites. We assessed arterial input impedance (Z), C, and R from central and peripheral arterial pressures, and aortic blood flow in an anesthetized porcine model (n = 19) of fluid resuscitated endotoxic shock induced by endotoxin infusion (7 μg·kg?1·h?1 increased to 14 and 20 μg·kg?1·h?1 every 10 min and stopped when mean arterial pressure <40 mmHg or Sv(O?) < 45%). Aortic, femoral, and radial artery pressures and aortic and radial artery flows were measured. Z was calculated by FFT of flow and pressure data. R and C were derived using a two-element Windkessel model. Arterial PP increased from aortic to femoral and radial sites. During stable endotoxemia with fluid resuscitation, aortic and radial blood flows returned to or exceeded baseline while mean arterial pressure remained similarly decreased at all three sites. However, aortic PP exceeded both femoral and radial arterial PP. Although Z, R, and C derived from aortic and radial pressure and aortic flow were similar during baseline, Z increases and C decreases when derived from aortic pressure whereas Z decreases and C increases when derived from radial pressure, while R decreased similarly with both pressure signals. This central-to-peripheral vascular tone decoupling, as quantified by the difference in calculated Z and C from aortic and radial artery pressure, may explain the decreasing precision of peripheral arterial pressure profile algorithms in assessing cardiac output in septic shock patients and suggests that different algorithms taking this vascular decoupling into account may be necessary to improve their precision in this patient population.     

Venous occlusion plethysmography reduces arterial diameter and flow velocity

The measurement of peripheral blood flow by plethysmography assumes that the cuff pressure required for venous occlusion does not decrease arterial inflow. However, studies in five normal subjects suggested that calf blood flow measured with a plethysmograph was less than arterial inflow calculated from Doppler velocity measurements. We hypothesized that the pressure required for venous occlusion may have decreased arterial velocity. Further studies revealed that systolic diameter of the superficial femoral artery under a thigh cuff decreased from 7.7 +/- 0.4 to 5.6 +/- 0.7 mm (P less than 0.05) when the inflation pressure was increased from 0 to 40 mmHg. Cuff inflation to 40 mmHg also reduced mean velocity 38% in the common femoral artery and 47% in the popliteal artery. Inflation of a cuff on the arm reduced mean velocity in the radial artery 22% at 20 mmHg, 26% at 40 mmHg, and 33% at 60 mmHg. We conclude that inflation of a cuff on an extremity to low pressures for venous occlusion also caused a reduction in arterial diameter and flow velocity.     

Computational model for simulation of vascular adaptation following vascular access surgery in haemodialysis patients

An important number of surgical procedures for creation of vascular access (VA) in haemodialysis patients still results in non-adequate increase in blood flow (non-maturation). The rise in blood flow in arteriovenous shunts depends on vascular remodelling. Computational tools to predict the outcome of VA surgery would be important in this clinical context. The aim of our investigation was then to develop a 0D/1D computational model of arm vasculature able to simulate vessel wall remodelling and related changes in blood flow. We assumed that blood vessel remodelling is driven by peak wall shear stress. The model was calibrated with previously reported values of radial artery diameter and blood flow after end-to-end distal fistula creation. Good agreement was obtained between predicted changes in VA flow and in arterial diameter after surgery and corresponding measured values. The use of this computational model may allow accurate vascular surgery planning and ameliorate VA surgery outcomes.     

Towards early diagnosis of atherosclerosis: the finite volume method for fluid-structure interaction

Blood flow through arteries represents a very complex, fluid-structure interaction (FSI) problem. Strong coupling between the blood and artery is due to the relatively low stiffness of the artery compared to that of blood. Hence, the pressure exerted by the flowing blood on the artery wall can result in considerable deformations of the artery, and vice-versa, arterial deformations can in turn affect the blood flow. In the present work, the finite volume method is employed to solve the problem where compressible fluid, representing blood, flows in healthy arteries as well as in unhealthy, i.e., partly stiffened arteries. The stiffening of the arterial wall is assumed to be the first key stage in the development of atherosclerosis. The comparison between various deformation profiles of healthy and unhealthy arteries demonstrates significant and measurable differences, in particular in the radial direction. This is hoped to help toward establishing procedures for early diagnosis of the disease.     

Heart rate,arterial distensibility,and optimal performance of the arterial tree

In this study we explore the ability of a previously developed model of pulsatile flow for explaining the observed reduction of arterial distensibility with heart rate. The parameters relevant for the analysis are arterial wall distensibility together with permeability and reflection coefficients of the end capillaries. A non-specific artery and the ensemble of tissues supplied by that artery were considered in the model. The blood current within that artery was equalized to the sum of all micro currents in the tissues supplied by that artery. A formula emerged that relates changes in arterial distensibility with heart rate, and also with some particular aspects of microcirculation. Then, that formula was tested with data of distensibilities of the radial and carotid arteries observed at the heart rates of 63, 90, and 110 b.p.m. The formula correctly predicted the trend of decreased distensibility with heart rate for both arteries. Moreover, due to the fact that the carotid artery supplies the brain, and because the Blood–Brain barrier is highly restrictive to colloids in the blood, for the carotid artery the formula predicted a less marked decrease in distensibility than in the case of the radial artery feeding muscle tissue, which has a greater permeability to colloids, a trend that was confirmed by data. It was found that reduction of arterial distensibility with heart rate was greater in arteries that supply end capillaries with high permeability and low reflection coefficients.     

Characterization of arterial wall mechanical behavior and stresses from human clinical data

This paper demonstrates the feasibility of material identification and wall stress computation for human common carotid arteries based on non-invasive in vivo clinical data: dynamical intraluminal pressure measured by applanation tonometry, and medial diameter and intimal-medial thickness measured by high-resolution ultrasound echotracking. The mechanical behavior was quantified assuming an axially pre-stretched, thick-walled, cylindrical artery subjected to dynamical blood pressure and perivascular constraints. The wall was further assumed to be three-dimensional and to consist of a nonlinear, hyperelastic, anisotropic, incompressible material with smooth muscle activity and residual stresses. Mechanical contributions by individual constituents-an elastin-dominated matrix, collagen fibers, and vascular smooth muscle-were accounted for using a previously proposed microstructurally motivated constitutive relation. The in vivo boundary value problem was solved semi-analytically to compute the inner pressure during a mean cardiac cycle. Using a nonlinear least-squares method, optimal model parameters were determined by minimizing differences between computed and measured inner pressures over a mean cardiac cycle. The fit-to-data from two healthy patients was very good and the predicted radial, circumferential, and axial stretch and stress fields were sensible. Hence, the proposed approach was able to identify complex geometric and material parameters directly from non-invasive in vivo human data.     

Mild Sensory Stimulation Completely Protects the Adult Rodent Cortex from Ischemic Stroke

Despite progress in reducing ischemic stroke damage, complete protection remains elusive. Here we demonstrate that, after permanent occlusion of a major cortical artery (middle cerebral artery; MCA), single whisker stimulation can induce complete protection of the adult rat cortex, but only if administered within a critical time window. Animals that receive early treatment are histologically and behaviorally equivalent to healthy controls and have normal neuronal function. Protection of the cortex clearly requires reperfusion to the ischemic area despite permanent occlusion. Using blood flow imaging and other techniques we found evidence of reversed blood flow into MCA branches from an alternate arterial source via collateral vessels (inter-arterial connections), a potential mechanism for reperfusion. These findings suggest that the cortex is capable of extensive blood flow reorganization and more importantly that mild sensory stimulation can provide complete protection from impending stroke given early intervention. Such non-invasive, non-pharmacological intervention has clear translational potential.     

High-Resolution Harmonics Ultrasound Imaging for Non-Invasive Characterization of Wound Healing in a Pre-Clinical Swine Model

This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on the dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle imaging and dual mode (B and Doppler) ultrasound imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 and decreased thereafter. Initially, blood flow at the wound edge increased up to day 14 and subsequently regressed to baseline levels by day 21, when the wound was more than 90% closed. Coinciding with regression of blood flow at the wound edge, there was an increase in blood flow in the wound bed. This was observed to regress by day 42. Such changes in wound angiogenesis were corroborated histologically. Gated Doppler imaging quantitated the pulse pressure of the primary feeder artery supplying the wound site. This pulse pressure markedly increased with a bimodal pattern following wounding connecting it to the induction of wound angiogenesis. Finally, ultrasound elastography measured tissue stiffness and visualized growth of new tissue over time. These studies have elegantly captured the physiological sequence of events during the process of wound healing, much of which is anticipated based on certain dynamics in play, to provide the framework for future studies on molecular mechanisms driving these processes. We conclude that the tandem use of non-invasive imaging technologies has the power to provide unprecedented insight into the dynamics of the healing skin tissue.     

Prostanoids and hemodynamics in man before and during cardiopulmonary bypass

The plasma concentration of 6-keto-PGF1 alpha, the stable degradation product of prostacyclin, was similar in the radial and pulmonary arteries and in the coronary sinus before and after the induction of the anesthesia in patients undergoing coronary artery bypass surgery. After the beginning of the mechanical ventilation and anesthesia the pulmonary vascular resistance decreased although no changes were detected in the plasma levels of 6-keto-PGF1 alpha or TXB2. During the prebypass period after the sternotomy and cannulation of the large vessels the plasma level of 6-keto-PGF1 alpha was increased similarly in the radial and pulmonary arteries and even more in the coronary sinus. During the cardiopulmonary bypass the concentration of 6-keto-PGF1 alpha remained at the increased level as compared to the values before the anesthesia. This indicates that pulmonary circulation is perhaps not the main source of prostacyclin in man. The plasma level of TXB2 was increased during the prebypass period significantly only in the coronary sinus, but during the bypass also in the radial artery. The concentration ratio of 6-keto-PGF1 alpha/TXB2 was increased significantly during the prebypass period in the radial and pulmonary arteries. At the same time the pulmonary vascular resistance was, however, returned to the preanesthesia level and was thus not decreased. The vascular resistance in the systemic circulation was increased during the prebypass period. The plasma level of 6-keto-PGF1 alpha or TXB2 in the radial and pulmonary arteries did not correlate significantly with the total vascular resistance in the systemic and pulmonary circulation, respectively. The vascular resistance in the coronary circulation did not correlate significantly with TXB2 level in the radial artery or coronary sinus. There was, however, a slight positive correlation between the blood flow and the concentration of TXB2 in the coronary sinus (r = 0.76, P less than 0.01). Coronary sinus flow did, however, not correlate with the plasma level of 6-keto-PGF1 alpha in the radial artery or coronary sinus. These results indicate that the detected plasma concentrations of prostacyclin and thromboxane A2 have no significant effects on the total vascular resistance in vivo.     

Cuffing‐based photoacoustic flowmetry in humans in the optical diffusive regime

Measuring blood flow speed in the optical diffusive regime in humans has been a long standing challenge for photoacoustic tomography. In this work, we proposed a cuffing‐based method to quantify blood flow speed in humans with a handheld photoacoustic probe. By cuffing and releasing the blood vessel, we can measure the blood flow speed downstream. In phantom experiments, we demonstrated that the minimum and maximum measurable flow speeds were 0.035 mm/s and 42 mm/s, respectively. In human experiments, flow speeds were measured in three different blood vessels: a radial artery in the right forearm, a radial artery in the index finger of the right hand, and a radial vein in the right forearm. Taking advantage of the handheld probe, our method can potentially be used to monitor blood flow speed in the clinic and at the bedside.

     

Intraoperative in situ radial artery conduit flow assessment

A technique is described for simple flow assessment of the in situ radial artery conduit during coronary bypass via a small incision. This technique allows morphologic and physiologic direct intraoperative assessment of radial artery quality and expands the use of radial artery during coronary artery surgery.     

Systemic blood flow to sheep lung: comparison of flow probes and microspheres.

Discrepancies exist between experimental measurements of the systemic blood flow to sheep lung by use of microsphere techniques and flow probes on the bronchial artery. In these studies, we simultaneously measured the blood flow through the bronchial artery, using a transit time flow probe, and the systemic blood flow to left lung, using radioactive microspheres. All measurements were made on conscious sheep previously prepared with chronic catheterizations of the left atrium, aorta, and vena cava and a flow probe around the bronchial artery. Inflatable occluder cuffs were placed around the pulmonary and bronchoesophageal arteries. Bronchial artery blood flow in six sheep was 25.3 +/- 5.2 ml/min or 0.4% of the cardiac output. Systemic blood flow to left lung, measured with microspheres, was 54.1 +/- 14.2 ml/min. Calculated systemic blood flow to that portion of sheep lung perfused by the bronchial artery was 127.6 +/- 35.3 ml/min or 1.9% of cardiac output. Occlusion of the bronchoesophageal artery reduced bronchial artery flow to near zero, whereas total systemic blood to the lung was reduced by only 55%. Blood flow to the intraparenchymal cartilaginous airways was reduced 60-90% after occlusion of the bronchoesophageal artery. Sheep, like most mammals, have multiple and complex systemic arterial inputs to the lungs. We conclude that multiple branches of the bronchoesophageal artery provide most but not all of the systemic blood flow to the intraparenchymal cartilaginous airways but that over one-half of the total systemic blood flow to sheep lung comes from sources other than the common bronchial artery.     

Evidence for a basal release of a cytochrome-related endothelium-derived hyperpolarizing factor in the radial artery in humans

Whether a cytochrome P-450 (CYP)-related endothelium-derived hyperpolarizing factor (EDHF), acting through calcium-activated potassium (K(Ca)) channels, interacts with nitric oxide (NO) to regulate the basal diameter of human peripheral conduit arteries is unexplored in vivo. Radial artery diameter (echo tracking) and blood flow (Doppler) were measured, after oral aspirin (500 mg), in eight healthy volunteers during local infusion for 8 min of tetraethylammonium chloride (TEA; 9 micromol/min), as K(Ca) channel inhibitor, and fluconazole (0.4 micromol/min), as CYP inhibitor, alone and in combination with N(G)-monomethyl-L-arginine (L-NMMA; 8 micromol/min), as endothelial NO synthase inhibitor. Endothelium-independent dilatation was assessed by using sodium nitroprusside (SNP). Radial diameter was unaffected by L-NMMA (0.4 +/- 0.9%) and fluconazole (-1.6 +/- 0.8%) but was decreased by TEA (-5.0 +/- 1.0%), L-NMMA + fluconazole (-5.3 +/- 0.5%), and L-NMMA + TEA (-9.9 +/- 1.3%). These effects are still significant even when the concomitant decreases in blood flow induced by L-NMMA (-24 +/- 4%), TEA (-21 +/- 3%), L-NMMA + fluconazole (-26 +/- 5%), and L-NMMA + TEA (-35 +/- 4%) were taken as covariate into analysis. Conversely, fluconazole alone slightly but not significantly increased radial flow (13 +/- 6%). L-NMMA alone or with TEA and with fluconazole enhanced radial artery dilatation to SNP, whereas TEA and fluconazole alone did not modify this response. These results confirm in humans the involvement of NO and K(Ca) channels in the regulation of basal conduit artery diameter. Moreover, the synergistic effect of combined inhibition of NO synthesis and CYP on the decrease in radial diameter in the absence of such effect after L-NMMA and fluconazole alone unmasks the role of CYP in this regulation and shows the presence of an interaction between NO and a CYP-related EDHF to maintain peripheral conduit artery diameter in vivo. Furthermore, the higher vasoconstrictor effect of TEA compared with fluconazole suggests that different K(Ca) channel-dependent hyperpolarizing mechanisms could exist in conduit arteries.