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Biomedical subjects

K H Parker

Publications and source records attributed to K H Parker.

At least 19 recordsLinked to original sources

Modelling the circle of Willis to assess the effects of anatomical variations and occlusions on cerebral flows.

Blood flow in the circle of Willis (CoW) is modelled using the 1-D equations of pressure and flow wave propagation in compliant vessels. The model starts at the left ventricle and includes the largest arteries that supply the CoW. Based on published physiological data, it is able to capture the main features of pulse wave propagation along the aorta, at the brachiocephalic bifurcation and throughout the cerebral arteries. The collateral ability of the complete CoW and its most frequent anatomical variations is studied in normal conditions and after occlusion of a carotid or vertebral artery (VA). Our results suggest that the system does not require collateral pathways through the communicating arteries to adequately perfuse the brain of normal subjects. The communicating arteries become important in cases of missing or occluded vessels, the anterior communicating artery (ACoA) being a more critical collateral pathway than the posterior communicating arteries (PCoAs) if an internal carotid artery (ICA) is occluded. Occlusions of the VAs proved to be far less critical than occlusions of the ICAs. The worst scenario in terms of reduction in the mean cerebral outflows is a CoW without the first segment of an anterior cerebral artery combined with an occlusion of the contralateral ICA. Furthermore, in patients without any severe occlusion of a carotid or VA, the direction of flow measured at the communicating arteries corresponds to the side of the CoW with an absent or occluded artery. Finally, we study the effect of partial occlusions of the communicating arteries on the cerebral flows, which again confirms that the ACoA is a more important collateral pathway than the PCoAs if an ICA is occluded.

Animals↗

Effects of osmotic pressure in the extracellular matrix on tissue deformation.

In soft tissues, large molecules such as proteoglycans trapped in the extracellular matrix (ECM) generate high levels of osmotic pressure to counter-balance external pressures. The semi-permeable matrix and fixed negative charges on these molecules serve to promote the swelling of tissues when there is an imbalance of molecular concentrations. Structural molecules, such as collagen fibres, form a network of stretch-resistant matrix, which prevents tissue from over-swelling and keeps tissue integrity. However, collagen makes little contribution to load bearing; the osmotic pressure in the ECM is the main contributor balancing external pressures. Although there have been a number of studies on tissue deformation, there is no rigorous analysis focusing on the contribution of the osmotic pressure in the ECM on the viscoelastic behaviour of soft tissues. Furthermore, most previous works were carried out based on the assumption of infinitesimal deformation, whereas tissue deformation is finite under physiological conditions. In the current study, a simplified mathematical model is proposed. Analytic solutions for solute distribution in the ECM and the free-moving boundary were derived by solving integro-differential equations under constant and dynamic loading conditions. Osmotic pressure in the ECM is found to contribute significantly to the viscoelastic characteristics of soft tissues during their deformation.

Animals↗

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.

Collateral Circulation↗

Wave-energy patterns in carotid, brachial, and radial arteries: a noninvasive approach using wave-intensity analysis.

The study of wave propagation at different points in the arterial circulation may provide useful information regarding ventriculoarterial interactions. We describe a number of hemodynamic parameters in the carotid, brachial, and radial arteries of normal subjects by using noninvasive techniques and wave-intensity analysis (WIA). Twenty-one normal adult subjects (14 men and 7 women, mean age 44 +/- 6 yr) underwent applanation tonometry and pulsed-wave Doppler studies of the right common carotid, brachial, and radial arteries. After ensemble averaging of the pressure and flow-velocity data, local hydraulic work was determined and a pressure-flow velocity loop was used to determine local wave speed. WIA was then applied to determine the magnitude, timings, and energies of individual waves. At all sites, forward-traveling (S) and backward-traveling (R) compression waves were observed in early systole. In mid- and late systole, forward-traveling expansion waves (X and D) were also seen. Wave speed was significantly higher in the brachial (6.97 +/- 0.58 m/s) and radial (6.78 +/- 0.62 m/s) arteries compared with the carotid artery (5.40 +/- 0.34 m/s; P < 0.05). S-wave energy was greatest in the brachial artery (993.5 +/- 87.8 mJ/m2), but R-wave energy was greatest in the radial artery (176.9 +/- 19.9 mJ/m2). X-wave energy was significantly higher in the brachial and radial arteries (176.4 +/- 32.7 and 163.2 +/- 30.5 mJ/m2, respectively) compared with the carotid artery (41.0 +/- 9.4 mJ/m2; P < 0.001). WIA illustrates important differences in wave patterns between peripheral arteries and may provide a method for understanding ventriculo-arterial interactions in the time domain.

Adult↗

Wave intensity in the ascending aorta: effects of arterial occlusion.

We examine the effects of arterial occlusion on the pressure, velocity and the reflected waves in the ascending aorta using wave intensity analysis. In 11 anaesthetised, open-chested dogs, snares were used to produce total arterial occlusion at 4 sites: the upper descending aorta at the level of the aortic valve (thoracic); the lower thoracic aorta at the level of the diaphragm (diaphragm); the abdominal aorta between the renal arteries (abdominal) and the left iliac artery, 2 cm downstream from the aorta iliac bifurcation (iliac). Pressure and flow in the ascending aorta were measured, and data were collected before and during the occlusion. During thoracic and diaphragm occlusions a significant increase in mean aortic pressure (46% and 23%) and in wave speed (25% and 10%) was observed, while mean flow rate decreased significantly (23% and 17%). Also, the reflected compression wave arrived significantly earlier (45% and 15%) and its peak intensity was significantly greater (257% and 125%), all compared with control. Aortic occlusion distal to the renal arteries, however, caused an indiscernible change in the pressure and velocity waveforms, and in the intensities and timing of the waves in the forward and backward directions. The measured pressure and velocity waveforms are the result of the interaction between the heart and the arterial system. The separated pressure, velocity and wave intensity are required to provide information about arterial hemodynamic such as the timing and magnitude of the forward and backward waves. The net wave intensity is simpler to calculate but provides information only about the predominant direction of the waves and can be misleading when forward and backward waves of comparable magnitudes are present simultaneously.

Animals↗

Wave propagation in a model of the arterial circulation.

The propagation of the arterial pulse wave in the large systemic arteries has been calculated using a linearised method of characteristics analysis to follow the waves generated by the heart. The model includes anatomical and physiological data for the 55 largest arteries adjusted so that the bifurcating tree of arteries is well matched for forward travelling waves. The peripheral arteries in the model are terminated by resistance elements which are adjusted to produce a physiologically reasonable distribution of mean blood flow. In the model, the pressure and velocity wave generated by the contraction of the left ventricle propagates to the periphery where it is reflected. These reflected waves are re-reflected by each of the bifurcations that they encounter and a very complex pattern of waves is generated. The results of the calculations exhibit many of the features of the systemic arteries, including the increase of the pulse pressure with distance away from the heart as well as the initial decrease and then the large increase in the magnitude of back flow during late systole going from the ascending aorta to the abdominal aorta to the arteries of the leg. The model is then used to study the effects of the reflection or absorption of waves by the heart and the mechanisms leading to the incisura are investigated. Calculations are carried out with the total occlusion of different arterial segments in order to model experiments in which the effects of the occlusion of different arteries on pressure and flow in the ascending aorta were measured. Finally, the effects of changes in peripheral resistance on pressure and velocity waveforms are also studied. We conclude from these calculations that the complex pattern of wave propagation in the large arteries may be the most important determinant of arterial haemodynamics.

Aorta↗

Local and regional wave speed in the aorta: effects of arterial occlusion.

Arterial wave speed is widely used to determine arterial distensibility and has been utilised as a surrogate marker for vascular disease. A comparison between the results of the traditional foot-to-foot method for measuring wave speed to those of the pressure-velocity loop (PU-loop) method is one of the primary objectives of this paper. We also investigate the regional wave speed along the aorta, and the effect of arterial occlusion on the PU-loop measured in the ascending aorta. In 11 anaesthetised dogs, a total occlusion lasting 3 min was produced at four sites: upper thoracic, diaphragm, abdominal and left iliac artery. Pressure and flow in the ascending aorta and pressure proximal to the occlusion site were measured, and data were collected before, during the occlusion and after the occlusion had been removed. In control conditions, the wave speeds determined by the PU-loop in the aortic root were systematically lower than those measured by the foot-to-foot method. During thoracic and diaphragm occlusions, mean aortic pressure and wave speed increased significantly but returned to control values after each occlusion had been removed. The PU-loop is an objective and easy to use method for determining wave speed and can be advantageous for use in short arterial segments when local measurements of pressure and velocity are available.

Animals↗

Semiautomated computer analysis of vessel growth in preterm infants without and with ROP.

AIMS: To measure characteristics of the retinal blood vessels close to the optic disc in full term and preterm infants, with and without retinopathy of prematurity (ROP), using digital imaging. To determine whether these measures are indicative of the presence or severity of ROP in the retinal periphery. METHODS: 52 digital fundus images from 42 babies were analysed with a semiautomated analysis program developed at Imperial College London. Analysis was limited to the principal temporal vessels close to the optic disc: recording venular diameter and arteriolar diameter and tortuosity. RESULTS: Each result was categorised by the gestational age of the infant ("very premature" 24-27 weeks, "moderately premature" 28-31 weeks, and "near term" > or =32 weeks) and by the highest stage of ROP present ("no ROP," "mild ROP" stage 1 or 2, and "severe ROP" stage 3). Arteriolar tortuosity was found to vary significantly (Kruskal-Wallis p=0.002) with ROP severity. Although venular and arteriolar diameters increased monotonically with ROP severity the differences were not significant. Venular diameter, arteriolar diameter, and arterial tortuosity did not vary significantly between gestational age groups. CONCLUSIONS: This study confirms it is possible to quantify the size and tortuosity of retinal blood vessels in term and preterm babies using digital image analysis software. This method detected significant increases in arteriolar tortuosity with increasing ROP severity.

Case-Control Studies↗

Measurements of wave speed and reflected waves in elastic tubes and bifurcations.

Wave intensity analysis is a time domain method for studying waves in elastic tubes. Testing the ability of the method to extract information from complex pressure and velocity waveforms such as those generated by a wave passing through a mismatched elastic bifurcation is the primary aim of this research. The analysis provides a means for separating forward and backward waves, but the separation requires knowledge of the wave speed. The PU-loop method is a technique for determining the wave speed from measurements of pressure and velocity, and investigating the relative accuracy of this method is another aim of this research. We generated a single semi-sinusoidal wave in long elastic tubes and measured pressure and velocity at the inlet, and pressure at the exit of the tubes. In our experiments, the results of the PU-loop and the traditional foot-to-foot methods for determining the wave speed are comparable and the difference is on the order of 2.9+/-0.8%. A single semi-sinusoidal wave running through a mismatched elastic bifurcation generated complicated pressure and velocity waveforms. By using wave intensity analysis we have decomposed the complex waveforms into simple information of the times and magnitudes of waves passing by the observation site. We conclude that wave intensity analysis and the PU-loop method combined, provide a convenient, time-based technique for analysing waves in elastic tubes.

Arteries↗

Quantification of the non-planarity of the human carotid bifurcation.

The carotid bifurcation has been a region of particular interest due to its predilection for clinically significant atherosclerosis. It has been shown that the vessel geometry is a major determinant of the local haemodynamic properties which are believed to be associated with the location of atherosclerotic lesions. Current knowledge of the geometry of the carotid bifurcation is insufficient and restricted to basic geometric parameters. To provide some means of quantifying the degree of complexity of the 3D shape of the bifurcation, we made an initial attempt by evaluating the non-planarity of an arterial bifurcation based upon the singular value decomposition theorem. In this paper we present our results obtained on the right carotid bifurcations of six normal subjects, each of whom was scanned twice using the 2D time-of-flight MR sequence. The acquired 2D cross sectional images were processed by using our in-house software which comprises 2D segmentation, 3D reconstruction and smoothing. The centroids of each transverse slices were determined and used as input data for the non-planarity analysis. Our results using the singular value decomposition method have demonstrated discernible differences in non-planarity among individuals. Comparisons with the planarity definition proposed by other investigators suggest that the singular value decomposition method offers more information about the linearity and planarity of the bifurcation. However, it is also realised that a single measure of non-planarity can never fully characterise a bifurcation owing to the great variety of geometries.

Adult↗

Changes in aortic rotational flow during cardiopulmonary bypass studied by transesophageal echocardiography and magnetic resonance velocity imaging: a potential mechanism for atheroembolism during cardiopulmonary bypass.

The human aorta is a curved conduit with a complex three-dimensional geometry. The curvature influences axial velocity distribution and introduces transverse velocity components. Rotational flow in the aorta can be demonstrated during normal pulsatile flow using transesophageal echocardiography. Cardiopulmonary bypass may affect the pattern of rotational flow in the aorta and thus influence the generation of atheroemboli. We investigated rotational flow in the descending aorta using color flow mapping and pulse-wave Doppler on transesophageal echocardiography before and during cardiopulmonary bypass. We correlated our findings with magnetic resonance velocity imaging in a model of a human aortic arch connected to a cardiopulmonary bypass circuit. Before cardiopulmonary bypass, rotational flow in the descending aorta was seen in 37 of 40 patients (93%). In the majority of these patients, rotational flow was in the clockwise direction during systole, looking in the direction of flow (30 of 37 patients, 81%, P < 0.01 vs counterclockwise rotation). During cardiopulmonary bypass, there were almost equal numbers of patients with clockwise (18 patients) and counterclockwise rotation (19 patients). Forty-seven percent of patients with clockwise rotation before cardiopulmonary bypass developed reversal in the direction of rotation to counterclockwise during cardiopulmonary bypass. Twenty-nine percent of patients with counterclockwise rotation developed reversal of the direction of rotation during cardiopulmonary bypass. The transverse velocity component increased during cardiopulmonary bypass regardless of the direction of rotation. We also demonstrated clockwise rotation in the descending aorta of a human aortic arch model connected to a cardiopulmonary bypass circuit using magnetic resonance velocity mapping. Before cardiopulmonary bypass, rotation was predominantly clockwise, while during cardiopulmonary bypass, there was no preferred direction of rotation. The geometry of the aorta, which is fairly constant in all patients, imposes handedness to aortic flow before cardiopulmonary bypass. However, during cardiopulmonary bypass, other extrinsic factors such as aortic cannula orientation may influence the direction of rotation. The change in direction of rotational flow and increase in its transverse velocity component during cardiopulmonary bypass may have implications for atheroembolism and arterial branch perfusion during extended periods of non-pulsatile flow.

Aorta↗

Determination of wave speed and wave separation in the arteries.

Considering waves in the arteries as infinitesimal wave fronts rather than sinusoidal wavetrains, the change in pressure across the wave front, dP, is related to the change in velocity, dU, that it induces by the "water hammer" equation, dP=+/-rhocdU, where rho is the density of blood and c is the local wave speed. When only unidirectional waves are present, this relationship corresponds to a straight line when P is plotted against U with slope rhoc. When both forward and backward waves are present, the PU-loop is no longer linear. Measurements in latex tubes and systemic and pulmonary arteries exhibit a linear range during early systole and this provides a way of determining the local wave speed from the slope of the linear portion of the loop. Once the wave speed is known, it is also possible to separate the measured P and U into their forward and backward components. In cases where reflected waves are prominent, this separation of waves can help clarify the pattern of waves in the arteries throughout the cardiac cycle.

Arteries↗

Negative wave reflections in pulmonary arteries.

The pulmonary arterial branching pattern suggests that the early systolic forward-going compression wave (FCW) might be reflected as a backward-going expansion wave (BEW). Accordingly, in 11 open-chest anesthetized dogs we measured proximal pulmonary arterial pressure and flow (velocity) and evaluated wave reflection using wave-intensity analysis under low-volume, high-volume, high-volume + 20 cmH2O positive end-expiratory pressure (PEEP), and hypoxic conditions. We defined the reflection coefficient R as the ratio of the energy of the reflected wave (BEW [-]; backward-going compression wave, BCW [+]) to that of the incident wave (FCW [+]). We found that R = -0.07 +/- 0.02 under low-volume conditions, which increased in absolute magnitude to -0.20 +/- 0.04 (P < 0.01) under high-volume conditions. The addition of PEEP increased R further to -0.26 +/- 0.02 (P < 0.01). All of these BEWs were reflected from a site ~3 cm downstream. During hypoxia, the BEW was maintained and a BCW appeared (R = +0.09 +/- 0.03) from a closed-end site ~9 cm downstream. The normal pulmonary arterial circulation in the open-chest dog is characterized by negative wave reflection tending to facilitate right ventricular ejection; this reflection increases with increasing blood volume and PEEP.

Animals↗

Left ventricular wave speed.

Left ventricular (LV) wave speed (LVWS) was studied experimentally and confirmed in theory. Combining the definition of elastance (E) with the equations for the conservation of mass and momentum shows that LVWS is proportional to the square root of ELA, where L is long-axis length and A is the cross-sectional area, and the density of the blood. (We defined ELA = gamma, where gamma is compressibility.) We studied nine open chest, anesthetized dogs, three of which were studied during caval constriction when LV end-diastolic pressure was < or =0 mmHg. The hearts were paced at approximately 90 beats/min, and LV cross-sectional area was measured by using two pairs of ultrasonic crystals; E was calculated from the LV pressure-area loop. A pulse generator was connected to the LV apex, and LVWS was measured by using two pressure transducers: one near the apex and the other near the base. Their distance was measured roentgenographically and compared with the diameter of a reference ball. LVWS ranged from approximately 1 m/s during diastole to approximately 10 m/s during systole. The slope of the log c (where c is wave speed) vs. log gamma was 0.546, which is in agreement with theory (0.5). When gamma < or = 0, LVWS was approximately 1.5 m/s.

Animals↗

Arterial waves in humans during peripheral vascular surgery.

The purpose of this study was to investigate the effect of aortic clamping on arterial waves during peripheral vascular surgery. We measured pressure and velocity simultaneously in the ascending aorta, in ten patients (70+/-5 years) with aortic-iliac disease intra-operatively. Pressure was measured using a catheter tip manometer, and velocity was measured using Doppler ultrasound. Data were collected before aortic clamping, during aortic clamping and after unclamping. Hydraulic work in the aortic root was calculated from the measured data, the reflected waves were determined by wave-intensity analysis and wave speed was determined by the PU-loop (pressure-velocity-loop) method; a new technique based on the 'water-hammer' equation. The wave speed is approx. 32% (P<0.05) higher during clamping than before clamping. Although the peak intensity of the reflected wave does not alter with clamping, it arrives 30 ms (P<0.05) earlier and its duration is 25% (P<0.05) longer than before clamping. During clamping, left ventricule (LV) hydraulic systolic work and the energy carried by the reflected wave increased by 27% (P<0.05) and 20% (P<0.05) respectively, compared with before clamping. The higher wave speed during clamping explains the earlier arrival of the reflected waves suggesting an increase in the afterload, since the LV has to overcome earlier reflected compression waves. The longer duration of the reflected wave during clamping is associated with an increase in the total energy carried by the wave, which causes an increase in hydraulic work. Increased hydraulic work during clamping may increase LV oxygen consumption, provoke myocardial ischaemia and hence contribute to the intra-operative impairment of LV function known in patients with peripheral vascular disease.

Aged↗

Wave-intensity analysis: a new approach to coronary hemodynamics.

In 10 anesthetized dogs, we measured high-fidelity left circumflex coronary (P(LCx)), aortic (P(Ao)), and left ventricular (P(LV)) pressures and left circumflex velocity (U(LCx); Doppler) and used wave-intensity analysis (WIA) to identify the determinants of P(LCx) and U(LCx). Dogs were paced from the right atrium (control 1) or right ventricle by use of single (control 2) and then paired pacing to evaluate the effects of left ventricular contraction on P(LCx) and U(LCx). During left ventricular isovolumic contraction, P(LCx) exceeded P(Ao), paired pacing increasing the difference. Paired pacing increased DeltaP(X) (the P(LCx)-P(Ao) difference at the P(Ao)-P(LV) crossover) and average dP(LCx)/dt (P < 0.0001 for both). During this time, WIA identified a backward-going compression wave (BCW) that increased P(LCx) and decreased U(LCx); the BCW increased during paired pacing (P < 0.0001). After the aortic valve opened, the increase in P(Ao) caused a forward-going compression wave that, when it exceeded the BCW, caused U(LCx) to increase, despite P(LV) and (presumably) elastance continuing to increase. Thus WIA identifies the contributions of upstream (aortic) and downstream (microcirculatory) effects on P(LCx) and U(LCx).

Animals↗

Physicochemical properties of arterial elastin and its associated glycoproteins.

Microfibrillar glycoproteins are a significant component of vascular elastic tissue, but little is known about their contribution to vascular physiology and pathology. We have investigated some physicochemical properties of the glycoproteins that may be pertinent to these roles. Because of the difficulty in isolating intact glycoproteins in a form and quantity suitable for physicochemical examination, we based our analysis on a comparison of the properties of porcine thoracic aorta and pulmonary artery extracted with GuHCl and collagenase (preparation GC) and after further treatment with dithioerythritol to remove glycoproteins (preparation GC/DTE). Amino acid analysis showed that GC/DTE had the amino acid composition of pure elastin while GC contained a higher proportion of polar amino acids, particularly in the aortic preparation. GC stained with alcian blue, particularly in the intimal region, but GC/DTE did not. GC had a higher water content and a slower viscoelastic response and the circumferential elastic modulus was approximately 50% lower (whether expressed in terms of sample weight or elastin content). Clearly, therefore, the microfibrils do not stiffen the network and may prevent the alignment of elastin fibers in the circumferential direction. Their effect on hydration may arise either because they impose mechanical constraints on the geometry of the network or because they modify the inter- and intramolecular hydrophobic or electrostatic interactions that influence the tissue organization and hydration. Molecular probe measurements of the intrafibrillar pore structure using radiolabeled and fluorescent probes showed that removal of the microfibrils caused a slight decrease in the extrafibrillar water space and a larger decrease in the intrafibrillar water space. Sucrose, a small probe molecule, was able to penetrate most of the intrafibrillar water space when microfibrils were present but was virtually excluded when they were not. Potentiometric titration and radiotracer assays of ion binding both showed that the microfibrils contribute a considerable negative charge (-9 mumoles/g wet tissue in the aortic preparation and -16 mumoles/g wet weight in the pulmonary artery) and increase calcium binding by approximately 30%.

Animals↗