Pathophysiology and diagnosis for arteriosclerosis obliterans

Patients with arteriosclerosis obliterans, or peripheral arterial disease have been conventionally diagnosed and treated from only the viewpoint of peripheral arterial circulation. These concepts may have improved the quality of life for patients, but could not contribute the prognosis of life, because peripheral arterial disease is associated with an increased risk of the coronary disease and cerebrovascular disease. Intermittent claudication, the most common symptom of peripheral arterial disease, results from flow-reducing lesions in the arteries of the lower extremity that cause exercise-induced muscle ischemia. In order to evaluate intermittent claudication, many kinds of noninvasive diagnostic studies, including ABPI (ankle brachial pressure index) and the measurement of claudication distance, et al have been proposed. We have used the recovery time of the ischemic reaction at foot sole, plethysmography, thermography, laser doppler flowmetry, or NIRS (near-infrared spectroscopy) after walking test, rather than ABPI. These examinations will be superior to ABPI to evaluate effects after ergotherapy or pharmacotherapy for patients with intermittent claudication. Carotid artery sclerosis may be a good marker of systemic atherosclerosis. By our assessment of risk factors, the progression of atherosclerotic change in carotid artery was strongly correlated with two risk factors, such as smoking and systolic blood pressure. In the cholesterol analysis, Lp (a) was only high risk factor for atherosclerotic change of carotid artery. Recent technical advances, adequate evaluation of systemic atherosclerosis, and reduction of risk factors should improve the prognosis of patients with peripheral arterial disease.     

Impact of bioengineering on noninvasive diagnostics

Out of a number of important methods used in laboratory angiology, only a limited group was selected to be discussed in this symposium. Phonoangiography is reviewed from the qualitative and quantitative viewpoint for its practical value and accessibility. Various aspects of pressure and volume detection of the eye pulse are discussed from the viewpoint of carotid artery disease and its noninvasive diagnosis, with special reference to oculoplethysmography as well as the Gee-pneumooculoplethysmography. Impedance plethysmography (IPG) is one of the controversial techniques used in laboratory angiology, with its main application currently in the area of diagnosis of venous obstructive disease. The dilemma of application of IPG in the diagnosis of arterial disease is discussed mainly from an engineering point of view. Spectral analysis will be covered in view of the fast emergence of Doppler Duplex scanning as the major diagnostic mode in extracranial carotid artery disease.     

Local regulation of subcutaneous blood flow and capillary filtration in limbs with occlusive arterial disease. Studies before and after arterial reconstruction

The aim of the study was to examine the local blood flow regulation and the capillary filtration rate in patients with occlusive arterial disease before and after arterial reconstructive surgery. Fourty-seven normal subjects and 99 patients were studied. Subcutaneous blood flow was measured on the forefoot by the local 133Xenon method. Forefoot arterial blood pressure was measured indirectly by cuff and strain-gauge technique. Capillary filtration rate was measured by strain-gauge plethysmography on the forefoot. The arterial and venous pressures of the forefoot were changed by elevating or lowering the foot in relation to heart level. In normal limbs autoregulation was demonstrated during elevation of the limb when blood flow remained almost constant despite the reduction in arterial and perfusion pressures. The local vasoconstrictor response to increased venous transmural pressure was demonstrated when the limb was lowered and blood flow decreased about 30% despite a constant perfusion pressure. In limbs with occlusive arterial disease both local blood flow regulation mechanisms became progressively more abnormal the severe the symptoms and the lower the distal blood pressure. Estimations of the changes in local vascular resistance suggested that the abnormalities in blood flow regulation in all but the severest cases are the result of changes in local perfusion pressure rather than the result of inability of the arteriolar smooth muscle to dilate and constrict in response to changes in arterial and venous pressures. After arterial reconstruction the two mechanisms generally normalized within about a week. However, disturbances occurred in some cases in the early postoperative period, possibly as the result of postoperative pain and stress. Postreconstructive hyperaemia developed in most limbs despite the early normalization of local blood flow regulation. Compared with normal limbs, the forefoot capillary filtration rate was reduced in limbs with occlusive arterial disease. In the early postoperative period the filtration rate remained reduced, but it increased to normal values within three months. Postreconstructive oedema developed independently of the normalization of blood flow regulation, and almost exclusively after femoro-distal by-pass surgery. The study supports the hypothesis that the postreconstructive oedema is a lymphoedema due to surgical trauma, rather than the result of microvascular derangement.     

Sleep apnea and autonomic cerebrovascular dysfunction

Changes in common carotid blood flow (CCF) and resistance index (RI), calculated from velocity waveforms by a noninvasive pulsed Doppler technique, were measured during apneic episodes and voluntary breath holding in five sleep apnea patients (SA) and during breath holding in five normal subjects (N). During apneic episodes averaging 27 s, CCF was reduced by 9% and RI increased by 4%, both trends being related to apneic duration. Internal carotid artery measurements in one SA indicated more dramatic changes in blood flow and RI than noted in CCF. During breath holding, CCF decreased significantly in SA but not in N, and RI showed a smaller reduction in SA. These changes in CCF and RI during sleep apnea are similar to those noted in anesthetized dogs where vasomotor waves and associated apneas were induced by elevating intracranial pressure. Previously reported recordings of ventilatory and systemic cardiovascular responses in SA are similar to these recordings in dogs, and it is therefore proposed that vasomotor responses to intermittent cerebral ischemia and hypercapnia may be the principle event in SA and periodic breathing only a secondary consequence of the prevailing autonomic dysfunction.     

Developments in cardiovascular ultrasound. Part 2: Arterial applications

Many of the changes resulting from arterial disease can be measured, using Doppler ultrasound for measurement of blood velocity and B-scan imaging for measurement of tissue structure and composition. Wall thickness, the degree of arterial narrowing and plaque volume can be measured using B-scan imaging, and 3D ultrasound can be used to improve the accuracy of measurements of plaque volume and for improved visualisation of complex arterial geometries. Measurement of the dynamic properties of the arterial wall permits estimation of wall elasticity and plaque motion. From the Doppler signal, measurements of blood velocity are used to estimate the degree of arterial narrowing and volumetric flow, although measurement errors can be large. Wall shear stress can be estimated by measuring the velocity gradient at the vessel wall. The problems of inadequate spatial resolution and interference from overlying tissue are largely removed when intravascular systems are used, and these have superior capability in the assessment of arterial structure and tissue composition. However, measurement of quantities relating to blood flow is more difficult using the intravascular approach, as the indwelling cather disturbs the blood flow pattern, and currently, assessment of flow and vessel cross-section are not performed at the same site.     

The effects of changes in the carotid sinus baroreceptor activity on splanchnic blood flow in anesthetized man

In 9 patients being subjected to abdominal surgery, electromagnetic blood flow measurements were obtained from the hepatic, mesenteric and iliac beds while the carotid sinus baroreceptors were stimulated by carotid sinus massage. Carotid sinus stimulation produced an average maximum decrease in mean arterial pressure of 21%. Hepatic and mesenteric blood flows decreased by 15% and calculated vascular resistances were not significantly changed in these vascular beds. Iliac blood flow, on the other hand, showed a slight increase and iliac vascular resistance was decreased by 29%. It is concluded that the splanchnic vascular bed is of less importance in the carotid sinus baroreflex control of systemic arterial pressure in anesthetized man.     

Determination of fractional flow reserve (FFR) based on scaling laws: a simulation study

Fractional flow reserve (FFR) provides an objective physiological evaluation of stenosis severity. A technique that can measure FFR using only angiographic images would be a valuable tool in the cardiac catheterization laboratory. To perform this, the diseased blood flow can be measured with a first pass distribution analysis and the theoretical normal blood flow can be estimated from the total coronary arterial volume based on scaling laws. A computer simulation of the coronary arterial network was used to gain a better understanding of how hemodynamic conditions and coronary artery disease can affect blood flow, arterial volume and FFR estimation. Changes in coronary arterial flow and volume due to coronary stenosis, aortic pressure and venous pressure were examined to evaluate the potential use of flow and volume for FFR determination. This study showed that FFR can be estimated using arterial volume and a scaling coefficient corrected for aortic pressure. However, variations in venous pressure were found to introduce some error in FFR estimation. A relative form of FFR was introduced and was found to cancel out the influence of pressure on coronary flow, arterial volume and FFR estimation. The use of coronary flow and arterial volume for FFR determination appears promising.     

Model-based noninvasive estimation of intracranial pressure from cerebral blood flow velocity and arterial pressure

Intracranial pressure (ICP) is affected in many neurological conditions. Clinical measurement of pressure on the brain currently requires placing a probe in the cerebrospinal fluid compartment, the brain tissue, or other intracranial space. This invasiveness limits the measurement to critically ill patients. Because ICP is also clinically important in conditions ranging from brain tumors and hydrocephalus to concussions, noninvasive determination of ICP would be desirable. Our model-based approach to continuous estimation and tracking of ICP uses routinely obtainable time-synchronized, noninvasive (or minimally invasive) measurements of peripheral arterial blood pressure and blood flow velocity in the middle cerebral artery (MCA), both at intra-heartbeat resolution. A physiological model of cerebrovascular dynamics provides mathematical constraints that relate the measured waveforms to ICP. Our algorithm produces patient-specific ICP estimates with no calibration or training. Using 35 hours of data from 37 patients with traumatic brain injury, we generated ICP estimates on 2665 nonoverlapping 60-beat data windows. Referenced against concurrently recorded invasive parenchymal ICP that varied over 100 millimeters of mercury (mmHg) across all records, our estimates achieved a mean error (bias) of 1.6 mmHg and SD of error (SDE) of 7.6 mmHg. For the 1673 data windows over 22 hours in which blood flow velocity recordings were available from both the left and the right MCA, averaging the resulting bilateral ICP estimates reduced the bias to 1.5 mmHg and SDE to 5.9 mmHg. This accuracy is already comparable to that of some invasive ICP measurement methods in current clinical use.     

Estimation of distributed arterial mechanical properties using a wave propagation model in a reverse way

To estimate arterial stiffness, different methods based either on distensibility, pulse wave velocity or a pressure-velocity loop, have been proposed. These methods can be employed to determine the arterial mechanical properties either locally or globally, e.g. averaged over an entire arterial segment. The aim of this study was to investigate the feasibility of a new method that estimates distributed arterial mechanical properties non-invasively. This new method is based on a wave propagation model and several independent ultrasound and pressure measurements. Model parameters (including arterial mechanical properties) are obtained from a reverse method in which differences between modeling results and measurements are minimized using a fitting procedure based on local sensitivity indices. This study evaluates the differences between in vivo measured and simulated blood pressure and volume flow waveforms at the brachial, radial and ulnar arteries of 6 volunteers. The estimated arterial Young's modulus range from 1.0 to 6.0 MPa with an average of (3.8 ± 1.7) MPa at the brachial artery and from 1.2 to 7.8 MPa with an average of (4.8 ± 2.2) MPa at the radial artery. A good match between measured and simulated waveforms and the realistic stiffness parameters indicate a good in vivo suitability.     

Suitable image parameters and analytical method for quantitatively measuring cerebral blood flow volume with phase-contrast magnetic resonance imaging

The aim of this study was to determine suitable image parameters and an analytical method for phase-contrast magnetic resonance imaging (PC-MRI) as a means of measuring cerebral blood flow volume. This was done by constructing an experimental model and applying the results to a clinical application. The experimental model was constructed from the aorta of a bull and circulating isotonic saline. The image parameters of PC-MRI (repetition time, flip angle, matrix, velocity rate encoding, and the use of square pixels) were studied with percent flow volume (the ratio of actual flow volume to measured flow volume). The most suitable image parameters for accurate blood flow measurement were as follows: repetition time, 50 msec; flip angle, 20 degrees; and a 512 x 256 matrix without square pixels. Furthermore, velocity rate encoding should be set ranging from the maximum flow velocity in the vessel to five times this value. The correction in measuring blood flow was done with the intensity of the region of interest established in the background. With these parameters for PC-MRI, percent flow volume was greater than 90%. Using the image parameters for PC-MRI and the analytical method described above, we evaluated cerebral blood flow volume in 12 patients with occlusive disease of the major cervical arteries. The results were compared with conventional xenon computed tomography. The values found with both methods showed good correlation. Thus, we concluded that PC-MRI was a noninvasive method for evaluating cerebral blood flow in patients with occlusive disease of the major cervical arteries.     

Erythrocyte deformability in peripheral occlusive arterial disease.

A rheological study of 32 patients with peripheral occlusive arterial disease (POAD), compared with 32 matched healthy controls, has shown no loss of erythrocyte deformability as measured by filtration methods (using initial flow rate and positive pressure instruments, polycarbonate and silver membranes, and 3 microns and 5 microns diameter pores) or by viscometry (using laser visco-diffractometric and high shear rate viscosity methods). Erythrocyte ATP concentration in POAD was also normal. Patients with POAD showed a small (4 fl) increase in mean erythrocyte volume, associated with a raised serum gamma-glutamyl transpeptidase concentration, which correlated with erythrocyte filtration and viscometric measurements. Previous reports of impaired blood filterability in POAD probably reflect the effects of accompanying leucocytosis, plasma hyperfibrinogenaemia, or an increase in erythrocyte size, but not an intrinsic loss of erythrocyte deformability.     

Circulatory effects of carotid sinus stimulation and changes in blood volume distribution in hypertensive man

In 8 patients with moderate hypertension and 8 normotensive subjects an attempt was made to study the circulatory effects of high and low pressure baroreceptor stimulation. Intrathoracic low pressure receptors were stimulated by changes in blood volume distribution using lower body negative pressure (LBNP) and lower body positive pressure (LBPP). The carotid sinus was stimulated by sinusoidal neck suction. Blood pressure, central venous pressure, heart rate, cardiac output and forearm blood flow were recorded. During LBNP and LBPP changes in central blood volume, reflected in changes in central venous pressure, induced significantly greater changes in cardiac output and forearm blood flow in the hypertensive subjects. In both normotensive and hypertensive subjects mean arterial blood pressure was essentially unchanged during LBNP and a slight increase was found during LBPP. Heart rate and blood pressure response to stimulation of the carotid sinus decreased with increasing resting mean arterial pressure. The results suggest impairment of reflex adjustments, via arterial baroreceptors, possibly in particular to dynamic stimuli, rather than via intrathoracic “low pressure” baroreceptors in subjects with moderate hypertension.     

Continuous measurement of renal blood flow changes to renal nerve stimulation and intra-arterial drug administration in the rat

A method is described for continuous measurement of renal blood flow in the anesthetized rat without dissection of the renal artery. Blood flow and arterial pressure were measured in an extracorporeal flow circuit between the carotid artery and an aortic pouch from which the left renal artery was the only outlet. Injection into the flow circuit allowed delivery of drugs directly into the arterial blood supply of the kidney. Electrical stimulation of undamaged periarterial renal kidney. Electrical stimulation of undamaged periarterial renal nerves was possible since the renal artery remained undisturbed. Extracorporeal autoperfusion of the rat kidney produced renal flow and resistance measurements that did not differ from those obtained with a flow probe placed directly on the renal artery. Renal nerve stimulation was found to cause renal vasoconstriction due to activation of alpha-adrenergic receptors by norepinephrine released from postganglionic sympathetic neurons. Renal vascular responses to a variety of intra-arterial vasoactive agents were also determined. The method described here allows the evaluation of renal vascular control in the variety of disease states for which suitable rat models have been developed.     

Pulse pressure waveform estimation using distension profiling with contactless optical probe

The pulse pressure waveform has, for long, been known as a fundamental biomedical signal and its analysis is recognized as a non-invasive, simple, and resourceful technique for the assessment of arterial vessels condition observed in several diseases. In the current paper, waveforms from non-invasive optical probe that measures carotid artery distension profiles are compared with the waveforms of the pulse pressure acquired by intra-arterial catheter invasive measurement in the ascending aorta. Measurements were performed in a study population of 16 patients who had undergone cardiac catheterization. The hemodynamic parameters: area under the curve (AUC), the area during systole (AS) and the area during diastole (AD), their ratio (AD/AS) and the ejection time index (ETI), from invasive and non-invasive measurements were compared. The results show that the pressure waveforms obtained by the two methods are similar, with 13% of mean value of the root mean square error (RMSE). Moreover, the correlation coefficient demonstrates the strong correlation. The comparison between the AUCs allows the assessment of the differences between the phases of the cardiac cycle. In the systolic period the waveforms are almost equal, evidencing greatest clinical relevance during this period. Slight differences are found in diastole, probably due to the structural arterial differences. The optical probe has lower variability than the invasive system (13% vs 16%). This study validates the capability of acquiring the arterial pulse waveform with a non-invasive method, using a non-contact optical probe at the carotid site with residual differences from the aortic invasive measurements.     

On Coupling a Lumped Parameter Heart Model and a Three-Dimensional Finite Element Aorta Model

Aortic flow and pressure result from the interactions between the heart and arterial system. In this work, we considered these interactions by utilizing a lumped parameter heart model as an inflow boundary condition for three-dimensional finite element simulations of aortic blood flow and vessel wall dynamics. The ventricular pressure–volume behavior of the lumped parameter heart model is approximated using a time varying elastance function scaled from a normalized elastance function. When the aortic valve is open, the coupled multidomain method is used to strongly couple the lumped parameter heart model and three-dimensional arterial models and compute ventricular volume, ventricular pressure, aortic flow, and aortic pressure. The shape of the velocity profiles of the inlet boundary and the outlet boundaries that experience retrograde flow are constrained to achieve a robust algorithm. When the aortic valve is closed, the inflow boundary condition is switched to a zero velocity Dirichlet condition. With this method, we obtain physiologically realistic aortic flow and pressure waveforms. We demonstrate this method in a patient-specific model of a normal human thoracic aorta under rest and exercise conditions and an aortic coarctation model under pre- and post-interventions.     

Assessment of the agreement between photoplethysmographic and arterial waveform respiratory variation in patients undergoing spine surgery

Abstract

Respiratory variation in the arterial blood pressure and photoplethysmographic (PPG) waveforms have both been shown to predict the haemodynamic response to volume administration. Whether or not the two can be considered interchangeable is controversial. Twenty-three patients undergoing spine surgery received both a 20 gauge intra-arterial catheter and a Masimo adult adhesive SpHb sensor connected to a Radical-7 monitor. Pulse pressure variation (PPV) was calculated off-line at 1-min intervals. Pleth Variability Index (PVI) and Perfusion Index data were recorded. After exclusion of outliers, agreement between PPV and PVI was assessed using a repeated measures Bland-Altman approach. Concordance between changes in PPV and PVI was assessed using a four-quadrant plot with a 20% zone of exclusion. In total, 6549?min of data were collected. Repeated measures Bland-Altman analysis identified a bias of 2.2% and 95% confidence intervals of ±15.3% (limits of agreement ?13.1 and +17.6%). The concordance rate between changes in PPV and changes in PVI was 51%. The agreement between respiratory variation in the arterial blood pressure and PPG waveforms is poor and these two should not be considered interchangeable. Changes in PPV are unrelated to changes in PVI. The data, combined with recently published work from other authors, suggests that the low frequency oscillations in the PPG waveform are not related to the low frequency oscillation in the systemic arterial blood pressure tracing and may be related to changes in venous pressure, peripheral tone or other physiologic phenomena yet to be described.     

急性上肢哑铃训练对颈总动脉硬度和血液动力学的影响

抗阻力训练对于动脉硬度的影响存在着相互矛盾的结果。为研究不同负荷的急性上肢哑铃训练对颈总动脉硬度和血液动力学的影响,选择10名健康男性志愿者,年龄（21 ± 2）岁,分别进行5 kg和7 kg负荷的哑铃上肢曲臂训练各50次,两种负荷中间休息30 min。用彩色超声多普勒记录静息状态及不同哑铃负荷训练后颈总动脉的管径和轴心流速波形,用电子自动血压计同步测量心率和肱动脉血压。基于检测的实验数据,用经典血液动力学理论对颈总动脉硬度、压力-应变弹性模量以及相关血液动力学参数进行分析和计算。结果表明,受试者经过急性上肢哑铃训练后,心率、最大轴心流速、收缩压和最大壁面切应力等血液动力学参数明显增大,而颈总动脉管径、平均流量率、平均血压等参数没有明显变化。此外,在经过5 kg哑铃训练后,最大流量率和平均轴心流速显著增加,最小轴心流速显著减小,颈总动脉硬度、压力-应变弹性模量、舒张压、最小壁面切应力和振荡剪切指数无明显变化;而7 kg哑铃训练后,颈总动脉硬度、压力-应变弹性模量、振荡剪切指数明显增加,舒张压、最小壁面切应力显著降低,平均轴心流速和轴心流速最小值无明显变化。上肢急性哑铃训练会明显改变部分血液动力学参数,在高负荷训练时会急性增加颈总动脉的硬度。     

Redistribution of skin blood flow during leg dependency in peripheral arterial occlusive disease.

A disturbed autoregulation of cutaneous blood flow in legs with peripheral arterial occlusive disease (PAOD) has previously been demonstrated for circumscribed skin areas. In the present study, posturally-induced changes of skin perfusion distribution along ischaemic limbs were investigated topographically in 35 PAOD patients by means of fluorescein perfusography. Among the 68 legs studied, 7 had patent arteries and 61 could be assigned to FONTAINE stages I to IV. Limbs with peripheral skin lesions (stage IV) were further differentiated according to either healing (stage IV+) or non-healing (stage IV-) on conservative treatment. Sitting-up always led to prolonged calf as well as foot fluorescein appearance times (AT) except for legs in stage III or IV- disease. In the latter two groups, decreased sitting as compared to supine AT foot-to-calf ratios indicated a relative shift of dye delivery from proximal towards distal skin regions during posture. In contrast, this measure of blood flow redistribution did not change in the other groups. The redirection of fluorescein influx was significantly correlated with the systolic arterial pressure ankle-to-arm ratios. In conclusion, besides small perfusion pressure increases or passive microvessel distension, a shift of the peripheral resistance ratios may contribute to the improved blood supply of ischaemic skin regions during leg dependency. An arteriolar vasoparalysis does not regularly exist in limbs with skin lesions not primarily originating from ischaemia (stage IV+).     

Continuous estimation of systolic blood pressure using the pulse arrival time and intermittent calibration

A continuous noninvasive method of systolic blood pressure estimation is described. Systolic blood pressure is estimated by combining two separately obtained components: a higher frequency component obtained by extracting a specific frequency band of pulse arrival time and a lower frequency component obtained from the intermittently acquired systolic blood pressure measurements with an auscultatory or oscillometric system. The pulse arrival time was determined by the time interval from QRS apex in electrocardiogram to the onset of photoplethysmogram in a fingertip beat-by-beat via an oximetric sensor. The method was examined in 20 patients during cardiovascular surgery. The estimated values of systolic blood pressure were compared with those measured invasively using a radial arterial catheter. The results showed that the correlation coefficients between estimated values and invasively obtained systolic blood pressure reached 0.97±0.02 (mean±SD), and the error remained within ±10% in 97.8% of the monitoring period. By using a system with automatic cuff inflation and deflation to acquire intermittent systolic blood pressure values, this method can be applicable for the continuous noninvasive monitoring of systolic blood pressure.     

体外反搏对脑动脉血流量影响的建模和仿真研究

目的　研究体外反搏对脑动脉血流量的影响。方法　将实际测量的正常的颈动脉血压和进行体外反搏时的颈动脉血压作用于正常情况下和缺血情况下脑血流动力学数学模型，模拟上述情况下脑动脉血流的变化。结果　缺血和体外反搏都引起脑动脉血流的变化。结论　体外反搏可以明显增加大脑的血流灌注和改变脑动脉血流变化的时相模式。