Measurement Of Limb Blood Flow Research Articles

Allograft Model of Aortic Arch Segment Grafting to Abdominal Aorta Through End-to-Side Anastomosis in Mice

The mouse aortic transplantation model is a valuable tool for investigating the mechanisms of atherosclerosis regression, but few laboratories can generate it due to the operation difficulty, especially for the style of end-to-side anastomosis, which facilitates syngeneic heterotopic transplanting a plaque-rich aortic arch into the abdominal aorta. Here we provide a modified protocol for generating this allograft model, which is capable of overcoming several critical surgical challenges such as separating a longer abdominal aorta segment, reducing bleeding and thrombosis, optimizing aortotomy, and improving end-to-side anastomosis to guarantee a potent graft. By transplanting plaque-rich aortic arches into the abdominal aorta of wildtype mice, a high operation success rate (over 90%) was noted with aortic clamping time under 60 min, the graft potency was satisfactory evidenced by examinations of micro-CT, ultrasound, and lower limb blood flow measurement, while a significant atherosclerosis regression was observed in the grafts at 1 week after transplantation.Graphical

Methods for the determination of skeletal muscle blood flow: development, strengths and limitations

Since the first measurements of limb blood flow at rest and during nerve stimulation were conducted in the late 1800s, a number of methods have been developed for the determination of limb and skeletal muscle blood flow in humans. The methods, which have been applied in the study of aspects such as blood flow regulation, oxygen uptake and metabolism, differ in terms of strengths and degree of limitations but most have advantages for specific settings. The purpose of this review is to describe the origin and the basic principles of the methods, important aspects and requirements of the procedures. One of the earliest methods, venous occlusion plethysmography, is a noninvasive method which still is extensively used and which provides similar values as other more direct blood flow methods such as ultrasound Doppler. The constant infusion thermodilution method remains the most appropriate for the determination of blood flow during maximal exercise. For resting blood flow and light-to-moderate exercise, the non-invasive ultrasound Doppler methodology, if handled by a skilled operator, is recommendable. Positron emission tomography with radiolabeled water is an advanced method which requires highly sophisticated equipment and allows for the determination of muscle-specific blood flow, regional blood flows and estimate of blood flow heterogeneity within a muscle. Finally, the contrast-enhanced ultrasound method holds promise for assessment of muscle-specific blood flow, but the interpretation of the data obtained remains uncertain. Currently lacking is high-resolution methods for continuous visualization and monitoring of the skeletal muscle microcirculation in humans.

Measurement of Skeletal Muscle Blood Flow with Near‐infrared Diffuse Correlation Spectroscopy

Direct continuous noninvasive measurement of local muscle blood flow in humans remains limited. Conventional measurements of limb blood flow, such as Doppler ultrasound or venous occlusion plethysmography, measure changes in bulk conduit flow and do not provide regional information. Near‐infrared diffuse correlation spectroscopy (DCS) is an emerging technique for non‐invasive measurement of local muscle blood flow at the microvascular level. In order to better understand the strengths and limitations of this novel approach, we performed a validation study by comparing muscle blood flow changes measured by DCS and Doppler ultrasound during exercise. Ten subjects were recruited for this study (age: 27±3 yrs; female/male: 1/9; BMI: 27.0±3.6 kg/m2). The DCS probe was affixed to the forearm over the belly of the flexor digitorum profundus. Brachial artery blood velocity and diameter were measured with Doppler ultrasound, integrated, and reported as brachial artery blood flow. After a brief period of rest, each participant performed rhythmic handgrip exercise at 20% and 50% of their maximum voluntary contraction (MVC). As expected, brachial artery blood flow increased significantly from baseline by 312±56% at 20% MVC, and 613±90% at 50% MVC. Blood flow index (BFI), the primary output from DCS, shared a similar change from baseline, increasing 112±18% and 262±35%, respectively. To more appropriately compare these two approaches, the data were normalized to each person's individual maximum for each respective technique. Remarkably, the increase in skeletal muscle blood flow was strikingly similar between the two techniques, when reported in normalized units (20%: 0.42±0.03 vs. 0.45±0.03; 50%: 0.69±0.04 vs. 0.79±0.02, DCS vs. BA flow, respectively). The change in skeletal muscle blood flow by DCS and Doppler ultrasound were also strongly correlated (r2=0.77, P<0.001). Taken together, these data show that DCS and Doppler ultrasound quantify the same temporal dynamics of skeletal muscle blood flow during exercise. While these results are indeed encouraging, more work is needed to fully validate this approach for measuring local microvascular blood flow in humans.Support or Funding InformationThis work was support by an Interdisciplinary Research Program grant from the University of Texas at Arlington.

The effect of changing limb position on the validity of venous occlusion plethysmography

Venous occlusion plethysmography (VOP) is a technique used for the non-invasive measurement of limb blood flow. A fundamental technical consideration of venous occlusion plethysmography is that the limb in question must be placed above heart level. However, in light of advances in technology and methodology, the necessity of this has been questioned. We investigated the validity of the VOP technique with the forearm approximately 10 cm above and below the level of the heart in both resting and dynamic conditions. Nine healthy male participants performed four bouts of handgrip exercise, two at each of 15% and 30% maximum voluntary contraction (MVC) (one above and one below the heart). As hypothesized, resting forearm blood flow (FBF) measured below the level of the heart was significantly lower than for above the heart (p = 0.046). However, the opposite occurred during exercise, where FBF measured after the fifth minute of handgrip contractions was significantly higher below the level of the heart (p = 0.013). Furthermore, the ability to accurately quantify FBF below the level of the heart was severely impeded by artifact, and as such VOP appears to remain constricted to use above the phlebostatic level.

A reliable and readily available method of measuring limb blood flow in intermittent claudication.

To evaluate isotope limb blood flow measurement in intermittent claudication we have assessed 58 non-diabetic patients comparing our new method with treadmill testing and Doppler assessment. Limb blood flow was applicable to all 58 patients; 25 patients were unable to walk on a treadmill and of the 33 who could 12 failed to walk for one minute, making a standard one minute exercise test inappropriate. In those patients who could perform exercise tests there was a significant correlation between maximum walking distance and limb blood flow (r = 0.35, P = 0.02). Resting, post-exercise and post-hyperaemic ankle-brachial systolic pressure indices bore no relationship to the maximum walking distance. Isotope limb blood flow measurement is reproducible (r = 0.97), can be applied to those patients who cannot walk on a treadmill and provides information about both legs. It correlated significantly with all the other tests and can be recommended for the minimally invasive assessment of intermittent claudication.

A simple water-filled plethysmograph for measurement of limb blood flow in humans

Fundamental principles underpinning the study of cardiovascular physiology can be emphasized by measuring blood flow. Plethysmography is an appropriate, noninvasive technique to use but may not be available to some institutions. Therefore, for measurement of blood flow in human limbs, we developed a simple water-filled plethysmograph that may be built with minimal technical support. The device is formed from a plastic cylinder and houses a latex sleeve sealed at either end by means of circular flanges and rubber O-ring seals. Limb volume changes are transcribed using an air-filled piston recorder. This instrument proves to be sensitive and accurately determines limb volume changes over time. Utilizing an appropriate venous occlusion protocol, predicted vascular responses to postural challenge and physical exercise may be followed. In response to a questionnaire, a majority of students (n = 33) agreed that performing blood flow measurements succeeded in relating theory to practice, improved technical and observational skills, and made the learning experience real. This modified plethysmograph proves to be a valuable teaching tool in human physiology classes.

Assessment of reactive hyperaemia using real time zonal echo-planar flow imaging.

The measurement of limb blood flow at rest and during reactive hyperaemia has potential as a marker of vascular health and endothelial function because it is the stimulus that causes flow-mediated dilatation, commonly measured as brachial arterial reactivity. Because the flow increases are short lived, they represent a significant challenge for measurement by cardiovascular magnetic resonance. In this study we used a real time, single shot zonal echo-planar imaging method (ZEPI) to study reactive hyperaemia in the femoral artery of five healthy volunteers. Flow velocity was measured every 78 msec. Changes in peak forward flow velocity during systole (580 vs. 390 mm/sec, p < 0.01) and minimum flow velocity (160 vs. 100 mm/sec, p < 0.01) were shown. With progressing improvement in spatial resolution, this technique will allow the accurate noninvasive determination of total flow, flow profile, and peak velocities in real time.

Limb and skeletal muscle blood flow measurements at rest and during exercise in human subjects.

The aim of the present review is to present techniques used for measuring blood flow in human subjects and advice as to when they may be applicable. Since blood flow is required to estimate substrate fluxes, energy turnover and metabolic rate of skeletal muscle, accurate measurements of blood flow are of extreme importance. Several techniques have therefore been developed to enable estimates to be made of the arterial inflow to, venous outflow from, or local blood flow within the muscle. Regional measurements have been performed using electromagnetic flow meters, plethysmography, indicator methods (e.g. thermodilution and indo-cyanine green dye infusion), ultrasound Doppler, and magnetic resonance velocity imaging. Local estimates have been made using 133Xe clearance, microdialysis, near i.r. spectroscopy, positron emission tomography and laser Doppler. In principle, the aim of the study, the type of interventions and the limitations of each technique determine which method may be most appropriate. Ultrasound Doppler and continuous indo-cyanine green dye infusion gives the most accurate limb blood flow measurements at rest. Moreover, the ultrasound Doppler is unique, as it does not demand a steady-state, and because its high temporal resolution allows detection of normal physiological variations as well as continuous measurements during transitional states such as at onset of and in recovery from exercise. During steady-state exercise thermodilution can be used in addition to indo-cyanine green dye infusion and ultrasound Doppler, where the latter is restricted to exercise modes with a fixed vessel position. Magnetic resonance velocity imaging may in addition be used to determine blood flow within deep single vessels. Positron emission tomography seems to be the most promising tool for local skeletal muscle blood-flow measurements in relation to metabolic activity, although the mode and intensity of exercise will be restricted by the apparatus design.

Design and evaluation of a fibre-optic sensor for limb blood flow measurements

A fibre-optic microbending sensor for clinical use in venous occlusion plethysmography (VOP) has been developed. The sensor utilizes the microbending principle to detect the volume expansion of a limb following venous occlusion. This principle is based on the loss of energy in an optical fibre that undergoes mechanical perturbations. A comparative study of 10 healthy subjects has been made between the new fibre-optic sensor and a mercury strain-gauge sensor. Each subject's limb blood flow was recorded 10 times. The two sensor types were positioned closely together on the same limb. The result of the study shows a high correlation (r=0.949) verifying that the fibre-optic sensor's performance makes it a suitable alternative to the mercury strain-gauge sensor.

Correlation between peripheral vascular resistance and time to peak flow during reactive hyperaemia

Earlier studies have proposed that the time to reach peak hyperaemic flux recorded with laser Doppler (tp) is a simple and accurate method of evaluating ischaemic limbs and possibly a method of estimating the peripheral vascular resistance (PR). The aim of this study was to investigate the relationship between the tp and changes in limb vascular resistance caused by arterial stenosis. Forty postocclusive hyperaemia tests with arterial stenoses of different pressure gradients were performed in four pigs. A laser Doppler fluxmeter was used to record postocclusive hyperaemia in the skin of one hind limb. A specially designed tourniquet was used for the arterial occlusion. Proximal and distal to the occlusion level a snare was used to form different grades of stenosis. The PR (mmHg.ml-1.min-1) was either estimated by infusion of a known blood volume into the tested limb over a given time period with simultaneous measurement of pressure or calculated on the basis of measurements of limb blood flow and blood pressure gradients. The tp was closely related to total limb vascular resistance assessed by the blood infusion method (r = 0.83, p < 0.0003) and to the resistance calculated from volume blood flow and intraarterial pressures (r = 0.86, p < 0.0001). This study suggests that the tp accurately reflects limb vascular resistance in an experimental model. Thus tp may be used as a quantitative indicator of overall blood flow impairment, and should be evaluated in patients with lower-limb atherosclerosis.

Strain gauge plethysmography and Doppler ultrasound in the measurement of limb blood flow

The maintenance of adequate oxygen delivery (DO2) and tissue uptake (VO2) has become central dogma in the management of the critically ill. However, these parameters are derived using gas tensions measured in mixed venous blood and may not reflect changes in regional blood flow. Therefore, it has become necessary to provide estimates of blood flow to specific organs and to evaluate the most adequate techniques available. In order to define the best means of assessing blood flow to the lower limb noninvasively in normal subjects, measurements of superficial femoral arterial blood flow using Doppler ultrasound (DU) and strain gauge plethysmography (SGP) were compared in 10 normal volunteers at rest and during exercise. To evaluate the effect of strain gauge positioning, results of measurements made under four different combinations of cuff/strain gauge placement were compared in 15 other volunteers. The correlation of the limb blood flow obtained using the two methods at rest and exercise was 0.57 and 0.62 and the limits of agreement (d +/- 2SD) were 0.40 +/- 2.49 and -0.86 +/- 5.22 ml 100 ml-1 tissue min-1 at rest and on exercise, respectively. Results obtained using SGP were more reproducible (Coef. repeat. 0.45 vs. 0.94 ml 100 ml-1 tissue min-1, for SGP and DU, respectively). The various combinations of cuff/strain gauge positioning showed a tendency to over-read when the latter was placed on the thigh, but were not significantly different (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Radionuclide limb blood flow measurements to resolve diagnostic problems in vascular surgery.

This paper describes the application of radionuclide limb blood flow measurements in 60 patients presenting to the vascular surgeons with exercise-induced leg pain. All patients were considered to be diagnostic problems since either their symptoms were atypical for peripheral vascular disease, or they had normal peripheral pulses and/or a normal ankle/brachial pressure index. Thirty-one patients were ultimately shown to have peripheral vascular disease and underwent treatment. In all these cases the limb blood flow to one or both legs was below the normal range. Twenty-three patients were shown, by myelography, computed tomography or plain radiography, to have orthopaedic disease and in all cases their limb blood flow to both legs was within the normal range. In five patients, the limb blood flow was normal and the symptoms spontaneously resolved, no cause for the leg pain having been found (one patient refused angiography). Radionuclide limb blood flow is a simple and reliable diagnostic test which is superior to the assessment of peripheral pulses or their ankle to brachial pressure index in resolving diagnostic problems in vascular surgery.

103. Radionuclide limb blood flow measurements to resolve diagnostic problems in vascular surgery

103. Radionuclide limb blood flow measurements to resolve diagnostic problems in vascular surgery

Venous occlusion plethysmography using a fiber-optic sensor.

This paper presents the results of comparative testing of a fiber-optic sensor used as an alternative to the mercury strain-gauge in a clinically well-established technique for limb blood flow assessment, venous occlusion plethysmography. In this research the measurement of volume changes following venous occlusion has been performed with a variety of methods including the commonly used mercury strain-gauge. Temperature drift and long-term instability are problems associated with the mercury strain-gauge. In addition, environmental protection authorities are prohibiting the marketing of mercury sensors, beginning in 1993. Evaluation and optimization of the fiber optic microbending sensor is described in detail. Comparison with the mercury strain-gauge sensor is made for in lower limb blood flow measurements.

Radionuclide limb blood flow in peripheral vascular disease

Radionuclide limb blood flow measurements using 99Tcm-labelled human serum albumin and a gamma camera have been performed on normal volunteers and on patients with suspected or confirmed peripheral arterial disease. The normal range of flow was found to be 10.0-22.3 ml per 100 ml tissue per min. Flow in the symptomatic legs of patients with arterial disease varied from 9.0 ml per 100 ml tissue per min in mild claudication to less than 1.0 ml per 100 ml tissue per min in rest pain. The technique has been used as an initial screening procedure, to resolve diagnostic problems, to measure objectively the treatment response and to assess patients with critical ischaemia. The results of 1100 measurements are reported and the clinical utility in routine vascular surgical practice is discussed.

Isotope limb blood flow measurement in patients undergoing peripheral laser angioplasty

A technique of isotope limb blood flow (ILBF) measurement employing Technetium-labelled human albumin and a gamma camera, was used to assess limb perfusion in 19 patients undergoing percutaneous laser angioplasty, both before and one month after treatment. Twenty-three limbs with femoro-poplited occlusions ranging in length from 3–35 cm (median 8cm) were recanalized using an Nd-YAG laser and sapphire tipped optical fibre. Primary angiographic success was achieved in 19 lesions of which 6 re-occluded within the first month, and 13 remained patent with relief of symptoms. Clinically successful procedures were associated with a large increase in ILBF. However, normal blood flow was restored in only 54% of limbs. There was a slight decrease in limb perfusion after failed laser angioplasty but this was not statistically significant in this small series. Furthermore, there was no clinically apparent circulatory compromise, or need for urgent surgical bypass in failed cases. We conclude that ILBF is a useful means of assessing patients undergoing laser angioplasty, particularly for detecting small flow changes in patients who are unable to complete a standard exercise test. Its use can be recommended for assessing blood flow changes following other forms of limb revascularization.

Antihypertensive Treatment in Concomitant Peripheral Vascular Disease

The relative importance of hypertension as a risk factor for peripheral vascular disease is of the same order as coronary artery disease. The design of drug studies in occlusive vascular disease presents several problems. First, investigations must be placebo-controlled and crossover in design. Second, since these patients are very much at risk from other vascular occlusions, length of treatment phase is critical. Third, drug doses are also critical--probably best chosen by titration to similar antihypertensive effect. Fourth, patients must be trained in treadmill procedure. Fifth, measurements of limb blood flow must be accompanied where possible by "functional" assessment, e.g., claudication distance. With respect to the specific problem of low perfusion pressure distal to the blockage of peripheral vasculature, resting blood flow may remain normal, implying compensatory reduction in tone of arteriolar resistance vessels. Thus, regional circulation distal to blockage is sensitive to changes in perfusion pressure. There is the risk of "steal" with vasodilator agents; however, conflict exists in the literature over effects of beta-blockers in this situation. In view of its peripheral hemodynamic profile, the theoretical possibilities with the beta-blocker/vasodilator carvedilol in patients with hypertension and peripheral vascular disease seem extremely rewarding, but remain to be borne out in practice.

Skeletal muscle response to exercise training in congestive heart failure.

To examine the ability of the skeletal muscle of congestive heart failure (CHF) patients to adapt to chronic exercise, five patients performed localized nondominant wrist flexor training for 28 d. Inorganic phosphate (Pi) and phosphocreatine (PCr) were monitored by magnetic resonance spectroscopy in both forearms at rest and during submaximal wrist flexion exercise at 6, 12, 24, and 36 J.min-1 before and after exercise training. Simultaneous measurements of limb blood flow were made by plethysmography at 12, 24, and 36 J.min-1. Forearm muscle mass and endurance were measured by magnetic resonance imaging and wrist flexion exercise before and after training. The Pi/PCr ratio and pH were calculated from the measured Pi and PCr. Exercise cardiac output, heart rate, plasma norepinephrine, and lactate measured during training were not elevated above resting values, confirming that training was localized to the forearm flexor muscles. After training, muscle bioenergetics, as assessed by the slope of the regression line relating Pi/PCr to submaximal workloads, were improved in the trained forearm of each patient, although muscle mass, limb blood flow, and pH were unchanged. Forearm endurance increased by greater than 260% after training. In the dominant untrained forearm, none of the measured indices were affected. We conclude that localized forearm exercise training in CHF patients improves muscle energetics at submaximal workloads in the trained muscle, an effect which is independent of muscle mass, limb blood flow, or a central cardiovascular response during training. These findings indicate that peripheral muscle metabolic and functional abnormalities in CHF can be improved without altering cardiac performance.

Application of a New Method of Limb Blood Flow Measurement Using a Radioactive Isotope and a Gamma Camera

The aim of this paper is to report our early experience using this technique in the assessment of peripheral vascular disease. In particular we describe its application in a large group of patients with intermittent claudication. These have been subdivided into two groups: those who could and those who could not successfully complete a treadmill test. We also describe its use in a group of patients with ischemic rest pain

Limb volume measurements in peripheral arterial disease.

A simple method for measuring limb volumes of patients with peripheral arterial disease undergoing limb blood flow measurement is described. The device uses the change in surface level of water in a cylindrical reservoir to generate a voltage which is amplified and converted to a volume. The plethysmograph is stable and accurate over a wide range of limb volumes. For patients with leg ulcers or gangrene, where water immersion is not possible, a geometrical model has been developed which allows the volume to be calculated from a series of six external measurements. Comparison with measured volumes in 46 patients has shown this model to be accurate with a mean error of 3.3%. It provides a convenient alternative to direct measurement in these patients.