Radionuclide plethysmography for noninvasive evaluation of peripheral arterial blood flow

We validated a noninvasive radionuclide plethysmography technique to evaluate peripheral arterial blood flow during reactive hyperemia. This method, based on the measurement of blood volume variations during repetitive venous occlusions, was compared with strain-gauge venous impedance plethysmography. The technique uses 99mTc-labeled autologous red blood cells scintigraphy to determine the rate of change of forearm scintigraphic counts during venous occlusion. Thirteen subjects were simultaneously evaluated with radionuclide and impedance plethysmography. Six baseline flow measurements were performed to evaluate the reproducibility of each method. Twenty-seven serial measurements were then made to evaluate flow variation during forearm reactive hyperemia. After 30 min of recovery, resting forearm blood flows were again evaluated. Impedance and radionuclide methods showed excellent reproducibility with intraclass correlation coefficients of 0.96 and 0.93, respectively. There was also good correlation of flows between both methods during reactive hyperemia (r = 0.87). Resting flows at 30 min after reactive hyperemia were slightly lower than at baseline with both methods. We conclude that radionuclide plethysmography could be used for the noninvasive evaluation of forearm blood flow and its dynamic variations during reactive hyperemia.     

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.     

Influence of tissue compressibility on calibration for strain-gauge plethysmography

Strain gauges employed in plethysmography for determination of limb blood flow tend to counter the expansion of the limb during venous occlusion. Traditionally a mechanical calibration is performed in situ to compensate for tissue compressibility. Greenfield, Whitney, and Mowbray stated that, otherwise, large errors would result (Br. Med. Bull. 19: 101-109, 1963). Nonetheless, not all of the recent reports on skin blood flow in humans have been based on a calibration procedure that corrects for tissue compressibility. To evaluate the significance of this problem, we developed a new strain-gauge holder that made possible frequent, reproducible, stretching of a single-strand Whitney gauge in situ. We compared the apparent sensitivity thus obtained to electrical or bench mechanical determinations. We independently determined tissue compressibility by recording limb circumference as tension in a circumferential tube was varied. Both techniques showed that tissue compressibility is a small source of error (5%) and that compressibility decreases during occlusion. Therefore the cumbersome holder and potential artifacts associated with the traditional technique need not be tolerated. We also investigated the consequences of nonuniform tension distribution and temperature changes; practical considerations for dealing with these are discussed.     

Venous cuff pressures from 30 mmHg to diastolic pressure are recommended to measure arterial inflow by plethysmography.

Venous occlusion strain gauge plethysmography (VOP) is based on the assumption that the veins are occluded and arterial inflow is undisturbed by the venous cuff pressure. Literature is not clear concerning the pressure that should be used. The purpose of this study was to determine the optimal venous occlusion pressure at which the highest arterial inflow is achieved in the forearm, calf, and leg by using VOP. We hypothesized that, for each limb segment, an optimal (range of) venous cuff pressure can be determined. Arterial inflow in each limb segment was measured in nine healthy individuals by VOP by using pressures ranging from 10 mmHg up to diastolic blood pressure. Arterial inflows were similar at cuff pressures between 30 and 60 mmHg for the forearm, leg, and calf. Arterial inflow in the forearm was significantly lower at 10 mmHg compared with the other cuff pressures. In addition, arterial inflows at 20 mmHg tended to be lower in each limb segment than flow at higher cuff pressures. In conclusion, no single optimum venous cuff pressure, at which a highest arterial inflow is achieved, exists, but rather a range of optimum cuff pressures leading to a similar arterial inflow. Venous cuff pressures ranging from 30 mmHg up to diastolic blood pressure are recommended to measure arterial inflow by VOP.     

Blood flow measurement from plethysmographic pulse waves without venous occlusion

An air plethysmograph with a sensitive phototransducer was constructed so that plethysmographic volume-change pulsations could be displayed in detail without using venous occlusion. Software was developed to allow analysis of the pulses using a modification of the backward extrapolation technique. This allowed calculation of the forward arterial blood flow and noninvasive derivation of the resting arterial flow waveform. There is good reproducibility of the technique, with 8% variability between pairs of measurements at rest and 4% variability after hand exercise. Direct comparison made with blood flows measured by venous occlusion plethysmography showed good average agreement. The mean blood flow for venous occlusion (rest and exercise) was 0.76 +/- 0.07 mL/beat (mean +/- SEM), and the mean blood flow for backward extrapolation (rest and exercise) was 0.74 +/- 0.09 mL/beat (mean +/- SEM). This corresponds to 3.86 +/- 0.36 mL/min/100 mL and 3.76 +/- 0.46 mL/min/100 mL, respectively. Important assumptions when using this method are that venous return is constant and that forward arterial flow is over before the end of the cardiac cycle.     

Measurement of forearm blood flow by venous occlusion plethysmography: influence of hand blood flow during sustained and intermittent isometric exercise

The requirement for using an arterial occlusion cuff at the wrist when measuring forearm blood flows by plethysmography was tested on a total of 8 subjects at rest and during and after sustained and intermittent isometric exercise. The contribution of the venous effluent from the hand to the forearm flow during exercise was challenged by immersing the arm in water at 20, 34, and 40 degrees C. Occlusion of the circulation to the hand reduced the blood flow through the resting forearm at all water temperatures. There was an inverse relationship between the temperature of the water and the proportion in the reduction of forearm blood flow upon inflation of the wrist-cuff, ranging from 45 to 19% at 20 degrees to 40 degrees C, respectively. However, during sustained isometric exercise at 10% of the subjects maximum voluntary contraction (MVC) there was no reduction in the measured forearm flow when an arterial occlusion cuff was inflated aroung the wrist. Similarly, there was no alteration in the blood flow measured 2 s after each of a series of intermittent isometric contractions exerted at 20% or 60% MVC for 2 s whether or not circulation to the hand was occluded nor of the post-exercise hyperemia following 1 min of sustained contraction at 40% MVC. These results indicate that a wrist-cuff is not required for accurate measurement of forearm blood flows during or after isometric exercise.     

Measurements of vascular function using strain-gauge plethysmography: technical considerations, standardization, and physiological findings

The main purpose of the present study was to examine the relationships between measures of fitness [estimated peak oxygen consumption (V(O2) peak) and handgrip strength] and forearm vascular function in 55 young (22.6 +/- 3.5 yr) adults. In addition, the present study considered methodological and technical aspects regarding the examination of the venous system using mercury in-Silastic strain-gauge plethysmography (MSGP). Forearm venous capacitance and outflow were examined using five different [7, 14, 21, 28, and 35 mmHg < diastolic blood pressure (DBP)] venous occlusion pressures and after a 5- and 10-min period of venous occlusion. A pressure of 7 mmHg < DBP and a period of 10 min venous occlusion produced the greatest (P < 0.05) venous capacitance and outflow, without altering arterial indexes. Reproducibility of forearm arterial and venous indexes were evaluated at rest and after 5 min of upper arm arterial occlusion at 240 mmHg on three different occasions within 10 days with the interclass correlation coefficient ranging from 0.70 and 0.94. Estimated V(O2) peak correlated with postocclusion arterial inflow (r = 0.54, P = 0.012) and resting venous outflow (r = 0.56, P = 0.016). Finally, handgrip strength was associated with venous capacitance (r = 0.57, P = 0.007) and outflow (r = 0.67, P = 0.001). These results indicate that the examination of forearm vascular function using MSGP is reproducible. Moreover, the data show the importance of careful consideration of the selection of venous occlusion pressure and period when implementing these measures in longitudinal trials. Finally, the associations between fitness and venous measures suggest a link between venous function and exercise performance.     

Developing the methodology of examining the lower limb veins in cosmonauts for the space medicine practice

The article focuses on development of a methodology for evaluating the function of lower limb veins of cosmonauts in microgravity. The whys and wherefores of the choice of occlusive plethysmography equipment and procedure are explained. Much place is given to arguments for the body and limb positioning during venous plethysmography before and after space fight. To minimize the gravity effect on venous blood flow, the body should be in the level position, with the shin aligned with the hydrodynamically indifferent point. Determining the type of occlusion test, occlusion adjustments, venous parameters of interest, and data processing procedure constitute the methodology.     

Strain-gauge plethysmography in the evaluation of the evolution of deep vein thrombosis of the legs

Previous research has shown that MVO (Maximum Venous Outflow), VR (Venous Reflux), VE (Venous Emptying) and the respiratory waves recording are useful in differentiating occlusion and recanalization in postphlebitic syndrome. In the present work strain-gauge plethysmography was employed to quantitate the venous function after deep venous thrombosis of the legs. The studies were performed in a vascular laboratory with controlled temperature (23 to 25 C); records were obtained by a plethysmograph Parks mod. 270 connected to a Hewlett-Packard multi-channel mod. 7700. 17 patients (12 males, 5 females), mean age 55 years (range 24-75) that presented femoropopliteal thrombophlebitis documented by phlebography at the admission to the hospital were examined. MVO with and without superficial veins occlusion was measured by a mercury in silastic strain-gauge placed circumferentially about the calf. A pneumatic cuff thigh was inflated to 60 mm Hg. VE was measured in patients lying in inclined bed with the lower extremities 100 cm below the heart level compressing the calf with a pneumatic cuff 10 times for 5 seconds; the strain-gauge was placed on the foot level. VR after Valsalva's maneuver and the respiratory waves were recorded by a strain-gauge positioned at the maximum girth about the calf in patients lying on inclinated bed with the lower extremities 50 cm below the heart level. The result are here indicated: (Table: see text) There was differences in the evolution of venous function after deep venous thrombosis of the legs for each patient. Strain-gauge plethysmography may become evaluable non invasive technique in the evaluation of deep venous thrombosis evolution in the legs. The therapeutic assessment of postphlebitic syndrome.     

From Belfast to Mayo and beyond: the use and future of plethysmography to study blood flow in human limbs.

Venous occlusion plethysmography is a simple but elegant technique that has contributed to almost every major area of vascular biology in humans. The general principles of plethysmography were appreciated by the late 1800s, and the application of these principles to measure limb blood flow occurred in the early 1900s. Plethysmography has been instrumental in studying the role of the autonomic nervous system in regulating limb blood flow in humans and important in studying the vasodilator responses to exercise, reactive hyperemia, body heating, and mental stress. It has also been the technique of choice to study how human blood vessels respond to a variety of exogenously administered vasodilators and vasoconstrictors, especially those that act on various autonomic and adrenergic receptors. In recent years, plethysmography has been exploited to study the role of the vascular endothelium in health and disease. Venous occlusion plethysmography is likely to continue to play an important role as investigators seek to understand the physiological significance of newly identified vasoactive factors and how genetic polymorphisms affect the cardiovascular system in humans.     

Local Blood Flow in Human Leg Muscle Measured by a Transient Response Thermoelectric Method

The initial transient response of a Gibbs type thermoelectric probe embedded in human resting leg muscle was used for absolute quantitative measurement of local blood flow per unit tissue volume (local perfusion). The probe consisted of two thermistor-containing needles, one of which was heated by a constant electrical power input. The temperatures of both thermistors were recorded continuously on a two-channel, fast-response recorder. Upon sudden occlusion of the blood flow to the leg, each temperature vs. time record exhibited a change of slope. The change in slope of the temperature difference, divided by the temperature difference, (degrees/minute degree) was identified with the local perfusion (milliliters/minute milliliter) existing just before occlusion. The local perfusions determined agreed in range and mean with literature values of average perfusion by venous occlusion plethysmography. The nature of the local blood flow measured by the present method is discussed relative to that by other methods.     

Vascular adaptation to 4 wk of deconditioning by unilateral lower limb suspension

Physical inactivity or deconditioning is an independent risk factor for atherosclerosis and cardiovascular disease. In contrast to exercise, the vascular changes that occur as a result of deconditioning have not been characterized. We used 4 wk of unilateral lower limb suspension (ULLS) to study arterial and venous adaptations to deconditioning. In contrast to previous studies, this model is not confounded by denervation or microgravity. Seven healthy subjects participated in the study. Arterial and venous characteristics of the legs were assessed by echo Doppler ultrasound and venous occlusion plethysmography. The diameter of the common and superficial femoral artery decreased by 12% after 4 wk of ULLS. Baseline calf blood flow, as measured by plethysmography, decreased from 2.1 +/- 0.2 to 1.6 +/- 0.2 ml.min(-1).dl tissue(-1). Both arterial diameter and calf blood flow returned to baseline values after 4 wk of recovery. There was no indication of a decrease in flow-mediated dilation of the superficial femoral artery after ULLS deconditioning. This means that functional adaptations to inactivity are not simply the inverse of adaptations to exercise. The venous pressure-volume curve is shifted downward after ULLS, without any effect on compliance. In conclusion, deconditioning by 4 wk of ULLS causes significant changes in both the arterial and the venous system.     

Comparison of two plethysmography systems in assessment of forearm blood flow.

Venous occlusion plethysmography is widely used to assess forearm blood flow (FBF). We compared the established Hokanson system (HEC4) with a newly developed Filtrass 2001 system (F2001). The HEC4 uses mercury-in-Silastic strain gauges, whereas F2001 detects volume changes with a nonmercury linear displacement device. The aim of this study was to evaluate the new F2001 against the HEC4 in terms of repeatability and systematic bias. Ten subjects were studied on 4 separate days in random order using either the HEC4 on both arms, the F2001 on both arms, the HEC4 on the right arm with the F2001 on the left, or the F2001 on the right arm and the HEC4 on the left. Stroop's colored word conflict test and postocclusive hyperemia were used to increase FBF, and lower body negative pressure was used to lower FBF. Stroop's colored word conflict test and lower body negative pressure increased (24.6 +/- 1.5%, n = 240, P < 0.0001) and decreased (18.7 +/- 0.8%, n = 240, P < 0.0001) FBF, respectively. Postocclusive hyperemia after occlusion times of 5, 8, and 13 min substantially increased FBF by 390 +/- 86, 756 +/- 217, and 851 +/- 132%, respectively. Repeatability was not different between the devices (0.10 +/- 2.37 vs. -0.47 +/- 1.92 l/min, n = 125, P > 0.05), and there was no systematic bias. The F2001 is a newly developed plethysmography system that does not utilize mercury and is suitable for assessing changes of FBF in physiological studies.     

Local vascular responses affecting blood flow in postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 +/- 0.2 vs. 4.4 +/- 0.5 and 2.7 +/- 0.4 ml.min-1.100 ml-1) but increased during leg lowering (1.2 +/- 0.5 ml.min-1. 100 ml-1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 +/- 13 vs. 15 +/- 3 and 22 +/- 5 mmHg.ml-1. 100 ml. min) but decreased to 29 +/- 13 mmHg.ml-1.100 ml. min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 +/- 2 vs. 29 +/- 4 and 28 +/- 4 s; cutaneous time constant = 60 +/- 25 vs. 149 +/- 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.     

An alternative method for calculating changes in arterial calf blood flow at rest. An initial study

In 20 patients we studied the changes in calf arterial blood flow (AF) following spinal and epidural blocks, using venous occlusion strain gauge plethysmography (SGP). AF was calculated both in the conventional way by drawing a tangent to the initial upslope of the curve, and by a new method which measures the time to the point when 50% of venous capacity is reached (tVC50). The statistical differences within and between the spinal and epidural groups for AF and tVC50 were determined. In measuring the post-block changes in AF as compared with the control values, a statistically significant correlation (rs = -0.85, p less than 0.01) was observed between the two methods. We conclude that the new variable, tVC50, seems to be potentially useful in calculating changes in arterial blood flow at rest, and could be used, for example, in connection with surgical and pharmacological interventions, especially when the initial upslope of the SGP curve is equivocal.     

Cross transfer effects of muscular training on blood flow in the ipsilateral and contralateral forearms

Blood flow in the right and left forearms was determined by venous occlusion plethysmography in ten healthy male subjects before and after training with a hand ergometer. The subjects in group A and B were trained using work loads of 1/3 and 1/2, respectively, of maximum grip strength 6 days/week for 6 weeks. It was found that the blood flow in the left (untrained or contralateral) forearm during exhaustive training of the right hand increased gradually with increasing training periods, and that after 6 weeks of training, grip strength, endurance and peak blood flow of the forearm increased significantly not only in the trained forearm, but also in the untrained forearm. From these results, it is suggested that the increase of blood flow in the contralateral limb after training may, at least in part, be related to the cross transfer effect of muscular endurance.     

Regional blood volume and peripheral blood flow in postural tachycardia syndrome

Variants of postural tachycardia syndrome (POTS) are associated with increased ["high-flow" POTS (HFP)], decreased ["low-flow" POTS (LFP)], and normal ["normal-flow" POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.     

MRI measures of perfusion-related changes in human skeletal muscle during progressive contractions.

Although skeletal muscle perfusion is fundamental to proper muscle function, in vivo measurements are typically limited to those of limb or arterial blood flow, rather than flow within the muscle bed itself. We present a noninvasive functional MRI (fMRI) technique for measuring perfusion-related signal intensity (SI) changes in human skeletal muscle during and after contractions and demonstrate its application to the question of occlusion during a range of contraction intensities. Eight healthy men (aged 20-31 yr) performed a series of isometric ankle dorsiflexor contractions from 10 to 100% maximal voluntary contraction. Axial gradient-echo echo-planar images (repetition time = 500 ms, echo time = 18.6 ms) were acquired continuously before, during, and following each 10-s contraction, with 4.5-min rest between contractions. Average SI in the dorsiflexor muscles was calculated for all 240 images in each contraction series. Postcontraction hyperemia for each force level was determined as peak change in SI after contraction, which was then scaled to that obtained following a 5-min cuff occlusion of the thigh (i.e., maximal hyperemia). A subset of subjects (n = 4) performed parallel studies using venous occlusion plethysmography to measure limb blood flow. Hyperemia measured by fMRI and plethysmography demonstrated good agreement. Postcontraction hyperemia measured by fMRI scaled with contraction intensity up to approximately 60% maximal voluntary contraction. fMRI provides a noninvasive means of quantifying perfusion-related changes during and following skeletal muscle contractions in humans. Temporal changes in perfusion can be observed, as can the heterogeneity of perfusion across the muscle bed.     

Finger vasodilation correlates better with tympanic than esophageal temperature

The relationship of finger blood flow (FBF) measured by venous occlusion plethysmography to tympanic temperature (Tty) was compared with that of FBF to esophageal temperature (Tes) during exercise at 50% VO2max for 40 min at an ambient temperature of 25 degrees C. The relationship of FBF to Tes showed an inflexion as Tes increased during exercise. The slope of the regression line showing the relationship between FBF and Tes was initially moderate, and then suddenly became steeper at the inflexion point. The relationship of FBF to Tty, however, was linear, without an inflexion. The results suggest that finger vasodilation during moderate exercise correlates better with tympanic than esophageal temperature.     

Lumped parameter thermal model for the study of vascular reactivity in the fingertip

Vascular reactivity (VR) denotes changes in volumetric blood flow in response to arterial occlusion. Current techniques to study VR rely on monitoring blood flow parameters and serve to predict the risk of future cardiovascular complications. Because tissue temperature is directly impacted by blood flow, a simplified thermal model was developed to study the alterations in fingertip temperature during arterial occlusion and subsequent reperfusion (hyperemia). This work shows that fingertip temperature variation during VR test can be used as a cost-effective alternative to blood perfusion monitoring. The model developed introduces a function to approximate the temporal alterations in blood volume during VR tests. Parametric studies are performed to analyze the effects of blood perfusion alterations, as well as any environmental contribution to fingertip temperature. Experiments were performed on eight healthy volunteers to study the thermal effect of 3 min of arterial occlusion and subsequent reperfusion (hyperemia). Fingertip temperature and heat flux were measured at the occluded and control fingers, and the finger blood perfusion was determined using venous occlusion plethysmography (VOP). The model was able to phenomenologically reproduce the experimental measurements. Significant variability was observed in the starting fingertip temperature and heat flux measurements among subjects. Difficulty in achieving thermal equilibration was observed, which indicates the important effect of initial temperature and thermal trend (i.e., vasoconstriction, vasodilatation, and oscillations).