Can an intermittent pneumatic compression system monitor venous filling in the leg?

OBJECTIVE: Intermittent pneumatic compression (IPC) systems are used for prophylaxis of venous thromboembolism. Both legs are wrapped with inflatable sleeves connected to a pneumatic controller to allow compression of the legs causing expulsion of venous blood. Venous refill between inflation periods causes leg expansion, which can be tracked by measuring pressure changes in the sleeve. The aim of our study, which utilized the SCD RESPONSE compression system in conjunction with an independent pressure transducer, was to investigate whether factors such as temperature changes within the sleeves during inflation and deflation affect the measured venous refill time (VRT). METHODS: Transducers were used to measure air pressure in the middle chamber of the sleeve. A thermocouple was also inserted into the bladder to measure temperature changes. Inflation, deflation and refill measurements were made with the sleeves around model systems (static, rigid plastic pipes or compliant paper rolls, and dynamic, latex tubes inserted between a rigid pipe and the sleeve to simulate veins) and on 10 subjects in semi-recumbent, supine and sitting positions. RESULTS: In all the experiments the maximum temperature change was 0.023 degrees C. With the static model systems, the pressure in the venous refill measuring bladder fell from the inflation pressure of 40 - 50 mmHg to 9 +/- 1 mmHg, but then rose by 2.1 +/- 0.2 mmHg (rigid pipes) and 1.4 +/- 0.2 mmHg (paper rolls). These pressure changes were associated with reported 'filling times' of 21 - 24 s (rigid pipes) and 22 - 29 s (paper rolls). In experiments on dynamic filling of the latex tube, there was a strong linear relationship between the filling time indicated by the SCD system and the time to empty the filling reservoir. In 170 measurements on human subjects, there were only three VRTs less than 30 s and 36 less than 35 s. VRT increased in all subjects when going from supine (34.6 +/- 1.8 s) to semi-recumbent (38.9 +/- 1.9 s) to sitting (42.6 +/- 0.9 s) positions. DISCUSSION: In all cases, temperature changes during the refill phase were too small to result in significant pressure changes that would affect VRT. The pressure increases observed with the static models after deflation appeared to be due to viscoelastic relaxation. Viscoelastic responses were present in human subjects, but the effect on VRT was negligible. This indicates that the increased VRT observed in humans is due to blood return. Body position affected VRTs, indicating the system's ability to detect changes in filling times and venous blood volume.

Toward the clinical application of time-domain fluorescence lifetime imaging.

High-speed (video-rate) fluorescence lifetime imaging (FLIM) through a flexible endoscope is reported based on gated optical image intensifier technology. The optimization and potential application of FLIM to tissue autofluorescence for clinical applications are discussed.

Influence of heart rate and vasoactive drugs on blood flow patterns at the canine ilio-femoral bifurcation.

OBJECTIVE: The aim was to study the effects of altered heart rate and vasoactive drugs on the blood velocity patterns in the region of an arterial bifurcation. METHODS: Blood velocity profiles were measured in an exposed iliofemoral bifurcation of paced dogs using a pulsed Doppler ultrasound velocimeter with high temporal and spatial resolution. RESULTS: Decrease of the heart rate from 120 beats.min-1 (2 Hz) to 60 beats.min-1 (1 Hz) increased the peak forward velocity (30%), the peak reverse velocity (20%), and the duration of reverse flow (25%). Each drug caused qualitatively similar changes in velocity patterns at both heart rates. The systemic administration of angiotensin II reduced peak forward velocity (-26% at 2 Hz and -33% at 1 Hz) and forward flow duration (-15% at 1 Hz), the peak reverse velocity (-30% at 1 Hz), and reverse flow duration (-20% at 2 Hz and -28% at 1 Hz). Glyceryl trinitrate also reduced the peak forward velocity (-19% at both 2 and 1 Hz) but prolonged forward flow duration (28% at 2 Hz and 17% at 1 Hz) and that of reverse flow (45% at 2 Hz and 24% at 1 Hz), and also decreased the degree of oscillation (-16% at 2 Hz). Barnidipine hydrochloride (a calcium channel antagonist) also increased the duration of forward flow (48% at 1 Hz) and of reverse flow (31% at 2 Hz) but reduced the peak reverse velocity (-29% at 1 Hz) and flow oscillation (-22% at 2 Hz and 20% at 1 Hz). CONCLUSIONS: These dramatic changes in the pattern of blood flow, including alterations in the amplitudes and durations of the different phases of the flow cycle, are expected to have important consequences on the shear dependent responses of endothelial cells in the region of the bifurcation.

Effect of vasoactive agents and applied stress on the albumin space of excised rabbit carotid arteries.

Experiments were undertaken on excised rabbit common carotid arteries to assess whether the distribution volume for radioactively labelled albumin is influenced by smooth muscle tone or externally applied stress. In arteries at relaxed length and zero transmural pressure, the distribution volume in the media was reduced by noradrenaline at concentrations exceeding 10(-9) M and increased by both sodium nitrite and isosorbide dinitrate at concentrations exceeding 10(-4) M. The distribution volume was lower in both the media and adventitia of segments at in vivo length pressurized with air to prevent convection through the wall, than in segments at relaxed length and zero transmural pressure. Noradrenaline decreased and sodium nitrite increased the medial distribution volume of the tracer in these air-pressurized segments. The vasoactive agents did not change the [51Cr]EDTA space in vessels at relaxed length and zero transmural pressure, although there were small alterations of medial water content. Transient conditions raise interpretative difficulties because of uncertainty about endothelial permeability and time-dependent changes of wall properties. The changes of the distribution volume for labelled albumin are thought to reflect changes in the properties of the interstitium.

Effect of noradrenaline, sodium nitrite and isosorbide dinitrate on albumin transport in the wall of the excised rabbit common carotid artery.

The effects of noradrenaline (NA), sodium nitrite (NaNO2) and isosorbide dinitrate (ISDN) on the steady state distribution of 125I-labelled albumin in the wall of excised rabbit common carotid arteries were studied. The vessels were incubated in Tyrodes solution either at relaxed length and zero transmural pressure (non-pressurized) or at in vivo length and a transmural pressure of 70 mm Hg (pressurized). Label was applied in the same concentration at both the luminal and outer surfaces. The mean medial uptake in pressurized vessels was greater after treatment with 10(-7) M NA than after additional treatment with either 10(-3) M NaNO2 or 10(-3) M ISDN. The opposite was found for non-pressurized vessels. The medial uptake by NA-treated pressurized vessels was greater than that by NA-treated non-pressurized vessels, while the reverse was found for NaNO2- or ISDN-treated vessels. We conclude that the different patterns of uptake seen in these vessels results from the relative effects of externally applied stress (elongation and pressurization), smooth muscle tone and convection through the wall, on the properties of the interstitium, and possibly from the effects of the vasoactive agents on endothelial permeability.

Net albumin transport across the wall of the rabbit common carotid artery perfused in situ.

We have studied the transport of radioactively labelled albumin in the rabbit common carotid artery perfused in situ at 100 cm H2O luminal pressure in the anaesthetized living animal, assessing the distribution of concentration across the wall by means of sequential frozen sectioning. We have compared the findings with those of experiments in which we have attempted to saturate the wall with label. Our findings support the belief that there is a net transport of macromolecules across the arterial wall. They show in addition that the wall is inhomogeneous. The distribution volume for label is greater in the adventitia than the media, which appears to offer a larger resistance. The transport process is seemingly dominantly diffusional.

Coronary vasodilatation induced by calcitonin gene-related peptide in the anaesthetised pig.

The ability of CGRP to increase blood flow in the coronary circulation of the anaesthetized pig was studied in a constant pressure perfusion model. Human alpha-CGRP, when infused close-arterially into the left anterior descending coronary artery perfused at constant pressure, produced a marked and prolonged dose-related increase in coronary flow, at doses above 10 pmol min-1. The gradient of the flow/pressure curves at each dose increased with an increase in pressure, indicating a drop in the resistance of the coronary bed. No significant change was observed in heart rate, left ventricle pressure, mean arterial pressure or cardiac output.

Changes in vein interstitium following distension for aortocoronary bypass.

Some patients who undergo aortocoronary bypass develop lesions in the graft and recurrence of symptoms. Hydraulic distension is used for preparation of veins. We have studied properties of vein interstitium, before and after peroperative distension, in 30 consecutive unselected patients. Segments of vein were studied for water content, swelling behaviour, tracer distribution, and uronic acid content. Initial water content was the same in distended and undistended vein; initial uronic acid content was slightly lower in distended veins, 8.7 (SD = 2.3) micrograms/m, n = 4 vs 10.5 (SD = 5.1) micrograms/mg dry weight, n = 6, not significant. The initial ratio, uronate/hydroxyproline was less in distended veins, 0.14 (SD = 0.05) n = 4 vs 0.19 (SD = 0.07), n = 6 in controls, not significant. Distended veins swelled less during incubation in saline. Average weight gain/initial weight was 0.65 (SD = 0.45), n = 27, and 1.1 (SD = 0.66), n = 25 in controls (p less than 0.01); change in water content/dry weight was 1.2 (SD = 1.1), n = 22, and 1.7 (SD = 1), n = 23 (p less than 0.02), in controls. Distended veins desorbed less uronic acid into the bath; 0.40 (SD = 0.2) microgram/mg wet tissue, n = 26 and 0.59 (SD = 0.3), n = 25 in controls (p less than 0.01). The pattern of uptake of two tracers 125I Serum albumin and 51Cr EDTA, was similar in both groups. These findings suggest alteration of the interstitial matrix of veins during distension. Histologic examination of glutaraldehyde-fixed tissue by light and electron microscopy revealed mural thinning and endothelial cell damage in distended veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors influencing arterial wall mass transport.

Arterial wall mass transport has particularly attracted attention because it may be implicated in the development of arterial disease, including arteriosclerosis. A short review is presented of the structure of the arterial wall and of studies of mass transport within it. Recent findings confirm that mass transport occurs across the entire arterial wall apparently from the lumen to the adventitial lymphatics. Evidence has emerged of inhomogeneity of the distribution volume for extracellular tracers in different layers of the wall. An attempt is made to interpret results which indicate that distension per se of arteries and increase of medial smooth muscle tone tend to compact the medial interstitium whereas pressure driven convection across the wall tends to expand that tissue. These findings imply a potentially important role of endothelial permeability, smooth muscle tone and luminal pressure in influencing solute transport in the wall and wall transport properties.

Effects of high molecular weight solutes on fluid flux across the arterial wall.

To investigate the mechanisms controlling the flux of plasma proteins into and through the walls of blood vessels, we have studied the effects of two inert protein analogues, Dextran 500 and Poly(ethylene)oxide (PEO) on fluid transport across the walls of intact rabbit common carotid arteries. Transmural fluxes were first measured in vessels pressurized to 150 cmH2O with a solution containing 10 mg/ml albumin alone (control solution) and then with one containing 10 mg/ml albumin plus 10 or 50 mg/ml dextran, or 10 or 30 mg/ml PEO (test solutions). The macromolecule solutions caused a decrease in transmural filtration; the ratios of fluxes with the test solutions to those with the control solutions were 0.89 +/- 0.11 (7), 0.63 +/- 0.08 (8), 0.69 +/- 0.24 (9) and 0.41 +/- 0.09 (4), respectively (Mean +/- SD (n)). These reductions in fluid movement through the vessel wall may be explained quantitatively in terms of the formation of concentration-polarized layers of the macromolecules at the luminal surface or interactions of the macromolecules with the endothelial glycocalyx, causing a decrease in its permeability.

Convective and diffusive transport of plasma proteins across the walls of large blood vessels.

The early stages of atherosclerosis involve the accumulation of plasma constituents, including fibrinogen, lipoproteins and lipids and their modified forms. To assess the role of haemodynamics in these processes, we have measured the pressure dependence of the fluxes of albumin, fibrinogen and fluid through the whole thickness of the walls of the carotid artery and the inferior vena cava. Fluxes were much higher across the vein, the vessel which is less susceptible to atherosclerosis. Protein fluxes showed a marked non-linear dependence on transmural pressure which was greater than the pressure dependence of the fluid fluxes. Protein movement across the artery wall could be modelled assuming a significant convective component with the protein reflection coefficient decreasing as the wall tissue was stretched by the increasing pressure. Protein movement across the vein wall appeared to be dependent on ultrafiltration with the formation of a concentration polarization layer at the luminal interface; such a layer would be extremely sensitive to flow within the vessel lumen.

Effect of pressure and intimal damage on 131I-albumin and [14C]sucrose spaces in aorta.

To measure the distribution volume for sucrose and albumin in the media of the rabbit thoracic aorta, we studied the uptake of tracers in vitro. In most cases the tracers were applied to both luminal and adventitial surfaces at the same concentration. When transmural convection was prevented by pressurization of the arteries with air, there was a decrease in sucrose space (19% at 70 mmHg and 28% at 180 mmHg) and in albumin space (60% at 70 mmHg and 66% at 180 mmHg), compared with the respective spaces in relaxed arteries (0.42 for sucrose and 0.08 for albumin). Much smaller changes were found when intact vessels were pressurized with liquid (insignificant for sucrose, decreases of 24% at 70 mmHg and 14% at 180 mmHg for albumin). Removal of the endothelium, which increases transmural fluid flux, increased the space for sucrose (not significantly at 70 mmHg and 17% at 180 mmHg) and particularly for albumin (100% at 70 mmHg and 250% at 180 mmHg). We conclude that the interstitial volume and consequently the protein space within the media can be modified both by distending stresses applied to the vessel and by transmural fluid flux.

The mass transport of the arterial wall: effect of mechanical stresses and vasoactive agents, including nitrates.

Arteriosclerosis is a slowly progressing disease. It is important, therefore, to seek means of delaying its progress both in pre-symptomatic patients and in patients with circulatory disorders. Various features of the disease, among them the focal distribution of the lesions, imply that changes in blood composition cannot alone account for its occurrence and that a contribution must come from the arterial wall, possibly from its mass transport properties. We review recent findings concerning arterial wall mass transport. Movement of material occurs right across the arterial wall from the lumen to the adventitial lymph and it appears that the media may act as a barrier to the efflux of material from the wall. Work currently in progress suggests that among factors which influence arterial wall mass transport are the level of arterial blood pressure, endothelial permeability and the tone of the medial smooth muscle. Further fundamental study is needed but consideration would now seem justified as to whether the progression of arteriosclerosis might be influenced by pharmacological agents which affect the wall mass transport.

Filtration through damaged and undamaged rabbit thoracic aorta.

The influence of luminal pressure and endothelial removal on fluid filtration across the arterial wall has been studied in the rabbit thoracic aorta. Segments of aorta were excised in such a way as to prevent shortening and depressurization and were filled with a 4% albumin-Tyrode solution. Experiments were carried out at two controlled pressure levels (70 and 180 mmHg). The hydraulic conductivity (Lp) of the total wall, calculated from the filtration data, was 4.00 +/- 1.31 and 2.44 +/- 0.80 (SD) X 10(-8) cm/(s X mmHg) in intact wall at 70 and 180 mmHg, respectively (P less than 0.01), whereas values for deendothelialized arteries were higher (P less than 0.01), being 5.36 +/- 1.62 and 5.27 +/- 0.84, respectively. The apparent pressure dependence of conductivity of the intact wall may be due to altered strain of the interstitial matrix. Removal of the endothelium can increase the hydration and porosity of the medial interstitium but, assuming that the conductivity of the deendothelialized wall at 70 mmHg is the same as that of the normal media, the calculated conductivity of the endothelium is 15.76 X 10(-8) cm/(s . mmHg).

Albumin and Cr-EDTA uptake by systemic arteries, veins, and pulmonary artery of rabbit.

Experiments have been performed both in vivo and in vitro to measure the steady-state uptake of labeled albumin and Cr-ethylenediaminetetraacetate by various blood vessels of the rabbit: the ascending and descending portions of the thoracic aorta, the carotid artery, the pulmonary artery, and the inferior vena cava. The in vitro experiments indicated that the wall tissues of the pulmonary artery and the vena cava have much greater distribution volumes for albumin than do the systemic arteries. This may in part explain the differences in wall tissue concentrations in vivo and, in turn, the differences between vessels in their susceptibility to atherosclerosis.

The interaction of convection and diffusion in the transport of 131I-albumin within the media of the rabbit thoracic aorta.

The interaction of convection and diffusion in the transport of 131I-labeled albumin within the wall of rabbit thoracic aorta was studied in vessels excised at in vivo length. They were pressurized with a solution containing no tracer and immersed in a solution containing labeled albumin. The label then entered the wall tissue via the adventitia and had to diffuse against the convective flux which occurred from the lumen to the adventitia. Experiments were performed on intact and deendothelialized vessels pressurized to 70 and 180 mm Hg. At the end of each experiment the vessels were subjected to sequential frozen sectioning parallel to the lumenal surface. The radioactivity of the 20-micron-thick sections was determined and expressed as a tissue:labeled solution concentration ratio. Transmural profiles of these ratios were thus obtained. The steady state was found to be achieved by about 90 minutes. When the convection was enhanced by removal of the endothelium, the average ratios were lower than when the endothelium was intact, and the profile was much flatter. The results suggest that convection influenced macromolecular transport within the arterial wall, even in vessels with intact endothelium.

The effect of luminal flow in rabbit carotid artery on transmural fluid transport.

The steady-state flow of fluid across the wall of the isolated rabbit common carotid artery has been measured in the presence and absence of flow within the lumen of the vessel. The perfusate solution contained either 10 or 40 mg ml-1 albumin and transmural flux was measured by monitoring the rate of movement of fluid into a chamber enclosing the artery. Vasomotion was minimized by the inclusion of the vasodilator sodium nitrite in both the perfusate and the outer bathing solution. A relatively slow luminal flow caused a reversible increase in the transmural flux by 20-30% relative to the value in the absence of flow. The mechanism responsible for the increase is not clear, but since it was not affected by the H1 antagonist, mepyramine, it would not appear to have been mediated by histamine release.

The effect of varying albumin concentration of the hydraulic conductivity of the rabbit common carotid artery.

Rabbit common carotid arteries were cannulated in situ, after ligation of their branches, and transferred to a perfusion apparatus in such a way that they were maintained at their physiological dimensions and the endothelium remained intact. The vessels were pressurized to 150 cm H2O with Krebs solution and the wall smooth muscle was relaxed with 10(-4) M NaNO2. The rate of inflow of perfusate into the vessels was measured by following the movement of a bubble in a calibrated capillary which, when steady, was taken to indicate the transmural filtration rate. The filtration rate was 1.48 +/- 0.26 X 10(-6) cm sec-1 (11) (mean, SD, n) with 1 g/dl bovine serum albumin in Krebs solution. The values with 0, 4, 7, and 10 g/dl, normalized by the 1 g/dl value were 1.38 +/- 0.16 (7), 0.80 +/- 0.05 (9), 0.65 +/- 0.03 (8), and 0.47 +/- 0.06 (9), respectively. The hydraulic conductivity of the wall was also found to depend on perfusate albumin concentration. The 1 g/dl value was 0.92 +/- 0.17 X 10(-8) cm sec-1 (cm H2O)-1 (11) and the values with 0, 4, 7 and 10 g/dl normalized by the 1 g/dl value were 1.35 +/- 0.16 (7), 0.87 +/- 0.06 (9), 0.81 +/- 0.03 (8), and 0.72 +/- 0.06 (9), respectively. The findings were analyzed in relation to models involving interaction of albumin with the endothelial glycocalyx, concentration polarization at the blood/wall interface, dependence of flux on solvent viscosity and dependence of the porosity of the wall interstitium on solvent flux. Both concentration polarization and variation of the porosity of the wall interstitium provide reasonable quantitative explanations for the findings.

Plasma protein entry and retention in the vascular wall: possible factors in atherogenesis.

Various experiments are described that relate to measuring the uptake of plasma proteins by the walls of various large blood vessels of the rabbit. The rate of uptake across the intimal surface is not uniform, there being punctate regions of elevated transport. In addition, the rate of transport appears to be considerably higher across veins, pulmonary vessels, and the ascending aorta than across more peripheral arteries. Although larger proteins such as fibrinogen and low-density lipoprotein are transported more slowly than smaller ones, they appear to be retained to a greater extent in the inner layers of arteries than in pulmonary vessels and veins. Retention is greatly enhanced when collars are placed around the arteries and may be involved in the intimal hyperplasia that is seen in such vessels. Thus it appears that it may be the relative extent of entrapment of large atherogenic proteins that determines the appearance of lesions at different sites in the cardiovascular system, in addition to the rates at which they exchange across the blood-wall interface.

Acid-base curve nomogram for chimpanzee blood and comparison with human blood characteristics.

An acid-base nomogram for chimpanzee blood was constructed. Blood was drawn from eight lightly anesthetized chimpanzees. Each sample of blood was oxygenated and nine aliquots were prepared with three different concentrations of hemoglobin and three different amounts of added acid or base. Each aliquot was equilibrated at two PCO2 levels and the pH was measured and plotted on pH-logPCO2 coordinates. Using the intersection point of these pH-logPCO2 lines as a point of equal hemoglobin-independent "base excess" for each condition, values for true base excess were plotted. Connecting these values provided a Cartesian PCO2-pH base excess nomogram for the chimpanzee comparable to that devised by Siggaard-Andersen for humans. Examination of blood from normal human subjects by the same methods showed no appreciable differences from the original Siggaard-Andersen nomogram. However, the PCO2-pH-base excess nomogram for chimpanzee blood deviated slightly from that for human blood. It is possible that the deviation is related to an arterial bicarbonate concentration in the chimpanzee slightly higher than that in human.