Skin damage in chronic venous insufficiency: does an oxygen diffusion barrier really exist? T R Cheatle FRCSI G M McMullin Fcs J Farrah BSc P D Coleridge ...
Journal of the Royal Society of Medicine Volume 83 August 1990
493
Skin damage in chronic venous insufficiency: does an oxygen diffusion barrier really exist?
T R Cheatle FRCSI
G M McMullin Fcs
J Farrah BSc
P D Coleridge Smith FRcs
J H Scurr FRCS Department of Surgery, University College and Middlesex School of Medicine, Middlesex Hospital, Mortimer Street, London WIN 8AA Keywords: xenon radioisotopes; venous insufficiency; microcirculation; diffusion; lipodermatosclerosis
Summary Eleven patients with lipodermatosclerosis (LDS) and 14 patients without venous or arterial disease underwent measurement of xenon-133 (138Xe) halfclearance times from the gaiter region of the leg. Xenon has similar diffusion characteristics to oxygen, and the investigation reflects the ability of the isotope to diffuse from the skin surface into capillary blood. Median skin half-clearance time for skin in the LDS group was 2.2 min and in the control group 2.1 mim. From the subcutaneous tissues, the respective times were 14.1 and 17.4 minutes. These differences are not statistically significant. The study fails to yield evidence suggesting that an oxygen diffusion barrier exists in lipodermatosclerosis. Introduction Venous ulceration of the lower limb has been attributed to failure of -oxygenation of the skin, perhaps due to an oxygen diffusion barrier produced by pericapillary fibrin cuffs. It is proposed that these are deposited as a result of venous hypertension, leading to increased inter-endothelial cell pore size allowing the extravasation of fibrinogen, which then polymerizes outside the capillary. This theory, first proposed by Browse and Burnand in 19821, is supported by firm histological evidence for such cuffs. However, little data is available to show that they actually hinder the diffusion of oxygen. Work on transcutaneous P02 measurements indicates that values in lipodermatosclerotic skin tend to be lower than those in normal skin2, but this would be equally consistent with a perfusion defect such as would be produced by the recently-proposed white cell trapping theory3, or even alterations in the permeability in the keratinized layers of the skin. This study compares the diffusion characteristics of 133Xe in the gaiter skin of patients with lipodermatosclerosis with those in normal subjects. The aim ofthis investigation was to assess the impairment caused by the skin microcirculation in supplying a molecule of similar size and diff-usion characteristics as oxygen. Patients and methods Eleven patients with lipodermatosclerosis (LDS) and 14 subjects without venous or arterial disease were studied. The patients with LDS had chronic deep or superfi'cial venous insufficiency proven on Duplex scanning. All underwent measurement of 133Xe clearance rate from the skin and subcutaneous fat of the gaiter region, using the epicutaneous-labelling
method described by Sejrsen4. In an environmentcontrolled chamber, subjects lay supine for an acclimatization period of 20 min, with the study leg lying on a specially moulded cushion designed to accommodate a scintillation counter. A below-knee tourniquet inflated above arterial systolic pressure was then -applied for 3 min to induce maximal capillary flow upon release. At the start of the ischaemic period, a bolus of 370 MB of 133Xe was applied to the skin surface via a rubber port and held in position with a transparent dressing. The xenon was allowed to diffuse into the skin for 3 min, after which the remainder was aspirated, the skin tightly covered with a non-permeable dressing (Saranwrap) to prevent backdiffusion, and the tourniquet deflated. Scintillation counts were then collected for 20 min and recorded on a pen-chart recorder. The result was a biphasic graph, with an initial sharp decline in xenon levels, representing its rapid clearance from the skin during hyperaemia. This was followed by a slower decline, representing clearance from the subcutaneous fat. Xenon is a relatively lipophilic molecule and the blood supply to this layer is less profuse than that to the skin, so xenon is less readily removed from this compartment. Data was analysed on a microcomputer with spread sheet software (Lotus 1-2-3, Lotus Development Corporation), using a curve-stripping technique to extract the fast and slow phase half-clearance times. Statistical analysis was performed using a MannWhitney U test.
Results The half-clearance times of xenon clearance from the skin and subcutaneous tissues in the two groups are shown in Figures 1 and 2, respectively. In the LDS group, the median half-clearance time from the skin was 2.24 min (range: 0.7-5.6 min), while in the normal 6-
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Figure 1.
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Xenon half-clearance times from skin
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Figure 2. Xenon half-clearance times from subcutaneous fat
group it was 2.08 min (range: 1.1-4.0 min). From the subcutaneous fat, the respective times are 14.1 min (range: 6.1-87.4 min) and 17.4 min (range: 7.6-36.1 min). These differences are not statistically significant.
Discussion Evidence that the fibrinous cuffs seen microscopically in lipodermatosclerosis act as a barrier to the diffusion of oxygen is scant. Burnand et al. have studied the influence of a sheet of commercial fibrin on the diffusion of oxygen through water, and found that it reduced the rate of passage of oxygen across a diffusion chamber some 25-fold5. The fibrin in this experiment was probably not of the same composition as that in human tissues since it originated from a commercial surgical suture manufacturer and was intended for tissue repair procedures. The results are of uncertain relevance to the clinical situation. A study using positron emission tomography has shown decreased oxygen extraction ratios in legs affected by venous ulcers6. However, as the capillary blood flow was also increased, conclusions cannot be drawn concerning the absolute quantities of oxygen being delivered to the tissue endpoint. '33Xe has a molecular weight of 133 daltons, approximately four times that of oxygen (molecular weight 32). It would be expected to diffuse approximately half as quickly as oxygen, but this is counteracted by the fact that it is more lipophilic and therefore less hampered by cellular membranes7.
The two molecules are therefore roughly equivalent in their diffusion characteristics. The epicutaneous labelling technique allows diffusion of isotope to occur across the skin and subcutaneous tissues. Assuming that back-diffusion is eliminated by application of a non-permeable dressing, the only route by which it can be removed from the tissues is via the microcirculation. Measurement of the half-clearance time therefore, in effect, measures the rate of isotope diffusion from skin to blood - the reverse direction to that taken by oxygen, but encountering exactly the same chemical and physical barriers. This study has failed to demonstrate any difference in the diffusion characteristics of 133Xe between normal subjects and patients with lipodermatosclerosis. We can derive from it no support for the proposition that the delivery of oxygen is impaired in lipodermatosclerotic skin. These data suggest that the skin changes may be due to the failure of delivery of some other nutritional substance or to the effect of toxic substances released by white cell activation, suggested by the white-cell-trapping hypothesis3. References 1 Browse NL, Burnand KG. The cause of venous ulceration. Lancet 1982;ii:243-5 2 Clyne CAC, Ramsden WH, Chant ADB, Webster JHH. Oxygen tension on the skin of the gaiter area of limbs with venous disease. Br J Surg 1985;72:644-7 3 Coleridge Smith PD, Thomas P, Scurr JH, Dormandy JA. Causes of venous ulceration: a new hypothesis. Br Med J
1988;296:1726-7 4 Sejrson P. Blood flow in cutaneous tissue in man studied by washout of radioactive xenon. Circ Res 1969;25:215-29 5 Burnand KG, Whimster I, Naidoo A, Browse NL. Pericapillary fibrin in the ulcer-bearing skin of the leg: the cause of lipodermatosclerosis and venous ulceration. Br Med J 1982;285:1071-2 6 Gowland Hopkins NF, Spinks TJ, Rhodes CG, Ranicar ASO, Jamieson CW. Positron emission tomography in
venous ulceration and liposclerosis: study of regional tissue function. Br Med J 1983;286:333-6 7 Lassen NA, Lindbjerg J, Munck 0. Measurement ofbloodflow through skeletal muscle by intramuscular injection of xenon-133. Lancet 1964;i:686-9
(Accepted 19 March 1990)
