Fluorescence Microlymphography Research Articles

Diagnostic Accuracy of Fluorescence Microlymphography for Detecting Limb Lymphedema

Fluorescence microlymphography (FML) is a minimally invasive technique for visualization of the cutaneous lymphatic network. The aim of the study was to assess the accuracy and safety of FML in patients with unilateral lymphedema. This was a cross sectional study. Patients with unilateral leg swelling were assessed and compared with the unaffected contralateral limb. FML was performed in all index legs and the contralateral leg by injecting 0.1mL of fluorescein isothiocyanate (FITC)-labeled dextran intradermally in both limbs at the same level. The most prominent swelling of the affected limb was the anatomical reference. The spread of the dye in the lymphatic capillaries of the skin was measured in all dimensions by epiluminator intravital microscopy and the maximum dye spread value 10min after injection was used for statistical analysis. The contralateral leg served as control. Test accuracy and receiver operator characteristic (ROC) analysis was performed to assess threshold values that best predict lymphedema. Between March 2008 and February 2014 seventy patients with unilateral chronic leg swelling were clinically diagnosed with lymphedema. The median age was 45 (IQR 27-56) years. Of those, 46 (65.7%) were female and 71.4% had primary and 28.6% secondary lymphedema. Sensitivity, specificity, positive and negative likelihood ratio, and positive and negative predictive value were 94.3%, 78.6%, 4.40, 0.07, 81.5%, and 93.2% for the 12mm cut off level and 91.4%, 85.7%, 6.40, 0.10, 86.5%, and 90.9% for the 14mm cut off level, respectively. The area under the ROC curve was 0.89 (95% CI: 0.83-0.95). No major adverse events were observed. FML is an almost atraumatic and safe technique for detecting lymphedema in patients with leg swelling. In this series the greatest accuracy was observed at a cut off level of ≥14mm maximum spread.

Sensitivity and specificity of fluorescence microlymphography for detecting lymphedema of the lower extremity

Fluorescence microlymphography (FML) is used to visualize the lymphatic capillaries. A maximum spread of the fluorescence dye of ≥ 12 mm has been suggested for the diagnosis of lymphedema. However, data on sensitivity and specificity are lacking. The aim of this study was to investigate the accuracy of FML for diagnosing lymphedema in patients with leg swelling. Patients with lower extremity swelling were clinically assessed and separated into lymphedema and non-lymphatic edema groups. FML was studied in all affected legs and the maximum spread of lymphatic capillaries was measured. Test accuracy and receiver operator characteristic (ROC) analysis was performed to assess possible threshold values that predict lymphedema. Between March 2008 and August 2011 a total of 171 patients (184 legs) with a median age of 43.5 (IQR 24, 54) years were assessed. Of those, 94 (51.1%) legs were diagnosed with lymphedema. The sensitivity, specificity, positive and negative likelihood ratio and positive and negative predictive value were 87%, 64%, 2.45, 0.20, 72% and 83% for the 12-mm cut-off level and 79%, 83%, 4.72, 0.26, 83% and 79% for the 14-mm cut-off level, respectively. The area under the ROC curve was 0.82 (95% CI: 0.76, 0.88). Sensitivity was higher in the secondary versus primary lymphedema (95.0% vs 74.3%, p = 0.045). No major adverse events were observed. In conclusion, FML is a simple and safe technique for detecting lymphedema in patients with leg swelling. A cut-off level of ≥ 14-mm maximum spread has a high sensitivity and high specificity of detecting lymphedema and should be chosen.

The Lymphatic Biology of Aging

Lymphatic Research and BiologyVol. 10, No. 2 EditorialThe Lymphatic Biology of AgingStanley G. RocksonStanley G. RocksonSearch for more papers by this authorPublished Online:21 Jun 2012https://doi.org/10.1089/lrb.2012.1021AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"The Lymphatic Biology of Aging." , 10(2), p. 45FiguresReferencesRelatedDetailsCited byLymphaticovenous Anastomosis for Age-Related Lymphedema31 October 2021 | Journal of Clinical Medicine, Vol. 10, No. 21Lymphology and translational medicineInternational Angiology, Vol. 39, No. 5Indocyanine green lymphography findings in older patients with lower limb lymphedemaJournal of Vascular Surgery: Venous and Lymphatic Disorders, Vol. 8, No. 2Characteristics and outcomes of lymphaticovenular anastomosis in older patients with bilateral involvement versus younger patients with unilateral involvement in lower extremity lymphedemaJournal of Vascular Surgery: Venous and Lymphatic DisordersDiagnostic Accuracy of Fluorescence Microlymphography for Detecting Limb LymphedemaEuropean Journal of Vascular and Endovascular Surgery, Vol. 49, No. 4Sensitivity and specificity of fluorescence microlymphography for detecting lymphedema of the lower extremity26 April 2013 | Vascular Medicine, Vol. 18, No. 3The Aging Lymphatics Become More Mature Stanley G. Rockson26 March 2013 | Lymphatic Research and Biology, Vol. 11, No. 1 Volume 10Issue 2Jun 2012 InformationCopyright 2012, Mary Ann Liebert, Inc.To cite this article:Stanley G. Rockson.The Lymphatic Biology of Aging.Lymphatic Research and Biology.Jun 2012.45-45.http://doi.org/10.1089/lrb.2012.1021Published in Volume: 10 Issue 2: June 21, 2012PDF download

Increased vessel density in psoriasis: involvement of lymphatic vessels in the papillary dermis

Conflicts of interest: none declared. Dedicated to Terence J. Ryan, DM FRCP (Oxon) on the occasion of his being awarded an Honorary Doctorate by the Medical Faculty of Martin Luther University Halle‐Wittenberg, 7 September 2007. Sir, The histology of psoriasis vulgaris plaques is characterized by epidermal hyperplasia with uniformly elongated rete ridges enclosing presumably enlarged dermal papillae, dilated, prominent blood vessels in the upper dermis and an inflammatory infiltrate of leucocytes. Recently, Griffiths and Barker1 noted that since the basic ultrastructural examinations by Braverman2 over 30 years ago, the vessels have received little attention in psoriasis research. The ultrastructure and function of the lymphatic vessels within the enlarged dermal papillae have been observed by Braverman,3 Cliff et al.,4 Ryan5 and Bacharach‐Buhles et al.6 The papillae of normal skin have few such vessels or none at all. The lymphatic vessel density reported in psoriasis plaques varies strongly with the detection procedure. While Braverman3 described an increase in lymphatic vessel density compared with normal skin by means of ultrastructural studies, Bacharach‐Buhles et al.6 simply formulated a shift of existing lymph vessels from the upper dermal plexus to the dermal papillae based on three‐dimensional reconstructions of the ultrastructure, while Cliff et al.4 concluded from a reduced lymph outflow in fluorescence microlymphography that there is a decrease in lymphatic vessel density within a plaque.

Of mice and men; the translational physiology of a genetic form of lymphoedema

Of mice and men; the translational physiology of a genetic form of lymphoedema

Microangiopathy of split-skin grafts in venous ulcers.

In patients with chronic venous insufficiency, microangiopathy of blood and lymph capillaries caused by venous hypertension plays a major role in the development of venous ulceration. Conservative treatment of venous leg ulcers often fails, and split-skin grafting is sometimes performed. To evaluate the microcirculation and especially the regeneration and function of lymphatic vessels in skin grafts in patients with chronic venous insufficiency. The microcirculation of 15 split-skin grafts was studied by fluorescence microlymphography and measurement of transcutaneous oxygen tension (tcpO2) in 13 patients. The mean age of the skin grafts was 70.9 months. In only two skin grafts were a few intact lymph meshes found. In all other cases, only fragments of lymphatic capillaries have been detected. In seven skin grafts, cutaneous backflow of dye through insufficient deeper lymph channels was observed. The maximal spread of the dye in the lymphatic network was increased in the skin grafts (17.6 +/- 22.9 mm). The mean value of tcpO2 was only 27.1 +/- 18.1 mm Hg. In split-skin grafts of patients with venous ulcers, severe microcirculatory changes are present and characterized by hypoxia and abnormal regeneration and function of lymphatic vessels.

Severe Lymphatic Microangiopathy in Fabry Disease

Lymphedema has been described in a few cases of Fabry disease. The etiology of lymphedema in Fabry disease is unknown. The aim of the study was to evaluate morphology and function of lymphatic microvessels in this disease. In five male patients with Fabry disease, the initial lymphatic microvessels of the skin were studied in vivo, using a nearly atraumatic technique of fluorescence microlymphography and measurement of lymph capillary pressure. In addition, five female patients heterozygous for Fabry disease and 12 healthy controls were studied. The maximum spread of the fluorescent macromolecular dye into the network of superficial skin lymphatics was increased in the three male patients presenting with lymphedema (25, 26, and 45 mm, respectively). In the two male patients without swollen legs, the maximum spread of the dye was 3 and 7 mm, respectively, and in the female patients 8.8 mm (range, 4-17 mm), whereas in the healthy controls it reached only 4.3 mm (range, 1-7 mm). Fragmentation of the microlymphatic network was found in all patients, but not in controls. In controls, the diameter of the microvessels varied in a very narrow range (45-75 microm); in patients, the range was 15-150 microm. In patients with lymphedema, microlymphatic hypertension was present. In patients with Fabry disease severe structural and functional changes of the initial lymphatics of the skin are present.

Isoprostane 8-Epi-Prostaglandin F2α Decreases Lymph Capillary Pressure in Patients with Primary Lymphedema

In patients with lymphedema, reduced lymph drainage capacity results in an overloaded superficial microlymphatic network and microlymphatic hypertension. In in vitro experiments, it has been shown that 8-epi-prostaglandin F2α (PGF) induced contractions in human lymphatics. Since lymphatic contractility plays a crucial role in the regulation and generation of lymph transport, we studied the effect of PGF on microlymphatic dynamics by measuring lymph capillary pressure (LCP). Twenty healthy volunteers and 13 patients with primary lymphedema were studied after either PGF or placebo was applied to the skin and occlusively covered for 30 min. Glass micropipettes (7–9 µm) were inserted under microscopic control into initial lymphatics visualized by fluorescence microlymphography and pressure measurements were performed using the servo-nulling technique. The mean LCP in patients with lymphedema was significantly higher (19.8 ± 12.1 mm Hg) than that in healthy controls (8.4 ± 4.1 mm Hg) at the placebo-treated site and decreased to normal values after PGF (10.0 ± 7.7 mm Hg). In healthy volunteers, there was no significant decrease of LCP with PGF compared to placebo. PGF normalizes microlymphatic hypertension in patients with lymphedema by improving lymph transport into deeper channels.

Enhanced Cutaneous Lymphatic Network in the Forearms of Women with Postmastectomy Oedema

Postmastectomy oedema (PMO) of the arm is a common aftermath of axillary lymphatic damage during treatment for breast cancer. The aim of the present study was to quantify the forearm dermal lymphatic capillaries in order to determine whether they exhibit adaptive responses to PMO. Both forearms were examined by fluorescence microlymphography in 16 patients with oedema following treatment for breast cancer (mean swelling 25 ± 4%) and 19 patients treated for breast cancer but without oedema. Delineated lymphatic networks were analysed stereologically. The main findings were: (1) lymphatic density at any specified distance from the injection site was greater in the swollen arm than the control arm (p < 0.01, t test); (2) taking into account the increased skin area, the total length of lymphatic capillaries in a 1-cm annulus of skin was 676 ± 56 cm (swollen), compared with 385 ± 30 cm (control) (p < 0.001, t test); (3) fluorescent marker was transported over a greater distance before draining deep in the swollen arm (2.74 ± 0.33 cm) than in the control arm (1.59 ± 0.24 cm) (p = 0.02); (4) there was no evidence of lymphatic dilatation in the swollen arm, and (5) in breast cancer patients without swelling, the arm on the side of radiotherapy/surgery (otherwise referred to as the unswollen arm) showed none of the above changes, indicating that the changes are linked to the oedema rather than being universal responses to breast cancer or its treatment. It is concluded that microlymphatic changes occur in the swollen arm, namely a local superficial rerouting of lymph drainage and either lymphangiogenesis and/or increased recruitment of dormant lymphatic vessels. Since blood capillary angiogenesis occurs in the swollen arms, and lymphangiogenesis occurs in experimental lymphoedema, there is a precedent for proposing lymphangiogenesis in PMO. An increased number of functional vessels would help to maintain the ratio of local tissue drainage capacity to filtration capacity.

Effect of Venous and Lymphatic Congestion on Lymph Capillary Pressure of the Skin in Healthy Volunteers and Patients with Lymph Edema

The aim of the present study was to assess the influence of venous and lymphatic congestion on lymph capillary pressure (LCP) in the skin of the foot dorsum of healthy volunteers and of patients with lymph edema. LCP was measured at the foot dorsum of 12 patients with lymph edema and 18 healthy volunteers using the servo-nulling technique. Glass micropipettes (7–9 μm) were inserted under microscopic control into lymphatic microvessels visualized by fluorescence microlymphography before and during venous congestion. Venous and lymphatic congestion was attained by cuff compression (50 mm Hg) at the thigh level. Simultaneously, the capillary filtration rate was measured using strain gauge plethysmography. The mean LCP in patients with lymph edema increased significantly (p < 0.05) during congestion (15.7 ± 8.8 mm Hg) compared to the control value (12.2 ± 8.9 mm Hg). The corresponding values of LCP in healthy volunteers were 4.3 ± 2.6 mm Hg during congestion and 2.6 ± 2.8 mm Hg during control conditions (p < 0.01). The mean increase in LCP in patients with lymph edema was 3.4 ± 4.1 mm Hg, and 1.7 ± 2.0 mm Hg in healthy volunteers (NS). The maximum spread of the lymph capillary network in patients increased from 13.9 ± 6.8 mm before congestion to 18.8 ± 8.2 mm during thigh compression (p < 0.05). No increase could be observed in healthy subjects. In summary, venous and lymphatic congestion by cuff compression at the thigh level results in a significant increase in LCP in healthy volunteers as well as in patients with lymph edema. The increased spread of the contrast medium in the superficial microlymphatics in lymph edema patients indicates a compensatory mechanism for lymphatic drainage during congestion of the veins and lymph collectors of the leg.

Lymphatic microangiopathy of the skin in systemic sclerosis.

The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopathy.

An in vivo study of the microlymphatics in psoriasis using fluorescence microlymphography.

Angiogenesis is a recognized event in psoriasis. Previous ultrastructural studies have demonstrated lymphatic capillaries extending high into the dermal papillae. Using the novel method of fluorescence microlymphography which permits visualization of upper dermal initial lymphatics in vivo we tested the hypothesis that lymphangiogenesis exists within plaque psoriasis. Six patients underwent fluorescence microlymphography with fluorescein isothiocyanate-dextran administered intracutaneously within a psoriatic plaque on the leg. Stereological analysis permitted quantification of the lymphatic network opacified both within (lesional) and without (perilesional) the plaque. Results showed a greater spread of tracer from the depot into perilesional skin than into the plaque (P < 0.006). The mean length of lymphatics per unit area at increasing distance from the centre of the depot was also increased for the perilesional skin, 10.5 +/- 1.9/cm2 (mean +/- SEM), compared with lesional skin, 3.06 +/- 0.8/cm (P < 0.001). The cumulative lymphatic length was also greater in perilesional, 22 +/- 7.3 cm2, compared with lesional skin, 3.6 +/- 0.3 cm (P < 0.006). Fluorescence microlymphography has proved to be an effective in vivo technique for the assessment of the dermal microlymphatics in psoriasis. Stereology provided quantitative analysis of the lymphatic network visualized. Overall, there is a greater network of lymphatics in perilesional compared with lesional skin in patients with plaque psoriasis. This finding is at odds with the accepted view that the lymphatic dermal vessels are increased within the psoriatic plaque.

Arm and leg skin lymphatic density studied in different racial types using quantitative fluorescence microlymphography

Arm and leg skin lymphatic density studied in different racial types using quantitative fluorescence microlymphography

Long-term follow-up after finger and upper-limb replantation: clinical, angiologic, and lymphographic studies.

This 10-year follow-up study evaluates 25 patients with a total of 57 successfully replanted fingers and six successfully replanted upper limbs. The global functional loss, including loss of range of motion, sensibility, and strength of the hand, was determined using the "Millesi score." The hemodynamic parameters of replanted and control fingers under resting and stress conditions were measured using a laser Doppler flowmeter. The lymphatic system at the site of replantation was examined by fluorescence microlymphography. All patients showed a considerable functional loss, according to the Millesi score, that averaged 56 percent of the normal function of the hand. In order to overcome functional deficit, many patients had developed successful compensatory mechanisms. In general, the patients themselves subjectively rated their functional deficits lower than indicated by the Millesi score. Laser Doppler flowmetry at rest and after arterial occlusion, and capillaroscopy before, during, and after a cold provocation test, revealed subnormal resting flow conditions and significantly decreased vascular capacity in the replanted fingers. Lymphatic drainage capacity was also significantly reduced despite documented reanastomosis between the skin microlymphatic network distal and proximal to the scar (fluorescence microlymphography). The coexistence of functional loss with compensatory mechanisms, decreased reactive hyperemia, and deficit in lymphatic drainage, present in all patients, must be considered as definitive sequelae of the initial injury.

Diurnal and long-term variations of lymph capillary pressure in health

The variability of pressure in the cutaneous lymph capillaries on the forefoot was determined in 2 groups of healthy volunteers. In group A, including 12 subjects (8 men, 4 women; mean age 28 years, range 22 to 37 years) measurements were performed in the morning and late afternoon of the same day. In group B (12 subjects, 5 women, 7 men; mean age 53 years, range 23 to 72 years) measurements of lymph capillary pressure were repeated within an interval of 7 weeks. The superficial microlymphatics were visualized by intravital fluorescence microlymphography, cannulated with glass micropipettes, and the lymph capillary pressure was measured using a servo-nulling pressure system. The lymph capillary pressure measured in the morning (mean 7.5±4.4 mm Hg; range −4 to 16 mm Hg) did not differ (p>0.05) from the pressure in the late afternoon (mean value 5.6±3.4 mm Hg; range −1 to 13 mm Hg). In group B initial lymph capillary pressure (mean 3.9±2.9 mm Hg, range −1.1 to 9.7 mm Hg) was not different (p>0.05) compared to the pressure after 7 weeks (2.9±2.7 mm Hg; range −1.0 to 6.8 mm Hg). In conclusion, lymph capillary pressure in healthy subjects does not exhibit significant changes during the daytime and the long-term reproducibility is good.

Quantification of the Initial Lymphatic Network in Normal Human Forearm Skin Using Fluorescence Microlymphography and Stereological Methods

Fluorescence microlymphography enables the visualization of the initial lymphatic network in human dermisin vivo.In order to determine which objective, measurable parameters are likely to be of value in future studies, microlymphangiograms were obtained from normal forearm skin of eight men and nine women of a range of ages and analyzed stereologically to calculate: (1) lymphatic length density at a specified radial distance,r, from the site of injection of the fluorescent dye (LDr, cm−1); (2) maximum lymphatic density (LDmax, cm−1); (3) total length of filled lymphatic (LL, cm); (4) maximum radial spread of vessels (mm). There was no significant difference between the right and left arms for peak LDr, LDmax, LL, or spread. Mean values (±SD) for the right and left arms combined (n= 24) were 13.34 ± 7.61 cm−1; 19.31 ± 8.96 cm−1; 12.04 ± 10.04 cm; and 7.58 ± 3.30 mm, respectively. Unexpectedly, three of the four parameters were significantly lower in women compared to men. For women LDmaxwas 30% lower than for men (P= 0.04), LL was 59% lower (P= 0.032), and spread was 39% lower (P= 0.007). Peak LDrdid not differ significantly. Stereological analysis of fluorescent microlymphangiograms enables quantification of the dermal initial lymphatic network and hence the objective study of the influence of gender, age, and disease (including treatment interventions).

Combined physical therapy for lymphedema evaluated by fluorescence microlymphography and lymph capillary pressure measurements.

The treatment of patients with lymphedema is still controversial. Combined physical therapy with manual lymph drainage and compression therapy is most frequently used to reduce lymphatic leg swelling. However, objective evidence is rare that this empirical form of treatment has a scientific basis. In a prospective study fluorescence microlymphography and pressure measurements in cutaneous lymph capillaries were used to assess objectively the effect of combined decongestive physical therapy on abnormal microlymphatic dynamics in lymphedema. 12 patients with primary and secondary lymphedema were studied before treatment, after 2 weeks of intensive physical therapy and 3 months of continuing compression and ergotherapy. After 2 weeks of intensive manual lymph drainage and compression bandaging (phase 1) microlymphatic hypertension (12.8 +/- 5.7 mm Hg) was significantly (p = 0.01) reduced to a mean lymph capillary pressure of 5.9 +/- 4.5 mm Hg. More than 3 months later after continuing compression lymph capillary pressure (3.2 +/- 5.2 mm Hg) was still significantly (p = 0.03) reduced. Simultaneously the maximum spread of the fluorescent contrast medium in the superficial lymph capillary network decreased significantly (p = 0.01) from 21.3 +/- 14.3 to 11.3 +/- 4.8 mm. Accordingly the clinical condition improved, and the mean circumferences of the forefoot and ankle were significantly (p < 0.05) reduced. Combined decongestive physical therapy is an effective treatment for lymphedema which results in a normalization of microlymphatic hypertension and an improvement of the clinical appearance.

Effect of postural changes on human lymphatic capillary pressure of the skin.

1. The influence of postural changes on cutaneous lymphatic capillary pressure and venous pressure was measured at the dorsum of the foot in twelve healthy volunteers. Measurements were performed in the supine and sitting positions. 2. Lymphatic skin capillaries were visualized by fluorescence microlymphography with fluorescein isothiocyanate (FITC)-Dextran 150000. Subsequently a lymphatic capillary was punctured with a glass micropipette and pressure was measured using the servo-nulling technique. Lymphatic capillary pressure, venous pressure, heart and respiration rates were recorded simultaneously. 3. Mean lymphatic capillary pressure was significantly higher (P = 0.0096) in the sitting (9.9 +/- 3.0 mmHg) than in the supine (3.9 +/- 4.2 mmHg) position. There was no significant difference (P = 0.09) between lymphatic capillary pressure and venous pressure (6.8 +/- 3.4 mmHg) in the supine position. During sitting mean lymphatic capillary pressure was significantly lower (P = 0.0022) than mean venous pressure (53.3 +/- 4.1 mmHg). The smaller increase in lymphatic capillary pressure may be caused by the discontinuous fluid column in the lymphatic system and enhanced orthostatic contractile activity of lymphatic collectors and precollectors. Spontaneous low frequency pressure fluctuations occurred in 89% of recordings during sitting, which was significantly (P = 0.02) higher than in the supine position (54%). 4. The present results support the suggestion of enhanced intrinsic contractile activity of lymph precollectors and collectors in the dependent position. This mechanism is primarily responsible for the propulsion of lymph from the periphery to the thoracic duct during quiet sitting, when extrinsic pumping by the calf muscles is not active.

Flow velocity in the superficial lymphatic network of the mouse tail.

The present study had two goals: 1) to establish an animal model in which a large network of the initial lymphatics of the skin can be investigated in vivo and 2) to measure effective flow velocity (defined as axial component of the flow velocity) in the lymph capillary network of the skin for the first time. A fluorescence microlymphography technique was used to stain the lymph capillaries in the superficial layer of the skin of the nude mouse tail in 10 female animals (mean age 45.8 +/- 2.4 days; mean wt 21.2 +/- 0.8 g). With the use of densitometric image analysis, effective flow velocity along the tail was measured. The network consisted of a honeycomb-like layer of hexagonally shaped meshes that could be stained in all animals. Effective lymph flow velocities were in the range of 1.4-20.4 microns/s with a mean value of 7.7 +/- 5.9 microns/s; median value was 6.2 microns/s (4.5-10.5; 25 and 75% percentiles). This new animal model allows studies of a large network of lymph capillaries in the skin and should provide new insight into the physiology and pathophysiology of the initial lymphatics.

Fluctuation of skin lymphatic capillary pressure in controls and in patients with primary lymphedema.

The microlymphatic pressure was monitored by using the servo-nulling technique at the forefoot skin in 24 healthy volunteers (number of capillaries studied: 97) and in 27 patients with primary lymphedema (capillary number: 67). The lymphatic capillaries were stained by fluorescence microlymphography with fluorescein isothiocyanate-dextran 150 and cannulated using glass needles with a diameter between 7 and 9 microns. The lymphatic capillary hypertension described recently in primary lymphedema was confirmed in this series (mean pressure of controls 6.7 +/- 3.8 and, of patients 12.8 +/- 5.9 mm Hg; p < 0.001). Two patterns of pressure fluctuation were observed: rhythmic low-amplitude (mean value 3.7 mm Hg) waves with a frequency identical to respiration (respiratory movements of the thorax recorded simultaneously by a photo cell) and spontaneous nonrhythmic, low-frequency waves with a higher amplitude (mean value 5.5 mm Hg). The prevalence of waves synchronous with respiration was identical in patients and controls, whereas the low-frequency waves exhibited a significantly (p < 0.05) higher prevalence in the patients (41.7%) than in the controls (70.4%). The hypothesis is advanced that in primary lymphedema a considerable amount of lymphatic fluid is removed by lymphatic pathways with small calibre and high resistance, resulting in microvascular hypertension, and that contractions of the few preserved large proximal lymphatic collectors are enhanced. The latter mechanism could explain the increased prevalence of spontaneous microlymphatic pressure fluctuations with high amplitude and low frequency.