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Skin Research and Technology 2004: 10: 174–177
Copyright & Blackwell Munksgaard 2004
Capillary blood cell velocity in periulcerous regions of the
lower leg measured by laser Doppler anemometry
Markus Stu¨cker, Christina Huntermann, Falk Georges Bechara, Klaus Hoffmann
Department of Dermatology and Allergology, Ruhr-University Bochum, Germany
Background: The capillary blood flow of the nailfold can be
Results: Laser Doppler flow was increased in all patients
measured by means of modern non-invasive techniques like
during resting period, whereas the tcpO2 was significantly
the videocapillary microscope in vivo. To quantify the capil-
decreased. LDF did not show an extension of tpCBV during
lary blood cell velocity, apart from the nailfold capillaries, we
reactive hyperemia after suprasystolic occlusion compared
used a new technique, the so-called laser Doppler anemo-
to the control group (73.6 Æ 31.1 vs. 164.1 Æ 52.5 s, P 5 0.003).
TcpO2 revealed significantly dereased tpCBV in patients with
Objective: The present study investigated how far laser
venous and mixed venous/arterial ulcers (90.1 Æ 61.7 vs.
Doppler fluxmetry (LDF), transcutaneous partial pressure
162.7 Æ 65.5 s, P 0.0001). LDA showed no significant differ-
of oxygen (tcpO2), and LDA are capable of quantifying
ences between patients and control group (P40.8). After appli-
differences of cutaneous microcirculation between patients
cation of prostaglandin E1, LDA revealed a significant increase
with leg ulcera and a healthy control group. The effects of
intravenous prostaglandin E1 and pentoxifylline were also
[P 5 0,01]), whereas pentoxifylline had no significant effect.
Capillary density increased significantly after application of
Patients and methods: Ten patients with venous leg ulcers
prostaglandin E1 (5,1 Æ 2.7/mm2 to 8.9 Æ 3/mm2 [P 5 0.001])
and 10 patients with mixed venous/arterial ulcers were
and pentoxifylline (5.3 Æ 1.8/mm2 to 8 Æ 2.1/mm2 [P 5 0.006]).
investigated with LDF, tcpO2, and LDA before and after
Conclusion: The LDA is an important additional investiga-
injection of prostaglandin E1 and pentoxifylline. We mea-
tion tool for cutaneous microcirculation.
sured the resting capillary blood cell velocity (rCBV), themaximum hyperemia, and the time to peak capillary blood
Key words: microcirculation – leg ulcer – blood flow – laser
cell velocity (tpCBV) during hyperemia after 4 min of supra-
systolic occlusion and compared them with the results of acontol group of 20 patients.
& Blackwell Munksgaard, 2004Accepted for publication 6 February 2004
the nipple or the nailfold, the capillary loops run
ulcerous lesions show disturbances in cu-
parallel to the skin surface. However, there has
taneous microcirculation (1, 2). Pharmacologial
been almost no technique available to measure skin
treatment with prostaglandin E1 and pentoxifyl-
blood flow in capillary loops located at a 901 angle
line aims at an improvement of microcirculation
to the skin surface, like the lower leg. Therefore, it
was not possible to quantify the erythrocyte velo-
city in capillaries of periulcerous regions.
means of non-invasive capillary microscopy,
mostly performed on the nailfolds (7). Thus
(LDA) a device is available to measure the capil-
pathological changes and therapy effects can be
lary blood flow in human capillaries oriented
quantified. In general, capillary loops of the skin
perpendicular to the skin surface. The reprodu-
are perpendicularly oriented to the skin surface.
cibility of this method has already been docu-
Only in a few areas of the human body, the lips,
In the present study, the following problems
(1.5 mW Laser Diode, wavelength 780 nm), fo-
cused by a microscope objective lens to a spotsize of approximately 10 mm diameter. This re-
(1) Is the LDA capable of demonstrating differ-
sults in a very small sample volume, so that the
ences in cutaneous microcirculation of the
velocity in capillaries of 9.8–32.1 mm diameter can
periulcerous regions of venous/arterial ul-
be singled out. Using the capillarometry, capil-
laries per field of view were counted.
(2) Are the effects of prostaglandin E1 and pen-
toxifylline in periulcerous regions detectableby LDA?
Test procedureAll subjects were investigated in a lying positionafter acclimatization for at least 20 min (room
temperature: 22–24 1C). Before suprasystolic oc-clusion, all parameters in rest were investigated
for 2 min (2–4 cm from the ulcers). After occlu-
We investigated 20 patients, 10 with venous
sion, parameters were again registered for 2 min.
ulcers (age: 62.1 Æ 11.6 years, five females, five
Following parameters were determined: resting
males), 10 with mixed venous/arterial ulcers
capillary blood cell velocity (rCBV), time to peak
(age: 78.2 Æ 4.6 years, six females, four males).
capillary blood cell velocity (tpCBV) during hy-
Seven of 10 patients with venous ulcers had a
peremia, and the maximum hyperemia. All mea-
deep venous insufficiency, all patients showed an
insufficiency of the longer saphenous vein (grade
Patients with venous ulcers were again inves-
tigated 15 min after application of 100 mg pentox-
Patients with mixed venous/arterial ulcers
ifylline (Trentals, Aventis Pharma, Bad Soden,
showed an ankle-arm index of 0.59 Æ 0.07 (ankle
Germany). Patients with peripheral arterial oc-
artery pressure: 88.5 Æ 10.7 mmHg). All patients
clusive disease received 40 mg of prostaglandin E1
had no signs of skin disease at place of measure-
(Prostavasins, Schwartz Pharma, Mannheim,
ment, apart from typical changes due to venous
Germany) and were also examined 15 min after
infusuion. Infusion time in all patients was 2 h.
Both groups were compared to a control group.
The control group for venous ulcers consisted ofthree healthy males and seven females (age
64.1 Æ 11.7 years). The control group for patients
The values of the patient groups were compared
with peripheral arterial occlusive disease also
to those of the control groups using Student’s
consisted of three healthy males and seven fe-
t-test for unpaired samples. Differences between
males (age: 56.4 Æ 9.7 years). Clinical examina-
the values before and after infusion therapy were
tested using Student’s t-test for paired samples
chronic venous insufficiency or peripheral arter-
(SPSS for Windows 11.0, SPSS, Chicago, IL, USA).
ial occlusive disease in the control groups. Sub-jects suffering from skin diseases (psoriasis,
eczema) were excluded. Taking of medicaments,which have an influence on hemorheology,
LDF was significantly increased in both patient
thrombocyte aggregation, or vessel tonus was
groups (venous ulcers: 31.7 Æ 12.4 AU vs. mixed
venous/arterial ulcers: 61.7 Æ 46.3 AU) comparedto the respective control group (15.8 Æ 6.94/16.8 Æ 6.4 AU [P 0.01]). TcpO2 was significantly
decreased in both groups (9.5 Æ 11.7 vs. 23.6 Æ
Cutaneous microcirculation was investigated by
13.46 mmHg, P 5 0.004/6.8 Æ 4.0 vs. 18.7 Æ 6.3
laser Doppler fluxmetry (LDF) (DRT4, Moor-In-
struments, Exminster, Great Britain), measuring
0.5 Æ 0.2 mm/s in all groups. Time to maximum
hyperemia after suprasystolic occlusion was not
(TCM3, Radiometer, Koppenhagen, Denmark),
extended compared to the control group by LDF
(P40.05). TcpO2 was significantly decreased in
ford, UK). The CAM 1 includes a laser source
patients with venous ulcers (73.6 Æ 31.1 vs. 164.1
Fig. 3. Capillary density before and after application of pentoxifylline
in venous leg ulcers. Significant increase of capillary density
(5.3 Æ 1.8/mm2 to 8 Æ 2.1/mm2 [P 5 0.006]).
Fig. 1. Resting capillary blood cell velocity (rCBV) before and afterapplication of prostaglandin E1 measured by LDA. Significant
measurement techniques: the LDF, the tcpO2, and
increase of rCBV (0.5 Æ 0.18 mm/s to 0.74 Æ 0.28 mm/s [P 5 0.01]).
The LDA offers a combination of video capil-
laroscopy and laser Doppler measurement. The
system includes a laser source (1.5 mW Laser
Diode, wavelength 780 nm), focused by a micro-
scope objective lens to a spot size of approxi-
mately 10 mm diameter. This results in a very
small sample volume, so that the velocity in
capillaries of 9.8–32.1 mm diameter can be singledout. By this, almost every blood cell velocity is
Fig. 2. Capillary density (capillaries/mm2) before and after applica-
measurable, and for the first time a device is
tion of prostaglandin E1 in mixed venous/arterial ulcers. Significantincrease of capillary density (5.1 Æ 2.7/mm2 to 8.9 Æ 3/mm2
available to measure the resting capillary blood
cell velocity in human capillaries oriented per-pendicular to the skin surface. The instrument
Æ 52.5 s of control group, P 5 0.003) and also with
can be placed on almost all parts of the body
mixed venous/arterial ulcers (90.1 Æ 61.7 vs.
162.7 Æ 65.5 s of control group, P 0.0001).
The conventional LDF only registers the pro-
Before drug application, the LDA showed no
duct of erythrocyte velocity and number of velo-
significant differences between patients and con-
city in a tissue volume of about 1 mm3. However,
trol group (P40.8). Fifteen minutes after applica-
the LDA is capable of analyzing a single capillary.
tion, there was no difference detected by LDF or
Measurement depths depend on the constitution
tcpO2. In contrast, the LDA revealed a significant
and blood circulation of the investigated tissue
increase of erythrocyte velocity after application
(10). Therefore, the LDF only allows relative
of prostaglandin E1 (from 0.5 Æ 0.18 to 0.74 Æ
measurements, given in arbitrary units (11, 12).
0.28 mm/s [P 5 0.01]). No significant changes
The tcpO2 reflects the local nutritive situation
were demonstrated after application of pentox-
of the skin surface. It depends mainly on the local
ifylline (increase from 0.53 Æ 0.52 to 0.66 Æ 0.8
blood circulation, and diffusion properties (12),
mm/s [P 5 0.29]). Capillary density raised from
and is frequently used to reveal how vessel
5.1 Æ 2.7/mm2 to 8.9 Æ 3/mm2 (P 5 0.001) after
diseases have influence on local skin situation
application of prostaglandin E1, and from
5.3 Æ 1.8/mm2 to 8 Æ 2.1/mm2 (P 5 0.006) after
To compare the relevance of these methods in
medication with pentoxifylline (Figs 1–3).
therapy, we quantified the effects of prostaglan-din E1 and pentoxifylline on cutaneous micro-circulation in periulcerous lesions.
The missing increase of tcpO2 after infusion of
The present study investigated the cutaneous
prostaglandin E1 may be caused by the fact that
microcirculation of venous leg ulcers and mixed
patients with mixed venous/arterial ulcera were
venous/arterial ulcers. We used three different
examined. This is reflected by relatively high
rates of tcpO2 in rest. In isolated peripheral
measured by a new laser Doppler anemometer. Micro-
bined with a prolongation of time to maximum
¨ cker M, Herde M, Baier V, Hoffmann K, Altmeyer P.
Klinische Provokationsmano¨ver mit dem Laser Doppler
Anemometer. Phlebologie 1998; 27: 152–158.
However, the LDA could demonstrate an in-
10. Johansson K, Jakobsson A, Lindahl K, Lindhagen J,
crease of erythrocyte velocity and capillary den-
Lundgren O, Nilsson GE. Influence of fibre diameterand probe geometry on the measuring depth of laser
Doppler flowmetry in the gastrointestinal application.
prostaglandin E1. The capillary density was also
Int J Microcirc: Clin Exp 1991; 10: 219–229.
increased after application of pentoxifylline.
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tion: an update. Int J Microcirc Clin Exp 1995; 15 (Suppl.
The effect of both hemorheologica could only
be shown by LDA, whereas the LDF and tcpO2
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did not reveal any significant changes in cuta-
flux motion in man by the laser Doppler technique.
Blood Vessels 1991; 28: 21–26.
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13. Rooke TW. The use of transcutaneous oximetry in the
the effects of prostaglandin E1 and pentoxifylline
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on venous and arterial ulcers have been pre-
14. Stu¨cker M, Falkenberg M, Reuther T, Altmeyer P, Lu¨b-
bers DW. Local oxygen content in the skin is increased in
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The Economics of Mental Health: The Perspective and Role of the Research-Intensive \ Pharmaceutical Industry Plenary Speech to the 10th Scientific Meeting of the International Government and Public Relations Domo arragato , Chairman Nishizono. Good morning, ladies and gentlemen and thank you, Prof. Singh, for the opportunity to join you here today in Melbourne. It’s an honor to b
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