ARTICLE
Therapy for peripheral arterial occlusive disease is chosen on the basis
of the stage of the disease. In Fontaine stage II, it involves not only
the treatment of risk factors and secondary prophylactic measures aimed
at slowing the progress of the disease, but above all it seeks, through
a special training program to lengthen walking distance. In the advanced
stages, III and IV, revascularization measures are taken wherever possible.
The physician also has therapeutic measures at his disposal such as lumbar
sympathectomy or epidural electrostimulation (implantation of a neurostimulator),
which can alleviate pain and improve cutaneous circulation. Vasoactive
drugs can be used as supportive therapy in Fontaine stages II to IV and
may be administered during training programs after the measures listed
above and when revascularization is not possible. In the medical literature,
there is no consensus about the effectiveness of Ginkgo biloba
extract EGb 761 (Rökan®) in the treatment of peripheral
arterial occlusive disease (PAOD). However, there are several reports
of the positive effects of EGb 761 on this syndrome. As early as 1984,
Bauer [1] confirmed the efficacy of Ginkgo biloba in a 6-month
double-blind study of 79 patients in stage IIb. The evaluation criteria
chosen were a combination of pain-free and maximum walking distance, subjective
status and plethysmographic values. A number of other publications reported
good results from therapy with Ginkgo biloba extracts [2, 3]. A
study carried out by Letzel and Schoop to evaluate the effectiveness of
EGb 761 and penoxifylline demonstrated a clinically relevant, mean increase
in walking distance after treatment with both substances in contrast to
patients treated with placebo [3].
Case report
History
The patient was a 75-year-old man with peripheral arterial occlusive
disease in the right leg. A minor trauma 3 years earlier resulted in a
therapy-resistant, pretibial ulcer on the right leg. Because of poor healing
and the severity of the symptoms the patient was under continuous outpatient
treatment. Nine years previously, total prosthetic replacement of the
right hip joint had been performed. One year later replacement operation
was necessary. There was compensated cardiac insufficiency. Five years
before the study, an iliac-profunda bypass operation was performed on
the left side because of intermittent claudication in the left calf. This
alleviated the subjective complaints and extended the pain-free walking
distance from 133 to 228 m. Three and a half years ago, an iliac-profunda
bypass was implanted in the right leg (the focus of interest in this study).
For three years the patient has been an outpatient in the Dermatology
Hospital's Department of Cardiac and Vascular Surgery and has participated
regularly in a vascular sports program for patients with peripheral, arterial
occlusive disease.
Examination findings
A seventy-five-year-old patient presenting good general health and state
of nutrition. There were multiple, small varicose dilatations in the skin
of both thighs and non-irritated scars in the inguinal area after bypass
and hip operations. A 4 x 5 cm pretibial ulcer was localized on the right
leg with a small pellicle (Fig.
1A).
Peripheral pulse
The left femoral artery was clearly palpable. In comparison, the pulse
on the right side was weaker. Distal to the femoral artery the pulses
could not be palpated on the right side (Table
I).
Because of a medial sclerosis, the peripheral systolic arterial pressure
does not accurately reflect the true extent of the impairment of arterial
hemodynamics (Table II).
Angiography of March 6, 1996
Sclerosis of the infrarenal artery with a 30% stenosis of the abdominal
artery was found at the level of the third lumbal vertebra. There was
extreme sclerosis of both pelvic arteries.
* Right. 50% stenosis of the common iliac artery, anastomosis
of the iliaco-profundal bypass without pathological findings. Inconspicuous
profundal anastomosis.
Refill of the P2-segments of the popliteal artery via strong
collaterals. The popliteal artery showed a long distance stenosis of 40-50%.
Normal caliber of the P3-segment.
* Left. Long distance 60% stenosis of the external iliac artery.
Occlusion of the internal iliac artery. The common femoral artery and
origin of the profunda artery were without pathological findings. Long
distance occlusion of the superficial femoral artery. Perfusion in the
P1-segment. Lower leg arteries were without pathological findings.
Therapy and progress
A total of 72 intravenous Prostavasin® infusions and
30 intravenous Lipo-PGE1 infusions failed to bring about healing. On August
17, 1992 a CT-guided, right lumbar sympathicolysis was performed as well
as debridement of the ulcer, ligature of the veins and a split-skin graft
on the right crus. These measures likewise failed to heal the ulceration.
In September 1994, a 4 x 5 cm ulcer appeared in the pretibial area of
the right lower leg, and showed no signs of healing. Because of a preexisting
cardiac condition, it was decided not to implant a Y- or femoral-popliteal
bypass. Instead, we began therapy with a Ginkgo biloba extract
(Rökan® film tablets, 40 mg 3 x 1, 120 EGb 761/day).
Local therapy with Varihesive® foil continued unchanged.
Furthermore, the patient continued to participate regularly in vascular
sports training twice a week, as he had been doing since April 1991. Fourteen
days after treatment with EGb 761 began, the ulcer had already shrunk
noticeably with good granulation. After three months of therapy with Ginkgo
biloba and regular participation in vascular sports training, the
ulcer had completely healed (Fig.
1B). In addition, subjective symptoms improved and the treadmill
walking distance increased. The ulcer did not reappear in the 4-month-long
follow-up period, during which the patient continued to take EGb 761.
Discussion
The great natural variation in the clinical picture and the difficulties
in standardizing and reproducing measurements make it difficult to assess
the effectiveness of any drug therapy in patients with a peripheral arterial
occlusive disease. Vasoactive drugs which improve the rheological properties
of the blood are being used more and more, and positive effects on ischemic
microangiopathies have been described repeatedly [2, 4]. Controlled studies
are available on the effectiveness of prostaglandin E1 infusions in the
treatment of peripheral arterial occlusive disease in stages III and IV
[5, 6]. Hemodilution is another possible therapy which can lead to an
improvement in clinical symptoms [7]. In the case presented here, a trial
therapy was carried out with a Ginkgo biloba extract (Rökan®,
40 mg 3 x 1). Previous attempts to treat the PAOD with Prostavasin®
and Lipo PGE1 had failed to lead to any improvement. Ginkgo biloba
therapy resulted in good granulation and a rapid decrease in the size
of the ulcer. Within 4 months the ulcer had healed completely and the
pain was eased. Throughout the treatment period neither local nor physical
therapy were changed. The patient continued to regularly attend the Tübingen
vascular sports group to which he had belonged for years. Although both
the pain-free and the maximum walking distance lengthened only slightly
we must bear in mind, that the patient was hindered by the implantation
of a total prosthetic replacement in the right hip. Transcutaneous oxygen
partial pressure in the forefoot increased to normal levels on both sides.
This is an indication of a favorable redistribution of cutaneous perfusion,
with an improvement in nutritive circulation in the capillaries of the
skin and consequently increased oxygen utilization in the ischemic areas.
Because of the positive effects of the therapy, primarily reflected in
the healing of the ulcer and the increased transcutaneous oxygen partial
pressure values, we decided to forego performing a bypass implantation.
During a 4-month observation period with continued Rökan®
therapy (dosage 40 mg, 3 x 1) we noted an encouraging stabilization of
the clinical picture, with improvements in the Doppler perfusion pressure,
and transcutaneous oxygen partial pressure as well as the pain-free and
maximum walking distance. The close correlation between the clinical picture,
subjective symptoms and transcutaneous oxygen partial pressure is very
important and underlines the positive effects of Ginkgo biloba
on the microcirculation. Ginkgo biloba extracts are tinctures of
the two-lobed leaves of the gingko tree, traditionally planted since ancient
times in Chinese and Japanese temple gardens. Ginkgo biloba extracts
have been used successfully in Chinese medicine for around 5,000 years.
The various substances such as the flavonoids, ginkgo heterosides, pro-anthocyanidins
and specific active ingredients like the ginkgolides and bilobalide have
a number of different therapeutic properties. Numerous pharmacological
studies have shown the positive effect of the extracts on various vascular
systems (arteries, capillaries, veins) and aggregation-inhibiting effects
stemming from its influence on the thrombocytes [8-12]. Some in vitro
studies showed the positive effect of Egb 761 on erythrocyte aggregation.
These effects might be important in patients suffering from circulatory
disorders associated with pathological hemorheology. Reducing erythrocyte
aggregation or "sludge" increases blood fluidity and thus blood flow,
especially in "low-flow" areas [13, 14]. The effect on the various vascular
systems is primarily attributed to its inhibitory effect on free radicals,
cell-damaging reaction products. This also seems to be the primary mode
of action involved in the long-term protective effect of Ginkgo biloba
[5, 15-20].
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