2. Application of Photodynamic Therapy in the Combined Treatment of Vasotrophic Disorders in Patients with Chronic Venous Insufficiency of Lower Limbs

B.N.Zhukov, S.M.Musienko, M.V.Nasyrov, V.E.Kostyaev

The venous ulcers of lower limbs are among the most serious complications of chronic venous insufficiency. This disease affects 1 to 2 % of able-to-work adults in industrial countries. It also strikes 4 to 5 % of elderly people. In the latter case, the disease shows high resistance to conservative therapy, predisposition to worsening, and tendency toward malignancy (in up to 1 % of cases). As a result, the problem of treatment of venous ulcers of lower limbs is of vital importance.

Photodynamic therapy (PDT) is among the promising approaches to the treatment of patients with the venous ulcers of lower limbs. The first experiments on applying PDT in the treatment of pyoinflammatory diseases, including trophic ulcers, yielded definitely positive results.

Photodynamic therapy is a three-component therapeutic technique. In our studies, we employed two exogenic components and one endogenic factor. As exogenic components, we used the Radachlorin photosensitizer in the form of sodium salt and laser radiation generated by semiconductor laser device Crystal 2000 operated at a wavelength of 662 nm with an output power of 3 W. As an endogenic factor, oxygen was used. It is required to bring about a photodynamic reaction.

Many authors described the PDT action mechanism as follows. At the first stage, when a photosensitizer molecule absorbs a quantum of light, it goes into an excited triplet state. The excited molecule may undergo photochemical reactions of two types. In the first type, the molecule reacts directly with biological molecules. This leads to the generation of free radicals. In the second type, an excited photosensitizer molecule reacts with an oxygen molecule. As a result, singlet oxygen is produced. This substance is a strong oxidant, which is cytotoxic in action.

As is known, pathologically changed tissues and microbial cells may accumulate photosensitizers. Hence, one may use PDT to fight pathological cells. This is of special importance for treating hospital infections and antibiotic-resistant strains of pathogenic germs. Bearing this fact in mind, we employed PDT to treat trophic ulcers that resulted from chronic venous insufficiency of lower limbs.

In our studies, PDT was used in the combined treatment of 18 patients suffering from a postthrombophlebitic disease of lower limbs. They also had some concomitant diseases at a decompensation stage, which resulted in contraindications to surgical treatment. The group consisted of 12 females and 6 males. Their average age was 64.8 years. The ulcerous defect persisted in them from 1 to 25 years. The average size of trophic ulcers was in the range of 5 to 130 cm². The second group consisted of 16 patients with a varicose disease of lower limbs complicated by trophic ulcers. The group was made up of 9 females and 7 males. The average age was 47.6 years. The average size of trophic ulcers ranged between 2 and 60 cm². The disease persisted in them from 1 to 8 years. The patients of the second group were subjected to PDT of trophic ulcers before surgery. The surgical treatment was performed under conventional principles. It was accompanied by split-skin autografting when the size of the ulcerous defect exceeded 5 cm².

The Radachlorin photosensitizer was applied topically onto an ulcer 2 hours before the PDT session at a dose of 0.5 ml per 1 cm². Laser radiation was generated by the Crystal 2000 device. The radiation was delivered to the treatment site through conventional light-guides. The laser device operated at a wavelength of 662 nm and produced an output power of 2.5 to 3 W per 1 cm². The PDT parameters (such as the light dose, exposure time, and number of sessions) were selected on an individual basis approach. These parameters depended on the patient’s adaptation characteristics, disease duration, ulcer size, microflora content, bacterial semination, wound process stage, and type of administered surgery.

The results were evaluated by means of clinical, immunological, microcirculatory, planimetric, and pathophysiological studies (such as the Doppler ultrasonography and thermogaphy). They were also assessed by microbiological, lipid-peroxidation, and morphological examinations (such as cytological and cytobacteriological examinations).

The results obtained led to the following conclusions:

• The functional activity of leucocytes was inhibited when the initial level of trophic ulcer infection and the endotoxin concentration were high.
• Bacterial cells accumulated the exogenic photosensitizer.
• Photodynamic therapy performed in the presence of a photosensitizer caused the destruction of bacteria, decreased the infection level, stimulated the phagocytic activity of leucocytes, facilitated the ulcer healing process, and improved blood microcirculation.
• The application of a photosensitizer onto infected ulcers produced neither toxic nor proinflammatory effect.
• The laser-based PDT produced a pronounced antibacterial effect, facilitated the first stage of wound process (necrolysis), stimulated granulation, and thus shortened the patients’ pretreatment period for dermatoautoplasty and healing by a factor of 1.5 to 2 in the case of conservative treatment.