Critical lower limb ischemia

The term "critical limb ischemia" was introduced by P.R.F. Bell in 982. The author introduced it in order to designate group of patients with pain at rest, trophic ulcers and distal necrosis. Suffering is also widespread. According to data of different authors, up to 2% of young and aging people have ischemia of lower limbs. According to materials of European compromissary committee, 500-1000 patients among one million people per year have critical lower limbs ischemia. The problem of treatment of chronic lower limb ischemia is one of the most time-consuming in angiologia and vessel surgery.

All patients with critical ischemia must be immediately taken to specialized centers for carrying out specialized treatment. Surgery connected with critical ischemia is aimed to saving of limb, and sometimes life of patient.

Development of critical lower limbs ischemia, which is the result of different diseases (obliterating endarteritis, obliterating atherosclerosis, diabetic macroangioapthy, thromboangiitis obliterans – Buerger’s disease, Raynaud's disease), on a certain stage defines bad prognosis independently from etiology. Chronic arterial impassibility can be met more often with advancing age: in general 2-3% of population have it, and at the age older than 70 years - 5-7% have it. There is age-related difference in the etymology of ischemia – at younger age it is, first of all, diabetes mellitus (especially of I type) and immune diseases, at advanced age – diabetes mellitus of II type and atherosclerosis. Among the risk factors the most important – smoking, diabetes mellitus, hyperlipidemia. With development of severe injury of lower limbs tissues, caused by infringement of possibility of main arteries, etymological features of disease vanish to a considerable extent, infringements, caused by tissue hypoxia, come to the foreground. Clinical aspects in case of ischemia are usually conditioned by infringement of microcirculation. It is point out three main composes of disease process:

1. which vessels, on which level, on which extension and to what extend are injured
2. to what extend collateral perfusion is developed, microcirculation infringements are evident, and hemostasis infringements are compensated
3. how fast the disease, which caused obstruction, is progressing and (or) how it can be compensated.

For evaluation of chronic lower limbs arterial perfusion, it is necessary to take into account clinical aspects of disease (subjective objective, and functional infringements) - pain, pulsation on vessels, walking distance, evidence of tissue injuries, plagues, necrosis, gangrene. Critical ischemia - III-IV stages, when there are evident tissue injuries, up to necrosis.

Clinical definition of chronic critical lower limb ischemia: constant pain at rest, which requires anesthesia during 2 weeks or more, trophic ulcer or gangrene of fingers and footstep, emerged on the background of chronic lower limb arterial insufficiency.

Pain syndrome is often represented by expressed pain, aggravating at night, and in most complicated cases patients cannot sleep at all. It is often preceded by intermittent lameness, after having asked patient, we can found that evidences of lameness were marked during several or уже в течение нескольких, and even dozen, years. Pain is localized in distal sections of limbs or in region of trophic ulcer. In order to decrease pain patient have to put his leg down from bed, and its return to the horizontal position again intensifies pain syndrome. Pain can be decreased by application of large doses of anesthetics; often it is necessary to insert narcotic analgesics.

Pain syndrome is potentiated by appeared ischemic neuropathy and than on the background of constant pain fulgurating acute pain can arise, most often at night. In case of associated diabetic neuropathy, vice verse, pain syndrome can be insufficient.

Arterial trophic ulcers are usually located on nail-bones of great toes, in calcaneal region, on the interface of finger, there can “kissing” ulcers on the in the interface of contacting fingers. Ulcers can be accompanied by emerging cellulites and limphangitis; they have blunt edges, bottom without granulations, covered with fibrinous flight, with pure purulent discharge. Gangrenous changes damage tips of fingers, often after injuries, pedicure, freezing or burn. They tendency to mummification in the absence of infection and rarely – to spontaneous amputation.

Usual drug therapy, including appointing anticoagulants, antiaggregants, spasmolytic, anti-inflammatory and analgesic substances, is not effective enough. Corrective surgery ob vessels is not always possible because of high risk of complications appearance, which are connected with associated pathology (especially in advanced age), several levels of vascular occlusion and injury of distal arterial bed. Thus, unfortunately, trophic changes of tissues cause almost in a half of cases the necessity to carry out necrectomy and limb amputation (sometimes repeated, "rising" amputation), which along with severe invalidization, can be the reason of lethal outcome (according to different data) among 7-20% of patients.

In the last few years vazaprostan finds its application in treatment of critical lower limb ischemia (Schwarz Farma, Germany), its active substance is prostaglandin Е1. Preparation is inserted intravenously. Optimal course of treatment – 10 days. Treatment by means of vazaprostan is usually suitable for all patients. Local reactions can be negative in the limb, in which injection can be carried out among 5% of patients (pain - 42%, reddening - 36%, puffiness - 16%), and gastro-intestinal phenomena among 6% of patients. At the same time, vazaprostan – expensive preparation, and this fact, according to the point of view of experts – vascular surgeons and facilitator of health protection, is one of the main obstacles for its widespread application in clinical practice.

Institute of cellular therapy in association with specialist from Coordination center of organs, tissues and cells transplantation of the Ministry of Health protection of Ukraine and National institute of surgery and transplantation named after Shalimov has worked out methods of treatment of chronic lower limb ischemia by means of transplantation of hematopoietic and mesenchymal progenitoric cells. The main essence of treatment – usage of stem cells ability to produce factors, stimulating the growth of new capillaries (angiogenesis) and vessels (vasculogenesis). In most complicated cases, in case of great vessel occlusion or multiple occlusion of vessels of middle size stem cells transplantation is carried out topically – in the course of obliterized arteries. In case of injury of smaller vessels or in case of contra indications to take surgical measures, systemic injection of large doses of hematopoietic and mesenchymal progenitoric cells is necessary.

Clinical expamles. Patient С., 67 years old, came under treatment with appeal from, puffiness of lower limbs, intermittent lameness (walk not more than 100 m), leg numbness. During examination, obliteration of magisterial and medium arteries of lower limbs was determined. Transplantation of mesenchymal and hematopoietic stem cells was carried out.

3 months later after surgery there was marked significant improvement of patient’s condition: pains and puffiness disappeared, distance of walk increased to 300 m. 6 months later patient can perform physical activity, connected with domestic work, without difficulties can scale to 2nd flour, distance of walk without appearance of pain increased to 1200 m.

Patient Н., 92 years old, came under treatment with appeal from constant exhausting melosalgia, leg puffiness. She could not walk without somebody’s help, could not sleep because of strong pain sense. Taking into account the fact that patient had heart cardial disease, preventing from surgical measures, there was carried out systemic injection of large doses of hematopoietic and mesenchymal progenitoric cells. 1 month later after transplantation patient felt herself better, pains disappeared, she could walk without somebody’s home, felt energy surge, significant improvement of life quality.