Clinical Significance of Apoptosis and Immune Disorders in Assessing the Need for Surgical Correction of Pathological Deformations of the Carotid Arteries

The dissertation is devoted to the study of the clinical significance of apoptosis and immune disorders in assessing the need for surgical correction of pathological deformations of the carotid arteries. It addresses the etiopathogenesis of course anomalies of the branches of the aortic arch, the interrelation of deformations with manifestations of systemic connective tissue dysplasia, and the role of chronic immunological inflammation and imbalance of apoptotic activity in vascular wall damage. The results of a comprehensive clinical and immunological examination of children and young adults are presented, including the assessment of regional angioarchitectonics, immunological status and the system of regulation of cell proliferation. On the basis of correlation and factor analysis, criteria for choosing an active surgical approach are substantiated, an algorithm of actions for different types of deformations and a scheme of arterial wall damage in this pathology are proposed.

The influence of stenosing and occlusive lesions of the brachiocephalic vessels on cerebral hemodynamics and the appropriateness of angiosurgical interventions in this field for the treatment of chronic cerebral circulatory insufficiency and the prevention of ischemic strokes is beyond doubt. However, despite the highly technological diagnostic and therapeutic potential of modern angioneurology, the constant search for ways of early diagnosis and timely prevention of vascular pathology of cerebral circulatory disorders remains one of the main causes of disability among the population of developed countries. Cerebrovascular diseases in Russia occupy the second place among all causes of death, second only to ischemic heart disease (Vereshchagin N.V., Varakin Yu.Ya., 1996). Every year 450,000 people suffer a stroke. Among European countries, Russia has the highest mortality rate from cerebrovascular diseases. The incidence of stroke ranges from 460 to 560 per 100,000 population (Pokrovsky A.V., 2003).

In the structure of causes of cerebral vascular insufficiency, pathological deformations of the branches of the aortic arch occupy the second place. At present, the possibility of the development of an acute ischemic cerebrovascular accident against the background of hemodynamic disorders caused by pathological deformations of the carotid arteries is beyond doubt (Vereshchagin N.V. 1977, Paulukas P.A. 1986, Lelyuk V.G., Leshok S.E. 1995, Kazanchyan P.O. 2001). The role of pathological tortuosities in the pathogenesis of cerebral ischemic disease has been proved in the works of many authors (Shmidt E.V. 1962, 1975, Garaseferyan R.O. 1965, Vereshchagin N.V. 1972, 1980, Pedachenko O.V., Voronin O.V. 1971, 1974, Paulukas P.A. 1983, 1989, Kuntsevich G.I. 1990, Kazanchyan P.O. 2005, Riser M.M. 1951).

In recent years, interest in vascular anomalies of the main arteries of the carotid and vertebrobasilar basins has grown particularly strongly. This tendency is directly related to the increased detection rate of this pathology, its high prevalence among children and young adults (Kazanchyan P.O. 2005), and the absence of a consensus on the hemodynamic significance of carotid artery deformation and the appropriateness of its surgical correction (Vereshchagin N.V. 1980, Fokin A.A., Alekhin D.I. 1997, Eremeev V.P. 1998, Barkauskas, Arunas 1992, Rogonovic et al. 1995, Van Damme et al. 1996, Schenk et al. 1996, Carcoforo et al. 1997, Fearn, McCollum 1998, Huemer 1998). Analyzing the scientific works of recent years, it should be noted that opinions on the need for surgical correction of blood flow in the zone of a pathologically tortuous segment of the artery and on the indications for surgical treatment in this group of patients are quite contradictory. Some specialists resort to surgical treatment only in the presence of cerebral vascular insufficiency (Paulukas P.A., Barkauskas E.M., 1989). Other authors emphasize the hemodynamic significance of the lesion regardless of the clinical picture (Van Damme H. 1996, Carcoforo P., Rocca T., Navarra G. 1997).

The question regarding asymptomatic patients, who according to various sources account for 40 to 50%, also remains debatable. A number of authors (Rudenko I.V., Nikiforov B.M. 1981, Metz K. 1961, Weibel J. and Fields W. 1963) believe that various types of tortuosities are most often asymptomatic and lead to cerebral ischemia only under certain conditions caused by concomitant pathology, such as acute heart failure and other disorders of central and peripheral hemodynamics.

The question of the etiological belonging of vascular anomalies of the carotid and vertebrobasilar basins also remains unresolved, namely, the factors that lead to degenerative changes in the vascular wall and aggravate already existing disorders have not been identified, even taking into account the possible congenital or genetically determined nature of the origin of the deformation. The frequent association of deformations with manifestations of systemic connective tissue dysplasia makes it necessary for specialists to use an integrated approach in the diagnosis of this group of patients, taking into account systemic disorders of homeostasis. In recent years, the role of apoptosis and immune disorders in the genesis of cardiovascular diseases has been discussed particularly actively. Undoubtedly, the data of instrumental research methods (USAS) and objective status (complaints) to some extent reflect the degree of cerebral vascular insufficiency, but in a number of cases they do not allow an objective assessment of pathological disorders, since they depend on the individual characteristics of the researcher and the patient, especially when working with children.

At present, a number of factors can be identified whose participation in the genesis of pathological deformations of the branches of the aortic arch is undoubted and has been proven. These include local weakness of the vascular wall caused by systemic connective tissue dysplasia and certain features of the regional angioarchitectonics. However, the mechanisms through which the connection of these factors with course anomalies of the carotid arteries is realized have not been studied.

The main problems of the diagnostic and therapeutic process when working with this group of patients have formed the basis of the priority tasks of modern angioneurology in recent years. The study of the etiopathogenetic belonging of pathological deformations of the branches of the aortic arch, the search for ways of their early and timely diagnosis, the determination of objective criteria for the activity of the local pathological process and systemic disorders of homeostasis will make it possible, with a certain degree of probability, to predict the main variants of the natural course of the disease, will guide the specialist in choosing one or another treatment strategy, and will make it possible to avoid unjustified surgical aggression with respect to this group of patients. All of the above has predetermined the goal and objectives of this study.

GOAL OF THE STUDY

To determine the clinical significance of changes in apoptosis activity and immunological disorders in assessing the need for an active surgical approach in patients with pathological deformations of the carotid arteries.

OBJECTIVES OF THE STUDY

1. To study the nature of the clinical course and to identify the features of the dynamics of regional angioarchitectonics in patients with pathological deformations of the carotid arteries.

2. To evaluate apoptosis activity in various types of pathological deformations of the carotid arteries in children and young adults; to determine its significance as an objective criterion of the activity of the local pathological process and systemic disorders of homeostasis.

3. To identify clinical and immunological interrelationships in patients with pathological deformations of the brachiocephalic vessels.

4. To determine the most typical pathophysiological processes in the arterial wall that lead to the formation of pathological deformations.

5. To substantiate the need for a comprehensive clinical and immunological examination of patients with pathological deformations of the carotid arteries.

6. To study the clinical significance of changes in apoptosis activity and immunological disorders in determining the management strategy for patients with pathological deformations of the carotid arteries.

SCIENTIFIC NOVELTY

1. The nature of the clinical course has been investigated and features of the dynamics of regional angioarchitectonics in patients with pathological deformations of the carotid arteries have been identified.

2. For the first time, a comprehensive assessment of the immunological status and the system of regulation of cell proliferation in pathological deformations of the branches of the aortic arch has been performed.

3. The activity of apoptosis and its association with deformations of the branches of the aortic arch in children and young adults has been evaluated.

4. Clinical and immunological interrelationships in individuals with pathological tortuosities of the carotid vessels have been identified.

5. The most typical pathophysiological processes in the arterial wall leading to the formation of pathological deformations of the carotid arteries have been determined.

6. The sequence of pathological changes leading to the formation and progression of deviations of the carotid arteries has been determined. A scheme of arterial wall damage in pathological deformations of the carotid vessels has been developed and presented.

PRACTICAL SIGNIFICANCE

Principles for diagnosing apoptosis activity and immunological disorders in children with pathological deformations of the carotid arteries have been developed and introduced into practice. A set of the most informative indicators of the immunological status and the system of regulation of cell proliferation has been selected to assess the need for an active surgical approach in symptomatic patients with pathological deformations of the branches of the aortic arch, regardless of the age of the patients. An algorithm of actions has been determined for assessing the need for surgical correction of blood flow in the zone of vessel deviation for each type of deformation separately. The necessity of a comprehensive clinical and immunological examination of patients with deformations of the vessels of the carotid basin has been proved in order to predict possible variants of the course of the disease. The necessity and appropriateness of surgical correction of blood flow in the zone of a pathologically tortuous segment of the artery has been substantiated.

STATEMENTS PUT FORWARD FOR DEFENSE

1. In patients with pathological deformations of the carotid arteries, one of the leading pathogenic factors is an imbalance of apoptosis activity caused by constant traumatization of the vascular wall and its response to damage under conditions of impaired hemodynamics.

2. The most typical pathophysiological process in the arterial wall leading to the formation of a pathological deformation is chronic immunological inflammation, leading to a decrease in smooth muscle cells, which, in turn, is provoked by high apoptotic activity.

3. Local weakness of the vascular wall in the zone of deformation, as a manifestation of the syndrome of systemic hereditary determined collagenopathy, is one of the key points contributing to the formation of tortuosity. The association of pathological deformations with manifestations of mesenchymal dysplasia is an unfavorable prognostic sign in the course of the disease.

4. The severity of disorders of the immune system and the system of control of cell proliferation objectively reflects the character of hemodynamic disorders in the zone of pathological deformation of the artery. These indicators are valuable criteria that allow predicting the natural course of the disease and assessing the need for an active surgical approach in symptomatic patients, regardless of the age of the patients.

5. The most unfavorable course of the disease is characteristic of Z/S-shaped deformations and loops of the carotid arteries. For this group of patients, surgical treatment is indicated at the earliest stages of detecting the pathology, before the appearance of clinical symptoms, in order to ensure timely prevention of severe neurological disorders.