Chapter II

 

MORPHOFUNCTIONAL MODIFICATIONS IN THE ORGANISM IN
RESPONSE TO DIFFERENT DEGREES OF INCORPORATION OF
RADIOISOTOPES

 

1. CARDIOVASCULAR SYSTEM

 

The problem of the effect of radiation upon the cardiac functions of man and animals has been reflected in local and foreign publications. In the majority of cases the cardiac functions have been rated with the consideration of external irradiation of the whole body or in the region of the heart primarily in experimental conditions. In particular, single time exposure of experimental animals (dogs, rabbits, rats) to a dose of 15 Gy and more produces degenerative and necrotic modifications of the myocardium (A.P. Amvrosjev et al., 1989) accompanied by the evolution of exhudative pericarditis (Schultz-Hector, 1992) leading to hemodynamic disorders in the form of minute and impact volume reduction, expansion of the diastolic volume of the left ventricle (Schultz-Hector et al., 1992). It has been observed that the functioning of the cardiovascular system is upset by general irradiation with 60Co gamma quanta of rats due to the exhaustion of the activating effect of the median brain blue spot (V.A. Fedorovich, 1991) and suppression of the modulating effect of the rear nuclei of the brain seam (V.A. Sjusukin, A.I. Ledeneva, 1991)].

 

The detected restructuring of the neurohormonal control governs the suppression of adaptation capabilities of the blood circulation system and may stimulate the evolution of prepathological conditions (L.M. Lobanok, 1991).

External exposure of the organism, including the heart, causes suppression of the contractile activity of myofibrils, reduction of the volume rate of coronary circulation (M.A. Tatarinchik, A.E. Kirienkov, 1991).

 

Functional modifications of the cardiovascular system can possibly be attributed to the damage of blood vessels, specifically arterioles (A.G. Zakharov et al., 1992), or capillaries (Darcourt et al., 1992), variation of the volume of catecholamines and electrolytes in vessel walls (S .A. Litvinov, 1992).

 

Using isolated rat heart preparations it has been demonstrated that external gamma irradiation with a dose 6 Gy suppresses the contractility of the myocardium and alters the chronotropic relations: the relationship between the frequency-force and the potentiating effect in the atria at the interval of rest increases, while the potentiating effect in the ventricles reduces. Modification of the chronotropic relationships may be due to the alteration of the calcium transport in the heart cells (V.V. Shilov, L.M. Lobanok, 1991).

 

After a single exposure to X-ray and neutron irradiation in doses 0.4 and 1.0 Gy the rabbits would not manifest any significant disorder of the functional condition of the cardiovascular system, yet pronounced responses to pharmacological preparations have been registered (G.P. Katsnelson, 1991). It is possibly due to the modification of the structural and functional density, the affinity to the "beta" agonist and sensitivity to the sulfohydril reagent (N.V. Gerasimovich, 1991).

 

The results of the experimental research accomplished by E.F. Konoplya et al. (1996) allow to conclude that acute gamma-irradiation with doses 0.25; 0.5 and 1.0 Gy upsets the calcium transport system of the sarcoplasmatic reticulum of the muscular tissue. The activity of Ca2+ATP at doses 0.25 and 0.5 Gy increases, while it is strongly suppressed at a dose 1.0 Gy.

 

It is assumed that the appearance of peroxide groupings in fatty acidic chains of phospholipids under the effect of ionizing radiation alters the structure of the membranes of the sarcoplasmatic reticulum, their penetrability by various substances and the activity of membrane-bound enzymes, specifically Ca2+ATP.

 

These results are corroborated by the data obtained while screening the population affected by the Chernobyl radiation. In particular, 95.5% of the children and adolescents have manifested disorders of the functional condition of blood circulation in the form of upset rhythm of the cardiac activity, conduction, metabolic and restorative processes in the myocardium, suppressed tolerance of physical exercise, elevated arterial pressure.

 

These disorders of the functional condition of the cardiovascular system are most pronounced among the children aged between 6 and 10 years assumed healthy before (V.N. Novikova, 1991).

 

I.S. Tsybulskaya et al. [143] indicate also that 74.4% of the children during their first year of life in the areas where the soil is contaminated with radiation within 5-20 Ci/km2 manifest pronounced electrocardiographic modifications: intricate rhythm disorders, alteration of the teeth of the ventricular repolarization.

 

Domination of the syndrome of premature repolarization of ventricles and elevated arterial pressure are typical for these groups of children (A.N. Arinchik, G.L. Nalivajko, 1991).

 

Vagotonia with asympathycotonic reactivity has been revealed among 36 out of 102 examined children aged 11-15 years living in the area with the 134Cs, 137Cs  soil contamination 0.4-10 Ci/km2. The children in this group have manifested disorders of the lipid metabolism in the form of hypocholesterinemia, hypolipidemia, hypophosphatemia ({.V. Kvashnina et al., 1992). V.V. Nedvestkaya and S.A. Ljalikov (1994) also indicate modifications of the vegetative regulation evolving among the children aged 6-17 years in the contaminated areas  of  Belarus which are more pronounced among girls than among boys. These modifications are characterized by the suppression of the tone of the sympathetic compartment of the nervous system, a tendency towards hyporeactivity and stress of the compensatory mechanisms of the parasympathetic compartment. Correlation analysis has revealed a close relationship between vegetovascular dystonia appearing among the children evacuated from the heavily contaminated areas, and thyroid hyperplasia, psychic disorders, disorders of digestive organs (A.U. Lagutin, V.M. Sidelnikov, 1992).

 

Children from the affected areas manifest modifications of the responses of the cardiovascular system to catecholamines (L.S. Valeva et al., 1993).

 

Arterial hypotonia detected among 34.3% of boys and 30.2% of girls in the Gomel and Moguilev regions reflects disorders of the vegetative regulation of cardiac functions (A.V. Sikorenskii, G.E. Vagel, 1992). Modifications of cardiac functions are registered among adults exposed to external irradiation, in addition to children.

 

It has been demonstrated that men aged 20-40 years who were involved in the cleaning-up operations in 1986-1988 after the disaster manifest disorders of neurohumoral regulation of the cardiac tone and myocardium contractility (S.S. Korytko, 1991). The incidence of cardiac ischemias and arterial hypertensions among liquidators of the Chernobyl aftermath is validly higher than among individuals in the control group in Moscow (V.M. Shamarin, et al., 1996). Disabled individuals with cardiac ischemias living in the contaminated areas have more frequent and stable cardiac rhythm disorders than individuals with similar pathologies living in "clean" areas (N.T. Arinchina, V.K. Milkamanovich, 1992).

 

Dysfunction of the vegetative nervous system in the form of secondary domination of the stray nerve tone as bradicardias and ectopic precardiac rhythm has been observed among male liquidators and evacuated individuals (G.P. Karaseva, 1991).

 

Evolution of arterial hypertension is one of the manifestations of the above condition (N.S. Zanozdra, E.G. Kuchinskaja, 1991). In particular, borderline hypertension has been detected among individuals in the contaminated areas 1.5 times more frequently than in the "clean" areas (I.I. Goncharik, 1992).

 

Thus, stable neurovegetative disorders in the form of the neurocirculatory dystonic syndrome among the individuals affected by radioisotopes indicate the involvement of hormonal and humoral mechanisms in the induction of functional pathology, including that of the cardiovascular system (A.M. Kovalenko, 1991). Yet, for evaluating the consequences of the Chernobyl disaster it is more essential to determine the effect of internal irradiation from incorporated radioisotopes upon the condition of vital systems, including the cardiovascular system.

 

In particular, when incorporated 131creates absorbed doses in the thyroid after 1-12 months at a level 94.6-94.7 Gy, the responses of the myocardium to the stimulation of aipha-adrenergic receptors is attenuated, while the responses of the coronary passage to such stimulation are intensified (A.E. Kirienko et al., 1992). Incorporation of 131I and 137Cs by rats induces modifications of the heart pace-maker activity, the functional condition of the coronary vascular passage, electric and contractile activity of cardiomyocytes and flat muscle vascular cells (A.E. Kirienko et al., 1990).

 

Examinations of the children living in the contaminated areas (Gomel - 1-5 Ci/km2) have revealed high frequency of disorders of cardiac activity - 72.3%, primarily due to the disorders of conduction of the cardiac impulse in the form of incomplete blockades of the His right stem bundle, upset redox processes and vegetovascular dystonias, together with a close relation between the doses of endogenously incorporated radioisotopes and electrocardiographic disorders. Though the average accumulated dose in the organisms of children in these two groups did not have any valid difference and amounted to 30.32 +- 0.66 Bq/kg in the test and 29.74 +- 0.67 in the control (p >0.1), the Gomel children have manifested a more pronounced and statistically valid direct proportionality between the accumulated dose and ECO modifications, valid differences between the subgroups of 11-25.9 Bq/kg and 37.0-74.0 Bq/kg (Fig. 6).

 

The children with the above accumulated doses but living in Grodno did not manifest any valid differences in the frequency of registered ECG modifications.

 

This fact in the main group is basically due to the disorders of intraventricular conduction in the form of incomplete blockades of the His right stem bundle (Fig. 7).

 

When children accumulate significantly higher doses of radioisotopes 89.93 +- 3.65 Bq/kg on the average (Vetka) the ECG-registerable effects have been detected among 86.8% with the disorders of the intracardiac conduction amounting to 53.95% (G.S. Bandazhevskaya, 1996).

 

Examinations of the students of the Gomel Medical Institute have yielded similar results (Yu.I. Bandazhevsky, et al., 1996).

 

Thus, investigation of the electrophysiological processes in the cardiac muscle among children in the areas with higher levels of radioactive contamination has revealed a number of modifications of electrocardiographic activity with the frequency being a function of the internally accumulated dose.

 

Damage of the myocardium structure is accompanied by the intensified activity of AST in the blood serum (Fig. 8).

 

Experimental studies of laboratory animals (the Vistar line rats) evidence the effect of endogenously incorporated radioisotopes upon the myocardium.

 

The experimental animals were kept during ten days on a diet of oats containing radioactive elements in the concentration exceeding the control level 10 times (137Cs  concentration was 445.7 Bq/kg, 90Sr - 15.5 Bq/kg). This diet would bring the 137Cs  concentration in the organisms of the animals in the test group to 63.35 +/- 3.58 Bq/kg versus 5.43 +/- 0.87 Bq/kg in the control group (p < 0.001).

 

 In this way the animals would accumulate radioisotopes within a relatively short period of time, 137Cs  in particular. A direct proportionality between the accumulated 137Cs  dose and the concentration of this element in the

 

16

 

Analysis of the results has indicated that the myocardium tissue acquires the maximum concentration of this radioactive element.

 

Significant concentrations of  137Cs have been registered among the residents of Gomel and the Gomel Region (Yu.I. Bandazhevsky, A. M. Perepletchikov, 1996). It is manifested by the suppressed activity of the most essential enzymes, such as alkaline phosphatase and creatin phosphokinase (Fig. 9). Considering that creatinin phosphokinase is a key enzyme of the energy metabolism in the cardiac muscle governing reactions between macroergic phosphate and creatinin, its suppressed activity leads to substantial disorders of the functions of cardiomyocytes.

 

 Disorders of energy processes in the heart modify its contractile apparatus, vis. myofibrils in the form of contractions or their declustering and lysis in various degrees of expression (L.M. Nepomnjashchikh, 1966).

 

Modification of the polarization behavior of cardiomyocytes in the form of expanding A-discs is a morphological criterion of this pathology (Fig. 9-10). The obtained data explain origination of disorders of cardiac conduction, including the cardiac rhythm, induced by incorporated radioisotopes.

 

Examinations of the biopsied material have manifested that contracted cardiomyocytes with ultrastructural modifications and disorders of the structures of insert discs and atrophic cardiomyocytes and cells with signs of apoptopic degeneration typical for this condition prevail in the arhythmogenic portions of the heart, unlike the nonarhythmogenic zones (Bakerija et al., 1995).

 

Thus, it has been experimentally demonstrated that incorporation of radioisotopes by laboratory animals with food (primarily 137Cs) damages the myocardium cells producing relevant structural and functional modifications. Clinical and experimental studies have revealed a significant sensitivity of the myocardium cells of a growing organism to incorporated radioisotopes. A whole combination of modifications evolves evidencing a direct injury of the cardiac muscle, organs and systems controlling its functions. The role of pathological processes evolving in the cardiac nervous apparatus should be taken into consideration by all means.

 

Hence, the problem of reducing doses of internal accumulation of radioisotopes comes into foreground, including application of sorption preparations (Yu.I. Bandazhevsky et al., 1994), requiring to project treatment actions for improving metabolic processes in the myocardium.

 

Analysis of the arterial pressure among children with different incorporated doses has revealed a dose-dependent effect. As the dose increases the number children with hypertension goes up. Totally 41.6% of the children in the areas contaminated with 137Cs in excess of 15 Ci/km manifested arterial hypertension (A.I. Kienja, N.M. Ermolitskii, 1997).