**Chemical Elements and Structural/Molecular Properties of Myocardium in Infants with Transposition of Great Arteries**

Okuneva G.N.1, Karaskov A.M.1, Trunova V.A.2, Zvereva V.V.2

Kliever Ye.E.1, Volkov A.M.1 and Vlasov Yu.A.1 *1E.N. Meshalkin Research Institute of Circulation Pathology, 2A.V. Nikolayev Institute of Inorganic Chemistry Russian Federation* 

### **1. Introduction**

330 Congenital Heart Disease – Selected Aspects

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The imbalance of chemical elements (CE) during the prenatal development of a foetus might cause foetal heart abnormalities and even miscarriages (Skalny, 1999; Kudriyn, 2000), while the deficit of many vital CE during the gestation period could lead to congenital heart diseases. The deficiency of Cu in the course of this period might provoke the development of aortic aneurysms and impairment of vessel elasticity (Panchenko, 2004), while the lack of Zn could bring about transposition of the great arteries (TGA) (Shankar & Prasad, 1998; Beerli et al., 2000). The content of Fe, Cu, Zn, Se and Mn in optimal quantities is indispensable for adequate support of the cellular cycle, growth and differentiation of cells, including cardiomyocytes (Ruff, 1999). TGA comprises a special group of congenital heart diseases (CHD) with concordant atrioventricular and discordant ventricular-arterial junctions (Fozzard et al., 1986; Hoffman, 2006). This complicated disease occurs in newborns with CHD in an excess of 10 % of cases, with significant mortality and morbidity (Bokeria & Gorbachevsky, 1996). This is because it is yet unclear why this disease occurs, how this pathology progresses during the growth and development of newborns and, most importantly, which metabolic processes get impaired in cardiomyocytes that lead to the death of myocardium. Nowadays, a high level of immunofluorescent methods allows for identifying the cardiomyocytes that are involved in DNA replication (Re, 1987; Bolli, 2002). The main difficulty encountered in treating this disease is to correctly evaluate the ventricular function providing an adequate cardiac output (Castaneda, 1993, 1998). Age is also an important factor in determining the speed and functional reaction of the myocardium to pressure overload (Isoyama et al., 1987; Re, 1987; Scholzen & Gerders, 2000). Further research is needed to answer the following questions: 1. How is CE distribution disrupted in different parts of the heart and how is this disruption related to pathomorphological abnormalities? 2. How are morphology and the molecular structure of cardiomyocytes changed in the course of growth and development of infants with TGA,

Chemical Elements and Structural/Molecular

respectively (Trounova et al., 1998).

to obtain a dry sample with a flat surface.

the basis of 1 µg per 1 g of tissue.

given in Table 1.

**3. The clinical examination of infants with TGA** 

excitation energy.

Properties of Myocardium in Infants with Transposition of Great Arteries 333

The concentrations of CE were determined by X-ray fluorescence analysis with synchronous radiation (SRXRF). All measurements were carried out at the station of X-ray fluorescent elemental analysis in the Siberian Centre of Synchrotron and Terahertz Radiation (Budker Institute of Nuclear Physics SB RAS). The parameters of the storage ring VEPP-3 and experimental station are as follows: Eex = 2 GeV, B = 2 T, Ie = 100 mA; chamber for the analysis is made from elconait; maximum diameter of the sample is 30 mm; the spot size is 1 ÷ 30 mm2; exposure time is 10 ÷ 1000 c; the excitation energy is from 12 to 45 keV; elements determined: from S to U; X-ray fluorescence from the sample is registered by 10mm2 Si(Li) detector (OXFORF, Oxford Instruments Inc., USA) with energy resolution 150 eV at 5.9 keV,

The advantages of the application of SR as a primary source of excitation are as follows: the high intensity → the better peak/background ratio → analysis of samples with low masses (down to 0.5 mg, dry weigh); linear polarization → lower background → lower detection limits (down to 0.02 ppm for organic matrices); the wide spectrum of radiation → optimization of excitation energy, the possibility to measure samples, as well as varying the

The concentrations of CE in the samples of heart muscle and vessels were calculated by the external standard method (different certified reference materials [CRM]) were used). The corresponding approaches were elaborated upon, using different certified reference materials with similar matrices: the applicability of different standards and the absorption characteristics of their matrices were investigated (Trunova et al., 2008). All spectra obtained were processed by the AXIL programme (Canberra Packard, Benelux). The samples investigated are the fragments of myocardium tissue with masses from 2 to 10 mg (dry weigh). At one of the steps of the sample procedure they are dried for 48 hours and longer

The content of CE was measured in 40 samples of myocardium of TGA infants aging from 1 to 4.5 months (mean age 3.0+0.7 months, heart's mass 54.0+5.0 g, body mass 4.2+0.3 kg). The concentrations of the following 14 CE were studied: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Se, Br, Rb, Sr by SRXRF (Okuneva et al., 2010). By using X-ray fluorescence analysis with synchronous radiation (XFA SR), concentrations of the following 14 CE were studied: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Se, Br, Rb, Sr (Okuneva et al., 2010). Myocardium samples were taken from ventricles and atria not later than 24 hours after death. Overall, more than 270 X-ray fluorescence spectra of CE were obtained. The content of CE was determined on

All patients with TGA were broken down in 2 groups: the first group included patients with intact ventricular septum (IVS), while the second one incorporated those with ventricular septum defects (VSD). Two tasks were set; firstly, to study the clinical characteristics of patients depending on their age, for which purpose all of them were classified into 3 age groups: newborns aged 1 to 6 months and babies aged 6 to12 months. The second task was to compare the clinical characteristics of the deceased patients (subgroup I) and patients with favourable outcomes after surgical repair of the disease (subgroup II). Anthropometric measurements of patients with IVS depending on their age in the first and second group are

from newborns to 1-year-old babies? 3. What pathomorphological distinctions are typical for 2 anatomical types of TGA: with intact ventricular septum (IVS) and with ventricular septum defect (VSD)?

The purpose of this research is to study the content of chemical elements and the morphological structure of the myocardium in infants with different TGA types. Three tasks were set to achieve this goal: 1. To investigate some features of the content of CE and the structure of cardiomyocytes in 3 age groups: newborns aged 1 to 6 months and babies aged 6 to 12 months. 2. To study the concentration of CE in different parts of the heart in infants with TGA and in patients whose death was not caused by cardiac problems (control group). 3. To compare the features of CE and pathomorphological structure of 2 anatomic types of TGA: with atrial septal defect (ASD) and intact ventricular septum (IVS) and with atrial septal defects (ASD) and (VSD).
