Electron microscopic study of left ventricle cardiomyocytes and quantitative analysis of their mitochondriom was performed in rats exposed to tail-suspension, as a model of weightlessness effects, to artificial gravity produced by intermittent 2G centrifugation and a combination of these effects. It was found that the cardiomyocytes ultrastructure changed slightly after tail-suspension and after intermittent 2G influence, as well as under a combination of these effects. However, the number of intermitochondrial junctions increased significantly in the interfibrillar zone of cardiomyocytes under a combination of tail-suspension and intermittent 2G influence, which agrees with the cell hypertrophy described earlier.

Semax, a member of ACTH-derived peptides family, has been employed in the treatment of acute ischemic stroke in patients. It decreased neurological deficit and reduced NO hyperproduction in the rat brain, caused by acute cerebral hypoperfusion. We suggested that semax is also able to protect rat heart from ischemic damage in acute myocardial infaction (AMI). AMI was induced by left coronary artery occlusion, myocardial ischemic area averaged 30 % of left ventricle. In 2 hours after coronary occlusion, the AMI group developed 11 % reduced mean arterial blood pressure and 48 % increased diastolic blood pressure in left ventricle in comparison with sham-operated control group. However, infusion of either dobutamine, which directly stimulates myocardial contractility, or sodium nitroprusside and phenylephrine, that change vascular resistance and thus cardiac afterload, did not reveal distinctions in hemodynamic parameters between groups. These data indicate absense or only moderate cardiac dysfunction in rats with AMI and are consistent wih morphometrical and histochemical studies that did not detect any necrotic or apoptotic (TUNEL-test) changes in left ventricular cardiomyocytes in spite of development of distinct ischemic disturbances of mitochondria and nuclear in about 50 % of cardiomyocytes in 2 hours after AMI. Semax (150 microg/kg), given i. p. 15 min and 2 hours after coronary occlusion, caused no effect on cardiac function, but completely prevented ischemia-induced ultrastructural changes of cardiomyocytes. This protective effect was accompanied by the ability of peptide to blunt the increase in plasma concentrations of nitrates, observed in AMI group.

Semax, a member of ACTH-derived peptides family, was used in treatment of ischemic stroke in patients. It decreased neurological deficiency and reduced NO hyperproduction in the rat brain caused by acute cerebral hypoperfusion. We suggest that semax is also capable of protecting the rat heart from ischemic damage 28 days after myocardial infarction (MI) induced by left descendent coronary artery occlusion. Semax (150 microg/kg) was given i. p. in the operating day twice: 15 min and 2 hours after coronary occlusion, and once a day for the following 6 days. In 28 days after infarction, the MI group developed cardiac hypertrophy, cell growth was caused mainly by the increase of contractile filaments not supported by the appropriate mitochondrial growth that indicated an impaired energy supply of the cells. Moreover, cardiac hypertrophy was accompanied by decreased mean arterial blood pressure and cardiac contractile function and increased left ventricular end-diastolic pressure. Pharmacological change of cardiac afterload revealed that, in 28 days after MI, the rat heart was not able to change its contractile performance in response to either increase or decrease of systemic blood pressure, and as a result could not maintain its diastolic pressure. All these changes obviously reflect development of heart failure. Semax did not affect cardiac work but partially prevented end-diastolic pressure growth in left ventricle as well as ameliorated cardiomyocyte hypertrophy and disproportionate growth of contractile and mitochondrial apparatus, thus exerting beneficial effect on the left ventricular remodeling and heart failure development late after myocardial infarction.

Changes in cardiomyocytes from the left ventricle of rat heart were studied by light and electron microscopic and morphometric methods in the myocardial regions neighboring necrotic foci formed after the injection of 80 mg/kg β adrenomimetic isoproterenol. TUNEL assay was used to detect apoptotic cardiomyocytes. Three types of cardiomyocytes (A, B, and C) differing by the ultrastructure of the nucleus and the degree of mitochondrial changes were identified at all studied stages of necrotic focus development (4–48 h). B and C type cardiomyocytes could represent cells at different stages of apoptosis. The apoptotic changes in cardiomyocytes proved to prevail in early lesion foci (4–18 h), while cardiomyocytes at later stages were prone to necrosis; cardiomyocytes can exhibit signs of apoptosis and necrosis at the same time.

The mitochondriom of left-ventricular cardiomyocytes in rats subjected to head-down tilt was studied at the electron microscopic level. The ultrastructure of individual mitochondria was disturbed and the number of intermitochondrial contacts in the perinuclear zone increased after 30-day head-down tilt. These parameters did not return to normal over 30 days after 30-day tilt. Repeated 14-day head-down tilt led to a more pronounced increase in the number of intermitochondrial contacts, mitochondria with abnormal ultrastructure were still observed.

Reactive changes in right atrial cardiomyocytes during antiorthostatic tail suspension of rats, which is commonly used to simulate effects of microgravity, have been studied by electron microscopy and morphometry. A 14-day tail suspension proved to increase contractile and secretory activities of cardiomyocytes. At the same time, signs of depleted activity are observed in some cells. Prolongation of the experiment to 30 days leads to development of adaptive compensatory responses and increases their secretory capacity. A 30-day rest in the normal orthostatic position does not completely restores the structure and functioning of cardiomyocytes and leads to accumulation of internal secretion in them. A repeated 14-day tail suspension to a certain extent facilitates cardiomyocyte adaptation to altered conditions as compared to a single exposure; apparently, secretion release decreases, while its production is activated.

For the first time, electron-microscopic morphometric analysis of the mitochondrial system in cardiomyocytes of the left ventricle was performed in rats exposed to hypergravity (2G) After five days of exposure, the number of long mitochondria sharply increased in the interfibrillar zone of cardiomyocytes. The numbers of inter-mitochondrial junctions (IMJ) were increased in all zones of mitochondria localization. The ultrastructure and numerical density of mitochondria remained within the normal range. Similar changes were also revealed on day 19 (the end of exposure), but the numbers of IMJ in the perinuclear and subsarcolemmal perivascular zones were lower than on day 5. One months after the end of 19-day exposure at 2G, the test parameters of the mitochondrial system did not return to the norm. Apparently, this is why the repeated exposure to hypergravity (2G for five days after 30-day rest) failed to evoke a similar response from the mitochondrial system of cardiomyocytes.

Changes in rat cardiomyocytes and their mitochondria and intermitochondrial junctions (IMJs) upon β-adrenoreceptor stimulation with isoproterenol were studied by the methods of light and electron microscopy and computer-aided morphometry. Isoproterenol injections (0.3 mg/kg for eight days) proved to induce myocardial hypertrophy, which was more pronounced in the right than in the left ventricle. In the hypertrophied cardiomyocytes of both ventricles, an adaptive response of mitochondria was observed: their ultrastructure, size, and number changed, and the number and average length of IMJs increased. A positive correlation between the degree of cell hypertrophy and the number of IMJs was revealed. The reactive properties of mitochondria, including IMJ formation, differed depending on their location in the cell (i.e., in the perinuclear, intermyofibrillar, or subsarcolemmal regions). These results suggest that the rates and intensities of adaptive compensatory processes developing in the mitochondria of cardiomyocytes exposed to β-adrenoreceptor stimulation differed in the left and right ventricles.