Introduction of isoproterenol (beta-adrenoreceptor agonist) into rats is one of the widespread experimental models of heart failure. It is caused by diffuse ischemic damage of cardiomyocytes, followed by development of substitutive fibrosis. Apelin is a natural regulator of the myocardial contractility. The effects of apelin molecule fragment, apelin-12 and its more stable synthetic analogue, apelin-12-2 on cardiac contractile function of rats with isoproterenol-induced myocardial lesion (IML) and control animals has been studied in this work using invasive (catheterization of the left ventricle) and non-invasive (echocardiography and impedansometry) methods. Infusion of both peptides was made by sequentially increasing rate from 0.5 to 50 µg/kg/min. In the control group, efficacy of apelin-12 was low while apelin-12-2 moderately but significantly increased indices of myocardial contractility and relaxability. These changes were more pronounced in rats with IML and, in addition, the heart rate and LV systolic pressure increased in this group. These results correlate well with echocardiographic studies which showed increases of LV end diastolic volume, stroke volume and ejection fraction by 17-38%. These alterations are probably due to improved Ca2+ transport in cardiomyocytes, as in experiments on isolated cardiomyocytes both apelins have facilitated and improved Ca2+ removal from myoplasma. The results allow to conclude that apelin-12-2 seems to be a promising candidate for further development as a therapeutic agent in heart failure.

Russian Scientific Center of Surgery named after B. V. Petrovsky has an experience of 30 orthotopic heart transplantations with the maximum follow-up 25 years. Nine patients survived 11-year period after operation, of those in 6 during long-term period of 11-25 years we studied ultrastructural assessment of cardiomyocytes of the donor heart. This article provides the results of mitochondrial particles: the data witnesses on the increase of destruction in mitochondria with time that finally leads to energy deficit of cardiomyocytes and progression of post-transplant cardiomyopathy.

On the material of endomyocardial and intraoperation biopsies from patients with noncoronarogenic heart diseases (dilated and diabetic cardiomiopathies, paroxysmal arrhythmia, arrhythmogenic right ventricular dysplasia) on semithin and ultrathin sections there was studied myocardial microcirculation bed. By morphometry there was found the decrease of capillaries density of myocardial bed, degenerative changes in endothelial cells and microthrombosis. It was supposed that these changes are the factors of progression of heart failure.

ОБРАЩЕНИЕ К ЧИТАТЕЛЯМ 93 МИОКАРДИТЫ, КЛАПАННЫЕ И НЕКОРОНАРОГЕННЫЕ ЗАБОЛЕВАНИЯ НАБЛЮДЕНИЕ ЗА ПАЦИЕНТКОЙ В

Mitochondrial ultrastructure was studied in endomyocardial biopsies of patients with different forms of cardiomyopathy and arrhythmias so as in animal models of alcoholic and adriamycin cardiomyopathies. Alterations in ultrastracture of mitochondria, their arrangment and quantity per cell were obtained. Both mitochondria accumulation near the nucleus and migration into the nucleus were found in patients and in experiments. Authors propose that mitochondria are the central echelon in pathology development and progress.

The orthotopic heart transplantation is an acknowledge method for the treatment of cardiomyopathies of various etiology. Specific vasculopathy of the transplanted heart is considered to be a significant problem of the long-term postoperative period and serves the reason of low 10-years survival rates (not more then 50%). The issue unites the experience of follow-up and intravital electronic microscopy of transplantated heart's biopsies from 20 patients. Previously unknown data can help the clarification of posttransplantational cardiomyopathy.

Endomyocardial biopsies performed in patients with various forms of cardiomyopathies (CMP) and chronic myocarditis in the presence of heart failure identified changes indicative of reduction of functioning cardiomyocytes (CMC) at the account of their destruction, dedifferentiation and inefficient hypertrophy". Energy apparatus of CMC was represented by large masses of destructed small mitochondria. Myofibrils were driven to periphery of CMC and appeared atrophic. Products of catabolism (lipofuscin, autophagous vacuoles, protein conglomerates) were accumulated in CMC. This led to impairment of CMC main function - to exert contraction. Reduction of number of capillary vessels per unit of myocardial cross-section area was also found. Discussion of problems of morphogenesis of the observed changes and of pathogenetic treatment is presented in the article.

The study of endomyocardial biopsy of patients with different noncoranary diseases with dilated cardiomyopathy and heart failure has been carried out. Hypertrophy of cardiac hystiocyte (CH) with dead mitochondrion, accumulation of lipofuscin, myeline-like mass, vacuoles with remains of organoids and conglomeration of dead mitochondrion was in the all biopsies studied by the light and electron microscopy. The possible mechanism of aging and death of CH could be functional impairment of lysosomal-autophagic and ubiquitin-proteosomal systems of CH and exocytosis. These changes probably are a crucial stage in the development of dilated cardiomyopathy and heart failure.

Functional, biochemical and morphological studies of rat cardiac muscle after single injection of adriamycin (2.2 mg/kg) were carried out. The myocardium was taken for studies in 2 hours and in 2-3 weeks after adriamycin injection. The isolated heart was perfused retrogradely with Krebs solution and left ventricular isovolumic pressure and perfusion pressure were continuously monitored. Two-fold increase in perfusion rate was accompanied by raised developed pressure, heart rate and perfusion pressure which in the given conditions reflected a tone of coronary vessels. The cardiac contractile function of rats that received adriamycin 2 hours before, remained unaltered as compared to control group, however, perfusion pressure was raised by 26%. These hearts responded to H2O2 introduction (100 microM) into coronary vessels by more profound fall in developed pressure, which fell to 31 +/- 8% after 40 minutes vs. 61 +/- 5% in the control group (p<0.01). In two-three weeks after adriamycin injection, both cardiac contractile function and its responsiveness to oxidative stress induced by H2O2 introduction did not differ from the control, however, perfusion pressure remained elevated and this was accompanied by slowed myocardial relaxation. The myocardial concentration of malonic dialdehyde was moderately increased in adriamycin-treated group in both terms while the activity of antioxidant enzymes (SOD, GPHx and catalase) remained unaltered. Results showed an absence of the direct connection between myocardial antioxidant status and the contractile function changes at adriamycin action.