Proliferative Potential of Cardiomyocytes in Hypertrophic Cardiomyopathy: Correlation with Myocardial Remodeling.

Proliferating Ki-67+ cardiomyocytes were detected in the interventricular septum myocardium of adult patients with hypertrophic cardiomyopathy. In the same patients, the severity of hypertrophy and the degree of cardiomyocyte differentiation were assessed by the content of myofibrils, ultrastructural morphology, and the pattern of connexin 43-containing gap junction distribution. Adult Ki-67+ cardiomyocytes containing sarcomeric α-actin (sarc α-act+) in the sarcoplasm (diameter 23.9±6.9 µ) were detected in the myocardium of patients with hypertrophic cardiomyopathy; their relative content varied from 2 to 3084 cells per 1 million cardiomyocytes. Small early differentiating Ki-67+/sarc α-act+ cardiomyocytes with a thin cytoplasm layer (diameter 5.9±1.7 µ) constituted from 3 to 2262 cells per 1 million cardiomyocytes. These cells were found in the myocardium with the most pronounced structural changes: hypertrophy of cardiomyocytes with signs of their partial dedifferentiation.

Isolated Atrial Amyloidosis in Patients with Various Types of Atrial Fibrillation.

The myocardium of the right and left atrial appendages (auricles) in patients with paroxysmal, persistent, and permanent forms of atrial fibrillation was examined by histological methods and electron microscopy. Isolated atrial amyloidosis was detected in the left (50.0-56.3% patients) and in the right (45.0-55.6% patients) atrial appendages. In all cases, immunohistochemistry revealed atrial natriuretic peptide in fibrillary amyloid deposits. Ultrastructurally, amyloid masses formed clusters of myofibrils 8-10 nm in diameter. They were chaotically located in the extracellular space along the sarcolemma as well as in membrane invaginations, dilated tubules of cardiomyocyte T-tubular system, and vascular walls. Amyloidosis was predominantly observed in women; its degree positively correlated with age of patients and duration of atrial fibrillation but negatively correlated with atrial fibrosis. The study revealed positive (in permanent atrial fibrillation) and negative (in paroxysmal atrial fibrillation) correlation of amyloidosis with myofibril content in atrial cardiomyocytes.

Age-Related Features of Cardiomyocyte Ploidy in Patients with Hypertrophic Obstructive Cardiomyopathy.

Endomyocardial biopsy samples of the interventricular septum from patients with hypertrophic cardiomyopathy isolated during myectomy were examined. We revealed significant variability of cardiomyocyte ploidy (from 2.9c to 13.5c) that directly correlated with myocyte size; the maximum ploidy was found in young patients. Ultrastructural signs of increased contractile and synthetic activity of cells were observed in patients with high DNA content in cardiomyocytes.

Resident stem cells in the myocardium of patients with obstructive hypertrophic cardiomyopathy.

Interventricular septum myocardium was studied in 40 patients with obstructive hypertrophic cardiomyopathy. Immunohistochemical assay revealed c-kit-positive resident cardiac stem cells in 82.5% patients. The content of the connective tissue and myofibrillar disarray zones and the degree of cardiomyocyte hypertrophy and myolysis were determined. In 30% cases, cardiomyocytes containing atrial natriuretic peptide were detected in the interventricular septum myocardium. The data were compared with clinical and functional parameters of patients. It was found that cardiac stem cells are present in patients, whose myocardium was characterized by increased density of the connective tissue, hypertrophy of mature cardiomyocytes, medium degree of myolysis in them, and accumulation of natriuretic peptide, a cardiac failure marker, in cardiomyocytes.

Resident cardiomyocyte precursor stem cells in the myocardium of infants of the first two years of life with tetralogy of Fallot.

We studied the content of resident myocardial stem cells, cardiomyocyte precursors, in myocardial biopsy specimens from the right ventricular outflow tract of patients of the first two years of life with tetralogy of Fallot. Myocardial resident stem cells were detected by the method of confocal immunohistochemistry using antibodies to c-kit and sarcomeric α-actin. The diameter of right ventricular cardiomyocytes was measured; the presence of myolysis zones was semiquantitatively evaluated. Electron microscopic analysis of right ventricular cardiomyocytes was performed. The data on the content of resident myocardial stem cells were compared with clinical and functional parameters of the patients and morphological peculiarities of the myocardium. C-kit-positive resident myocardial stem cells were detected in the right ventricle of 17.4% patients with tetralogy of Fallot. The content of resident myocardial stem cells in these patients varied from 4 to 45 (median 11) per 1 mln cardiomyocytes; this parameter was higher in patients with high content of small cardiomyocytes (diameter <10 µ) and cardiomyocytes with incomplete myofibril assembly in the right ventricular myocardium.

[Peculiarities of morphology and mechanisms of pathogenesis of hypertrophic cardiomyopathy].

Understanding the molecular basis and cell mechanisms, clinical course, and treatment of hypertrophic cardiomyopathy (HCMP) has progressed substantially in the last decade. The majority of genetic mutations associated with HCMP occur in genes encoding sarcomeric proteins, which are expressed only in cardiomyocytes. The spectrum of morphological features of HCMP includes: hypertrophy of myocardium, myocardial disarray, interstitial fibrosis, mitral valve abnormalities, and microvascular remodeling, is indicative of the involvement of other cell lineages. The link between sarcomeric gene defects and these HCM phenotypes remains elusive. Based on novel insights provided by cardiac developmental biology we can create new effective methods of treatment of this complex disease.

The use angiogenesis stimulators for the treatment of chronic ischemia of lower extremities.

We present the results of treatment of chronic ischemia of the lower extremities (distal form) with angiogenesis stimulators, autologous endothelioblast precursors (CD133+) and gene preparation of vascular endothelial growth factor VEGF165 (angiostimulin). Good clinical effect was attained in all patients, which was confirmed instrumentally 1, 3, and 6 months after administration of the stimulant: transcutaneous oxygen tension on the foot, index of malleolar pressure, and walking duration increased, parameters of microcirculation improved, the number of newly formed collateral arteries increased (angiography findings), quality of life improved (SF 36 questionnaire), and parameters of coagulogram also improved. The maximum positive dynamics was observed by month 3 of the study.

Use of human VEGF(165) gene for therapeutic angiogenesis in coronary patients: first results.

The paper presents the first results of therapeutic angiogenesis in clinical cardiosurgery: human VEGF(165) gene transplantation to coronary patients. The use of this therapeutic method is particularly effective in patients with inoperable cardiovascular injuries, i.e. patients with the most severe condition, in whom treatment remains little effective at the modern level of cardiosurgery development.

[New approaches to the treatment of ischemic heart disease: therapeutic angiogenesis in combination with surgical revascularization of the myocardium]. / Novye podkhody k lecheniiu ishemicheskoi bolezni serdtsa: terapevticheskii angiogenez v sochetanii s khirurgicheskoi revaskuliarizatsiei miokarda.

AIM: To evaluate the results of surgical treatment of patients with ischemic heart disease in combination with intraoperative intramyocardial introduction of the human gene VEGF165 (angiostimulin). MATERIAL AND METHODS: Twenty four patients enrolled in the study were examined using 12-lead ECG, echocardiography, treadmill exercise test, single-photon emission computed tomography of the myocardium with Tc-99m-tetrophosmine, fluorodesoxyglucose (FDG) positron-emission tomography of the myocardium, selective coronarography. Out of 24 patients, 10 patients have been reexamined so far. The effect of the treatment was assessed by the data obtained at the treadmill test, transthoracic echocardiography, myocardial scintigraphy and FDG. RESULTS: All the patients demonstrated a clinical response. The class of effort angina improved, the dose of the prescribed nitric drugs was decreased, exercise tolerance and total stress time rose, quality of life improved. Myocardial scintigraphy registered reduction of the total area and better accumulation of the radiopharmaceutical under load and at rest 3 and 6 months after the operation including myocardial areas which had not been revacularised at coronary artery bypass grafting but had been treated with the preparation of the human gene VEGF165. CONCLUSION: The results of the study suggest that therapeutic angiogenesis may be an alternative impact on those myocardial areas which are supplied by the affected but ineligible for bypass grafting coronary arteries.

[Clinico-immunological characteristics of patients with systemic lupus erythematosus and cryoglobulinemia]. / Kliniko-immunologicheskie osobennosti bol'nykh sistemnoi krasnoi volchsnkoi s krioglobulinemiei.

Sixty patients with systemic lupus erythematosus (SLE) were examined: 40 patients with cryoglobulinemia and 20 patients without it. Cryoglobulinemia was observed in patients with SLE, as a rule, in the acute course of the disease ending in renal affection. Cryoglobulinemia in SLE was accompanied by the phenomenon of generalized vasculitis in the form of skin and mucosa lesions with ulcero-necrotic changes and affections of the central and peripheral nervous system and the kidneys. The clinical picture of SLE accompanied by cryoglobulinemia was characterized by a polysyndrome phenomenon and infrequent presence of the ARA criteria. Cryoglobulinemia was accompanied by high titres of anti-DNA. Thus, cryoglobulinemia can be regarded as one of the important factors of immunocomplex damage in SLE.

[Cryoglobulinemia and fibronectin in systemic lupus erythematosus]. / Krioglobulinemiia i fibronektin pri sistemnoi krasnoi volchanke.

EIA was used to measure the concentration of fibronectin in plasma and cryoprecipitates of 37 patients suffering from systemic lupus erythematosus coupled with cryoglobulinemia. A definite relationship was discovered between the level of cryoglobulins and the activity of SLE, the concentration of fibronectin in plasma and liver damage. A tendency was revealed towards increase of the fibronectin content in plasma of patients with a high level of antibodies to native DNA and CIC as was a significant correlation between the concentration of cryoglobulin protein and the concentration of fibronectin in cryoprecipitates.

[Use of solid-phase Clq-ELISA for detecting circulating immune complexes in human diseases]. / Ispol'zovanie tverdofaznogo Clq-immunofermentnogo metoda dlia opredeleniia tsirkuliruiushchikh immunnykh komplksov pri zabolevaniiakh cheloveka.

The authors provide the results of studying the methodologic characteristics and of the clinical trial of the C1q-ELISA for detection of the circulating immune complexes. The C1q-ELISA is shown to have a high sensitivity and to make it possible to identify 3 micrograms/ml and more of aggregated gamma-globulin. The method can use for detection of CIC E (ab')2-fragments of antibodies to IgG of man and protein A labeled with peroxidase. Using the method, the circulating immune complexes were identified in the sera of 50% of patients with systemic lupus erythematosus, of 30% of patients with dilated cardiomyopathy and of 53% of patients with nonspecific aortoarteritis. It is concluded that the C1q-ELISA can be used in clinical practice for detecting the circulating immune complexes in different diseases of man.

[The immune system in coronary atherosclerosis]. / Immunnaia sistema pri koronarnom ateroskleroze.

A considerable imbalance in humoral and cellular factors of immunity characterized by high B-cell activity associated with a relative T-cell deficiency has been revealed in patients with coronary heart disease. Immunological imbalance is characteristic for all the clinically pronounced forms of coronary heart disease, forming long before obvious lesions of the coronary arteries. This makes it possible to regard patients without coronarographically documented atherosclerosis as having functional form of the process pathogenetically identical to atherosclerosis according to immunological criteria.

[Circulating immune complexes and apolipoproteins in ischemic heart disease]. / Tsirkuliruiushchie immunnye kompleksy i apolipoproteiny pri ishemicheskoi bolezni serdtsa.

Levels of circulating immune complexes (CIC) and apolipoproteins (apo-A and apo-B) were compared and correlated with the severity of atherosclerotic affection of heart vessels in coronary patients with coronarographically-verified coronary arterial atherosclerosis. An inverse correlation between blood CIC and apo-A levels, and a direct correlation between the CIC level and the apo-B/apo-A index were demonstrated. The variation of CIC levels in patients with atherosclerotic lesions of varying severity corresponded to that of the apo-B/apo-A index. The correlation of these parameters was particularly significant in coronary patients with 2 coronary vessels affected.

[Use of coagglutination for serotyping Shigella dysenteriae and Shigella boydii]. / Ispol'zovanie koaggliutinatsii dlia serotipirovaniia Shigella dysenteriae i Shigella boydii.

The coagglutination test was used to identify Shigella boydii and Shigella dysenteriae. A trial was carried out with 13 native rabbit antisera to S. boydii and 10 antisera to S. dysenteriae, as well as with coagglutinating reagents prepared from these antisera. The use of coagglutinating reagents was shown to ensure the complete specificity of the results, to prevent the adsorption of diagnostic antisera and to decrease their consumption 50 times. The importance of the coagglutination test for the identification of shigellae is discussed.