[Complex study of the rat heart at isoproterenol damage].

Introduction of isoproterenol (an agonist of beta-adrenoreceptors) to rats is one of the widespread experimental models of cardiac failure. It is caused by damage of cardiomyocytes with the subsequent development of substitutive fibrosis. The purpose of the given work was the complex characteristic of cardiac function by means of invasive and noninvasive (echocardiography and impedansometry) methods of research. Isoproterenol was injected twice with a daily interval in dozes 85, 120, 150 or 180 mg/kg. Echocardiographic study of the heart in 2 weeks revealed obvious attributes of cardiac failure (left ventricular dilatation, lowered ejection fraction) in the groups which have received high cumulative dozes of isoproterenol (300-360 mg/kg). The catheterization of the left ventricle in these groups has shown raised enddiastolic pressure, decreased maximal rate of pressure development and fall, and also lowered indices of myocardial contractility and relaxability. In the groups which have received smaller isoproterenol dozes, apparent decrease in relaxability parameters (constants of isovolumic and auxovolumic relaxation) has been revealed at only slightly changed parameters of contractility. A strong correlation between echocardiographic and invasive parameters of myocardial contractility has been found. The phase analysis of the cardiac cycle has shown a lengthening of isometric phases of contraction and relaxation, as well as duration of ejection due to shortening duration of filling of both ventricles. Cardiomyocytes isolated from hearts with obvious cardiac failure responded to electrostimulation by arrhythmic contractions and also by much slowed and incomplete removal of free Ca++ from the myoplasm. Results allow to conclude that relatively smaller extent of myocardial damage is accompanied by decreased relaxability at slightly changed contractility, while at greater degree of damage both processes fail, but delay of relaxation still prevails.

[T-cell subpopulations and macrophages in stable and unstable coronary atherosclerotic plaques].

Unstable atherosclerotic plaques are a cause of acute myocardium infarction. Because peripheral blood mononuclear cells are often present in atherosclerotic plaques, we've examined T-cells (CD4, CD8) and macrophages (CD68) in the different areas of atherosclerotic plaques. The cells were counted individually in the center, shoulder at the bottom and in the cap of plaque. All types of studied cells prevailed in the unstable plaque cap than in the stable one (p < 0.05). CD4 and CD68 cells dominated in the shoulder of atherosclerotic plaque (p < 0.05). The difference between the numbers of macrophages at the bottom or in the center of stable and unstable plaques was statistically insignificant (p > 0.05). Prevalence of peripheral blood mononuclears in the cap and at the periphery of unstable plaques points their participation in the development of atherosclerotic plaque instability.

[Adhesion of T cells and macrophages to the coronary artery endothelium in patients with coronary heart disease].

The study has found a close relationship between the early signs of atherosclerosis, i.e. between the fine-dropwise (dust-like) lipid deposition in the intima and the adhesion of monocyte clusters to the endothelium in these places. In the intimal areas without lipid depositions, adherent monocytes were absent or detectable as single cells in the field of vision. The coronary arteries displayed large clusters of T cells (CD4, CD8) adhered to the endothelium and migrated into the intima. The clusters of these cells were encountered not only in the vascular atherosclerotic lesion areas, but also in the invisibly altered ones. Some patients (with atheromas and fibroatheromas in the coronary artery segments) were found to have en face specimens with endothelial layer damages, with one or 3-5 cells being absent in the endothelial layer. The bottom of such microerosions was lined by T-cell and macrophage infiltrations and it was part of the cap of an atherosclerotic plaque. These surface erosions may be considered as an early developmental stage of an unstable plaque.

[Collagen fiber pathology in atherosclerotic plaques of the coronary arteries in ischemic heart disease].

Structure-metabolic changes of collagen fibers (CF) in atherosclerosis plaques of the coronary arteries in the conditions of ischemic heart disease (IHD) have been studied. Segments of the coronary arteries were received from 68 men after a coronary artery bypass grafting. CF was study with using of the Van Gieson's and the Masson's methods. Histologic slices were studied by polarization microscopy. The atherosclerosis plaques with IHD were notable for lipidosis of CF. We've suspected lipidosis of CF is a crucial factor for the development of atherosclerosis plaques instability. Evident lipidosis of CF was attended with destructive changes probably resulted in accumulation of atheromatous mass in atherosclerosis plaques.

[Morphometrical characteristic of atherosclerotic plaques in the coronary arteries of humans with ischemic heart disease according to their instability index].

Morphometrical research of the atherosclerosis plaques (AP) instability and responsible for decreasing of their stability structure has been carried out by estimation of the instability index (II). II is a ratio between sum of destabilizing (lipids and macrophages) and stabilizing (collagen fibers and smooth muscular cells) AP structures. Segments of the coronary arteries were received from 45-65 years old man after a coronary artery bypass grafting. Histologic, histochemical and computer morphometric methods were used. II for every AP was estimated according to the formula introduced by M. Shiomi [22]. 3 types of AP instability degree were distinguished: stable (II < 1 for AP and AP's cover), conditionally stable (II > 1 for AP and II < 1 for AP's cover) and unstable (II > 1 for AP and AP's cover). Unstable APs were subdivided into potentially dangerous with disruption risk and really dangerous with integrity disorders (tears, disruptions, erosion, and necrosis). The potentially and really dangerous instability AP was more than in 50% of researched AP. Instability degree of AP depended on quantity of stabilizing structures, especially collagen fibers.

[Coronary artery necroses and calcification in chronic ischemic heart disease].

AIM: To study some particularly inadequately studied mechanisms for the development of coronary artery calcification (CAC), which are unassociated with calcified atheromatous masses of atherosclerotic plaques. SUBJECTS AND METHODS: . Endarterectomized coronary artery (CA) segments obtained during aortocoronary bypass surgery were pathomorphologically studied in 150 patients aged 49-72 years with coronary heart disease (CHD). CAC was found in 92% of cases. Two types of CAC were identified: one of them was associated with calcified atheromatous masses of atherosclerotic plaques; the other was related to necroses in the fibrous plaque parts. The atheromatous masses exhibited calcareous deposits as fine-grained masses of small extent. In chronic CHD, morphological signs of instability of atherosclerotic plaques were observed in 23.3% of cases, these being associated with lamellar CAC in two thirds. CONCLUSION: Calcification in the necrotic area of fibrous parts of stenotic plaques is typical of chronic CHD and is frequently attended by the development of large-focal calcareous deposits generally as laminas (lamellar calcification). Impaired transmural perfusion of plasma is noted to be involved in the development of necroses in stenotic CA atherosclerotic plaques.

[Anti-inflammatory properties of statins in the study of atherosclerotic plaques in the endartectomized coronary arteries].

Statin therapy reduces blood cholesterol and lipids and exerts an anti-inflammatory effect. Certain statins bind adhesion molecules, including functional leukocytic antigen-1, and therefore block their interaction with T lymphocytes and macrophages expressing the counter-receptor intercellular adhesion molecule-1 (ICAM-1). Quantitation of endothelium-adherent T cells and macrophages revealed much smaller numbers of these cells in patients receiving statins. The authors consider that the lower count of T lymphocytes and macrophages in the upper layers of the intima and atherosclerotic plaques may facilitate the conversion of unstable to stable plaques, which reduces the risk of atherosclerotic plaque rupture and resultant vascular thrombosis.

[Morphological manifestations of the pleiotropic effect of statins on the human aorta in atherosclerosis].

The morphological manifestations of the pleiotropic effect of statins on the human aortic intima in atherosclerosis were studied. The aortic fragments from males aged 45-65 years, obtained at aortocoronary bypass surgery, served as a material. The thickness of the aortic intima and its levels of macrophages, smooth muscle cells (SMC), collagen fibers, and glycosaminoglycans (GAG) were measured in patients treated and untreated with statins. The macrophages were histochemically visualized, by detecting the activity of acid phosphatase, SMC-NADP-diaphorase, the collagen fibers were stained by the Masson procedure; GAG was stained with toluidine blue. The above structural components were quantified by computer-aid morphometric technique (Photoshop-7). The findings have indicated that statin therapy causes the following vascular wall changes: a 20% decrease in the aortic intimal thickness; a considerable reduction in the macrophage-occupied intimal area (by 2 times in primary extracellular lipoidosis, by 2.7 times in the lipid spots, and by 15.3% in the mature lipid spots), and lower levels of collagen fibers (by 15.1 in the lipid spots and by 18.4% in the mature lipid spots), an insignificant reduction in GAG), and larger numbers of SMC (by 20.3% in primary extracellular lipoidosis, by 17.6 and 20.4% in the lipid spots of varying maturity). The findings suggest that atherosclerosis regresses under the action of statins.

[Effect of statins on content of lipids in intima of the human aorta data of computer morphometry].

We carried out pathomorphological study of fragments of the thoracic aorta obtained at aorto coronary bypass surgery in order to elucidate effect of statins on lipid component of vascular wall using the system of computer processing and image analysis. Treatment of patients with ischemic heart disease with statins leads to decrease of area of aortic intima occupied by lipids. Most significant lipid lowering action of statins has been noted at initial stage of atherosclerosis - in primary extracellular lipoidosis, less significant - in fatty streaks with intracellular lipids, and least significantly pronounced - in fatty streaks with secondary lipoidosis formed as a result of degradation of foam cells.

[Comparative studies of the evolution of aortic and coronary atherosclerosis in Moscow, Ryazan, and Yakutsk males over 40 years].

Repeated epidemiological morphological investigations of atherosclerosis of the aorta and coronary arteries were performed in apparently healthy men aged 20-59 years in Moscow, Ryazan and Yakutsk at a 40-year interval. More severe atherosclerosis and different rates of its progression were revealed in males of these towns over 40 years.

[Immunomorphological study of angiotensin-converting enzyme in coronary shunts].

Coronary bypass surgery is the operation of choice in patients with coronary atherosclerosis. However, some time later, venous shunts frequently stop functioning after successful surgery. The reasons for this include intimal hyperplasia occurring in response to release of cytokines, angiotensin II in particular. In man, the latter is formed by angiotensin-converting enzyme or chimase. The findings show that elevated ATF concentrations are found in some cells in the area of intimal hyperplasia, in macrophages and smooth muscle cells of the shunt hyperplastic intima. The increased ATF concentration in the aorto-coronary shunt cells results in the elevated levels of angiotensin II, the migration of smooth muscle cells, their hypertrophy and hyperplasia, the formation of atherosclerotic plaques, thrombosis, and circulatory disorders.

[Activity of prostaglandin synthetase in human arteries in atherosclerosis (histochemical study)].

Synthesis of prostaglandin-synthetase at the stage of development of lipid spots and plaques is increased and the degree of this depends on the cell response. Increase of PgS depends on the number of cells in the intima and adventicia. Pg synthesis in vessels is decreasing at the stage at the fibrous plaques formation.

Monitoring of aortic and coronary atherosclerosis in native and non-native males of Yakutsk over 40 years.

We have analyzed the development of aortic and coronary atherosclerosis over 40 years in native and non-native males of Yakutsk by comparing the data obtained in 1963-1965, 1985-1987 and 2001-2003. The research was carried out in compliance with the WHO program for the atherosclerosis epidemiology studies using autopsy material. Subjects (361 natives and 692 non-natives) included in the research died of external causes at the age of 20-59 years and had no history of chronic diseases, which was confirmed by post-mortem examination. The prevalence and the extent of raised atherosclerotic lesions (fibrous plaques, complicated lesions and calcinosis) in the aorta and coronary arteries were determined by visual planimetry after staining with Sudan IV. An accelerated development of aortic and coronary atherosclerosis was revealed in both populations throughout the entire period of 40 years with more severe manifestations in non-native males. The severity of atherosclerosis increased considerably in native and non-native males aged over 40 years. The rate of the increase in the extent of raised atherosclerotic lesions tended to be greater in native than in non-native males.

[Inflammatory cell reaction and mast cells in aortic intima and pulmonary artery of humans at early stages of atherosclerosis].

The study of inflammatory reaction and morphofunctional characteristics of mast cells in aortic intima and pulmonary artery at initial stages of atherosclerosis was performed in 62 persons who had died of accidental causes at the ages of 4-49 years and 44 males who had died of myocardial infarction at the age of 42-73 years. Histological, histochemical and immunocytochemical tests showed permanent presence of lymphocyte-monocytic cell reaction in combination with mast cell infiltration in arterial intima that progressed with age and development of atherosclerosis. Lipoidosis was associated with an increase of T lymphocytes with (CD4+) domination, monocytes/macrophages (CD11+) and mast cells in different functional activity. Marked hyperplasia and high secretory activity of mast cells (expressed in their massive degranulation) were observed in acute myocardial infarction in aortic intima and pulmonary artery.

[A 40-year study of aortic and coronary artery atherosclerosis in male population of Yakutsk].

The trends in development of aortic and coronary atherosclerosis in healthy male population were studied by WHO methods in three trials: in 1963-1965, 1985-1987, 2001-2003. It was found that atherosclerosis and coronary arteries stenosis were less frequent in the native population of Yakutia than in migrants.

[Hibernation and stunning as manifestations of ischemic dysfunction of the myocardium].

Hibernation and stunning are phenomena which constitute a basis of dysfunction of the myocardium appearing as a consequence of chronic ischemic heart disease and of myocardial revascularization. Myocardial stunning is an acute derangement of contractility of ischemic myocardium at the moment of restoration of coronary blood flow by various interventions (bypass grafting, angioplasty, thrombolysis). Myocardial hibernation implies presence of chronically developing foci of reduced contractility located in the area of myocardium supplied by obstructed artery. There is a following difference between these phenomena: stunning is a complex of structural and metabolic disorders during the state of "ischemia-reperfusion" while hibernation is a process of adaptation of the myocardium to chronic ischemia consisting in switch of metabolism to alternative type of energy production (anaerobic glycolysis). Exploration of pathophysiology and morphology of hibernating and stunned myocardium is necessary for elaboration of methods of protection against ischemic injury.

[Major types of unstable atherosclerotic plaques and their distribution in coronary arteries in acute myocardial infarction].

A pathomorphological investigation of unstable atherosclerotic plaques and their distribution in coronary arteries were studied on successive (5 mm) transverse sections of autopsy material from 60 patients with acute myocardial infarction (AMI). Two morphological types of such plaques were distinguished: lipid one (70%) and dystrophic-necrotic (30%). Unstable plaques in AMI are spread. Numerous unstable plaques were more frequently observed in AMI with preceding unstable angina pectoris but single plaques were found in cases with absence of coronary anamnesis. There were no significant age, sex and risk factor differences between cases with multiple and single atherosclerotic plaques.

[Evolution of atherosclerosis of the aorta and coronary arteries in practically healthy men in Moscow for a 40-year period].

AIM: To assess 40 years evolution of atherosclerosis of the aorta and coronary arteries among practically healthy Moscow men. METHODS: We compared results of 2 studies of prevalence and extent (area) of atherosclerotic lesions in thoracic and abdominal aorta and 2 main coronary arteries. The studies were conducted in 1963-1965 and 2002-2003 according to WHO program. RESULTS: Prevalence of coronary artery stenoses as well as prevalence and area of raised lesions in these arteries were higher among violent death victims studied in 2002-2003. Raised lesions in both parts of aorta and in left anterior descending coronary artery were more pronounced also in men studied in 2002-2003.

[Immunomorphological study of coronary grafts].

Most patients subjected to coronary artery bypass grafting develop graft occlusions in some time after successful coronary surgery. Causes of graft occlusions comprise hyperplasia of intima occurring as a response to release of cytokines and angiotensin II. Angiotensin II is formed in human body with participation of angiotensin converting enzyme (ACE) or chymase. We found high concentrations of ACE in some smooth muscle cells in hyperplasia zone. Proliferation of smooth muscle cells, their hypertrophy and increased synthesis of intercellular space proteins facilitate graft occlusion. Moreover ACE was found in cytoplasm of macrophages infiltrating graft's intima. Thus ACE can be an important contributor to the process of coronary artery bypass graft obstruction.

[Effect of granulocyte-macrophage colony stimulating factor on the function and regeneration of myocardium in rats with experimental infarction].

To test the reparative capacity of stromal cells in myocardial infarction, rats were injected with granulocyte-monocyte-colony stimulating factor (GM-CSF) (leukomax), a cytokine known by its ability to raise a level of stromal cells in the blood, during first three days after coronary artery ligation. Only 10 of 17 rats (59%) survived 4 weeks in this group compared with 16 of 24 (67%) among rats not treated with leukomax. Echocardiographic and electromanometric studies showed that in both groups ventricular (LV) dilatation which developed during first hours after surgery persisted throughout 6-8 weeks and was combined with decreased ejection fraction and elevated LV end diastolic pressure. These alterations correlated with infarct size which varied from 0 to 28% of left ventricular weight in both groups. There were no statistically significant differences in functional and morphometric measurements between groups receiving and not receiving GM-CSF. However this result may be inconclusive due to small number of investigated animals and broad variation of ischemic zone size in each group.