[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.

[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.

[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.

[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.

[Apoptosis and hibernation of cardiomyocytes of periscar zone as factor of chronic cardiac aneurysm progression]. / Apoptoz i gibernatsiia kardiomiotsitov perirubtsovoi zony kak faktor progressirovaniia khronicheskoi anevrizmy serdtsa.

Tissue specimen from chronic aneurysms and adjacent myocardium obtained at aneurysmectomy and coronary bypass surgery from 46 patients were subjected to morphological study. Immunohistochemical methods and electronic microscopy were applied for detection of apoptosis and hibernation of cardiomyocytes in 11 cases and histochemical determination of activity of energetic enzymes succinate and lactate dehydrogenase was used in 5 cases. Cardiomyocytes from peri and intra scar layers of myocardium were found to be in a state of hibernation while some of them were in a state of apoptosis. Extent of apoptosis was different in aneurysms on different stages of organization. Number of altered cardiomyocytes was the greatest in immature aneurysms. Basing on these findings apoptosis of hibernating cardiomyocytes was suggested to be one of factors of expansion of sclerotic zone and aneurysm formation.

[Pathomorphological features of atherosclerotic plaques in acute coronary syndrome]. / Patomorfologicheskie osobennosti ateroskleroticheskikh bliashek pri ostrom koronarnom sindrome.

We studied transverse cross-sections (5 mm apart) of coronary arteries of 45 men and women who died of acute myocardial infarction at the age of 41-79 years. Both stable and unstable atherosclerotic plaques were found in all cases. Stable plaques consisted of solid fibrous tissue with small amount of lipids and cellular elements. Unstable plaques were represented by 2 types: lipid (75.6%) and dystrophic necrotic (24.4%). Various degree of inflammatory cellular reaction was present in all lipid plaques. Factors associated with fibrous cap rupture were identified. Lipid plaques were more frequent in subjects with elevated while dystrophic-necrotic - with normal levels of blood lipids (measured during life).

[Hyperplasia and degranulation of mast cells in intima of the aorta and pulmonary artery in acute myocardial infarction]. / Giperplaziia i degranuliatsiia tuchnykh kletok intimy aorty i legochnoi arterii pri ostrom infarkte miokarda.

AIM: To study morphological and functional state of mast cells from intima of the aorta and pulmonary artery associated with acute cardiovascular failure due to myocardial infarction. MATERIAL: Vessels of 44 men who died of acute myocardial infarction at the age of 42-73 years. METHODS: Intimal cellular elements were analyzed in membranous preparations of intima and transverse cross-sections of vessels. Parameters studied were density of mast cells (number per unit of intima area), percent of mast cells in the state of degranulation, degree of polymorphism of mast cells. Data obtained in victims of myocardial infarctions were compared with those from apparently healthy persons who died of accidental causes. RESULTS: Intima of both the aorta and pulmonary artery in all cases of myocardial infarction was characterized by: 1. hyperplasia of mast cells (44.9 cells/mm(2) compared with 9.6 in controls); 2. substantially increased number of cells in the state of secretory activity (36.9 cells/mm(2) compared with 4.0 in controls); 3. pronounced polymorphism of mast cells reflecting disturbed balance between processes of degranulation and regranulation. Increased number of mast cells in intima was accompanied by elevated content of various T-lymphocytes and monocytes. Changes of mast cell population in main vessels of the body observed in this study can be considered as reaction aimed at stabilization of circulation in acute myocardial infarction.

[Features of atherosclerosis in the ascending human aorta and the link between its development and the main risk factors of ischemic heart disease in patients after aortocoronary shunting]. / Osobennosti ateroskleroza v voskhodiashchei aorte cheloveka i sviaz' ego razvitiia s osnovnymi faktorami riska ishemicheskoi bolezni serdtsa u bol'nykh, perenesshikh aortokoronarnoe shuntirovanie.

Atherosclerosis was found in all ascending aorta biopsies of 125 patients aged 42 to 65 years who underwent aortocoronary bypass surgery. Lipid spots only were found in 91.2% of cases, in 11 patients (8.8%) there were lipid plaques. Three main types of lipid spots were recognized: type I--primary extracellular lipoidosis (40.0%); type II--mainly intracellular lipoidosis (24.8%) and type III--cell lipoidosis with a pronounced component of secondary extracellular lipoidosis (26.4%). A specific feature of ascending aorta atherosclerosis is a frequent combination of intima lipoidosis with media lipoidosis: 92% in type I, 100% in type II and 93.9% in type III. This is probably an important way of lipid elimination from the intima and this predetermines a "mild" course of atherosclerosis in this part of the aorta. Types II and III of lipoidosis occurred more frequently in lipid metabolism disturbances and only under these conditions clusters of foam cells were observed. Arterial hypertension and smoking have a leading role in development of intimal hyperplasia. When assessing atherosclerosis activity in the operated patients not only risk factors of ischemic heart disease but also the results of aorta biopsies studies should be taken into consideration.

Synthesis of some hydroxynaphthazarins and their cardioprotective effects under ischemia-reperfusion in vivo.

A series of hydroxynaphthazarins has been synthesized. Some of them were found in in vivo experiments to be protectors of myocardium under ischemia-reperfusion and to reduce the infarction zone by 50% without any adverse effect. All compounds exhibit a moderate or small toxicity and are active in low doses.

[Subpopulations of lymphocytes and monocytes/macrophages at the early stages of human aorta atherosclerosis]. / Subpopuliatsii limfotsitov i monotsity/makrofagi na rannikh stadiiakh razvitiia ateroskleroza aorty cheloveka.

Human aorta was studied at early stages of atherosclerosis: intimal edema, first signs of lipoidosis, lipid spots and lipid plaques. Adhesion of Mn/Mp and lymphocytes to the aortal intima directly correlated with lipid deposits in the vascular wall. The number of mononuclear cells in the intima increased in parallel to progression of lipidosis. T-lymphocyte adhesion passed ahead of that of Mn/Mp. Cytotoxic suppressors dominated among T-lymphocytes adhered to the intima surface. Mn/Mp do not contain enzymes participating in the lipid utilization (acid lipase, acid phosphatase, nonspecific esterase) at initial stages of atherosclerosis. The activity of these enzymes starts to appear in parallel to atherosclerosis progression. HLA-DR antigen is found on the surface of T-lymphocytes and Mn/Mp indicating increased immunity of these cells.

[Monocytes/macrophages and lipidosis of the human aortic intima in atherosclerosis]. / Monotsity/makrofagi i lipidoz intimy aorty cheloveka pri ateroskleroze.

Immunomorphological and histochemical studies were carried out on the aorta serial sections of 20-40-year-old males. The results demonstrate that monocytes appear in the aortal intima after fat deposition. Intensification of lipoidosis in the aorta promotes an increase in monocyte count in the intima. Enzymes utilizing fat in the macrophages were not revealed at early stages of lipoidosis. Activation of lipoidosis is followed by the appearance of acid lipase, acid phosphatase and nonspecific esterase in monocytes. This is evidence of these cells capacity to phagocyte and utilize fat. The quantity of these cells increases with intensification of lipoidosis. Monocytes/macrophages are expressing HLA-DR antigen on their surface, this expressing their active immunological state.

[Changes in the enzymatic activity in the myocardium of patients with idiopathic and secondary dilated cardiomyopathy]. / Izmeneniia aktivnosti fermentov v miokarde bol'nykh s idiopaticheskoi i vtorichnoi dilatatsionnoi kardiomiopatiei.

Myocardial biopsies from patients with dilated cardiomyopathy (DCMP) were studied histochemically. The patients were divided into the following groups: 1) idiopathic DCMP; 2) patients with postmyocarditis DCMP (an increase of lymphocytic-macrophagal elements in the myocardium); 3) secondary DCMP against alcoholic myocardial damage. Idiopathic and secondary DCMP are characterized by the following enzymatic changes: a decrease in the activity of the majority of oxidation-reduction mitochondrial enzymes, normal or increased activity of malate dehydrogenase, increased activity of lysosomal and microsomal enzymes. An increased activity of succinate dehydrogenase was observed only in patients who had previous myocarditis. Alterations in idiopathic and alcoholic DCMP were practically identical.

[Changes in myocardial enzyme activity of patients with dilated cardiomyopathy and the relationship of these parameters to disturbed myocardial contractility and coronary atherosclerosis]. / Izmeneniia aktivnosti fermentov miokarda bol'nykh dilatatsionnoi kardiomiopatiei i sviaz' étikh pokazatelei s narusheniiami sokratitel'noi funktsii moikarda i koronarnym arterosklerozom.

Endomyocardial biopsies from 20 patients with dilated cardiomyopathy (DCMP) were studied histochemically. The decrease of the mitochondrial enzyme activity and increase of the activity of lysosomal and hydrolytic enzymes were found. These alterations reflect degenerative processes in cardiomyocytes followed by activation of their degradation and utilization. This results in the decrease of the myocardium contractile volume and its contractile function damage. There was no correlation between the level of the enzyme activity in the myocardium and the degree of the contractile function activity. There was a tendency to the increase of the above changes in patients with early signs of coronary atherosclerosis.

[Disorders of myocardial metabolism in sudden coronary death in the presence of coronary atherosclerosis: findings of quantitative histoenzymologic studies]. / Narusheniia metabolizma miokarda pri vnezapnoi koronarnoi smerti na fone koronarnogo ateroskleroza po dannym kolichestvennogo gistoénzimologicheskogo issledovaniia.

The activity of human myocardial enzymes in sudden coronary death (SCD) was quantitatively histochemically examined. The activity of succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), beta-oxybutyrate dehydrogenase (beta-OBDH), alpha-glycerolphosphate dehydrogenase (alpha-GPDH), NAD-diaphorase (NAD-ase), and glucose-6-phosphate dehydrogenase (G-6-PDH) was measured on prompt autopsies (up to 3 hours of death onset). beta-OBDH and LDH showed an increase in activity in the myocardium from the subjects who had suddenly died from coronary heart disease without evident changes in the heart. In SCD in the presence of small cardiosclerosis, the activity of the enzymes characterizing the major processes of energy generation was also enhanced, which was caused by moderately severe myocardial hypertrophy. In the myocardium from the subjects who had died from coronary heart disease in the presence of large postinfarction cardiosclerosis, the activity of the enzymes was directly related to the degree of myocardial hypertrophy and the signs of chronic heart failure. As myocardial hypertrophy progressed, the enzymatic activity rose, but there were signs of chronic heart failure, it fell. The findings suggest that the changes in myocardial enzymatic activity in SCD are heterogeneous and associated with the type of prior abnormalities in the cardiovascular system.

Quantitative histoenzymological characteristics of the myocardium in sudden cardiac death.

Enzymes in the human myocardium following sudden death were examined for activity in a quantitative histoenzymological study, these were NAD-dependent dehadrogenases of succinate (SDG), lactate (LDG), beta-hydroxybutyrate (beta-HOBDG), alpha-glycerophosphate (alpha-GPDG), alcohol (ADG), glucoso-6-phosphate (G-6-PDG), and NAD-diaphorase (NADse), and catalase. Autopsies were performed within 3 h after death. beta-HOBDG and LDG were found to show an increase in activity in the cardiomyocytes of sudden death subjects with coronary heart disease without apparent changes. In the myocardium from death subjects with coronary heart disease and large postinfarct cardiosclerosis, the activity of the enzymes was directly related to the severity of myocardial hypertrophy and signs of chronic heart failure. As myocardial hypertrophy developed, the enzyme activity increased; when there appeared signs of chronic heart failure it decreased. The myocardium from sudden death subjects with alcoholic cardiomyopathy showed diminished redox enzyme activity and higher activity of the enzyme utilizing alcohol (ADG and catalase). The findings suggest that changes in the enzyme activity in the myocardium are of various type and depend on previous cardiac abnormalities.

[A histochemical study of enzyme activity in the myocardium of victims of sudden death with small-focal cardiosclerosis]. / Gistokhimicheskoe izuchenie aktivnosti fermentov v miokarde vnezapno umershikh s melkoochagovym kardiosklerozom.

On the material of early autopsies of the above patients the activity of the following myocardial enzymes was undergone the quantitative histochemical study: succinate, lactate, (beta-oxybutyrate, d-glycerophosphate, glucose 6-phosphate and alcohol dehydrogenase, NAD-diaphorase, catalase, phosphorylase. The increase of the activity of practically all enzymes studied was observed in the myocardial areas with no circulation disturbances. This increase was due to the moderate myocardial hypertrophy. On the contrary, in the areas with a non-even blood supply (ischemia) the decrease of the activity of all oxidative-reductive enzymes was observed. The presence of such foci in the myocardium which occur in 70% cases studied facilitates the development of the ventricular fibrillation with a fatal outcome. The enzyme depression is particularly pronounced against the background of a high alcoholic content.