[The Study of Biochemical Factors of Calcification of Stable and Unstable Plaques in the Coronary Arteries of Man].

OBJECTIVE: The aim of the study was to study biochemical factors of calcification in stable and unstable plaques of coronary arteries and in the blood of patients with severe coronary atherosclerosis, to find associations of biochemical factors of calcification with the development of unstable atherosclerotic plaque. MATERIALS AND METHODS: The study included 25 men aged 60,4±6,8 years who received coronary bypass surgery. In the course of the operation intraoperative indications in men were from coronary endarteriectomy (s) artery (a - d) and histological and biochemical analyses of the samples of the intima / media. Out of 85 fragments of intima / media of coronary arteries, 15 fragments of unchanged intima / media, 39 fragments of stable atheromatous plaque and 31 fragments of unstable plaque were determined. In homogenates of samples of intima / media (after measurement of protein by the method of Lowry) and in blood by ELISA were determined by biochemical factors of calcification: osteoprotegerin, osteocalcin, an osteopontin, osteonectin, as well as inflammatory factors (cytokines, chemokines). RESULTS: A significant direct correlation (Spearman coefficient =0.607, p<0.01) between the stages of atherosclerotic focus development to unstable plaque and the degree of calcification of atherosclerotic focus development samples was found. There was an increased content of osteocalcin in stable and unstable plaques by 3.3 times in comparison with the unchanged tissue of intima / media of coronary arteries, as well as in samples with small and dust-like, with coarse-grained calcifications in comparison with samples without calcifications by 2.8 and 2.1 times, respectively. According to multivariate logistic regression analysis, the relative risk of unstable atherosclerotic plaque in the coronary artery is associated with a reduced content of osteocalcin (OR=0.988, 95 % CI 0.978-0.999, p=0.028). Also, the relative risk of calcifications in the atherosclerotic plaque in the coronary artery is associated with an increased content of osteocalcin (OR=1,008, 95 % CI 1,001-1,015, p=0,035). In men with severe coronary atherosclerosis, a significant inverse correlation was found (Spearman coefficient -0.386, p=0.022) between the content of osteoprotegerin in the vascular wall and in the blood.

Association of some hemostasis and endothelial dysfunction factors with probability of presence of vulnerable atherosclerotic plaques in patients with coronary atherosclerosis.

OBJECTIVE: The study was dedicated to investigation of some hemostasis and endothelial dysfunction factors association with probability of presence of vulnerable atherosclerotic plaques in coronary arteries in men with atherosclerosis. RESULTS: The blood levels of factor VII, factor XII and MCP-1 were higher, and concentration of sVCAM-1 lower in men with vulnerable atherosclerotic plaques in the coronary arteries, compared to men who had stable plaques. Have been revealed correlation links between the blood levels of factor II, factor XII, MCP-1 and the presence of vulnerable atherosclerotic plaques in the coronary arteries. Results of logistic regression analysis showed that the relative risk of present of vulnerable atherosclerotic plaques in the coronary arteries is associated with an elevated blood level of factor XII and MCP-1.

Immunohistochemical Features of Different Types of Unstable Atherosclerotic Plaques of Coronary Arteries.

We performed a complex morphological study of samples of different types of unstable atherosclerotic plaques obtained from 33 men with occlusive coronary atherosclerosis, who underwent coronary artery endarterectomy during coronary artery bypass surgery. In the samples, expression of MMP-2 and MMP-9, collagen IV, CD31, CD34, factor VIII, and actin of smooth muscle cells was evaluated by morphometric and immunohistochemical methods. The maximum expression of MMP-9 was found in unstable plaques of the lipid type, where it 1.4- and 1.24-fold surpassed the corresponding levels in plaques of the inflammatory-erosive and degenerative-necrotic types. Unstable plaques of the degenerative-necrotic type are characterized by the most intensive expression of collagen IV in comparison with plaques of the inflammatory-erosive and lipid types (by 2.8 and 2.2 times, respectively). The maximum neovascularization was detected in inflammatory-erosive plaques, which was confirmed by enhanced expression of CD31 and CD34 markers in comparison with plaques of the lipid (by 7.6 and 18.95 times, respectively) and degenerative-necrotic (by 31.1 and 39.8 times) types.

Immunohistochemical Phenotypes of Stable and Unstable Occlusive Atherosclerotic Plaques in Coronary Arteries.

We performed a complex morphological analysis of atherosclerotic plaques obtained from 68 men with coronary atherosclerosis during coronary bypass surgery with endarterectomy. The expression of MMP-2 and MMP-9, collagen IV, CD31, CD34, factor VIII, and of smooth muscle cell actin was measured in the samples by morphometric and immunohistochemical methods. The expression of MMP-2 and MMP-9 as well as the intensity of neoangiogenesis estimated by the expression of CD31, CD34, and factor VIII in unstable plaques was significantly higher than in stable ones. Immunohistochemical analysis showed more intensive collagen IV expression in stable plaques. The observed differences in immunohistochemical phenotypes of stable and unstable atherosclerotic plaques reflect peculiarities of morphogenesis of atherosclerotic foci in the coronary arteries determining their further development.

[Changes of Content of Matrix Metalloproteinases and Their Tissue Expression in Various Types of Atherosclerotic Plaques].

AIM: to investigate diagnostically significant for atherosclerotic plaques (ASP) of various types parameters of activity of matrix metalloproteinases (MMP-3, MMP-7, MMP-9) in homogenates, as well as tissue expression of MMP-2, MMP-9 and collagen type IV. MATERIALS AND METHODS: We included in this study 54 men with coronary atherosclerosis without acute coronary syndrome who underwent coronary artery bypass surgery with endarterectomy. In the obtained samples we determined levels of MMP-3, MMP-7, and MMP-9 (by enzyme immunoassay), as well as tissue expression of antibodies to MMP-2, MMP-9 and collagen type IV. RESULTS: In unstable plaques we observed increased activity of MMP-7 and MMP-9, significant increase of tissue expression of MMP-2 and MMP-9, and decreased expression of type IV collagen. Of three types of unstable ASP the highest tissue expression of MMP-9 was found in plaques of lipid type compared with plaques of necrotic and inflammatory-erosive types. Expression of type IV collagen predominated in plaques of necrotic type. CONCLUSION: The data obtained allows us to speak about tissue expression of collagen as the marker of fibrous cap stability; the presence of metalloproteinases in necrotic detritus, collagen fibers, and cellular elements can characterize an ASP as unstable or being in the transitional structural state. The immunohistochemical method helps to detect structural elements that characterize instability in various types of ASP.

Associations of Osteocalcin, Osteoprotegerin, and Calcitonin with Inflammation Biomarkers in Atherosclerotic Plaques of Coronary Arteries.

We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1ß). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin. The exception is osteocalcin, its concentration significantly increased during calcification. The results suggest that severe vascular calcification can be regarded as non-specific marker of atherosclerosis. Instability of atherosclerotic plaques is associated with higher level of calcification.

[Comparative assessment of endoscopic and open methods of autovenous conduit exposure for coronary artery bypass grafting operations].

AIM: comparative assessment of endoscopic and open exposure of the great saphenous vein during the operation of coronary artery bypass grafting. MATERIAL AND METHODS: a total of 228 patients with endured coronary artery bypass graft operation were randomized depending on the method of exposing the great saphenous vein (GSV) - an open method of vein exposure (OVE) - 115 patients and endoscopic vein exposure (EVE) - 113 patients. The evaluated parameters included healing of the postoperative wounds, postoperative oedema, pain intensity, and neuropathies in the early postoperative period. We performed lymphoscintigraphy of the lower limbs, as well as morphological examination of the venous wall by means of light and electron scanning microscopy. RESULTS: the duration of vein exposure was less in the EVE group than in the OVE group, amounting to 31.8 ± 6.2 min and 40.3 ± 15.8 min, respectively (p<0.01). Complications after GSV isolation were encountered considerably less often in the EVE group (11.5%) as compared to 44.4% in the OVE (p=0.001). According to the results of the multivariate analysis, diabetes mellitus was the only risk factor for postoperative complications in OVE. According the findings of lymphoscintigraphy the EVE group had no significant impairments of lymph outflow after the operation, whereas during OVE, accumulation of radiopaque material in the lymph nodes decreased twofold (p ≤ 0.001). Histological assessment of the sampled vein specimens showed no considerable lesions of the venous wall in the examined groups. CONCLUSION: the obtained findings confirm high efficacy of using EVE during operations of CABG, lower traumaticity of this method with a conduit of good quality, which was proven based on electron microscopy of the vein fragments.

Ultrastructural and metabolic features of stress-adaptive rearrangements of myocardium in infants after surgery-induced up-regulation of lipoperoxidation processes.

Surgical correction of complicated congenital heart disease in infants is terminated by postischemic reperfusion of myocardium accompanied with closure of more than 20% microvessels in the coronary bed by edematous endothelial cells, their bleb-like fragments, and aggregates of the blood formed elements. Degradation of the transmission capacity of the coronary microvessels developed in parallel with moderation of activity of the antiradical protection enzymes and positively correlated with the level of LPO secondary products, whose elevation during the surgery stages was not reduced by catalase activation.

[Comparative analysis of immediate results of reoperative coronary artery bypass surgery depending on the procedure of operative intervention].

The operations of coronary artery bypass surgery were performed in 52 patients over the period of time since June 2004 till November 2012. The age of the patients was from 46 till 77 years (on average 60.8 +/- 7.8 years). These patients were divided three groups on the basis of features of methods of coronary artery bypass surgery. The groups were matched between each other due to the initial clinic data. Acute cardiovascular insufficiency predominated in the structure of complications of the early postoperative period in 9 (17.3%) patients. These 6 (11%) patients were operated under condition of the artificial circulation used. An average time of in-patient treatment was 13.6 +/- 5.6, 10.7 +/- 3.5 and 15.2 +/- 6.1 days of hospitalization respectively. The hospital lethality made up 3.8%. Reoperative myocardial revascularization is an effective method of treatment of recurrence of myocardial ischemia after coronary artery bypass surgery. The performance of coronary revascularization on the working heart facilitates to the reduction of the risk of the development of postoperative complications, including cardial ones and can lead to quick recovery.

[Features of surgical treatment of moderate ischemic mitral regurgitation in high risk patients].

The experience of surgical treatment of high risk group patients with ischemic mitral regurgitation of different degree of manifestations was analyzed. The basic approaches to the management and the choice of treatment strategy are reported in this article. The authors suggested the priority strategy on the background of completed investigation: 1) the performance of the annuloplasty on pressure ring in combination with coronary bypass surgery in surgical treatment of ischemic mitral regurgitation of Ill degree, as most effective kind of intervention; 2) the performance of operation of isolated coronary bypass surgery on working heart for high risk patients with the presence of moderate ischemic mitral regurgitation, that allows the significant improvement of indices of postoperative period and the decrease of evidence of mitral regurgitation at the expense of a salvage of myocardial contractility.

[State of the lower-limb lymphatic bed after open and endoscopic exposure of the great saphenous vein during coronary artery bypass grafting].

The article deals with the results of a comparative analysis of the state of the lower-limb lymphatic bed depending on the method of exposing the great saphenous vein (GSV) during the operation of coronary artery bypass grafting (CABA). Pronounced lesions of the lower-limb lymphatic system after surgical aggression provoke the development of complication such as lymphorrhea, lymphocele, and secondary oedema. The chosen objective method of assessment was radionuclide lymphoscintigraphy allowing of dynamically evaluating the alterations in the lymphatic system. We examined a total of 205 patients presenting with coronary artery disease and subjected to CABA. The patients were subdivided into two groups depending on the method used to expose the vein, including 109 patients with endoscopic exposure of the vein and group two consisting of 96 patients undergoing open exposure of the vein. Lymphoscintigraphy was performed in 18 patients with open exposure of the vein and in 23 patients with endoscopic exposure before and after the operation. Analysing the obtained findings revealed that according to the results of lymphoscintigraphy endoscopic exposure of the GSV was accompanied predominantly by an insignificant degree of impairment of the lymphatic drainage in 34.4%, whereas 94.4% were found to have mainly moderate-to-severe impairments. The lymphatic complications rate in the group with open exposure of the GSV was considerably higher which was mainly associated with the development of early oedema confirmed by an increased volume of the lower third of the crus of the operated limb. Radionuclide lymphoscintigraphy may be recommended as a method of early preclinical diagnosis of impairments of lower-limb lymphatic drainage in patients after exposure of the GSV in order to predict the development of clinically significant complications.

[Roentgenomorphological features of coronary artery lesions and coronary shunts in patients with relapse of myocardium ischemia after coronary bypass surgery].

The relapse of ischemia was detected in 127 patients in clinical series after coronary bypass surgery. It was noted in terms from 1 month till 204 months. The basic clinical manifestation or the relapse of ischemia was the recurrence of heart stroke in 74.8%. According to the data of coronary bypass angiography, the main cause of the ischemia relapse appears to be the dysfunction of early formed shunts in 64.6% patients. The development of early thrombosis of autografts is substantially determined by the pool and degree of stenosis of shunt coronary arteries.

[Treatment of giant diaphragmatic hernia].

The authors demonstrate the results of treatment (16 patients) with giant paraesophageal and posttraumatic diaphragmatic hernia. The article represents the main principles of operation management, key moments of the choice of access, operative techniques and also the features of the usage of modern reticular implants.

[Gender peculiarities of development of atherosclerosis and impairment of brain oxygen supply in excessive body weight].

Aim of the given study was to elucidate special characteristics of mechanisms of development of atherosclerosis and supply of oxygen to the brain in overweight men and women. We included into this study 80 patients with multifocal atherosclerosis without history of myocardial infarction. We analyzed parameters of blood lipid composition, data of cerebral oxymetry, echocardiography, and central hemodynamics. We found gender linked differences in structural-functional parameters of myocardium and in mechanisms of progression of atherosclerosis which increased with increase of excess body weight. This was associated with differences in oxygen brain supply between men and women.

Oxidation and endothelial dysfunction biomarkers of atherosclerotic plaque instability. Studies of the vascular wall and blood.

The concentrations of LPO products (including those present in LDL), oxidative modification of proteins, paraoxonase activity, concentrations of antioxidants, lipid values and biomarkers of endothelial dysfunction were studied in the blood and coronary artery intima/media of male patients with coronary atherosclerosis without acute coronary syndrome. Blood levels of LDL oxidized apolipoproteins and lipoprotein (a) were higher, while the content of NO metabolites, sVCAM endothelial adhesion molecules, and LDL oxidation resistance were lower in men with mainly unstable atherosclerotic plaques in the coronary arteries in comparison with men with mainly stable plaques in the coronary arteries. Of these blood biomarkers, only NO metabolites, oxidized proteins, and sVCAM correlated with the presence of unstable atherosclerotic plaques. A significant correlation between the levels of biomarkers in the vascular wall and blood was detected only for LPO parameters.

[Specific features of the technique of performing coronary bypass operations on the beating heart].

The article presents a technique of performing coronary bypass operations on the beating heart used by the authors in 847 patients which is based on high thoracic epidural anesthesia, primary formation of proximal anastomoses of the aorto-coronary bypasses and specified succession of the formation of distal, stabilization of the local part of the heart in the field of placing distal anastomosis and access to the lateral and posterior surface of the heart with vacuum stabilizers, using blower-humidifier and intracoronary shunts.

[Application of a device for determination of the transplant length during operation of the aorta-coronary bypass].

Determination of the necessary length of the bypass is one of the principal stages of operation of the aorta-coronary bypass. The greatest difficulty of the determination of the bypass length is the first-priority applying of proximal anastomoses. It requires the surgeon to have great experience, the operation to be longer. It also makes it necessary to prepare a conduit of deliberately excessive length. A device is proposed for the determination of the necessary bypass length during operation of aorta-coronary bypass consisting of a crocodile grip with a fixed to it polymer tube.

Activity of the inflammatory process in different types of unstable atherosclerotic plaques.

Inflammatory biomarkers and chemoattractants characteristic and important for different types (lipid; inflammatory erosive; degenerative necrotic) of unstable plaques in coronary arteries were identified and studied in male patients with coronary atherosclerosis without acute coronary syndrome we studied. Among the three types of unstable plaques, elevated concentrations of IL-1ß, IL-6, IL-8, IL-18 and monocyte chemotactic protein-1 were characteristic of not only inflammatory erosive type, but also lipid type compared with degenerative necrotic type. Thus, intensification of the inflammatory process plays an important role in the development of not only inflammatory and destructive, but also of lipid type of unstable atherosclerotic plaques.

[Inflammatory-destructive biomarkers of atherosclerotic plaques instability. Study of arterial wall and blood].

Concentrations of tumor necrosis factor, interleukin 1- and its receptor antagonist, IL-6, IL-8, IL-18, IL-2, ligand of CD40 receptor (CD40L), high sensitive C-reactive protein (hsCRP), monocyte chemotactic protein -1, endothelial monocyte activating protein II, adhesive molecules (sICAM-1 and sVCAM-1), matrix metalloproteinase (MMP-3, MMP-7, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) and endothelin-1 were studied in blood and in coronary artery intima/media of men with coronary atherosclerosis without acute coronary syndrome. Blood levels of hsCRP, IL-8, IL-6 and CD40L were higher, while blood levels of sVCAM and TIMP-1 were lower in men with prevalence of unstable atherosclerotic plaques compared to men with prevalence of stable atherosclerotic plaques in coronary arteries. Blood levels of hsCRP, IL-6 and IL-8 correlated with characteristics of coronary artery atherosclerotic plaques instability. Correlation between hsCRP blood level and hsCRP concentration in coronary artery intima/media material was also revealed.

[Heart failure and imbalance of chemical elements in myocardium of patients with ishemic heart disease].

Tissue content of chemical elements indirectly characterizes some metabolic processes. We have analyzed content of chemical elements in left and right ventricular myocardium of patients with ischemic heart disease with progressing heart failure and have shown that during development and progression of heart failure metabolic processes have unidirectional character in myocardium of both ventricles. Derangement of left ventricular contractile capacity is associated with lowering of content of microelements involved in antioxidant processes and energy metabolism in tissues (Cu, Mn, Cr) and elevated concentration of elements characterizing progressive of myocardial stiffness (Ca, Fe).