Effect of Natural Cytokine Complex on Metabolism of Smooth Muscle Cells in Myocardial Arteries under Normal Conditions and during Hemodynamic Overload.

Histoenzymological methods were employed to examine the effects of systemically administered natural cytokine complex including IL-1, IL-2, IL-6, TNFα, MIF, and TGFß on metabolism of smooth muscle cells in intramural myocardial arteries under physiological conditions and during acute hemodynamic overload of the heart. Natural cytokine complex markedly inhibited metabolism of vascular smooth muscle cells under control conditions and during acute experimental aortal stenosis. In vascular smooth muscle cells, deceleration of tricarboxylic acid cycle, redistribution of the fluxes in glycolytic cascade and its inhibition, down-regulation of oxidation of free fatty acids and their metabolites, and inhibition of the shuttle systems and biosynthetic processes were observed. Inhibition of metabolism in the vascular wall of myocardial arteries correlated with a decrease in their tone and could be partially determined by a decrease in contractile activity of smooth muscle cells. These findings do not exclude the involvement of other factors and mechanisms in down-regulation of metabolism in vascular myocytes in response to increased cytokines levels of in the blood, including their direct effect on biochemical processes in cells.

Effects of Natural Cytokine Complex on the Myocardial Blood Flow in Normal and under Conditions of Increased Hemodynamic Load.

The effects of a natural complex of cytokines IL-1, IL-2, IL-6, TNF, MIF, and GTFß on myocardial blood flow were studied under control conditions and during acute experimental aortal stenosis. Systemic administration of the cytokine complex under control conditions led to moderate impairment of the blood flow in the myocardium associated with plethora and perivascular edema. The number of functioning vessels in the myocardium significantly increased under these conditions, which reflected enhancement of the coronary blood flow. The comparison of the myocardial blood flow under conditions of acute heart overload alone and in combination with systemic administration of the cytokine complex revealed similar changes. In both cases, moderate plethora in all compartments of the vascular network, moderate perivascular edema, and moderate blood stasis in the myocardial capillaries were seen. The only difference the increase in the density of functioning capillaries that was significantly more pronounced after cytokine administration. These data indicate that the increase in the blood cytokine level induced dilatation of myocardial vessels and intensification of blood flow in normal and under conditions of acute hemodynamic heart overload. Against the background of pronounced vasodilatation, the dyscirculatory changes in the myocardium were moderate. It was assumed that the increase in the duration or frequency of hypercytokinemia episodes can induce more severe blood flow disturbances in the myocardium.

Effect of Natural Cytokine Complex on the Structure and Metabolism of the Cardiac Conduction System in the Myocardium under Normally and Increased Hemodynamic Load.

Effect of natural complex of cytokines with activity of IL-1, IL-2, IL-6, TNF, MIF, and GTFß on the structure and metabolism of conduction cardiomyocytes was assessed in the control and under acute experimental aortic stenosis. After systemic administration of the cytokine complex in the control, structural abnormalities were revealed in a relatively low number of conduction cardiomyocytes; their relative number increased in the left ventricle and interventricular septum. When the complex was administered against the background of aortic stenosis, morphological changes in the conduction system were seen in a significant number of cells with their plasma imbibition, especially in the left ventricle and interventricular septum. Systemic administration of the natural cytokine complex inhibited the major metabolic processes in the conduction system, both in the control and under conditions of sharply increased hemodynamic load. In conduction cardiomyocytes, deceleration of glycolysis and citric acid cycle, inhibition of oxidation of free fatty acids and their metabolites, and suppression of shuttle mechanisms and biosynthetic reactions were observed. Increased blood levels of cytokines, primarily of the proinflammatory ones, can cause structural and metabolic disturbances in the cardiac conduction system and promote the development of arrhythmias, especially in case of sharply increased hemodynamic load.

Effect of the Natural Cytokine Complex on the Structure and Metabolism of Contractile Myocardium Normally and under Increased Hemodynamic Load.

Effect of natural complex of cytokines with activity of IL-1, IL-2, IL-6, TNF, MIF, GTFß on the structure and metabolism of contractile ventricular cardiomyocytes was assessed in the control and under conditions of acute experimental aortic stenosis. Systemic administration of the complex in the control had no significant effect on myocardial morphology with low number of damaged cardiomyocytes and low degree of structural damage. Administration of the cytokine complex against the background of aortic stenosis did not exert any additional alterative effect on cardiomyocytes, structural damage of contractual nature was moderate. Systemic administration of the natural cytokine complex had a pronounced inhibitory effect on metabolic processes in the myocardium of both ventricles both in the control and against the background of increased hemodynamic load. In cardiomyocytes, glycolysis and citric acid cycle were slowed down, oxidation of free fatty acids and their metabolic products was inhibited as well as shuttle mechanisms and biosynthetic reactions. Inhibition of energy-producing processes is the cause of the lack of the contractile function energy supply and can worsen the course of cardiovascular diseases and increase the risk of their complications in conditions, accompanied by increased blood cytokine level.

[Pharmacological preconditioning in carotid endarterectomy].

The study was aimed at examining efficacy of preoperative preparation (pharmacological preconditioning) for carotid endarterectomy in patients with chronic cerebrovascular insufficiency. For this purpose, we analysed the outcomes of surgical treatment in a total of 80 patients presenting with haemodynamically significant unilateral and bilateral lesions of carotid arteries. Of these, 40 patients were operated on immediately and a further 40 patients underwent surgery after pharmacological preconditioning with Actovegin taken at a daily dose of 1,200 mg for 1.5 months. It was demonstrated that preoperative preparation prior to surgery increases cerebral perfusion which is determined by means of single-photon emission computed tomography, thus substantially improving the outcomes of surgical treatment. Statistically significant differences in cognitive function of these groups of patients were revealed 7 days and 6 months after the operation. Improvement of cognitive functions was associated with fewer symptom-free postoperative cerebral ischaemic foci in various regions of the brain. A conclusion was made on a positive role of pharmacological preconditioning with Actovegin in surgical management of cerebrovascular insufficiency, first of all in relation to more complete restoration of cognitive functions.

[Comparative assessment of antiaggregant efficacy of acetylsalicylic acid and clopidogrel in peripheral atherosclerosis].

Presented in the article are the results of studying antiaggregate activity of acetylsalicylic acid and clopidogrel in a total of 36 patients suffering from various-severity chronic arterial insufficiency of lower limbs on the background of atherosclerosis obliterans. The study was conducted prior to treatment for correct selection of a particular antiplatelet agent. The obtained results showed that clopidogrel was not always more efficient than acetylsalicylic acid, since there is individual sensitivity of each patients to a particular antiplatelet agent. Therefore, an individual approach is necessary to conservative therapy of arterial insufficiency of lower limbs. For some patients it is preferable to administer clopidogrel, for others - acetylsalicylic acid. In a series of cases combined treatment is justified, while some patients having low sensitivity to both acetylsalicylic acid and clopidogrel require careful selection of alternative agents influencing other thrombocyte receptors.

[Role of low-dose acetylsalicylic acid in comprehensive postoperative treatment of patients with lower-limb chronic arterial insufficiency].

The study comprised a total of 107 patients (all men) after endured femoropopliteal bypass grafting above the genicular fissure with a synthetic stent graft manufactured by the Gore Company for stage IIB and III chronic arterial insufficiency of the lower extremities according to the Fontain-Pokrovsky classification. Group One I (control group) was composed of fifty-four patients permanently taking in the postoperative period at the out-patient stage pentoxiphylline (trental 400 mg 1 tablet 3 times daily) and xantinol nicotinate at a dose of 150 mg one tablet thrice daily. Group Two (Study Group) consisted of fifty-three patients taking after reconstructive vascular surgery at the out-patient stage in addition to pentoxiphylline and xantinol nicotinate acetylsalicylic acid (cardiomagnil 75 mg 1 tablet once daily). The Control Group patients within 3 to 6 months of follow up were found to have a considerable progressing improvement of the functional abilities of the microcirculatory bed requiring in 44 (81.5%) cases hospitalization to the Surgical Department for intensive vascular therapy. Despite this fact four (7.4%) patients within the time frame from 6 to 9 months after surgery developed thrombosis of the vascular implant requiring a repeat surgical intervention. In the Study Group patients, the degree of functional capabilities of the microcirculatory bed in the postoperative period was less considerable, reaching the maximum after 10-12 months of follow up, with eighteen (34.0%) patients requiring hospitalization for additional vascular therapy to perform. There were no cases of implants' thrombosis in the Study Group patients. Pathological alterations in the functional state of the peripheral vascular bed correlated with viscosimetric indices and activity of blood platelet aggregation. The addition of antithrombocytic agents to conservative postoperative therapy considerably improved the outcomes of surgical treatment.

[Surgical treatment of giant spinal neuromas].

Several cases of successful surgical treatment of giant spinal neuromas are reported in this paper. Benign nature of these tumors promotes radical resection. Localization of giant extravertebral tumor nodes in eloquent areas produces difficulties for total removal. In certain cases single approach is not sufficient for radical resection.

[Haemorheological problems in lower-limb chronic arterial insufficiency].

Chair of Neurology of the Advanced Medical Training Department of the Federal Educational Facility of the Higher Vocational Education Russian State Medical University under the Russian Public Health Ministry, Moscow, Russia. The article deals with the findings obtained in examining and treating a total of eighty-seven patients suffering from atherosclerosis obliterans of the lower-limb arteries with stage IIB and III chronic arterial insufficiency. Studied were impairments of the theological properties of the blood and plasma, erythrocytic deformability and the concentration of malonic dialdehyde in blood at admission to the hospital, upon completion of the course of conservative treatment, and after the reconstructive vascular intervention performed. It was determined that the leading mechanism disturbing oxygen utilization by tissues is a decrease in erythrocytic deformability, which promotes shunting of the arterial blood flow and persists after the surgical vascular reconstruction preformed.

[Functional flowmetry in determining the indications for reconstructive surgical interventions on the major arteries of the pelvis and lower limbs].

The work was based on the findings of the examination and surgical management of 69 patients with obliterating atherosclerosis of the lower limbs with various degree of chronic arterial insufficiency. The authors analyzed the main causes promoting development of early reocclusion of the bypasses and prostheses following reconstructive surgical operations. They also proved the role of high peripheral vascular resistance and, in particular, diminished functional possibilities of the microcirculatory-bed vessels in the genesis of early reocclusions in patients with chronic arterial insufficiency of the lower limbs. They also suggested a new technique of determining the carrying capacity of the microcirculatory channel, the use of which in the preoperative period makes it possible to predict development of early thrombotic complications, and in some cases to wisely abstain from carrying out a reconstructive vascular intervention due to high risk of its poor outcomes. It is preferable for such patients to undergo conservative pathogenetic preoperative therapy aimed at improving the functional possibilities of the microcirculatory vessels.

Comparative pathomorphological study of contractile myocardium under conditions of increased left and right ventricular afterload.

Structural changes in the myocardium under conditions of increased left and right ventricular afterload were studied using polarization microscopy and histological, histochemical, and stereological methods. Increased afterload not complicated by heart failure was characterized by low number of damaged cardiomyocytes (3.3-6.5%) and moderate structural changes in the ventricular myocardium (contractures of different severity). Increased afterload complicated by heart failure was characterized by high ratio of damaged cardiomyocytes (5.6-19.2%) and severe reversible (grade I and II contractures) and irreversible (grade III contractures and lump degradation of myofibrils) structural changes. Irreversible damage to most cardiomyocytes included plasmatic impregnation, which was most pronounced in the subendocardial layer of ventricles operating under conditions of increased afterload. Comparative study showed that increased left and right ventricular afterload induces similar pathomorphological changes in the contractile myocardium. Our results indicate that increased afterload to the right or left ventricle is accompanied by the development of stereotypical structural changes in the myocardium. Profound and severe disturbances can cause heart failure.

Sympathoadrenal system under conditions of increased left and right ventricular afterload.

Adrenergic plexuses in the myocardium and adrenal medulla were studied histochemically under conditions of increased left or right ventricular afterload. Under conditions of high afterload not accompanied by heart failure the density of sympathetic myocardial innervation remained unchanged in the loaded ventricle, but increased in the intact ventricle. Comparison of the state of the sympathoadrenal system under conditions of increased afterload complicated or uncomplicated by heart failure revealed common prognostically unfavorable changes: sharp decrease in the density of adrenergic nerve plexuses in the ventricular myocardium and activation of adrenal chromaffin cells.

Heart rhythm disturbances during the acute period of massive pulmonary embolism.

We studied the type, incidence, and dynamics of arrhythmia during the acute phase of massive pulmonary embolism complicated or uncomplicated by cardiac insufficiency. Complicated and uncomplicated massive pulmonary embolisms were accompanied by the appearance of individual and allorhythmic ventricular extrasystoles, respectively. The rise of right ventricular pressure to 70 mm Hg was critical for the development of allorhythmia. Allorhythmia started 3-268 sec after attaining critical ventricular pressure. Heart rhythm spontaneously recovered in 100 and 78% animals with uncomplicated and complicated massive pulmonary embolism, respectively. The duration of paroxysmal allorhythmia varied from 15 sec to 15 min. Electrophysiological processes in the myocardium were normalized with progression of uncomplicated massive pulmonary embolism: the incidence of single and, in particular, allorhythmic extrasystoles decreased, and electrocardiographic parameters returned to normal.

Structural and metabolic changes in cardiac conducting system during massive pulmonary embolism.

We studied structural and metabolic changes in ventricular conducting cardiomyocytes during the acute phase of massive pulmonary embolism complicated or uncomplicated by cardiac insufficiency. During massive pulmonary embolism without cardiac insufficiency, glycolysis in conducting cardiomyocytes of both ventricles was activated, and its contribution to energy formation increased. Massive pulmonary embolism complicated by cardiac insufficiency was accompanied by inhibition of glycolytic enzymes and damages to conducting cardiomyocytes of the left and right ventricles. Our findings indicate that the development of cardiac insufficiency during the acute phase of massive pulmonary embolism provides structural and morphological basis for impairment of electrophysiological properties of the myocardium.