Age-Related Features of the Early Period of Liver Regeneration after Partial Hepatectomy in Rats.

Regenerative processes in the liver were studied in 3-month-old (young) and 9-month-old (aged) male Wistar rats on day 1 after 30 and 70% hepatectomy. Regardless of the resected liver volume, shifts in the biochemical parameters of the serum in aged rats were more pronounced than in young animals. After 30% hepatectomy, no age differences in the rate of hepatic regeneration were found, while after 70% liver resection this parameter was higher in young rats. Hepatectomy in young rats led to recruitment of MSC, hepatocyte precursors, endothelial and epithelial progenitor cells into the liver parenchyma and increased fluidity of the plasma and mitochondrial membranes of hepatocytes. In aged rats, the recruitment of MSC, hepatocyte precursors, and endothelial progenitor cells into the injured liver was impaired and the rigidity of the mitochondrial membranes of hepatocytes increased.

Age-Related Features of Ketanserin Effects in Experimental Liver Cirrhosis.

The effect of ketanserin on inflammation, liver fibrosis, and microviscosity of the plasma and mitochondrial membranes of hepatocytes was studied on young (3 months) and old (9 months) male Wistar rats with experimental liver cirrhosis. Ketanserin reduced inflammation, area of the connective tissue, and liver damage and improved serum biochemical parameters in rats of both age groups; in old rats, the effects were more pronounced than in young animals. In old rats, ketanserin reduced polarity of hepatocyte plasma and mitochondrial membranes in the area of protein-lipid contacts, which determined higher effectiveness of ketanserin during the treatment of liver cirrhosis in aged animals.

Expression of Genes and Proteins of the Sarcoplasmic Reticulum Са2+-Transport Systems in Cardiomyocytes in Concomitant Coronary Heart Disease and Type 2 Diabetes Mellitus.

We compared the expression of Са2+-ATPase (SERCA2a), calsequestrin (CASQ2), ryanodine receptors (RyR2) proteins and their genes (ATP2A2, CASQ2, and RYR2) in coronary heart disease (CHD) patients with and without comorbid type 2 diabetes mellitus. All studies were performed on the right atrial appendages resected during coronary bypass surgeries. Expression of SERCA2a and RyR2 proteins and their ATP2A2 (p=0.046) and RYR2 genes in comorbid pathology was significantly (p=0.042) higher (by 1.2 and 2 times; p=0.025). The expression of CASQ2 protein and its gene did not differ significantly between the groups (p=0.82 and p=0.066, respectively). It was concluded that the expression of SERCA2a and RyR2 proteins and their genes (but not CASQ2 and its gene) is elevated in CHD associated with type 2 diabetes mellitus. Expression of the studied proteins correlated with the expression of their genes. Increased expression of CASQ2 protein and its gene can probably prevent imbalance of the Ca2+-transporting systems in cardiomyocytes and contractile dysfunction of the myocardium, even in CHD associated with type 2 diabetes mellitus.

Age-Related Features of the Viscosity of Plasma and Mitochondrial Membranes of Hepatocytes in Liver Cirrhosis.

The viscosity of plasma and mitochondrial membranes of hepatocytes was studied in young (3-month-old) and old (9-month-old) male Wistar rats. It was shown that viscosity of hepatocyte plasma and mitochondrial membranes in young rats under optimal vital functions in the area of protein-lipid membrane contacts was significantly lower than in old rats. No age-related differences in the viscosity of lipid-lipid membrane contacts and in the polarity of protein-lipid contacts and lipid layers were found. Liver cirrhosis induced by carbon tetrachloride and ethanol administration was associated with increased fluidity of the plasma and mitochondrial membranes of hepatocytes in rats of both age groups. The decrease in membrane viscosity in young rats occurred due to a decrease of the viscosity in the area of protein-lipid and lipid-lipid contacts, while in old rats in the area of protein-lipid contacts. Carbon tetrachloride and ethanol did not affect the polarity of lipid contacts and lipid layers.

Age-Related Features of the Response of the Liver and Stem Cells during Modeling of Liver Cirrhosis.

We studied the age-related characteristics of the response of stem cells and liver in male Wistar rats to administration of carbon tetrachloride (CCl4) and ethanol. It was shown that modeling of liver cirrhosis caused inflammation, fibrosis, damage to sinusoidal capillaries, necrosis, and disturbances in the functional activity of hepatocytes in young rats. These processes were accompanied by mobilization of profibrotic mesenchymal stem cells (MSC), proinflammatory hematopoietic stem cells (HSC) and lymphocytes (CD45hiCD133+) from the bone marrow into the blood and migration to the liver. On the other hand, the number of hepatocyte precursors expressing Sox9 (cells of Hering's canal), immature cholangiocytes, Ito cells, oval cells, and endothelial cells of the liver sinusoids) sharply increased in the liver. In young rats, mobilization and migration of MSC, HSC, and hepatocyte precursors against the background of liver cirrhosis were more intensive than in old animals. The higher resistance of old rats to exposure is associated with age-related changes in the niches as well as in mobilization and migration of cells.

Myocardial Expression of SERCA2a and Structural and Functional Indices in Patients with Atrial Fibrillation.

The study examined the relationships between SERCA2a expression in the myocardium and structural and functional indices in patients with atrial fibrillation. In uniform cohort of patients, this expression differed significantly but positively correlated with the size of the left atrium, end-systolic volume, and end-diastolic volume. In contrast, SERCA2a expression negatively correlated with early (peak E) and late (peak A) diastolic filling rates in left ventricle. SERCA2a expression was also associated with echocardiographic parameters reflecting structural and functional status of the heart in patients with persistent atrial fibrillation.

Influence of Age Factor on Respiratory Control of Isolated Cardiomyocytes and Mitochondria in Rats.

We studied the peculiarities of oxidative and substrate phosphorylation in isolated cardiomyocytes and myocardial mitochondria in 2- and 15-month-old rats. It was shown that age factor reduces the degree of oxidation and phosphorylation coupling both in cardiomyocytes and in mitochondria, which was associated with the decrease in the rate of consumption of energy resources.

Experimental Cardiomyogenesis Under Conditions of Administration of Different Doses of the Allogeneic Biomaterial.

We studied the effect of different concentrations of the allogeneic biotransplant on myocardial recovery. In Wistar rats, coronary artery was ligated and intramyocardial injection of 12 or 24 mg Alloplant biomaterial suspension was performed. Histological analysis was conducted on paraffin sections stained by Mallory. The index of the scar area was measured on preparations of transverse sections of the hearts. Allogeneic biomaterial produced cardioprotective and regenerative effect in the myocardium damaged by ischemia. After administration of Alloplant in a dose of 12 mg, the index of scar area decreased by 2.74 times; after doubling the Alloplant dose (24 mg), the index of scar area decreased by 26 times.

Effect of Arachidonic Acid on the Rate of Oxygen Consumption in Isolated Cardiomyocytes from Intact Rats and Animals with Ischemic or Diabetic Injury to the Heart.

We studied the rate of oxygen consumption by isolated cardiomyocytes from intact rats and animals with experimental myocardial infarction or streptozotocin-induced diabetes mellitus. The measurements were performed in standard incubation medium under various conditions of oxygenation and after addition of arachidonic acid (20 µmol/liter). Under normoxic conditions, arachidonic acid improves respiration of cardiomyocytes from intact animals, but reduces this parameter in cells isolated from animals with pathologies. The intensity of O2 consumption by cardiomyocytes from intact rats and animals with pathologies was shown to decrease during hypoxia. Addition of arachidonic acid aggravated inhibition of respiration for cardiomyocytes from intact rats and specimens with myocardial infarction, but had no effect in diabetes mellitus. The effect of arachidonic acid on oxygen consumption rate is probably mediated by a nonspecific mechanism realized at the mitochondrial level.

Expression of Ca(2+)-ATPase in sarcoplasmic reticulum in rat cardiomyocytes during experimental postinfarction cardiosclerosis and diabetes mellitus.

We studied the expression of Ca(2+)-ATPase in sarcoplasmic reticulum of rat cardiomyocytes during isolated and combined development of postinfarction cardiosclerosis and diabetes mellitus. Postinfarction cardiosclerosis was formed within 6 weeks after coronary artery occlusion. Diabetes mellitus developed within 6 weeks after intraperitoneal injection of streptozotocin (60 mg/kg). Ca(2+)-ATPase in homogenate of rat myocardium was assayed by immunoblotting. Ischemic and diabetic remodeling of the myocardium was associated with reduced expression of Ca(2+)-ATPase in the sarcoplasmic reticulum. Combined pathology was characterized by minimum decrease in the level of this protein. It was concluded that induction of diabetes mellitus at the early stage of postinfarction cardiosclerosis triggered adaptive mechanisms that prevent the decrease in Ca(2+)-ATPase level in the sarcoplasmic reticulum of cardiomyocytes.

[Microviscosity of erythrocyte membranes in chronic coronary insufficiency in patients of middle and older age groups].

We examined the ratios microviscosity in the area of integral and annularly lipid membranes of erythrocytes of peripheral blood in patients of 35-50 and 60-75 years with chronic ischemic heart disease, as well as age-matched healthy controls. In healthy donors coefficients microviscosity in the area of integral and annularly lipids proved to be significantly higher in the older age group (60-75 years). In CHD, regardless of the age of the patients, erythrocyte membranes can be characterized as raising and lowering the parameters microviscosity of lipid-lipid interactions. In the protein-lipid contacts for patients aged 35-50 years an increase is typical, while for patients of 60-75 years, on the contrary, a decrease of the coefficient of microviscosity. It is concluded that the values of the microviscosity of erythrocyte membranes in patients of different age groups in the development of chronic ischemic heart disease, reflect both the implementation of the general mechanisms of adaptive changes of cell membranes, and the specifics of an individual, determined by their lipid and protein composition.

Comparative study of changes in energy metabolism in rat cardiomyocytes in postinfarction cardiosclerosis and diabetes mellitus.

Cardiomyocyte energy metabolism in experimental unfolding postinfarction cardiosclerosis and diabetes mellitus was studied. Postinfarction cardiosclerosis formed 6 weeks after coronary artery occlusion. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (60 mg/kg). The rate of oxygen consumption in postinfarction cardiosclerosis and diabetes increased by 3.4 and 4.2 times, respectively. Stimulation of mitochondrial respiration (ATP, palmitic acid) significantly increased oxygen consumption in animals with postinfarction cardiosclerosis and significantly reduced this process in diabetes. The content of LDH and SDH in the myocardium of animals with diabetes and postinfarction cardiosclerosis was significantly below the control. Hence, the development of postinfarction cardiosclerosis and diabetes mellitus were characterized by reduced generation of ATP in anaerobic and aerobic pathways and oxidative phosphorylation in cardiomyocytes.

[Noninvasive assessment of functional competence of the radial artery as a possible vascular graft for coronary artery bypass grafting].

Described herein is a variant of surgical treatment of a patient presenting with type A aortic dissection extending to the brachiocephalic branches accompanied by thrombosis of the false channel of the latter. In the rare cases in dissection and thrombosis of the brachiocephalic branches for adequate protection of the body (systemic protection) it is necessary to use bidirectional arterial perfusion under the conditions of moderate hyperthermia: through a preliminarily sewn into the carotid artery prosthesis - perfusion of the brain, through cannulated aortic arch or femoral artery - body perfusion.

[Influence of the long-term administration of torasemide on morphometric characteristics of cardiac muscle under conditions of developed experimental postinfarction cardiosclerosis].

The possible antifibrotic effect of torasemide used for the treatment of model chronic heart failure (CHF) has been studied in rats aged 12 months with developed postinfarction cardiosclerosis (PICS). The antifibrotic effect was evaluated of the course of torasemide administration in a daily dose of 0.13 mg/kg. A comparative analysis showed that torasemide did not affect the state of connective tissues in cardiac muscles of both intact rats and those with PICS. It was concluded that manifestations of the antifibrotic effect of torasemide can be related to the nosological form of CHF.

[Manifestations of polymorphism of ß1-adrenoreceptors in patients with newly diagnosed cardiac rhythm disorders].

Individual peculiarities of the receptor apparatus of cardiomyocytes may determine pathological features of heart activity and susceptibility to pharmaceuticals. The possible role of beta-adrenoreceptor polymorphism in the development of cardiac rhythm disturbances is assessed by PCR. Special attention is given to A145G polymorphism of the ADRB1 gene in 127 patients with primary cardiac rhythm disorders. It was shown that AJ45G polymorphism (Ser49Gly) at DNA sites encoding for the amino acid sequence of beta-1 adrenoreceptors can influence the development of sex-specific cardiac rhythm disorders.

[Auricular vagal stimulation in the treatment of patients with left ventricular dysfunction].

We assessed effect of enhancement of parasympathetic activity by indirect vagal stimulation via sensitive n. vagus-r. auricularis terminals on dynamics of clinical conditions, ejection fraction and global longitudinal left ventricle deformation in patients with chronic cardiac insufficiency (CCI). This comparative placebo-controlled parallel study 3 months in duration included 70 patients with chronic coronary heart disease, signs of IIl-IV FC CCI, and sinus rhythm. Auricular electric vagal stimulation (AEVS) was performed using a device for electric stimulation of sensitive vagus terminals (patent No 2327492 of 27.06.2008). The complex of clinical and instrumental studies included 6 min walk test, echocardiography, and speckle tracking imaging before, immediately and 3 months after AEVS. A course of AEVS improved clinical conditions in 58 (92.06%) of the 63 patients due to one-grade or greater decrease of CCI FC and increase of the walking distance. This effect persisted till month 3. It was absent in 5 (8.33%) patients. Improvement of clinical conditions with the decrease of CCI FC was accompanied by increase of left ventricular ejection fraction due to diminished end-systolic volume. The ejection fraction did not change in 4 patients with HR over 80/min. All patients with lowered HR after AEVS showed improved LV contractility in the longitudinal direction.

[Resistance to clopidogrel and polymorphism of P2RY12 and GPIIIA genes in patients with chronic coronary heart disease].

We studied the association between clopidogrel resistance, H1/NH2 polymorphism of the P2RY12 gene and T156C polymorphism of the GpIIIa gene in residents of Western Siberia suffering chronic CHD. It was shown that the occurrence of H1 and H2 haplotypes of the P2RY12 gene and 1565T and 1565C alleles of the GpIIIa gene was similar to that reported for European populations. Patients showing variable platelet response to the inhibitory action of clopidogrel were not significantly different in terms of P2RY12 and GpIIIa genotype distribution. To conclude, the study revealed no association between the risk of clopidogrel resistance and the presence of polymorphic variants of platelet receptor genes P2RY12 and GpIIIa.

Cell-free collagen-based scaffolds used for making blood vessels in cardiovascular surgery.

The present article deals with the technology of obtaining decellularized cell-free collagen-based scaffolds from arterial vessels and surgical assessment of the possibility of experimentally implanting them into the blood system of laboratory animals for experimental purposes. The study was performed on arterial vessels (n=60) and fragments of the human internal thoracic artery (n=20). Described herein is a method of obtaining a connective-tissue matrix of a blood vessel by means of vessel's perfusion for 2-3 hours with detergent solutions. Cell-free collagen-based conduits were implanted to a total of ten dogs. After the operation, the blood flow remained functional. The anastomoses established turned out to be leak-proof and the acellular vessels were able to withstand the haemodynamic load of the arterial blood flow.

[The experience of the application of ascorbinic acid as antioxidant after coronary artery surgery with use of cardiopulmonary bypass].

We have studied the role of oxidant stress in development of rhythm disturbances in early postoperative period after coronary artery bypass grafting and possibilities of their prevention with preparations of ascorbinic acid. It was shown that the use of ß-adrenoblockers allows to prevent arrhythmia on first day after operation only in 80% of cases. Patients with developed disturbances of cardiac rhythm were characterized by high parameters of lipid peroxidation (LPO) and substantial changes of activity of antioxidant enzyme catalase. Administration of ascorbinic acid at the stage of preparation of patients to surgery and in first 24 hours after operation allowed to effectively prevent development of oxidative stress and disturbances of cardiac rhythm. A conclusion was made that inclusion of ascorbinic acid in drug therapy of patients with ischemic heart disease could be recommended for prevention of arrhythmia in postoperative period.

Radiofrequency ablation as a possible method for preparing pathologically altered myocardium for intramyocardial cell transplantation.

We studied the effects of radiofrequency ablation on the results of intramyocardial transplantation of bone marrow NSC into the myocardium of rats with postinfarction cardiosclerosis. It was shown that exposure of the pathologically changed myocardium to radiofrequency radiation led to destruction of formed connective tissue. Transplantation of MSC into sites exposed to radiofrequency radiation promoted the development of regenerative processes (abundant infiltration with mononuclear cells, presence of granulation tissue, and numerous newly formed blood vessels). We concluded that preliminary radiofrequency irradiation of the myocardial areas promotes realization of the regenerative potential of cell transplantation.