[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.

[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.

[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.

[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.

[D allele of the angiotensin converting enzyme gene is a putative risk factor of restenosis after coronary stenting in patients with coronary heart disease].

We undertook a comparative analysis of allele frequency distribution and I/D polymorphism of the angiotensin converting enzyme (ACE) gene in patients with coronary heart disease (CHD) undergoing coronary stenting with and without signs of restenosis. There were no significant difference between the groups in the genotype frequency distribution of I/D polymorphism of the CAE gene (p = 0.061). The occurrence of D allele in the patients with restenosis was higher than that of I allele (chi-square test 4.117, p = 0.042). Relative risk for the carriers of D and I alleles was 0.35 and 2.83 respectively. It is concluded that the presence of D allele of I/D polymorphism of the CAE gene in patients with chronic CHD may be a risk factor of restenosis of stented coronary arteries.

[Age-related features of microviscosity of erythrocyte membranes in experimental cardiosclerosis].

The age-related changes in the coefficient of microviscosity and polarity in the area of lipid-lipid and protein-lipid contacts of erythrocyte membranes in 4 months old (group I, n = 20) and 12 months old (group II, n = 20) rats by the method of lateral diffusion of the pyrene probe were investigated. Each age group consisted of 10 intact animals and animals after postinfarction cardiac remodeling (PICS). An increase of microviscosity and polarity of the annular and total lipids of erythrocyte membranes in 12-month animals was found. When modeling PICS in 4-month animals is pronounced increase the polarity and microviscosity of erythrocyte membranes in the annular and total lipids. The 12-month animals after PICS demonstrate a decrease of microviscosity in a lipid bilayer, and its increase in the area of annular lipids for consistently high-polarity lipids.

[Inotropic reaction of myocardium rats with postinfarction and diabetic remodeling on extrasistolic influences].

Studied inotropic reaction papillary muscles of rats with postinfarction and diabetic remodeling on extrasistolic influences. It was found, that excitability of myocardium rats raises at a diabetes induced streptozotocin. Postextrasistolic contraction of myocardium rats with postinfarction cardiosclerosis it was considerably oppressed, and rhythmoinitropic reaction of myocardium rats was comparable to reaction of intact myocardium at a diabetes induced streptozotocin. The combination postinfarction and diabetic influence is paradoxical promoted preservation postextrasistolic potentiation of myocardium rats.

[Features of lipid peroxidation in rats of different age with postinfarction cardiosclerosis].

Results of research of a state of lipid peroxidation (LP) system at rats by age of 4 and 12 months with postinfarction cardiosclerosis are presented in this work. It has been shown, that in the remote terms after an experimental myocardium infarct, age-dependent alteration of the LP and antioxidizing enzymes activity were observed. Also distinction in expressiveness of the LP processes in the intact animals in these age groups was revealed. Such age features probably cause various intensities of the LP and the state of antioxidant protection at postinfarction remodeling of heart.

[Phospholipid composition of erythrocyte membranes under conditions of postmyocardial infarction cardiosclerosis].

Changes in phospholipid composition of the erythrocyte membranes have been studied in experimental postmyocardial infarction cardiosclerosis. Erythrocyte membranes from animals with cardiosclerosis formed after experimantal occlusions of coronary arteries were characterized by significant decrease of a minor phospholipid, phosphatydylinositol (by more than 40%) and the increase of the major phospholipid, phosphatydylethanolamine. There was high content of lipid peroxidation products, malondialdehyde and conjugated dienes and the decrease in the activity of antioxidant enzymes, catalase and superoxide dismutase in blood serum of these animals. We have concluded the formation of postmyocardial infarction cardiosclerosis is accompanied by the increase of free radical reactions. This causes changes in phospholipid composition of cell membranes and the decrease of compensatory capacities of the enzymatic antioxidant system. These changes form a metabolic background, [corrected] which can influence cardiac remodelling properties.

[Activity of lipid peroxidation and functional state of the myocardium in remodeling of rat heart after experimental myocardial infarction].

It was shown in experiments on Wistar rats that the processes of postinfarction remodeling of the heart in animals that survived myocardial infarction were characterized by lowering of excitability of cardiac muscle, impairment of ability of sarcoplasmic reticulum to accumulate calcium ions. High level of content of lipid peroxidation products both in blood serum and myocardial tissue, and lowering of activity of antioxidant enzymes were also noted. A conclusion was made that high level of lipid peroxidation, lowering of defense properties of endogenous antioxidants and impairment of myocardial contractile function induced by myocardial infarction were sustained minimally for subsequent 45 days. This could serve as a factor, capable to significantly affect the process of postinfarction remodeling and development of heart failure.

[Regulation by opiod peptides of the antioxidant enzyme activity and the prostanoid system in myocardium during stress].

The six hour stress in rats was modeled by the method of O. Desiderato. Cardiac damage was estimated by myocardial uptace of radioactive 99Tc-pyrophosphate. Intravenous administration of mixed mu and delta opioid receptor agonist, D- Ala2, Leu5, Arg6-enkephalin (dalargin), (non-penetrating through the blood brain barrier) at a dose of 0.1 mg/kg before stress decreased stress-induced 99Tc-pyroposphate uptake. Pretreatment with dalargin completely abolished the stress-induced increase in conjugated dienes and malondialdehyde levels in myocardium and prevented a decrease in total lipid soluble antioxidant levels in the heart after stress exposure. Stress is accompanied by an increase in activity of catalase, glutathione peroxidase, glutathione reductase and a decrease in activity of superoxide dismutase (SOD). Pretreatment with dalargin completely reversed stress-induced decrease in SOD activity but had minor effect on the activity of other antioxidant enzymes. Stress also resulted in an increase in myocardial content of thromboxane and a decrease in prostacycline and prostaglandin E levels in the heart. Pretreatment with dalargin completely eliminated these stress-induced changes in myocardial prostanoid levels. We propose that stress-induced heart injury depends on the activation of lipid peroxidation processes and changes in the prostanoid levels in the heart. Cardioprotective effect of dalargin during stress may be mediated via peripheral mu and delta opioid receptor stimulation and an inhibition of lipid peroxidation processes through SOD activation and also a recovery, of normal prostanoid levels in the heart.

[The protective effect of trimetazidine on the myocardium against reperfusion injury during thrombolytic therapy of acute infarction]. / Zashchita miokarda trimetazidinom ot reperfuzionnykh povrezhdenii pri tromboliticheskoi terapii ostrogo infarkta.

Investigation of the protective action of the antiischemic drug trimetazidine (60 mg/kg) used during thrombolytic treatment of acute infarction showed that the drug effectively inhibits lipid peroxidation and reduces the degree of the reperfusive damage of myocardium, as determined from ECG (QRS index calculation) or from data on the blood creatinin phosphokinase level.

[Activation of mu-opioid receptors and cardiomyocyte resistance to free radical damage]. / Aktivatsiia mu-opioidnykh retseptorov i ustoichivost' kardiomiotsitov k svobodnoradikal'nomu povrezhdeniiu.

It has been found that after intravenous administration of selective agonist of mu-opioid receptors DAGO (0.1 mg/kg 15 min before heart excision) isolated rat heart becomes resistant to ischemia (45 min) and reperfusion (60 min) ex vivo. The in vivo pretreatment with DAGO prevented reperfusion injury of cardiac cells and decreased myocardial content of conjugated dienes during ischemia and reperfusion of the heart in vitro. In addition, similar mu-opioid receptor stimulation promotes a postischemic recovery of myocardial contractility in the postischemic period. However, this receptor activation does not affect heart tolerance to free radical damage during perfusion of isolated heart by a solution containing Fe(2+)-ascorbic acid.

[The contribution of antioxidant enzymes in the cardioprotective effect of opioids during oxidative stress]. / Vklad sistemy antiokislitel'nykh frmentov v realizatsiiu kardioprotektnogo éffekta opioidov pri okislitel'nom stresse.

Intravenous administration of peptide delta 2-opioid receptor agonists increased cardiac sarcolemma resistance to subsequent oxidative stress in the isolated perfused rat heart in vitro. delta-Opioid receptor stimulation prevented oxidative stress-induced accumulation of lipid peroxides in myocardium and inhibition of superoxide dismutase. The cardioprotective and "antioxidant" effects of delta-agonists were completely abolished by in vivo pretreatment with the delta-receptor antagonist ICI 174,864. mu-Opioid receptor activation in vivo did not protect the isolated myocardium from cardiotoxic action of activated oxygen species.

[The role of mu- and delta-opiate receptors in resistance of the myocardium to free radical damage]. / Rol' mu- i del'ta-opiatnykh retseptorov v formirovanii rezistentnosti miokarda k svobodno-radikal'nomu povrezhdeniiu.

I.v. administration of the delta-opioid (OR) receptors' agonists DSLET or DTLET prevented creatine kinase leakage from the rat isolated heart in oxidative stress damage and abolished an increase in myocardial levels of conjugated diens and malondialdehyde. The agonists also prevented a stress-induced augmentation of the superoxide dismutase (SOD) activity. All protective effects of delta-receptor stimulation was completely abolished by the delta OR antagonist ICI 174,864. The data obtained suggest that the cardioprotective effect of the delta OR stimulation in vivo is not mediated via direct cardiac delta OR activation but, probably, rather via some unknown indirect circulating humoral factor(s).

[The use of delta-receptor antagonist DuP 734 for correction of the contractile diastolic cardiac dysfunction in reperfusion injury and oxidative stress]. / Ispol'zovane antagonista del'ta-retseptorov DuP 734 dlia korrektsii sokratitel'noi diastolicheskoi disfunktsii serdtsa v usloviiakh reperfuzionnogo povrezhdeniia i okislitel'nogo stressa.

Intraperitoneal administration of the sigma-receptor antagonist DuP 734 (1 mg/kg) 15 min before heart excision produces a decrease in the reperfusion heart contractility and prevented from the reperfusion induced cardiac cell lesion upon global ischemia of the isolated perfused rat heart. At the same time, a preliminary treatment with DuP 734 potentiated the reperfusion induced suppression of the cardiac pump function, while affecting neither the cardiac contractility dysfunction nor the cardiac cell injury during the oxidative stress. It is concluded that DuP 734 is not effective in preventing the myocardial stunning. The cardio-protector effect of DuP 734 during reperfusion is not related to inhibition of the free radical cell damage.

[Comparative analysis of the cardioprotective effect of antioxidant dibunol and agonists of mu- and delta-opioid receptors during oxidative stress]. / Sravnitel'nyi analiz kardioprotektornoi aktivnosti antioksidanta dibunola i agonistov mu- i del'ta-opioidnykh retseptorov pri okislitel'nom stresse.

Upon intravenous injection of the delta-opioid receptor agonists, the isolated perfused rat heart became resistant to free radical damage. The cardioprotector activity of the delta-receptor agonists is more pronounced than that of the antioxidant dibunol. Both dibunol and the delta-receptor agonists favored a decrease in the level of diene conjugates in myocardium. Stimulation of the mu-opioid receptors did not change the resistance of rat heart to the oxidative stress.

[The effect of synthetic enkephalins on prostaglandin synthesis and lipid peroxidation in the isolated heart during the activation of free-radical processes]. / Vliianie sinteticheskikh énkefalinov na sintez prostaglandinov i perekisnoe okislenie lipidov v izolirovannom serdtse pri aktivatsii svobodnoradikal'nykh protsessov.

The system Fe(2+)-ascorbate was used for lipid peroxidation (LPO) activation in isolated heart tissue. The stimulation of free radical processes in the myocardium caused a rise in the level of LPO products and a significant lowering of that of prostacyclin. Intravenous injection of synthetic analogues of enkephalins before LPO activation inhibited LPO and resulted in prostacyclin synthesis normalization. The addition of peptides under study into perfusion solution led to a decrease in LPO primary products level and in thromboxane synthesis.

[The participation of prostanoids in the realization of the cardioprotective, antistressor and anti-arrhythmic effects of enkephalins]. / Uchastie prostanoidov v realizatsii kardioprotektornykh, antistressornykh i antiaritmicheskikh éffektov énkefalinov.

It has been established that preliminary administration of D-Ala2-Leu5-Arg6-enkephalin, D-Met2-Pro5-enkephalinamide, and D-phenylalanine to experimental animals prevents a stress-induced increase of the content of thromboxane in the blood plasma and myocardium and induces a rise of the level of prostacyclin, PGF2 and PGE in the heart and blood plasma. The authors hold that the changes in the level of prostanoids may mediate cardioprotective and anti-stressor rather than antiarrhythmic effects of enkephalins.

[Effects of opioid neuropeptides on the prostaglandin system and lipid peroxidation processes in the myocardium during stress-induced damage]. / Vliianie opioidnykh neiropeptidov na sistemu prostaglandinov i protsessy perekisnogo okisleniia lipidov v miokarde pri ego stressornom povrezhdenii.

The stress was subsequenced by lowering of Thromboxane A2 level and activation of peroxidation of lipids without any changes of prostacyclin content in myocardium. It was found that the pre-increase of the opioid peptides in blood plasma led to the absence of prostacyclin and thromboxane dynamic and myocardial lipids peroxidation inhibition during the subsequent stress.