[Production of reactive oxygen species by monocyte-derived macrophages from the blood of healthy donors and patients with IHD].

Production of reactive oxygen species (ROS) by macrophages from blood monocytes of healthy donors (MP(N)) and patients with IHD (MP(IHD)) before, during, and after their incubation with low-density lipoprotein (LDL) isolated from the blood plasma of healthy donors (LDL(N)) and patients with a high cholesterol level (LDL(H)) was estimated by the method of luminol-dependent and stimulated by opsonized zymosan (OZ) or phorbol-12-myristate-13-acetate (PMA) chemiluminescence (CL). Intrinsic luminol-dependent, and zymosan- or PMA-stimulated chemiluminescence of MP(IHD) have exceeded the same types of chemiluminescence of MP(N) by factors of 1.4, 1.

[LDL oxidation and uptake by monocyte-derived macrophages from blood of patients with ischemic heart disease].

The aim of this study was to test our hypothesis that monocyte-derived macrophages of patients with ischemic heart diseases (IHD, MPIHD) were prestimulated (primed) or stimulated cells whose capacity for LDL oxidation and uptake exceeded that ofmacrophages from healthy donors (MPN). Monocytes were obtained from the blood of 18 healthy donors and 25 IHD patients; plasma LDL--from 16 another group healthy donors (LDLN) and 15 patients with family hypercholesterolemia. Incubation of LDLN or LDLH with MPIHD or MPN was carried out under aerobic and hypoxic conditions.

[The use of antioxidants and antihypoxants for decreasing of LDL oxidation by macrophages and endothelial cells in ischemia and reperfusion of vascular wall].

Oxidative modification of LDL is a key factor in pathogenesis of atheroslerosis. In this work the effects of antioxidants (K-phenosan, probucol, and desferal) and antihypoxants (succinic acid, hypoxen, and deltaran) on the macrophage- and endothelial cell-mediated oxidation of LDL was studied. Electrophoretic mobility of LDL, the content of lipid peroxide products (TBARS and diene conjugates, DC) and cell viability were used as the indexes of LDL oxidation.

Effect of antioxidant probucol on cell-mediated LDL oxidation in vitro and in vivo.

We studied the effect of phenol antioxidant probucol on free radical oxidation of LDL isolated from blood plasma of healthy donors. Oxidation was induced by co-incubation of LDL with cultured peripheral blood monocyte-macrophages and human umbilical vein endothelial cells under conditions of ischemia-reperfusion. In addition, the effect of probucol therapy on oxidability of plasma LDL in CHD patients was examined.

Tumor necrosis factor-alpha in low doses preactivates and activates macrophages by increasing their ability to produce reactive oxygen species and oxidize low-density lipoproteins: protective effect of antioxidants.

Tumor necrosis factor-alpha in low doses activated rat peritoneal macrophages and intensified production of reactive oxygen species (zymosan-depended chemiluminescence). Single or 2-fold incubation with tumor necrosis factor-a activated and preactivated human blood macrophages and promoted oxidative modification of low-density lipoproteins (increased their mobility in agarose gel). Antioxidants (potassium phenosan, probucol, and desferal) suppressed oxidative modification of low-density lipoproteins induced by nonactivated, preactivated, and activated macrophages.

[Comparative evaluation of the cytotoxic effect of hydrogen peroxide and tumor necrosis factor alpha on nonischemic and ischemic endothelial cells].

We studied cytotoxic effects (CTE) induced in confluent cultures of human umbilical vein endothelial cells (HUVEC) by initiators of free-radical reactions (FRR): H2O2 (10(-6)-10(-9) M), recombinant human tumor necrosis factor-[symbol; see text] (TNF-alpha, 0.05-100 ng/ml), and a combination of TNF-alpha with low-density lipoproteins (LDL, 100 microgram/ml). HUVEC were incubated with these substances for 6 or 24 h in parallel tests performed under aerobic (CO2-incubator) and ischemic conditions (a mixture of 95% N2 + 5% CO2 in RPMI-1640 medium containing no substrate additives, growth factor or protein).

[The evaluation of the possibility of using prodigiozan for isolating extracts that stimulate proliferative processes in the resected liver].

The experiments were performed on 126 white male rats. The inclusion of 3H-thymidine in nuclear DNA of the liver was studied on h 24 and 48 after 70% resection of the liver versus prodigiosan injection or combination of prodigiosan with 70% resection of the liver. Liver extracts stimulating proliferation (ESP) obtained under the above schedules were studied on the model of 30% liver resection.

[The effect of the antioxidant ionol as a liposome component on the function of the isolated and ischemic heart].

The anti-ischemic and toxic effects of different doses of the antioxidant ionol (butyl hydroxytoluene, BHT) introduced into the Krebs-Henseleit medium composed of monolayer liposomes of egg phospholipids before or 30 minutes after total ischemia of the heart were studied on a model of perfusion of isolated Wistar rat heart by the method of Langendorff-Fallen. It has been demonstrated that ionol, after its addition to the perfusate in the preischemic period, exerts an anti-ischemic effect in concentrations of 10(-6), 3 x 10(-6) and 10(-5) M; in the postischemic period, in concentrations of 3 x 10(-6) and 10(-5); the protective effect of ionol in the postischemic period is less pronounced. In higher doses (3 x 10(-5) and 10(-4) M) ionol produces a toxic action which is more remarkable and is less reversible in respect to the ischemized than to the nonischemized heart, and is realized rather through the dysfunction of heart muscle relaxation.

[Changes in EEG and higher nervous activity of rats during cerebral anti-ischemic protection by acelysin].

The water-soluble aspirin (acelysin) has been used as an anti-ischaemic protector when injected in the dose of 150 mg/kg 30 min before ischaemia. The EEG has been registered during the whole period of experiment and the total EEG power index has been calculated. The higher nervous activity has been evaluated during analysis of rat's abilities for elaboration of conditional reflex of an active escape reaction in Y-labyrinth.

[Anti-ischemic protection of the brain using water-soluble form of aspirin-acelisin].

The domestic water-soluble aspirin (acelisin) has been used as an anti-ischemic brain protector. The total brain ischemia has been implemented in accordance with an original technique for 17 to 35 min. The doses of acelisin from 25 to 250 mg/kg have been tested during experiments.

[Anti-ischemic action of a 1-hydroxy-2,2,6,6-tetramethylpiperidine derivative from a series of nitroxyl bioantioxidants].

The experiments have been performed on 216 Wistar rats to examine anti-ischaemic action of the 1-hydroxy-2,2,6,6-tetramethyl-piperidine derivative (I), whose antioxidant properties were, earlier shown for model systems. Introduction of I (10(-4) M) into the perfusion medium and the subsequent storage (37 degrees C) of isolated liver was shown to decrease the accumulation of lipid peroxidation products (MDA). Compound I administrated (5 x 10(-6)-10(-5) M) in perfuse medium of isolated (Langendorff method) and ischemized (30 min, 37 degrees C) heart improves contractile function (Pmax) and decreases end-diastolic pressure at postischaemic period.

[Membranes of subcellular organelles as the source of superoxide radicals in liver ischemia].

O2-generation rate (Vo2-) in microsomal, mitochondrial and nuclei liver membranes was measured by ESR method, by accumulation of stable nitroxide radicals. These Vo2- values were compared with Cu, ZnSOD and MnSOD activities after 2 hours ischemia and 24 hours reoxygenation. O2- radicals generated by electron transfer chains are concluded to damage mainly during the ischemia, but not the reoxygenation.

[Is xanthine oxidase a universal source of superoxide radicals in ischemic and reperfusion lesions?].

While studying xanthine-xanthine oxidase system it was found, that a considerable accumulation of xanthine and uric acid occurred whereas xanthine dehydrogenase did not transfer in xanthine oxidase during 2 hours of total rat liver ischemia. These data make it possible to reject the generally accepted hypothesis of xanthine oxidase key role in free radical mechanism of ischemia damage.

[Disorders of cardiac contractile function in ischemic shock; the protective effect of antioxidants and liposomes made from egg phospholipids].

Experiments were made on Wistar rats with 6h tourniqueting of the hind limbs to study animal survival rate, myocardial contractile function and protective action of antioxidants and egg phospholipid liposomes during ischemic shock. It has been shown that reperfusion of the limbs leads to a high animal lethality, make lower myocardial contractile function and coronary flow of the hearts isolated from rats following a 6h reperfusion of the limbs. Well-known antioxidant butylated hydroxytoluene and a new antioxidant tetramethylpiperidine derivative bring animal lethality down and improve coronary flow and contractile function of the isolated heart.

[Negative inotropic and vasoconstrictor effects of oxidized phospholipids].

Effects of oxidized yolk phospholipids (PL) on the coronary perfusion rate (CPR) and myocardial contractility were studied in the experiments with the isolated or isolated and 30-minute ischemia-induced heart of the rat or isolated myocardial strip of the frog. The oxidized PL were demonstrated to possess a more pronounced and steady negative inotropic effect than unoxidized PL, which was due to their direct dose-dependent damaging action on myocardial contractility. The oxidized PL also made the unrestored CPR worse in the early postischemic period, the concomitant administration of aspirin producing no effects and that of the antioxidant ionol making ischemic myocardial contractility better.

[Regeneration ability of ischemic liver and the effect of liver resection and extracts stimulating proliferation].

DNA synthesis was studied in liver nuclei of Wistar rats after 30% liver tissue resection, 2 hr ischemia of 70% liver tissue or 2 hr ischemia of 70% liver tissue with resection of intact lobes. DNA synthesis was markedly increased in ischemic lobes and was especially high in ischemic lobes if simultaneous resection of intact lobes occurred; maximum of the synthesis was observed within 32 hrs after the operation. Proliferation stimulating extracts, isolated from liver tissue within 48 hrs after the resection or after ischemia, intensified the regenerating processes in the resected liver tissue; the first preparation (from resected liver tissue) exhibited the most distinct effect as compared with the second extract (from ischemic liver tissue).

[Protective effect of antioxidant ionol in total ischemia of the heart].

The effect of antioxidant ionol in total myocardial ischemia during 30 and 60 min, t = 20 degrees C and 37 degrees C was studied in 60 Wistar rats. The models of isolated perfused myocardium by Langendorf, Neely and that of heterotopic transplantation of myocardium to the rat peritoneal vessels were used. It has been shown that pretreatment of ionol (240 mg/kg before 24 h of ischemia) was accompanied by improvement of myocardial contractile and diastolic functions.

[The state of lipid peroxidation and enzymes of calcium transport system in sarcoplasmic reticulum of ischemic myocardium].

In 30 experiments on mongrel dog hearts it was shown that 30 min of total ischemia (37 degrees C) followed by accumulation of MDA in the SR membranes and decrease of their Ca2+-uptake, but had no effect on activity Ca2+-ATPase. After 60-120 min ischemia marked a decrease of Ca2+-uptake and activity Ca2+-ATPase took place, MDA content remained at the increased level. The results show that lipid peroxidation take part in the increase of the permeability of SR membranes for Ca2+ and inhibiting of Ca2+-ATPase.