[Assessment of endogenous intoxication and thrombocyte functions in beta-thalassemia]. / Otsenka éndogennoi intoksikatsii i funktsii trombotsitov pri beta-talassemii.

The parameters of humeral immunity and of the aggregation function of blood platelets were comparatively analyzed in 11 healthy and 26 children with beta-thalassemia; 18 of them had beta-thalassemia of the homozygous type (spleen was extracted in 8 children, and it remained intact in 10 children). It was demonstrated that there was an increased quantity of antibodies to blood platelets and an increased quantity of large, medium-size and small circulating immune complexes in patients with beta-thalassemia and especially in those, who did not undergo splenectomy; there was also an increased quantity of immunoglobulins of classes A, M, and G, a reduced total activity of the complement and a high parameter of the degree of endogenous intoxication, i.e. the content of medium-size molecular peptides. The mentioned disorders were accompanied by worsened aggregation abilities of blood platelets and by their increased disaggregation. Finally, insignificant changes were detected in patients with beta-thalassemia of the heterozygous type.

[Study of the spectrum of rabbit myocardium nuclear DNAases using models of ischemia and diabetes mellitus]. / Izuchenie spektra iadernykh éndoDNKaz miokarda krolika na model'iakh ishemii i sakharnogo diabeta.

There were alterations in the spectrum of nuclear endo-DNAases in the rabbit myocardium on experimental models of diabetes mellitus and other diseases where the perfused heart was involved i.e. disappearance of the enzyme with 130 kDa from the control extracts was followed by a great increase in the content of low molecular forms in the nuclear preparations obtained from the ischemic heart, as well as that with 145 kDa in all the abnormalities under study.

[Nuclear endo-DNAse from rabbit myocardium in ischemia and diabetes mellitus]. / Iadernaia éndodnkaza miokarda krolika pri ishemii i sakharnom diabete.

The activity of deoxyribonucleases was altered in the myocardium of New Zealand rabbits under normal conditions, in diabetes mellitus as well as in various experiments, where model heart perfusion was carried out using media of various ion composition and pH value. Studies of Ca2+, MG(2+)- dependent deoxyribonuclease from myocardial nuclear extracts exhibited that protective cell mechanisms appear t be induced at the first steps of tissue ischemic impairments as well as that diabetes decreased cardiac sensitivity to ischemia.

[Energy metabolism and contractile function of the heart in diabetic cardiomyopathy: effect of ischemia and reperfusion]. / Issledovanie énergeticheskogo metabolizma i sokratitle'noi funktsii serdtsa s diabeticheskoi kardiomiopatiei: deistvie ishemii i reperfuzii.

Physiological parameters, rates of mitochondrial respiration, high energy phosphate levels and creatine phosphokinase (CPK) activity were investigated in the hearts from control and alloxan-induced diabetic rabbits before and after 40-min total ischemia and reperfusion. Diabetic hearts demonstrated significant decreases in the rates of contraction (+dP/dt) and relaxation (-dP/dt), heart rates and cardiac work compared to control hearts. Determination of mitochondrial respiration rates in saponin-skinned fibers showed a low mitochondrial respiratory function in diabetic hearts. It was found that the ATP and ADP levels and the total and mitochondrial isoenzyme activities of CPK in diabetic hearts were lowered in comparison with control. A post-ischemic recovery of cardiac performance for diabetic hearts was better than in controls. After reperfusion diabetic hearts had increased ATP levels. The data obtained demonstrate some abnormalities of both cardiac performance and energy metabolism in the hearts of diabetic animals and a decreased sensitivity of the latter to ischemic injury.

[Quantitative relationship between ischemic heart disease and parameters of energy metabolism]. / O kolichestvennoi sviazi mezhdu ishemicheskim porazheniem serdsa i parametrami énergeticheskogo metabolizma.

The relationship between coronary heart disease, postischemic work recovery and tissue ATP levels as well as mitochondrial respiration rates were studied. Respiration of mitochondria was assessed without their isolation by using a novel method applying skinned fibers in physiological saline. The maximal mitochondrial respiration rates were unchanged during 35 min of normothermic ischemia in St. Thomas Hospital cardioplegic solution in the subsequent 30 min aerobic reperfusion period. A reversible increase in the basal respiration and a decrease in creatine-stimulated oxygen uptake were observed. Thus, the combined determination of mitochondrial respiration in situ in skinned cardiac fibers and tissue ATP may be a useful approach to studies of the pathogenesis of cardiac diseases.

[Energy-related disorders of myocardial contractility in calcium overload of the cardiomyocytes]. / Energeticheskaia zavisimost' narushenii sokratitel'noi funktsii miokarda v usloviiakh kal'tsevoi peregruzki kardiomiotsitov.

Langendorff perfusion of euthyroid rat heart with 10 mM phosphocreatine (PCr) in Krebs-Henseleit solution in conditions of Ca2+-paradox significantly potentiated the development of contracture and produced a 4-fold increase in perfusion pressure as compared to heart contractility in PCr-free, but otherwise similar conditions. Similarly, in case of hyperthyroid myocardium, addition of PCr into hypoxic perfusate (glucose omitted) in the presence of supranormal extracellular Ca2+ (5.0 mM) irreversibly inhibited the restitution of resting tension and developed tension during aerobic reperfusion. In the same conditions, PCr did not modulate contractility of euthyroid myocardium. These results are consistent with Ruigrok's hypothesis (1978) that intracellular Ca2+ redistribution is energy-dependent, provided PCr can penetrate into cardiomyocytes and stimulate ATP-dependent accumulation of Ca2+ in mitochondria, leading to an impairment of energy production. It is concluded that PCr exerts its cardioprotective effect only in case of a reversible (acute) phase of ischemia.

[Effect of phosphocreatine on the lysophosphoglyceride levels in total ischemia of the rat myocardium]. / Vliianie fosfokreatina na uroven' lizofosfoglitseridov pri total'noi ishemii miokarda krysy.

The phospholipid composition of the crude plasma membrane fraction of Langendorff perfused rat hearts has been studied. The effect of phosphocreatine (PCr) and 3-phosphono-2-imino-1-methyl-4-oxoimidazolidine (PIMOI) on lysophosphoglycerides (LPG) level in this fraction isolated from hearts that were totally ischemic for 8 minutes, has been examined. The absolute and relative contents of LPG were significantly increased in ischemic hearts: the lysophosphatidylcholine content was elevated by 94% and that of lysophosphatidylethanolamine--by 77%. Accumulation of these LPG in ischemic myocardium was completely inhibited in the presence of 10 mM PCr or PIMOI in the perfusate. LPG may play a key role in the destruction of sarcolemma. Therefore, these data allow to assume that the protective effect of PCr and PIMOI on the sarcolemma of ischemic myocardium may be the result of their influence on the phospholipid metabolism in the ischemic region of the heart.

[Possible mechanism of the protective effect of phosphocreatine on the ischemic myocardium]. / Issledovanie vozmozhnogo mekhanizma zashchitnogo deistviia fosfokreatina na ishemicheskii miokard.

The uptake of 32P-phosphocreatine by control and ischemic isolated perfused rat hearts has been studied. The rate of phosphocreatine (PCr) uptake by the hearts after 35 minutes of ischemia was two times that in control hearts at 0.5-10 mM PCr in the perfusate. At 10 mM PCr in the perfusate, this rate was 182 nmoles/min/g dry weight. The 5'-nucleotidase and phosphatase activities were found in the crude plasma membrane fraction of rat heart. The pH-dependence of these enzymes was examined. The 5'-nucleotidase activity decreased with a drop in pH from 8.0 to 6.0. The phosphatase activity in the crude plasma membrane fraction of rat heart was increased 2-fold with a decrease in pH from 8.0 to 6.0. The 5'-nucleotidase activity was inhibited by 10 mM PCr in the presence of 5 mM Mg2+. This inhibition was pH-dependent with a maximum (58%) at pH 6.0. The inhibition of phosphatase activity by PCr was independent of pH and reached 20% in the presence of 10 mM PCr. Some feasible mechanisms of the protective effect of PCr on ischemic myocardium are discussed.

[Effect of phosphocreatine and phosphocreatinine on membrane phospholipid metabolism in acute myocardial ischemia]. / Vliianie fosfokreatina i fosfokreatinina na metabolizm membrannykh fosfolipidov pri ostroi ishemii miokarda.

The effect of phosphocreatine and phosphocreatinine on changes in crude lysophosphoglycerides (LPG) in the plasmatic membranes of canine heart, induced by short-term ischemia (an 8-minute-long occlusion of the left descending coronary artery), was examined. Ischemia caused a considerable rise in LPG level, with a mean 83% rise in lysophosphatidyl choline and a 168% rise in lysophosphatidyl ethanolamine. Intravenous administration of 300 mg/kg phosphocreatine or phosphocreatinine completely prevented the accumulation of LPG in the ischemic area. Since LPG have pronounced arrhythmogenic properties, the data obtained suggest that anti-arrhythmic activity of phosphocreatine and phosphocreatinine in acute myocardial ischemia results from the effect these substances have on membrane phospholipid metabolism in the ischemized area.