[Some special characteristics of vascular reactivity in heart failure].

We determined parameters of elasticity of peripheral arteries in patients with heart failure (HF) including those with pulmonary arterial hypertension. We also investigated pulmonary artery responses to vasoconstricting factors in vitro. Reactivity of the aorta and carotid artery was studied on the model of experimental HF. Lowering of elasticity of small arteries progressed with worsening of HF functional class and increase of pulmonary arterial hypertension. In the genesis of pulmonary hypertension definite role played elevated constrictor response of pulmonary artery to endothelin 1 at the background of dysfunction of endothelial ETB receptors. Endothelial dependent reactivity of the aorta and carotid artery was impaired and their constrictor effect augmented.

[Qualitative and quantitative changes of circulating in blood endotheliocyte precursor cells in patients with hypercholesterolemia].

Aim of this study was elucidation of diagnostic value of qualitative and quantitative parameters of circulating endotheliocyte precursor cells (EPC), in the state of apoptosis (apoptotic endotheliocytes A AE), as well as effect of main risk factors on the studied parameters in patients with coronary atherosclerosis and hypercholesterolemia. We examined 24 patients with ischemic heart disease (14 men, 10 women, mean age 58.4 +/- 2.3 years) with stenoses >75% in coronary arteries according to angiography data and hypercholesterolemia (main group). Control group comprised 15 healthy volunteers. Circulating EPC in peripheral blood were evaluated by cytofluorimetry. Functional parameters of isolated EPC were assessed after cultivation in human fibronectin. Adhesive properties were studied in cell culture by immunehistochemical method after 7 days of incubation. Proliferation capacity was assessed by number of EPC in 1 mm3 of medium at day 7 of incubation. Determination and counting of AE was carried out using cytofluorimetry with immunostaining of cells by anexin B and CDA31 after preliminary treatment of endotheliocyte culture with H2O2 and comparing the results with control culture of endotheliocytes. Number of circulating EPC in patients with IHD was 58.% less than in healthy persons. Adhesive capacity of EPC in patients with IHD was lowered by 43%. Number of EPC surviving in cell culture was 80.9% less than in control group. At the same time number of circulating AE in patients with IHD was 2.5 times greater. Reduction of number of EDC, adhesive capacity, and rise of number of AE correlated significantly with number of involved coronary arteries, presence of diabetes, and smoking status. Presence of arterial hypertension and blood cholesterol level did not correlate with quantitative and qualitative parameters of EPC. Thus qualitative and qualitative parameters of circulating EPC and apoptotic cells can be considered as markers of dysfunction of endothelium and predictors of atherosclerotic vascular lesions in patients with hypercholesterolemia.

[Changes of activity of the endothelial system in experimental heart failure].

Despite obvious participation of endothelins in pathogenesis of heart failure therapeutic approaches to the use of endothelin receptor antagonists remain to be elucidated. Experimental heart failure caused by prolonged infusion of norepinephrine is associated with diminished endothelin induced coronary constricting effect of stimulation of ET(A) receptors and inversion of coronary dilating effect of stimulation of these receptors. The latter effect is mediated by smooth muscle ET(B)-receptors and is indicative of functional derangement of vascular control by endothelial cells. The use of selective ET(A)-antagonist is effective on early stages of heart failure while on later stages administration of nonselective ET(AB)-antagonist produces more pronounced effect.

Myocardial alterations induced by prolonged noradrenaline administration in various doses.

Prolonged noradrenaline administration to rats in steadily increasing dosages for a period of one to four weeks (cumulative doses 25-35 mg/kg) resulted in the development of focal necrotic areas with abundant collagen fibers and marked hypertrophy of cardiomyocytes. Cellular diameter was higher by 37-44% and extracellular space area by 70-100%. A combination of overcontracted and overdistended sarcomeres in some cardiomyocytes and a twofold rise in serum creatine kinase presumably reflected cellular calcium overload. Myocardial high energy phosphate content was depleted to 50-62% of the control level. The extent of this depletion positively correlated with a decrease in heart rate and cardiac output of the isolated heart. The latter may be attributed to limited left ventricular filling caused by elevated LV diastolic pressure and stiffness. Minimal metabolic and functional changes were observed after lowest noradrenaline dose (5 mg/kg for nine days) that was followed by only moderate depletion of myocardial phosphocreatine content and moderate rise in LV diastolic stiffness. Results suggest that energy-deficient increase in myofibrillar stiffness may form the basis for decreased myocardial distensibility and cardiac pump failure.

Protective effect of taurine on the myocardial effects of prolonged treatment with norepinephrine in rats.

A steadily increasing dose of norepinephrine given to rats for 7 consecutive days (cumulative dose 25 mg/kg) resulted in the development of focal necrotic areas with abundant collagen fibers, marked hypertrophy of cardiomyocytes and a mild depletion of the myocardial level of high-energy phosphates. These changes were associated with a more than two-fold decrease in the external work of the isolated rat heart at a moderate functional load, that may be attributed mainly to limited filling of the left ventricle due to elevated diastolic pressure and increased diastolic stiffness. If 100 mg/kg taurine was given daily before the dose of norepinephrine, the functional and metabolic alterations induced by norepinephrine were significantly reduced. The external work of the isolated heart was 1.5 times higher when taurine was added than it was when the animals were treated with norepinephrine alone; and there was a significant reduction in the increase in left ventricular diastolic pressure and stiffness. The ability of the heart to respond to the injection of a bolus of Ca2+ by decreasing the minimal left ventricular diastolic pressure was almost lost after treatment with norepinephrine alone, but was partly restored when taurine was added. Taurine also prevented the occurrence of necrosis as well as depletion of the levels of myocardial ATP and phosphocreatine; while the extent of an increase in cellular diameter and the area of extracellular space was roughly the same as without taurine.

[Antioxidants, lipid peroxidation, and receptor-dependent increase in Ca2+ concentration in human platelets]. / Antioksidanty, perekisnoe okislenie lipidov i retseptorzavisimoe uvelichenie kontsentratsii Ca2+ v trombotsitakh cheloveka.

Content of tocopherol and total antiradical activity of hydrophobic antioxidants were estimated in human blood platelets. Two hydrophobic antioxidants--tocopherol and ubiquinone were detected in hexane extracts of thrombocytes using thin-layer chromatography. After incubation of thrombocytes with N-ethyl maleimide content of malonyl dialdehyde was increased and of tocopherol--decreased, receptor-dependent increase of Ca2+ concentration in cytoplasm was potentiated, while the Ca(2+)-blocking effect of nitroglycerol was decreased. Nitroglycerol did not inhibit the N-ethyl maleimide effect on content of malonyl dialdehyde in blood platelets. Addition of exogenous vitamin E to thrombocytes did not affect the receptor-dependent increase of Ca2+ concentration. Ascorbic acid inhibited the receptor-dependent increase of Ca2+ concentration. The data obtained suggest that nitrates may be used more rationally in combination with antioxidants and/or inhibitors of cyclooxygenase.

Energy-linked functional alterations in experimental cardiomyopathies.

Changes in high-energy phosphate content and cardiac contractile function of isolated rat hearts as well as changes in Ca2+ sensitivity and mitochondrial respiration of myocardial skinned fibers were assessed in hereditary cardiomyopathies and in cardiomyopathies induced by chronic treatment with adriamycin or norepinephrine, by autoimmunization, by diabetes, or by creatine deficiency. The sum of ATP and phosphocreatine contents as well as cardiac output at standard load conditions was substantially lower in almost all groups. The common features of cardiac pump failure were mild bradycardia, elevated left ventricular (LV) diastolic pressure, and stiffness that limited cardiac contractile adaptation to volume or resistance loads. The LV diastolic stiffness at maximal functional load was inversely correlated with high-energy phosphate content. Increased myofibrillar sensitivity to Ca2+ and defective function of mitochondrial creatine kinase were found in skinned myocardial fibers. These results suggested that both increased myofibrillar Ca2+ sensitivity and energy deficiency within myofibrils may contribute to increased myocardial stiffness. Increased stiffness limits LV filling but facilitates pressure development, which partly compensates for decreased contractility of cardiomyopathic hearts.

[Norepinephrine-induced heart failure and the protective effect of taurine]. / Porazhenie serdtsa, vyzyvaemoe noradrenalinom, i zashchitnyi éffekt taurina.

The prolonged noradrenaline treatment of rats (total dosage from 1 week--25 mg/kg), results in greatly reduced cardiac pump function and heart rate with a pronounced increase in left ventricular diastolic stiffness. These functional changes are associated with a deficiency of energy supply, especially depletion of phosphocreatine content. The taurine administration (100 mg/kg prior to 20 min noradrenaline injection) is accompanied by reliably less essential cardiac insufficiency. Moreover, the ATP, ADP level is normal and phosphocreatine content enhances by 15%.

Cellular mechanisms of alterations in myocardial contractile function in experimental cardiomyopathies.

The high-energy-phosphate content, myocardial ultrastructure, left ventricular (LV) pressure, and pump function of isolated rat hearts were determined in four kinds of chronic myocardial damage induced by either autoimmunization, treatment of rats with adriamycin or noradrenaline in increasing doses, or infection with smallpox virus. Mild fibrosis, swollen mitochondria, and hyper-contracted and overdistended sarcomeres were typical ultrastructural alterations. The ATP and phosphocreatine content as well as cardiac output at standard load conditions were substantially lower in all four experimental groups. Mild bradycardia and increased LV diastolic pressure and stiffness occurred in all except the autoimmunized group. LV diastolic stiffness was inversely correlated with cardiac output and phosphocreatine content and directly correlated with LV systolic pressure. Both increased myofibrillar sensitivity to Ca2+ ions and energy deficiency within myofibrils may have contributed to increased myocardial stiffness. The increased stiffness limits LV filling but facilitates pressure development, and in this way partly compensates for the decreased contractility of cardiomyopathic hearts.

[Nerve regeneration after correction of its defect with a vascularized autologous nerve transplant]. / Regeneratsiia nerva pri zameshchenii ego defekta krovosnabzhaemym autoneirotransplantatom.

In chronic experiment performed on 6 dogs, by means of some neurohistological techniques peculiarities of regeneration of nerves have been studied, when their defects are substituted for vascularized and common autoneurotransplants. When the vascularized autoneurotransplants are applied, more favourable conditions are made for the nerve regeneration, than at a free plastisity and amount of regenerated fibers distal to the graft reaches 34-88%, more often making 48-52% of the initial number of fibers in the proximal parts of the nerves in 3 months after the operation. When in the same animals in the contralateral side common autoneurotransplants have been applied, during the same time the amount of fibers regenerated into the peripheral parts of the nerves makes 10-26%, more often 17-20% from the initial level, or in 2-2.5 times less than at substitution of the defects for the vascularized grafts. Absence of an active cellular reaction of the surrounding tissues to the sutural material supramid is used.

Adaptation of cardiac contractile function to conditions of chronic energy deficiency.

Left ventricular (LV) contractile function and pump function were depressed in isolated working hearts from rats treated with either guanidinopropionic acid (GPA), an inhibitor of creatine influx, or the anthracycline antibiotic, adriamycin, for 6 and 10 weeks, respectively. In both groups of treated animals myocardial phosphocreatine content was lower than in control hearts, while ATP content was unchanged. Hearts of treated animals exhibited only a minor depression of cardiac output with a submaximal pressure load or during volume overload. However, at maximal pressure load GPA- and adriamycin-treated hearts performed 43% and 37% less pressure-volume work than control hearts. These changes were due both to decreased LV pressure development and diminished cardiac output. LV diastolic stiffness was significantly higher at the submaximal pressure load and the LV filling pressure area, which reflected LV filling, was lower in hearts of both treated groups. The differences in both indices were exaggerated when the maximal pressure load was applied. Limited LV filling due to incomplete myocardial relaxation appeared to represent the underlying cause of cardiac failure when afterload was increased. These results may be explained if adaptation of cardiac contractile function in some chronic cardiac diseases arises from a limited energy supply to the myofibrils.

[Modification of the thiobarbituric method for determining sialic acids in biological material]. / Modifikatsiia tiobarbiturovogo metoda opredeleniia sialovykh kislot v biologicheskom materiale.

The authors have examined the possibility of replacing sodium arsenite with acetyl thiourea and of using butanol acidified with phosphoric acid in measuring sialic acids in biologic material. The results evidence a sufficient specificity, reproducibility, higher sensitivity and lower toxicity of the modification as compared to the routine technique, for this modification does not involve the use of highly toxic sodium arsenite and of highly volatile aggressive butanol/hydrochloric acid mixture.