Disturbances in Energy Metabolism during Traumatic Shock and Their Pharmacological Correction

In compression traumatic shock caused by mechanical crushing of the lower limbs and eventuating in death of 80% animals, hemodynamic disorders by the end of day 1 lead to the development of energy deficiency most pronounced in skeletal muscles and less pronounced in the liver and kidneys. Energy production in the brain and heart was not impaired. Inhibition of ATP synthesis correlated with decreased SOD activity in organs, but not always with activation of lipid peroxidation, which can occur without concomitant disorders in energy metabolism (in the heart and brain). Therapy with succinate-containing hydroxypyridine derivative decreased animal mortality to 10%; this treatment did not modify hemodynamic parameters, but normalized energy metabolism in organs and activity of the antioxidant and prooxidant systems. These findings suggest that tissue (bioenergetic) hypoxia plays an important role in the pathogenesis of compression traumatic shock and that antihypoxic drugs are essential components of therapy of this condition.     

Role of noradrenalin in regulation of myocardial oxidative metabolism in rats differing in resistance to hypoxia

Laboratory of Bioenergetics, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow. (Presented by Corresponding Member of the Russian Academy of Medical Sciences L. D. Luk'yanova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 12, pp. 586–588, December, 1992.     

Brain Energy Metabolism in Angiotensin-Induced Acute Hypertension in Rats

In order to study if rapid elevation of blood pressure is associated with cerebral ischemia, anesthetized (70% N₂O) and artificially ventilated rats were subjected to angiolensin-induced hypertension. After a 5 min hypertensive period, cerebral cortex tissue was frozen in situ for subsequent measurements of labile glycolytic metabolites, ammonia, and organic phosphates. The degree of hypertension induced, which gave evidence of blood–brain barrier damage in 7 of 8 rats, did not affect the tissue concentrations of labile metabolites. It is concluded that ischemia does not contribute to the barrier damage, nor is it likely to be the cause of the clinical symptoms that may occur in conscious rats in the same experimental model.     

Effects of Succinic and Glutamic Acid Combination on Energy Metabolism in the Liver of Mice under Conditions of Hypoxia

Treatment of mice by a combination of succinic and glutamic acids prevented the metabolic disorders in the liver under conditions of normobaric hypoxia. In addition, the activity of the mitochondrial fast metabolic cluster remained intact and lipid peroxidation was limited. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 3, pp. 307–310, March, 2009     

Adenylate cyclase activity of human nasal polyps during stimulation of serotonin biosynthesis in vitro

The tissue of human nasal polyps possesses adenylate cyclase activity. After injection of reserpine (1 mg) into the tissue of nasal polyps, to activate serotonin biosynthesis in the tissue, a significant increase in adenylate cyclase activity was observed; during the first minutes of incubation of the polyp with reserpine, activity increased tenfold. The role of the adenylate cyclase system was confirmed in the initial stages of morphological and biochemical differentiation accompanying serotonin biosynthesis in human nasal polyps.Laboratory of Biochemistry, Central Institute of Hematology and Blood Transfusion, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR K. V. Bunin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 4, pp. 428–430, April, 1976.     

Metabolic effects of trekrezan during adaptation of rats to intermittent hypoxic hypoxia

The animals were adapted to intermittent hypoxic hypoxia in a flow pressure chamber for 3 days. Each one-day training session consisted of 4 elevations to an altitude of 6000 m for 20 min (15 m/sec, 20-min intervals between assents). Trekrezan (25 mg/kg intraperitoneally) was injected immediately after the end of daily training over 3 days. We showed that trekrezan increased the degree of adaptive metabolic changes in the brain, heart, and liver of rats during adaptation to hypoxic hypoxia. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 1, pp. 53–56, January, 2008     

Potential of Phosphorus Nuclear Magnetic Resonance Spectroscopy in Studies of the Energy Metabolism of Skeletal Muscles

The aim of the present study was to investigate the possibility of phosphorus magnetic resonance spectroscopy (MR spectroscopy) in the diagnosis of metabolic lesions of skeletal musculature in patients with intermittent claudication syndrome, chronic cardiac failure, and varicose diseases of the lower limbs. Studies included 50 males: 20 patients with intermittent claudication, 10 patients with chronic cardiac failure, and 10 patients with varicose veins. The control group consisted of 10 healthy volunteers. The following measures were determined: the phosphocreatinine index, the intracellular pH in the gastrocnemius muscle, and the half-recovery time for the phosphocreatinine index. The phosphocreatinine index and the pH at rest did not differ between study groups. Isotonic exercise produced no change in the phosphocreatinine index in the control group; patients with intermittent claudication showed a 26.1% decrease, patients with chronic cardiac failure showed an 8% decrease, and patients with varicose veins showed a 25.6% decrease. The only group showing a significant decrease in pH during exercise was the group of patients with intermittent claudication. This group also showed an inverse correlation between the pressure index and the extent of the decrease in the phosphocreatinine index. Thus, MR spectroscopy provides a non-invasive diagnostic method for lesions of energy metabolism in skeletal musculature in patients with deranged peripheral hemodynamics.     

应激对模拟高原低压低氧环境下大鼠海马单胺递质的影响

目的:探讨心理和生理应激对模拟高原低压低氧环境下大鼠海马单胺递质含量的影响。方法:用旁观电击的方法建立大鼠心理和生理应激模型。低氧处置为将大鼠置于模拟海拔6000m的低压舱内24小时。比较不同方式和强度的应激对低压低氧性环境下大鼠海马细胞外液中去甲肾上腺素(NE),多巴胺(DA),高香草酸(HVA)和5-羟色胺(5-HT)含量的影响。用高效液相色谱-电化学法检测其中的单胺递质的含量。结果:(1)低氧组大鼠海马细胞外液中NE含量低于正常对照组(813.8±196.1/1209.2±282.0,P<0.01);心理性(应激2次 低氧组:906.0±227.6,应激4次 低氧组:1103.7±270.6)和生理性(应激2次 低氧组990.3±93.7,应激4次 低氧组:610.8±104.1)应激 低氧组大鼠海马NE含量均高于低氧环境下(813.8±196.1)大鼠(P<0.05)。(2)低氧组大鼠海马细胞外液中5-HT含量高于正常对照组(82.7±23.4/52.3±27.9,P<0.05);生理应激2次 低氧组5-HT含量高于低氧组(134.2±51.5/82.7±23.3),生理应激4次 低氧组5-HT含量则低于低氧组(41.9±13.4/82.7±23.4,P<0.05)。结论:不同方式和强度的应激对低压低氧环境下大鼠海马单胺递质的影响存在差异。     

Effects of hypoxia on phosphoinositide metabolism and the adenylate cyclase system in endothelial cell cultures

Institute for Medico-Biological Problems, Ministry of Health of the USSR. Institute of Experimental Cardiology. All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Smol'yannikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 5, pp. 464–466, May, 1991.     

Changes in Granulocytic Hemopoietic Stem and Their Mechanisms during Hypoxia of Different Genesis

We studied reactions of the granulocytic hemopoietic stem during hypoxia of different genesis and severity. Stimulation of granulocytopoiesis was determined by an increase in functional activity of granulomonocytic precursors due to changes in feeder capacity of cells in the hemopoiesis-inducing microenvironment and colony-stimulating activity of the plasma. The development of encephalopathy caused by oxygen deficiency was accompanied by a decrease in the number of bone marrow granulomonocytic precursors due to reduction of proliferative activity (despite the increase in secretory activity of microenvironmental cells and increase in plasma colony-stimulating activity). Severe hypoxia accelerated maturation of hemopoietic cells and produced neutrophilic leukocytosis.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 3, pp. 254–258, March, 2005     

Myocardial ultrastructure of rats differing in resistance to hypoxia,after acute and periodic exposure to it

Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 8, pp. 148–151, August, 1991.     

Comparative analysis of cerebral cortical proteins of rate differing in sensitivity to hypoxia

Laboratory of Bioenergetics, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 12, pp. 657–660, December, 1992.     

Role of Cholinergic Structures in Individual Resistance of Rat Circulatory System to Posthemorrhagic Hypoxia

Experiments employing ultrasound technique showed that nonselective blockade of central muscarinic cholinoceptors with amizyl significantly increases the number and lifespan of rats highly resistant to acute massive blood loss. This pretreatment increased individual resistance of the circulatory system to posthemorrhagic hypoxia (blood pressure and portal blood flow rate). Preliminary blockade of central nicotinic cholinoceptors and peripheral muscarinic cholinoceptors with cyclodol and methacin, respectively, had no effect on the percentage of rats highly and low resistant to acute blood loss. Preliminary blockade of peripheral muscarinic cholinoceptors with methacin prevented the decrease in the cardiac output in low resistant animals during the posthemorrhagic period. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 8, pp. 142–145, August, 2005     

Effect of Transitory Ischemia on Liver Lysosomal Apparatus in Rats with Different Resistance to Hypoxia

We studied the state of lysosomal apparatus and pro- and antioxidant activity in the liver of rats with different resistance to hypoxia during postischemic recovery. Under normal conditions the lysosomal apparatus did not differ in highly and low resistant animals. During ischemia and reperfusion the damage to hepatic lysosomal membranes in rats highly resistant to hypoxia was less pronounced than in low resistant animals. These differences also concerned labilization of lysosomes during exposure to damaging factors (hypotonia and Triton X-100). The rats highly resistant to hypoxia differed from low resistant animals by higher stability of lysosomal membranes, lower prooxidant activity (malonic dialdehyde content), and higher tissue concentration of -tocopherol during reperfusion.     

Role of O2 in Regulation of Lactate Dynamics during Hypoxia: Mathematical Model and Analysis

The mechanistic basis of the relationship between O₂ and lactate concentration in muscle is not fully understood. Although hypoxia can cause lactate (LA) accumulation, it is possible for LA accumulation to occur without hypoxia. Nevertheless, during conditions of low O₂ availability, blood and tissue LA accumulation are used as indicators of hypoxia. To provide a framework for analyzing changes in energy metabolism and its regulation, we developed a mathematical model of human bioenergetics that links cellular metabolic processes to whole-body responses. Our model is based on dynamic mass balances and mechanistic kinetics in muscle, splanchnic and other body tissues for many substrates (glycogen, glucose, pyruvate, LA, O₂, CO₂, etc.) and control metabolites (e.g., ATP) through coupled reaction processes. Normal substrate concentrations in blood and tissues as well as model parameters are obtained directly or estimated indirectly from physiological observation in the literature. The model equations are solved numerically to simulate substrate concentration changes in tissues in response to disturbances. One key objective is to examine and quantify the mechanisms that control LA accumulation when O₂ availability to the muscle is lowered. Another objective is to quantify the contribution of different tissues to an observed increase in blood lactate concentration. Simulations of system responses to respiratory hypoxia were examined and compared to physiological observations. Model simulations show patterns of change for substrates and control metabolites that behave similarly to those found experimentally. From the simulations, it is evident that a large decrease can occur in muscle O₂ concentration, without affecting muscle respiration ( ) significantly. However, a small decrease in (1%–2%) can result in a large increase in LA production (50%–100%). The cellular rate of oxygen consumption, , which is coupled to ATP formation and NADH oxidation, can regulate other processes (e.g., glycolysis, pyruvate reduction) with high sensitivity through its effects on ADP/ATP and NADH/NAD. Thus, although LA metabolism does not depend directly on O₂ concentration, it is indirectly affected by , through changes in ADP/ATP, and NADH/NAD. Arterial LA concentration (C_a,LA) follows the pattern of change of muscle LA concentration (C_m,LA). Nevertheless, changes in C_a,LA, due to C_m,LA, are unlikely to be detected experimentally because changes in C_m,LA are small relative to the total LA concentrations in other tissues. © 1998 Biomedical Engineering Society. PAC98: 8710+e, 8722Fy     

Responses of Respiratory Neurons in the Medulla Oblongata to Stimulation of the Septal Nuclei during Hypoxia

Dynamic studies were performed in conditions of hypoxia on the effects of stimulation of the ventral, lateral, and medial nuclei of the septum on the spike activity of bulbar respiratory neurons and respiration. The various phases of hypoxia provided a model experiment over which the overall effects of the septal neurons were summed. Electrical stimulation of these septal nuclei in conditions of normal atmospheric pressure had both facilitatory and inhibitory effects on the spike activity of respiratory neurons in the respiratory center of the medulla oblongata, inhibitory effects being predominant. The ventral nucleus had the most effective inhibitory effect on the activity of respiratory neurons. Electrical stimulation of the septal nuclei in the initial phase (4000-5000 m) of hypoxia, on the background of activation, had a predominantly inhibitory influence on the activity of respiratory neurons. During the phase of severe hypoxia (7500-8000 m), on the background of marked hypoxic suppression of respiratory neuron activity, stimulation of the septal nuclei produced no characteristic changes in the activity of these neurons.