[Relation between the energy state of the myocardium and the release of products of anaerobic metabolism]. / [Sviaz' mezhdu énergeticheskim sostoianiem miokarda i vykhodom iz nego produktov anaérobnogo obmena.

The relationships between cellular energy parameters and succinate, alanine and creatine release from isolated guinea pig hearts were studied during a 50 min perfusion (0.2 ml/min) with 5.5 mM glucose or 5 mM sodium acetate. Compared to glucose-perfused hearts, a more rapid ATP depletion accompanied by an increased succinate and creatine release was observed during underperfusion with acetate. The succinate and alanine accumulation in the myocardial effluent was related to a decrease in tissue ATP; the creatine release showed a close inverse correlation with the tissue phosphocreatine/creatine ratio. Hyperbolic and linear relationships were found between these indices for glucose- and acetate-perfused hearts, respectively. The logarithm of tissue ATP had negative linear correlations with the perfusate succinate/creatine ratio for the both substrates. The experimental results suggest that succinate, creatine and alanine assays in the myocardial effluent may be used for the assessment of the energy state of ischemic heart.

[Formation of products of anaerobic metabolism in the ischemic myocardium]. / Obrazovanie produktov anaérobnogo obmena v ishemicheskom miokarde.

The effect of ischemia on the formation of products of anaerobic metabolism and their release into the cardiac effluent in isolated perfused guinea pig hearts was studied. During 30 min normothermal ischemia, the myocardial ATP and phosphocreatine levels decreased to 34% and 15% of the initial values, respectively. The net alanine formation in ischemia was approximately a stoichiometric glutamate decrease; the increase in the tissue malate content corresponded to the aspartate----oxaloacetate----malate anaplerotic flux, the succinate production being commensurable to alpha-ketoglutaric acid formation in the alanine aminotransferase reaction. Using 1H-NMR, it was shown that the release of trace amounts of lactate, alanine, succinate, creatine and pyruvate into cardiac effluents occurred during the first 5 minutes of reperfusion. The rate of metabolite release decreased in the following order: lactate much greater than alanine greater than succinate greater than creatine. By the 30th minute of reperfusion, the decrease in the tissue levels of these metabolites to preischemic values was accompanied by the recovery of ATP and phosphocreatine to 65% and 90% of the initial levels, respectively. The data obtained suggest that the formation and release of alanine, creatine or succinate as well as lactate from ischemic myocardium may testify to significant disturbances in energy metabolism of the myocardium.

[Mechanisms for improving the energy metabolism and function of the hypoxic myocardium with amino acids]. / Mekhanizmy uluchsheniia énergeticheskogo obmena i funktsii gipoksicheskogo miokarda aminokislotami.

The relationship between metabolism of the main myocardial amino acids, glutamate, aspartate and alanine, and energy state of hypoxic myocardium, was studied. Depression of cardiac contractile function during asphyxia in rats was accompanied by a decrease in glutamate mitochondrial and tissue contents and an increase in the tissue alanine and mitochondrial aspartate. The reduction of mitochondrial glutamate in asphyxia was related to losses of intramitochondrial ATP and state 3 respiration with glutamate and malate. Using NMR technique, exogenous glutamate and oxaloacetate were shown to increase succinate formation coupled with ATP and CTP production in the rat heart mitochondria in absence of aeration. These data suggest that glutamate and products of its transamination decrease the contraction of hypoxic myocardium stimulating anaerobic energy formation in the tricarboxylic acid cycle.

[The NMR study of succinate formation from exogenous precursors in anaerobic rat heart mitochondria]. / Izuchenie metodom IaMR obrazovaniia suktsinata iz ékzogennykh predshestvennikov v neaériruemykh mitokhondriiakh serdtsa krysy.

Succinate formation during incubation of isolated rat heart mitochondria with exogenous precursors, malate, alpha-ketoglutarate, oxaloacetate and L-glutamate was studied in the absence of aeration. The formation of succinate, the end product of the tricarboxylic acid cycle, occurs via two pathways: through reduction of oxaloacetate or malate and via oxiation of alpha-ketoglutarate. The highest rate of succinate synthesis was observed when mitochondria were incubated with a mixture of 5 mM L-glutamate and 10 mM oxaloacetate, i.e., when both routes were used simultaneously. The [U-13C]succinate/succinate and aspartate/succinate ratios were equal to 2, when mitochondria were incubated with 5 mM [U-13C]glutamate and 10 mM oxaloacetate. Therefore, the amount of succinate formed from [13C]alpha-ketoglutarate via transamination of [13C]glutamate with oxaloacetate exceeds twice succinate production from oxialoacetate. These data suggest that GTP formation in the succinic thiokinase reaction should exceed twice the ATP yield coupled with NADH-dependent reduction of fumarate.

A 1H NMR study of succinate synthesis from exogenous precursors in oxygen-deprived rat heart mitochondria.

Succinate synthesis from exogenous malate, alpha-ketoglutarate, oxaloacetate and L-glutamate in isolated oxygen-deprived rat heart mitochondria was studied using 1H NMR. The highest rate of succinate synthesis was observed during incubation of mitochondria with a mixture of L-glutamate and oxaloacetate. When mitochondria were incubated with [U-13C] glutamate and oxaloacetate the [U-13C] succinate/succinate and aspartate/succinate ratios were equal to 2. This suggests that the succinate produced from [U-13C] alpha-keto-glutarate formed via transamination of [U-13C] glutamate with oxaloacetate by aspartate aminotransferase exceeds twofold that synthesized via oxaloacetate reduction. It may thus be expected that GTP yield in a reaction catalyzed by the succinic thiokinase will be 2 times higher that of ATP production coupled with NADH-dependent fumarate reduction.