[Molecular mechanisms of hypoxia and adaptation to it. Part II]. / Molekulyarnye mekhanizmy razvitiya gipoksii i adaptatsii k nei. Chast' II.

Reprogramming of the mitochondrial electron transport chain (ETC) is the most important physiological mechanism that provides short- and long-term adaptation to hypoxia. The possibilities of additional pharmacological regulation of ETC activity are of considerable practical interest in correcting hypoxia-associated disorders. This review considers the main groups of antihypoxic compounds that exhibit their effect at the interface of ETC and the cycle of tricarboxylic acids, including succinate-containing and succinate-forming antihypoxants. The role of succinate during adaptation to hypoxia, the biological activity of the succinate, and its potentially adverse effects are currently not fully understood and require further clarification.

[Molecular mechanisms for hypoxia development and adaptation to it. Part I]. / Molekulyarnye mekhanizmy razvitiya gipoksii i adaptatsii k nei. Chast' I.

Hypoxia is a typical pathological process characterized by the occurrence of oxygen deficiency in tissues and cells and accompanied by the development of immediate and delayed compensatory and adaptive reactions. Reprogramming of the mitochondrial electron transport chain (ETC) function is one the most essential regulatory mechanisms that allow for immediate adaptation to hypoxia. Succinic acid, or succinate, is involved in this process not only as one of the intermediates of the tricarboxylic acid (TAC) cycle, but also as a signaling molecule. In this connection, the purpose of this review was to systematize the available data on the molecular mechanisms for the development of hypoxia and its adaptation at the ETC/TAC coupling site, as well as on the role of succinic acid in these processes.

[The effect of uridine and uridine nucleotides on isolated rat heart performance in regional myocardial ischemia]. / Vliianie uridina i uridinovykh nukleotidov na raboty izolirovannogo serdtsa krys pri regionarnoi ischemii.

We studied the effects of uridine, uridine-5'-monophosphate (UMP), uridine-5'-diphosphate (UDP) and uridine-5'-triphosphate on contractility, coronary flow and heart rate in isolated perfused rat hearts under 60-minute regional ischemia of the left ventricle. All the compounds (50 mumol/l) induced a positive inotropic effect but had no effect on the heart rate. Uridine and UMP prevented the development of the contracture. UDP and especially UTP increased coronary flow. Probably, a protective effect of uridine and UMP is due to activation of myocardial glycogen synthesis while favourable effects of UDP and UTP on contractility and coronary flow are explained by their influence on P2U-receptors of cardiomyocytes. In addition, coronary dilatation induced by UDP and UTP promoted the reduction of the damaged zone.

[The role of the muscarinic, adenosine and adrenoreceptors of the heart in the development of postischemic reperfusion ventricular fibrillation]. / Rol' muskarinovykh, adenozinovykh i adrenoretseptorov serdtsa v razvitii postishemicheskoi reperfuzionnoi fibrilliatsii zheludochkov.

The authors studied the effect of m-cholino-, adreno-, and purinotropic agents on the development of postischemic reperfusion fibrillation of isolated rat hearts. Pilocarpine, norepinephrine, phenylephrine, and adenosine caused a proarrhythmogenic effect. Atropine, trimedoxim, prazosin, and chloroquine made fibrillation less expressed. A direct correlation was found between the arrhythmogenic effect of reperfusion and the size of the no-reflow zone, with the use of the drugs too. It is concluded that the phospholipid mechanism contributes to realization of the arrhythmogenic effect of reperfusion and vascular disorders, leading to the occurrence of the no-reflow phenomenon.

[Effect of purine nucleosides on the contractile function of the rat heart in ischemia and reperfusion]. / Vliianie purinovykh nukleotidov na sokratitel'nuiu funktsiiu serdtsa krys pri ishemii i reperfuzii.

The Langendorf isolated rat hearts underwent 30-minute total ischemia followed by 60-minute reperfusion. Adenosine, inosine or guanosine was added at a concentration of 50 mumol/l into the perfusate in the first 30 minutes. The nucleotides significantly increased the developed pressure and the maximum left ventricular contractility rate. The most effective agent was adenosine which also made blood flow higher. Guanosine was more effective than adenosine and inosine in protecting the heart from ischemic contracture. At the same time adenosine augmented the arrhythmogenic effect of reperfusion, by significantly elevating the cardiac levels of diene conjugates and malonic dialdehyde. It is suggested that the arrhythmogenic effect of adenosine is the result of activated lipid peroxidation due to adenosine exchange via the xanthine reaction during nucleotide-induced vasodilation.

[The effect of adenosine on the contractile function of the heart during experimental ischemia and reperfusion]. / Deistvie adenozina na sokratitelnuiu funktsiiu serdtsa pri éksperimentalnoi ishemii i reperfuzii.

It has been shown that 30 min ischemia followed by 30 min reperfusion inhibits cardiac contractility. The addition of adenosine at a concentration of 50 or 100 mumol/l into the perfusate normalized a decreased cardiac contractility and prevented the onset of contracture.

[Hemodynamic effects of purine nucleosides in regional ischemia and reperfusion]. / Gemodinamicheskie éffecty purinovykh nukleozidov pri regionarnoi ishemii i reperfuzii.

The rat hearts were subjected to 60-min ischemia by left coronary artery ligation followed by 60-min reperfusion, involving intravenous adenosine inosine or guanosine given in a dose of 1 mg/kg.min-1 in the first 30 minutes of reperfusion. Ischemia and subsequent reperfusion caused a progressive decrease in cardiac output and coronary blood flow. Adenosine was found to enhance coronary blood flow and increase cardiac and stroke outputs. Inosine produced nearly the same, but less pronounced effect. Guanosine increased cardiac output without changing coronary blood flow.