Biomedical subjects
Publications and source records attributed to V V Alabovskiĭ.
The concentration of mean molecule peptides is by far less in serum versus plasma. The concentration of mean molecule peptides in serum can go down, in endotoxicosis degrees 3-4, to normal values, whereas it can exceed 3-4-fold the normal value in plasma. The most pronounced reduction of peptides' concentration in serum was registered for the fraction with the molecular weight ranging from 800 to 3000 D.
The level of medium molecular peptides (MMP) grows up in blood plasma of patients with diabetes mellitus (DM), which results in endogenous intoxication. The MMP concentration is high in patients with insulin-independent DM at compensation and without renal affection versus insulin-dependent DM, which is explained by presence of 1-3 kDa peptides. An aggravated course of DM including subcompensation is associated with a higher MMP level in patients with both DM types. The onset of the initial stage of diabetic nephropathy brings about an essential decrease of all MMP fractions in both DM types.
A possibility of preventing the "calcium paradox" with the aid of adenosine was studied as well as some mechanisms of adenosine effect upon the heart in case of the "calcium paradox". Adenosine was found to suppress release of amino acids from the heart in perfusion with calcium-free medium, to efficiently prevent disorders in the energy-dependent functions of mitochondrion and myoglobin release from the heart in reperfusion with Ca2+ -containing solution. Adenosine was also found to increase 2-10-fold lactate release from the heart. Adenosine seems to be able to activate glycolysis. Iodine acetate was shown to completely suppress the adenosine ability to decrease amino acid release from the heart perfused with calcium-free medium. Under conditions of iodine acetate blocking of glycolysis was found to possess no protective properties against cytolysis in the "calcium paradox". The heart mitochondria isolated in the end of the experiment revealed low values of free or phosphorylating respiration and complete dissociation of oxidation. Also a protective effect of adenosine in inhibition of Na+, K+ -ATPhase with Strophantinum, was studied.
Perfusion of the rat isolated hearts with calcium-free and calcium containing solution revealed a complex and deep myocardial damage called the calcium paradox. The reperfusion of the rat heart with calcium rich media resulted in myoglobin loss from the heart, significant decreasing of ATP and phosphocreatine level, complete uncoupling of respiration and phosphorylation in mitochondria, occurrence of myocardial contracture. Decreasing of sodium level to 30 mM--80 mM in calcium free media exacerbates the heart damage due to the calcium paradox with absence of contracture. Addition of phosphocreatine (1 mM, 5 mM, 10 mM) evoked some restoration of ATP contents in the tissue with appearance of significant contracture. Phosphocreatine exacerbated the loss of myoglobin from the heart subjected to the calcium paradox. A discrepancy between myocardial contracture and degree of cellular damage has been observed during the calcium paradox.
It is well-known that the first stage of the calcium paradox involves decreasing of Na+ gradient. The decreased sodium gradient is a cause of activation of the Na(+)-Ca+ exchange and formation of cardiac injury during the calcium repletion. Potassium ions are natural extracellular activators of Na(+)-pump. It has been shown that heart perfusion by Ca(2+)-free medium evoked extrusion from cells of hydrophilic amino acids whose transport-depends on sodium gradient. The heart reperdusion with Ca(2+)-containing agent leads to myofibrillar contracture and extensive myoglobin release. The simultaneous events are: elevation in tissue water contents, decreasing of intracellular concentration of adeninnucleotides, uncoupling of oxidation and phosphorylation in mitochondria. The decreasing of K+ level to 0.5 mM exacerbates myocardial damage during the calcium paradox, despite absence of myocardial contracture. The elevation of K+ (to 10 mM or 20 mM) attenuated the calcium paradox development in the heart. The elevated K+ concentration protected isolated heart from extensive myoglobin release, development of myocardial contracture. The high K+ concentrations alleviate mitochondrial damage and elevate contents of adeninnucleotide in the tissue. The positive effect of the elevated K+ concentration can be completely blocked by strophanthine, the selective Na+, K(+)-pumb blocker.
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The findings reveal that the degree of myocardial damage in the "calcium paradox" does not depend on the contracture strength, that the contracture attenuation due to a decreased concentration in the Ca-free medium is not equal to the cardiocytes protection as compared with other means. Mg2+ and the studied means of myocardial protection seem to play a major role in assessment of the "calcium paradox" development and explain the difference in results of the hyposodium medium effects in the "calcium paradox".
The data obtained reveal that elevation of extracellular osmolarity with sucrose during reintroduction of Ca-containing medium after 10 minutes of Ca2+ removal prevents loss of haemoglobin in a concentration-dependent mode. Reducing the extracellular osmolarity of the reperfusion medium by means of decreasing the concentration of sodium chloride and calcium chloride exacerbates the loss of haemoglobin from the cardiomyocytes. There is a close correlation between the water contents in tissues and the loss of haemoglobin during the "calcium paradox". The findings suggest dependence of the heart damage during the "calcium paradox" on anionic composition of extracellular space and activity of anionic transporters.
Following a reduced pressure in the left ventricle, elevated concentrations of sodium ions enhanced by half the contraction force of the rat isolated heart. This effect was shown to be independent of the Na-channels blockers or Na/H exchange of caffeine but quite susceptible to sodium channel blockers, caffeine, and the blocking agent for Na-Ca exchange Ni2+. A decrease in potassium concentration amplified, and elevation of K+ level attenuated the positive inotropic effect of the elevated concentration of sodium ions. The effect was preserved even after heart arrest induced by verapamil. The findings suggest that elevated concentration of sodium ions may affect the Na+/Ca2+ exchange and provoke Ca2+ release from sarcoplasmic reticulum by means of changing the sodium gradient. These data corroborate the Leblanc and Hume hypothesis of the sodium-induced calcium ions release from sarcoplasmic reticulum.
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Isolated guinea pig heart were perfused with the Tyrode solution followed in 15 min. by a 10-min. Ca(2+)-free solution with subsequent return to the normal Ca(2+)-containing Tyrode solution. Sarcolemma damage was measured by myoglobin release. The perfusion resulted in damage of the myocardium cells. The data obtained show that elevation of the extracellular pressure during reperfusion with the Ca(2+)-containing medium is more important than the absolute value of the osmotic pressure.
The interrelationship between contracture development and heart damage during the calcium paradox under different sodium concentration in Ca-free media was studied on isolated rat hearts. It had been shown that calcium paradox development accompanied contracture development, intensive membrane disruption and alteration of tissue energy state. We had not found relation between contracture magnitude and degree of myocardial alterations in calcium paradox. Our dates confirm so-called intracellular hypothesis of calcium paradox. The experiments had shown close correlation between transmembrane sodium gradient in Ca-free media and degree of cellular damage and energy state alterations during calcium readmission in solution.
Calcium repletion (2.0 mM) after 10 min of calcium depletion (pCa = 7) resulted in the loss of myoglobin, decreased contents of ATP and adeninucleotides. Adenosine in concentration 50-1000 mcM depressed the release of myoglobin and prevented depletion of ATP and adenine nucleotides during the "calcium paradox". Theophylline, a non-selective A1-receptors blocker did not alter either "calcium paradox" development or protective effect of adenosine. Dipiridamole, an inhibitor of transmembrane transport of adenosine, protected hearts against the "calcium paradox" depending on the concentration. Dipiridamole (50 mcM) abolished protective effect of high concentrations (100-1000 mcM) of adenosine. The results obtained prove that transmembrane transport of adenosine is more important than its interaction with receptors for its protective effect under the "calcium paradox".
Nucleotides were examined for their effects on the development of calcium paradox in the isolated rat heart. The protective action of nucleotides was found to be unassociated with the structure of their nitrogen base. The products of extracellular hydrolysis, such as ribose (deoxyribose), uridine or adenosine at a concentration of 100 microM caused no less protective effects than nucleotides. In calcium paradox, the protective action of adenosine was not suppressed by theophylline, but sensitive to dipyridamole and transmembrane Na gradient values. Nucleotides and their hydrolytic products were demonstrated to exert a positive myocardial effect not only at the physiological (140 microM), but increased Na ion concentrations. The high extracellular Na concentration-induced potentiation of the protective action of nucleotides or their hydrolytic products was blocked by strophanthin. It is suggested that the high Na gradient can increase the protective action of nucleotides and their hydrolytic products due to decreased Na-Ca metabolism and to the altered metabolism of nucleotide hydrolytic products.
Perfusion of isolated rat hearts with a phosphocreatine (10(-4) M) containing solution to which strophanthin or KCl had been added up to a concentration of 27 mM as well as Ca2+ depletion decreased phosphocreatine concentration in the perfusate with a simultaneous increase in creatine and phosphocreatine concentrations in the myocardium. Neither high extracellular concentrations of Na+ (200 mM), nor phosphocreatine increased creatine and phosphocreatine levels in the myocardium. The effect of high sodium perfusion media was completely reversed by strophanthin. Phosphocreatine decreased the lactate content in the perfusate. Strophanthin or potassium chloride enhanced the effect of phosphocreatine on the lactate release. Conversely, creatine augmented the lactate content in the perfusate. A high specificity of the phosphocreatine effect on the myocardium independently of the ionic composition of the perfusate was postulated. A mechanism of protective effects of phosphocreatine and high sodium perfusion media on "calcium paradox" is proposed.
Increasing of extracellular sodium concentration up to 200 mM diminishes heart damage under "calcium paradox". Phosphocreatine (10(-4) M) potentiates the effect of high sodium perfusion media; in this case myoglobin release from the myocardium is minimal (5-9% of control). An the same time, ATP and phosphocreatine concentrations and oxidation to phosphorylation coupling in mitochondria remain at a sufficiently high level. Elevation of osmotic pressure by the effect of 120 mM sucrose enhances heart damage under "calcium paradox" both in the presence and absence of phosphocreatine. The protective effects of superhigh (200 mM) sodium concentrations and phosphocreatine are completely reversed by strophanthin or decreasing K+ concentration down to 0.5 mM.