ABSTRACT
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.
Subject(s)
Adenosine/pharmacology , Calcium/physiology , Heart/drug effects , Myocardial Reperfusion Injury/prevention & control , Protective Agents/pharmacology , Animals , Calcium/pharmacology , Glycolysis/drug effects , Heart/physiology , In Vitro Techniques , Mitochondria/metabolism , Myocardial Reperfusion , Myoglobin/metabolism , Rats , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Sodium-Potassium-Exchanging ATPase/physiology , Strophanthins/pharmacologyABSTRACT
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.
Subject(s)
Calcium/pharmacology , Myocardial Contraction/drug effects , Myocardium/metabolism , Potassium/metabolism , Adenine Nucleotides/metabolism , Animals , Creatine/metabolism , Extracellular Space/metabolism , In Vitro Techniques , Intracellular Fluid/metabolism , Myocardial Reperfusion , Myocardium/pathology , Myoglobin/metabolism , Osmotic Pressure , Phosphocreatine/metabolism , Potassium/pharmacology , Rats , Rats, Wistar , Sodium/metabolism , Sodium-Potassium-Exchanging ATPase/metabolismABSTRACT
The anti-ischemic properties of thymogen were studied on an isolated heart model. Its cardioprotective effect was higher than that of dalargin and verapamil. The mechanism of the thymogen anti-ischemic action is realized without the participation of the opiate receptors and blockade of calcium entrance into the cardiomyocytes.
