The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: a 31P, 23Na and 87Rb NMR spectroscopic study.
An increase in intracellular Na+ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na+/K+ ATPase activity contributes to this increase and whether Na+/K+ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used 31P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. 23Na NMR spectroscopy, with DyTTHA3- present as a shift reagent, was used to measure changes in intracellular Na+ and 87Rb NMR spectroscopy was used to estimate Na+/K+ ATPase activity from Rb+ influx rates, Rb+ being an NMR-sensitive congener of K+. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb+ influx rate was threefold higher, intracellular Na+ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na+/K+ ATPase activity to prevent the increase in intracellular Na+ that would otherwise have led to myocardial injury.
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Department of Biochemistry, University of Oxford, United Kingdom.
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Clarke
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D000818:Animals; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010758:Phosphorus / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012413:Rubidium / Q000378:metabolism*; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D007773:Lactates; D012414:Rubidium Radioisotopes; D010758:Phosphorus; D019344:Lactic Acid; D006003:Glycogen; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D012413:Rubidium