Protective effects of adenosine in the perfused rat heart: changes in metabolism and intracellular ion homeostasis.
Increased concentrations of intracellular H+, Na+, and Ca2+ have been observed during ischemia, and these ionic alterations have been correlated with several indexes of cell injury in a number of studies. Recently, adenosine was proposed to play a role in ischemic preconditioning, since adenosine antagonists block the protective effects of these brief intermittent periods of ischemia and reflow. In this study we evaluated the protective effects of adenosine (20 microM) on high-energy phosphate metabolism, H+ and Ca2+ accumulation, and glycolytic rate during 30 min of no-flow ischemia. Adenosine was observed to slow the onset of contracture (7.0 +/- 0.9 min) and to improve left ventricular developed pressure (62 +/- 7% of initial) during reperfusion compared with untreated hearts (5.0 +/- 0.6 min and 18 +/- 5%, respectively). Intracellular Ca accumulation at the end of 30 min of ischemia was higher in the untreated (2,835 +/- 465 nM) than in the adenosine-treated (2,064 +/- 533 nM) hearts, while intracellular pH fell more in the untreated (5.85 +/- 0.17) than in the adenosine-treated hearts (6.27 +/- 0.16). Glycolytic rate and the rate of ATP decline were significantly attenuated in the adenosine-treated hearts during ischemia. Thus adenosine treatment slowed the rate of metabolism and delayed the accumulation of H+ and Ca2+ during ischemia, resulting in better recovery of function upon reflow.
Fralix
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Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Murphy
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London
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Steenbergen
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D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D010710:Phosphates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium