Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium.
Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each) cardioplegia ameliorated cytosolic calcium ([Ca2+]i) accumulation and was associated with enhanced functional recovery after surgically induced global ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic cytochrome oxidase I activity and mRNA levels, suggesting that enhanced functional recovery may involve the preservation of high-energy phosphates. To investigate this hypothesis, 31P nuclear magnetic resonance was used to measure serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH (pHi) in Langendorff-perfused, aged (135 wk) rabbit hearts during preischemia, global ischemia (30 min), and reperfusion (30 min). K-Mg cardioplegia retarded PCr depletion (P < 0.05) and significantly enhanced NTP preservation (P < 0.05) during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase in Mgf during ischemia (P < 0.05). These results were correlated with amelioration of [Ca2+]i accumulation during ischemia and preservation of left ventricular function after reperfusion and suggest that optimal functional recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the aged myocardium.
Tsukube
T
T
Division of Cardiothoracic Surgery, New England Deaconess Hospital, Boston, Massachusetts, USA.
McCully
J D
JD
Metz
K R
KR
Cook
C U
CU
Levitsky
S
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002314:Cardioplegic Solutions / Q000627:therapeutic use; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism; D006321:Heart / Q000254:growth & development* / Q000502:physiology / Q000503:physiopathology; D006324:Heart Arrest, Induced; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000378:metabolism / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism*; D011188:Potassium / Q000627:therapeutic use; D011817:Rabbits; D012265:Ribonucleotides / Q000378:metabolism*
D002314:Cardioplegic Solutions; D010710:Phosphates; D012265:Ribonucleotides; D010725:Phosphocreatine; D008274:Magnesium; D011188:Potassium; D002118:Calcium