Mitochondrial protein and HSP70 signaling after ischemia in hypothermic-adapted hearts augmented with glucose.
Hypothermia improves resistance to subsequent ischemia in the cardioplegic-arrested heart (CAH). This adaptive process produces mRNA elevation for heat shock protein (HSP) 70-1 and mitochondrial proteins, adenine nucleotide translocator (ANT(1)), and beta-F(1)-ATPase. Glucose in cardioplegia also enhances myocardial protection. These processes might be linked to reduced ATP depletion. To assess for synergism between these protective processes, isolated rabbit hearts (n = 91) were perfused at 37 degrees C and exposed to ischemic cardioplegic arrest for 2 h. Hearts were in four groups: control (C), hypothermia adapted (H) perfused to 31 degrees C 20 min before ischemia, 22 mM glucose (G) in cardioplegia, and hypothermic adaptation and glucose (HG). Developed pressure (DP), dP/dt(max), and pressure-rate product (PRP) improved (P < 0.05) in G, H, and HG compared with C during reperfusion. DP and PRP were elevated in HG over H and G. ATP was higher in G, H, and HG, although no additional increase in HG over H was found. Lactate and CO(2) production were elevated in G only. The mRNA expression for HSP70-1, ANT(1), and beta-F(1)-ATPase was elevated severalfold in H and HG, but not G over C during reperfusion. In conclusion, glucose provides additional functional improvement in H. Additionally, neither ATP levels nor anaerobic metabolism are linked to mRNA expression for HSP70, ANT(1), or beta-F(1)-ATPase in CAH.
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Cardiology Division, Department of Pediatrics, University of Washington, Seattle 98195, USA.
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Portman
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D000251:Adenosine Triphosphatases / Q000096:biosynthesis; D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D007035:Hypothermia; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000096:biosynthesis; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D011817:Rabbits
D018840:HSP70 Heat-Shock Proteins; D000226:Mitochondrial ADP, ATP Translocases; D000251:Adenosine Triphosphatases; D005947:Glucose