Mitochondrial protein and HSP70 signaling after ischemia in hypothermic-adapted hearts augmented with glucose

Abstract

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 (ANT1), and β-F1-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°C and exposed to ischemic cardioplegic arrest for 2 h. Hearts were in four groups: control (C), hypothermia adapted (H) perfused to 31°C 20 min before ischemia, 22 mM glucose (G) in cardioplegia, and hypothermic adaptation and glucose (HG). Developed pressure (DP), dP/d tmax, 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 CO2production were elevated in G only. The mRNA expression for HSP70–1, ANT1, and β-F1-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, ANT1, or β-F1-ATPase in CAH.