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Am J Physiol Heart Circ Physiol 274: H786-H793, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 3, H786-H793, March 1998

Hypothermia preserves function and signaling for mitochondrial biogenesis during subsequent ischemia

Xue-Han Ning, Cheng-Su Xu, Ying C. Song, Yun Xiao, Ying-Jia Hu, Flavian Mark Lupinetti, and Michael A. Portman

Cardiology Division, Department of Pediatrics and Cardiovascular Surgery Division, Department of Surgery, University of Washington, Seattle 98195; and Children's Hospital and Regional Medical Center, Seattle, Washington 98105

Hypothermia is known to protect myocardium during ischemia, but its role in induction of a protective stress response before ischemia has not been evaluated. As cold incites stress responses in other tissues, including heat shock protein induction and signaling mitochondrial biogenesis, we postulated that hypothermia in perfused hearts would produce similar phenomena while reducing injury during subsequent ischemia. Studies were performed in isolated perfused rabbit hearts (n = 77): a control group (C) and a hypothermic group (H) subjected to decreasing infusate temperature from 37 to 31°C over 20 min. Subsequent ischemia during cardioplegic arrest at 34°C for 120 min was followed by reperfusion. At 15 min of reperfusion, recovery of left ventricular developed pressure (LVDP), maximum first derivative of left ventricular pressure (LV dP/dtmax), LV -dP/dtmax, and the product of heart rate and LVDP was significantly increased in H (P < 0.01) compared with C hearts. Ischemic contracture started later in H (97.5 ± 3.6 min) than in C (67.3 ± 3.3 min) hearts. Myocardial ATP preservation and repletion during ischemia and reperfusion were higher in H than in C hearts. mRNA levels of the nuclear-encoded mitochondrial proteins adenine nucleotide translocase isoform 1 (ANT1) and beta -F1-adenosinetriphosphatase (beta -F1-ATPase) normalized to 28S RNA decreased in C hearts but were preserved in H hearts after reperfusion. Inducible heat shock protein (HSP70-1) mRNA was elevated nearly 4-fold after ischemia in C hearts and 12-fold in H hearts. These data indicate that hypothermia preserves myocardial function and ATP stores during subsequent ischemia and reperfusion. Signaling for mitochondrial biogenesis indexed by ANT1 and beta -F1-ATPase mRNA levels is also preserved during a marked increase in HSP70-1 mRNA.

adenine nucleotide translocase isoform 1; beta -F1-adenosinetriphosphatase; cold adaptation; inducible heat shock protein; myocardial reperfusion


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