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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/H2119    most recent 00123.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ning, X.-H. Articles by Portman, M. A. Search for Related Content PubMed PubMed Citation Articles by Ning, X.-H. Articles by Portman, M. A.

Moderate hypothermia (30°C) maintains myocardial integrity and modifies response of cell survival proteins after reperfusion

Divisions of ¹Cardiology and ²Genetics and Development, Department of Pediatrics, and ³Department of Pathology, University of Washington, and ⁴Children's Hospital and Regional Medical Center, Seattle, Washington

Submitted 30 January 2007 ; accepted in final form 23 July 2007

Hypothermia preserves myocardial function, promotes signaling for cell survival, and inhibits apoptotic pathways during 45-min reperfusion. We tested the hypothesis that signaling at the transcriptional level is followed by corresponding proteomic response and maintenance of structural integrity after 3-h reperfusion. Isolated hearts were Langendorff perfused and exposed to mild (I group; n = 6, 34°C) or moderate (H group; n = 6, 30°C) hypothermia during 120-min total ischemia with cardioplegic arrest and 180-min 37°C reperfusion. Moderate hypothermia suppressed anaerobic metabolism during ischemia and significantly diminished left ventricular end-diastolic pressure at the end of ischemia from 52.7 ± 3.3 (I group) to 1.8 ± 0.9 (H group) mmHg. Unlike the I group, which showed poor cardiac function and high left ventricular pressure, the H group showed preservation of myocardial function, coronary flow, and oxygen consumption. Compared with normal control hearts without ischemia (n = 5), histological staining in the I group showed marked disarray and fragmentation of collagen network (score 4–5), while the H group showed preserved collagen integrity (score 0–1). The apoptosis-linked tumor suppressor protein p53 was expressed throughout the I group only (score 4–5). The H group produced elevated expression for hypoxia-inducible factor 1 and heme oxygenase 1, but minimally affected vascular endothelial growth factor expression. The H group also elevated expression for survival proteins peroxisomal proliferator-activated receptor- and Akt-1. These results show in a constant left ventricular volume model that moderate hypothermia (30°C) decreases myocardial energy utilization during ischemia and subsequently promotes expression of proteins involved in cell survival, while inhibiting induction of p53 protein. These data also show that 34°C proffers less protection and loss of myocardial integrity.

Akt-1; collagen; heme oxygenase 1; hypoxia-inducible factor 1; p53; succinate dehydrogenase