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

Autor: Ying Tzang Tien, Shi Han Chen, Xue Han Ning, Cheng Su Xu, Ming Ge, Michael A. Portman, Norman E. Buroker, Emil Y. Chi, Outi M. Hyyti
Rok vydání: 2007
Předmět:
Vascular Endothelial Growth Factor A
Time Factors
Transcription
Genetic
Cell Survival
Physiology
Myocardial Ischemia
Myocardial Reperfusion Injury
In Vitro Techniques
Biology
Ventricular Function
Left
Coronary circulation
Oxygen Consumption
Hypothermia
Induced
Coronary Circulation
Physiology (medical)
Ventricular Pressure
medicine
Animals
RNA
Messenger
PPAR-beta
chemistry.chemical_classification
Myocardium
Intracellular Signaling Peptides and Proteins
Hypothermia
Hypoxia (medical)
Hypoxia-Inducible Factor 1
alpha Subunit
Myocardial Contraction
Cell biology
Disease Models
Animal
medicine.anatomical_structure
Enzyme
chemistry
Biochemistry
Apoptosis
Circulatory system
Ventricular pressure
Collagen
Rabbits
Tumor Suppressor Protein p53
medicine.symptom
Cardiology and Cardiovascular Medicine
Glycoprotein
Proto-Oncogene Proteins c-akt
Heme Oxygenase-1
Signal Transduction
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 293:H2119-H2128
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.00123.2007
Popis: 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 degrees C) or moderate (H group; n = 6, 30 degrees C) hypothermia during 120-min total ischemia with cardioplegic arrest and 180-min 37 degrees 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 1alpha 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-beta and Akt-1. These results show in a constant left ventricular volume model that moderate hypothermia (30 degrees 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 degrees C proffers less protection and loss of myocardial integrity.
Databáze: OpenAIRE
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