title: Cardioprotective effect of a hemoglobin-based oxygen carrier on cold ischemia/reperfusion injury.
abstract: OBJECTIVE
  The etiology of myocardial ischemia/reperfusion (I/R) injury is multifactorial, but activation of the innate immune system and the resulting inflammatory response are important components of I/R injury. The aim of this study was to investigate the protective effect of a hemoglobin-based oxygen carrier (HBOC) on cold I/R heart and to explore the underlying mechanisms.
  
  
  METHODS
  Isolated Sprague-Dawley rat hearts were perfused in the Langendorff mode. After 30 min of basal perfusion, rat hearts were arrested with histidine-tryptophan-ketoglutarate solution (HTKs) with or without an HBOC and hypothermically stored (4°C) for 9 or 14 h, followed by 2 h of reperfusion.
  
  
  RESULTS
  Compared with HTKs alone, the HBOC in HTKs greatly improved heart contraction and decreased infarct size, necrosis and apoptosis, which was related to the reduced expression of Toll-like receptor 2 (TLR 2), TLR 4, TNF-α, IL-1β and nuclear factor-κB (NF-κB) activation.
  
  
  CONCLUSIONS
  Our results demonstrated that the HBOC protected isolated rat heart from cold I/R injury and this protection was associated with attenuation of the expression of the TLR 2 and TLR 4/NF-κB signaling pathway, which may down-regulate the inflammatory response.
authors.affiliation: Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Ruo-Bin
authors.initials: RB
authors.lastname: Wu
authors.forename: Cheng-Min
authors.initials: CM
authors.lastname: Yang
authors.forename: Shao-Yi
authors.initials: SY
authors.lastname: Zheng
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D050377:Cold Ischemia / Q000379:methods*; D015536:Down-Regulation; D005947:Glucose / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001802:Blood Substitutes; C039984:Bretschneider cardioplegic solution; D006454:Hemoglobins; D015850:Interleukin-6; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C030939:polyhemoglobin-pyridoxal-5-phosphate; D008353:Mannitol; D011343:Procaine; D011732:Pyridoxal Phosphate; D011189:Potassium Chloride; D005947:Glucose