Cardioprotective effect of a hemoglobin-based oxygen carrier on cold ischemia/reperfusion injury

Cardiology. 2011;120(2):73-83. doi: 10.1159/000333106. Epub 2011 Dec 2.

Abstract

Objectives: 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.

MeSH terms

  • Animals
  • Blood Substitutes / pharmacology*
  • Cold Ischemia / methods*
  • Down-Regulation
  • Glucose / pharmacology
  • Hemoglobins / pharmacology*
  • Interleukin-6 / metabolism
  • Mannitol / pharmacology
  • Myocardial Infarction / prevention & control
  • Myocardial Reperfusion Injury / prevention & control*
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Potassium Chloride / pharmacology
  • Procaine / pharmacology
  • Pyridoxal Phosphate / analogs & derivatives*
  • Pyridoxal Phosphate / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Blood Substitutes
  • Bretschneider cardioplegic solution
  • Hemoglobins
  • Interleukin-6
  • NF-kappa B
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • polyhemoglobin-pyridoxal-5-phosphate
  • Mannitol
  • Procaine
  • Pyridoxal Phosphate
  • Potassium Chloride
  • Glucose