Polymerised placenta haemoglobin attenuates cold ischaemia/reperfusion injury in isolated rat heart

Microvasc Res. 2011 Nov;82(3):430-8. doi: 10.1016/j.mvr.2011.08.010. Epub 2011 Aug 31.

Abstract

Ischaemia/reperfusion (I/R) injury is harmful to the cardiovascular system and is responsible for the inflammatory response, which, in turn, aggravates cardiac dysfunction. This study was designed to investigate the protective effect and potential mechanism of a haemoglobin-based oxygen carrier on cold I/R-injured hearts. Isolated Sprague-Dawley rat hearts were perfused in Langendorff mode. After a 30-min basal perfusion, rat hearts were arrested and hypothermically stored at 4°C for 12h followed by a 2-h reperfusion. Compared with histidine-tryptophan-ketoglutarate solution (HTKs), polymerised placenta haemoglobin (PolyPHb) in HTKs greatly improved heart contraction and decreased infarction size, necrosis, and apoptosis, which was related to reduced expression of TLR2, TLR4, TNF-α, and IL-1β, and NF-κB activation. Our results demonstrate the cardioprotective effect of PolyPHb on cold I/R-injured hearts and revealed that this protection was mediated in large part by attenuation of TLR2 and -4/NF-κB signalling pathway and could possibly down-regulate the inflammatory response.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cold Ischemia*
  • Female
  • Glucose / pharmacology
  • Hemoglobins / isolation & purification
  • Hemoglobins / metabolism
  • Hemoglobins / pharmacology*
  • Interleukin-1beta / genetics
  • Mannitol / pharmacology
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-kappa B / genetics
  • Necrosis
  • Organ Preservation Solutions / metabolism
  • Organ Preservation Solutions / pharmacology*
  • Oxidative Stress / drug effects
  • Oxygen / metabolism
  • Perfusion
  • Placenta / chemistry*
  • Potassium Chloride / pharmacology
  • Pregnancy
  • Procaine / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Time Factors
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Ventricular Function, Left / drug effects

Substances

  • Bretschneider cardioplegic solution
  • Hemoglobins
  • Interleukin-1beta
  • NF-kappa B
  • Organ Preservation Solutions
  • RNA, Messenger
  • Tlr2 protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Mannitol
  • Procaine
  • Potassium Chloride
  • Glucose
  • Oxygen