Effects of endotoxin on neutrophil-mediated I/R injury in isolated perfused rat hearts

Am J Physiol Heart Circ Physiol. 2001 Feb;280(2):H802-11. doi: 10.1152/ajpheart.2001.280.2.H802.


With the use of a syngeneic model, we demonstrate that rat polymorphonuclear neutrophils (PMNs) exacerbate ischemia-reperfusion injury in the isolated rat heart. However, PMNs (19 x 10(6) cells) from lipopolysaccharide (LPS)-treated rats (LPS-PMNs; 100 mg/kg administered 7 h before exsanguination) induce less reperfusion injury in the isolated heart. Average recovery of left ventricular developed pressure after 20 min of ischemia and 60 min of reperfusion was 51 +/- 4% in hearts receiving PMNs from saline-treated control rats (saline-PMNs) versus 78 +/- 2% in hearts receiving LPS-PMNs. Ischemic hearts reperfused with LPS-PMNs recovered to the same extent as did hearts reperfused with Krebs buffer only. LPS-PMNs and saline-PMNs showed no difference in basal or phorbol ester-induced superoxide production. Whereas twice the number of LPS-PMNs was positive for nitroblue tetrazolium, the percent positive for L-selectin, a receptor integral in PMN-adhesion to endothelium, was 50% less in LPS-PMNs than in controls. After reperfusion, three-fourths of the saline-PMNs remained within the hearts, whereas only one-fourth of LPS-PMNs were trapped. These data suggest that PMNs from LPS-treated rats do not exacerbate ischemia-reperfusion injury as do control PMNs, possibly, due to impaired PMN adhesion to endothelium as a result of decreased L-selectin receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / analysis
  • Animals
  • Carcinogens / pharmacology
  • Cell Adhesion / immunology
  • Diastole / drug effects
  • Diastole / immunology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology
  • In Vitro Techniques
  • L-Lactate Dehydrogenase / analysis
  • L-Selectin / analysis
  • Lipopolysaccharides / pharmacology*
  • Male
  • Malondialdehyde / analysis
  • Myocardial Reperfusion Injury / immunology*
  • Myocardium / enzymology
  • Neutrophils / chemistry
  • Neutrophils / drug effects
  • Neutrophils / immunology*
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Systole / drug effects
  • Systole / immunology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Ventricular Function, Left / drug effects*
  • Ventricular Function, Left / immunology*
  • Ventricular Pressure / drug effects
  • Ventricular Pressure / immunology


  • Carcinogens
  • Lipopolysaccharides
  • L-Selectin
  • Malondialdehyde
  • Adenosine Triphosphate
  • L-Lactate Dehydrogenase
  • Tetradecanoylphorbol Acetate