Effects of endotoxin on neutrophil-mediated I/R injury in isolated perfused rat hearts.
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.
Lipton
B P
BP
Department of Physiology and Cell Biology, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA.
Bautista
A P
AP
Delcarpio
J B
JB
McDonough
K H
KH
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion / Q000276:immunology; D003971:Diastole / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D019041:L-Selectin / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D015428:Myocardial Reperfusion Injury / Q000276:immunology*; D009206:Myocardium / Q000201:enzymology; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000276:immunology*; D017725:Ventricular Pressure / Q000187:drug effects / Q000276:immunology
D002273:Carcinogens; D008070:Lipopolysaccharides; D019041:L-Selectin; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D013755:Tetradecanoylphorbol Acetate