Neutrophil activation, tumor necrosis factor, and survival after endotoxic and hemorrhagic shock.
Polymorphonuclear neutrophils (PMNs) may contribute to organ injury in both hemorrhagic and endotoxic shock. Both models of shock exhibit a "flight of the leukocytes," but the mechanisms for entrapment of leukocytes in the microcirculation differ. The objective of this study was to investigate lipopolysaccharide (LPS)-induced shock and hemorrhagic shock with similar survival rates, in terms of circulating PMNs, activated circulating PMNs, plasma tumor necrosis factor (TNF) activity, and PMN adhesion. In the LPS protocol, rats received 6.5 mg/kg E. coli LPS i.v., which resulted in 50% survival. In the hemorrhagic shock protocol, rats were maintained for 3 h at 40 mm Hg mean arterial pressure, and survival during a 24-h observation period was 40%. LPS injection and hemorrhage caused rapid neutropenia in survivors and nonsurvivors. Low circulating PMN counts persisted during hypotension in the hemorrhagic protocol and among nonsurvivors in the LPS protocol, but in both protocols a tendency toward significantly higher circulating PMN counts in survivors compared with nonsurvivors was found. In both protocols, survivors had significantly lower fractions of circulating activated PMNs and lower adhesion of circulating PMNs to nylon fibers. In the LPS protocol, higher plasma TNF activity was found in nonsurvivors than in survivors, but no TNF activity in plasma could be found throughout the hemorrhagic protocol. These results indicate that nonsurvivors in both shock models exhibit higher levels of PMN activation. No correlation was detected between PMN activation and plasma TNF activity to suggest that TNF serves as the primary mediator of circulating PMN activation.
Barroso-Aranda
J
J
Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093-0412, USA.
Zweifach
B W
BW
Mathison
J C
JC
Schmid-Schönbein
G W
GW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006400:Hematocrit; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D018375:Neutrophil Activation / Q000502:physiology*; D009580:Nitroblue Tetrazolium; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000503:physiopathology*; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology*; D013534:Survival; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009580:Nitroblue Tetrazolium