Kupffer cell activation after no-flow ischemia versus hemorrhagic shock.
Kupffer cell-derived oxidant stress is critical for reperfusion injury after no-flow ischemia. However, the importance of Kupffer cells as source of reactive oxygen formation is unclear in a hemorrhagic shock model. Therefore, we evaluated Kupffer cell activation after 60 or 120 min of hemorrhage and 90 min of resuscitation (HS/RS) in pentobarbital-anesthetized male Fischer rats. Plasma glutathione disulfide (GSSG) as indicator for a vascular oxidant stress showed no significant changes after HS/RS. Plasma ALT activities were only moderately increased (100-200 U/L). Kupffer cells isolated from postischemic livers did not generate more superoxide than cells from sham controls. In contrast, the 10-fold increase of plasma GSSG and the 9-fold higher spontaneous superoxide formation of Kupffer cells after 60 min of hepatic no-flow ischemia followed by 90 min of reperfusion demonstrated the activation of Kupffer cells in this experimental model. Plasma ALT activities (1930 +/- 240 U/L) indicated severe liver injury. These results demonstrate a fundamental difference in the degree of Kupffer cell activation between the two models of warm hepatic ischemia. Our findings suggest that different therapeutic strategies are necessary to ameliorate the initial injury after low flow ischemia (hemorrhage) compared to cold (transplantation) or warm (Pringle maneuver) no-flow ischemia.
Jaeschke
Hartmut
H
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA. jaeschkehartmutw@uams.edu
Farhood
Anwar
A
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D002273:Carcinogens / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D004731:Endotoxins; D017382:Reactive Oxygen Species; D000410:Alanine Transaminase; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate