Despite maintenance of systemic and regional perfusion, endotoxemia following complement depletion produces hepatocellular dysfunction.
Experimental endotoxemia causes hypotension and a reduction in regional blood flow, including hepatic blood flow. Complement depletion prior to endotoxemia is known to attenuate these perfusion deficits. We depleted complement with cobra venom factor prior to the administration of Escherichia coli lipopolysaccharide in Sprague-Dawley rats and studied the effects of this treatment on systemic hemodynamics, regional hepatic perfusion, and hepatocellular integrity. Complement-depleted endotoxemic rats were compared with untreated rats, rats with complement depletion alone, and rats with endotoxemia alone. Systemic hemodynamics (cardiac index, mean arterial pressure), regional hepatic perfusion (effective hepatic blood flow), and hepatocellular integrity (adenosine triphosphate [ATP], lipid peroxidation) were determined 4-6 hr after the onset of endotoxemia. The endotoxemic animals exhibited a significant decrease in systemic hemodynamic performance and regional perfusion. Complement depletion prior to endotoxemia resulted in preservation of normal systemic and hepatic perfusion. ATP and lipid peroxide levels were significantly abnormal in both groups of endotoxemic animals. Complement depletion alone did not significantly affect any of the variables studied. The maintenance of systemic and regional perfusion during endotoxemia was not cytoprotective implicating direct cellular injury independent of perfusion deficits in the pathogenesis of hepatic failure during endotoxemia.
Pelias
M E
ME
Department of Surgery, Ohio State University, Columbus 43210-1228.
Townsend
M C
MC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001775:Blood Circulation; D003165:Complement System Proteins / Q000172:deficiency*; D004731:Endotoxins / Q000097:blood*; D005260:Female; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D008054:Lipid Peroxides; D000255:Adenosine Triphosphate; D003165:Complement System Proteins