Protection of dogs from lethal consequences of endotoxemia with plasma or leukocyte transfusions

The contribution of cellular and humoral factors of normal blood to resistance to endotoxin was evaluated by selectively transfusing them into beagle dogs prior to IV challenge with a lethal (2.75 mg/kg) dose of Salmonella typhi endotoxin. Supplementation of normal host defenses with 250 ml of plasma containing a heatlabile (56 degrees C for one hour) factor protected the dogs from lethal effects of the toxin. A similar volume of heparinized saline or a lesser volume of plasma (100 ml) was ineffective. The presence of 1 X 10(9) platelets and 7 X 10(10) leukocytes from leukapheresed foxhounds in some transfusion preparations did not affect survival. Protection by treatment with plasma was accompanied by severe tissue injury and loss of circulating platelets and leukocytes. Granulocyte concentrates also afforded protection and decreased tissue injury, as indicated by SGPT and taurine levels. Survivor and nonsurvivor animals experienced an early hyperglycemia as well as elevation of serum glutamic pyruvic transaminase and taurine levels. Thrombocytopenia was great in all experimental groups but was less marked in dogs transfused with cells. Leukopenia was comparable in all groups until six hours after challenge, at which time numbers of circulating leukocytes began a significant return toward normal levels in the cell-transfused group. Impairment of macrophage function was indicated by the depression of the release of colony-stimulating factor in survivor and nonsurvivor animals. Thus, normal plasma alone can protect dogs from endotoxin, but not without a significant amount of injury to the host.