Preserved liver function and leukocyte response in superlethal endotoxic shock

Recent studies reveal that endotoxin-pretreated awake dogs become markedly leukocytotic and survive superlethal endotoxin challenge without hypoglycemia. The purpose of this study was to determine if an association exists between leukocytosis, liver function, and survival in endotoxin shock. Studies were conducted on awake, conditioned adult dogs, with the experimental group (N=5) injected intravenously with 1/1,000 LD ₁₀₀ E. coli endotoxin on Days 1 and 2, LD ₁₀₀ on day 3, and 2 x LD ₁₀₀ on Day 4. A control group (N=6) received equal volumes of saline on Days 1, 2, and 3, but on Day 4 received 2 x LD ₁₀₀ endotoxin. All saline-pretreated dogs died within seven hours following superlethal endotoxin challenge. Each animal in the experimental group was sacrificed at the time of its paired saline control's death for a comparison of liver pathology, since in parallel studies all endotoxin pretreated dogs (N=11) survived for 30 days. Animals in the experimental group exhibited a marked leukocytosis of 39,000/cu mm (mature neutrophils, 28,000/cu mm, immature neutrophils, 8,300/cu mm (P<0.001) on Day 4 compared with saline-pretreated controls. At the time of death the liver enzymes, arginase, and SGPT were significantly elevated in the saline pretreated controls compared with endotoxin-pretreated dogs (P<0.02). Liver pathology in endotoxin-pretreated dogs consisted of mild necrosis, while saline-pretreated animals demonstrated massive hepatocellular necrosis. Results support the view that increased numbers of neutrophils protect liver function and enhance survival in endotoxin shock.