Adenine nucleotide and lactate metabolism in the lung in endotoxin shock

In this study we investigated the effects of endotoxin shock on concentrations of lung tissue ATP, ADP, AMP, inorganic phosphate (Pi), lactate, and pyruvate and the ability of lung slices to metabolize glucose and lactate. Fasted guinea pigs were intravenously injected with saline or S enteritidis endotoxin (10 mg/kg) and sacrificed 4 hr later. In separate experiments, control and endotoxic animals received histamine (5 micrograms/kg) 30 min prior to sacrifice. Significant reductions in ATP (38%), and AMP (34%) levels were observed with shock, but ADP levels did not change. Pi levels were significantly higher (77%). Lung lactate levels increased more than two-fold, whereas pyruvate concentration remained unchanged. Lung slices from endotoxic animals exhibited enhanced ability to oxidize in vitro glucose to CO2 and metabolize glucose to lactic acid, as compared to slices from control animals. Their capacity to oxidize lactate to CO2 was not affected. When histamine was administered to endotoxic animals, it failed to produce effects other than those caused by endotoxin alone. We conclude that endotoxin deleteriously affects lung steady-state ATP contents with concomitant increases in lactate production.