Lung function and structure after Escherichia coli endotoxin in rabbits: effect of dose and rate of administration.

We evaluated the effect of increasing doses of Escherichia coli endotoxin and its rate of administration on systemic blood pressure, alveolar-arterial oxygen gradient (A- aDO2 1.0), dynamic compliance (Cdyn), circulating platelets and leukocytes, and postmortem bloodless wet to dry ratios in anesthetized rabbits. Infusion of endotoxin resulted in systemic hypotension, diminished Cdyn, thrombocytopenia, and leukopenia, but did not influence venous admixture. These parameters were not affected by the rapidity of administration, but changes in Cdyn and circulating platelets were dose-dependent. High (15 mg/kg), but not low (0.5 mg/kg), doses of endotoxin resulted in an early but transient increase in lung water, but bloodless wet to dry weight ratios were not increased at 4-6 h following endotoxin even when high doses were injected. Ultrastructural studies done in six rabbits showed an early but transient platelet sequestration in pulmonary capillaries, progressive increase in intracapillary leukocytes, interstitial edema, and focal, although minimal, endothelial injury at 4 h after injection. Thus, infusion of E coli endotoxin in rabbits does not result in increased lung water and intrapulmonary shunting acutely; this tolerance to endotoxin is not related to the dose or rates of administration studied.