The pulmonary and systemic response to recurrent endotoxemia in the adult sheep.

The pulmonary and systemic hemodynamic effects of recurrent endotoxemia were studied in the adult sheep with lung lymph fistulas. Six sheep were given 1 mu/kg Escherichia coli endotoxin every 12 hours for 5 days, after which animals were monitored for another 3 days. The pulmonary response to the first three injections was characterized by an initial severe pulmonary hypertension, hypoxia, and a two- to threefold increase in lymph flow, QL. Lymph and plasma thromboxane A2 (TxB2) and prostacyclin (6-keto-PGF1 alpha) levels increased from baseline values of nearly 200 pg/ml to values exceeding 2000 pg/ml. The systemic response to initial doses was characterized by an increase in systemic vascular resistance, a decrease in cardiac index, and a transient 20% increase in oxygen consumption. With later endotoxin doses, the pulmonary response was markedly attenuated, with only modest changes in pulmonary artery pressure, lymph flow, and arterial oxygen tension noted. TxB2 increases were less than 800 pg/ml, and 6-keto-PGF1 alpha levels remained unchanged. However, we noted the progressive onset of a hyperdynamic state characterized by a sustained increase in cardiac index and body temperature, and a 50% increase in oxygen consumption, whereas systemic vascular resistance decreased by 45%. Three days after endotoxin injections were discontinued, the hyperdynamic state (including leukocytosis) was still present, whereas pulmonary variables returned to baseline levels. We conclude that a hyperdynamic state can be produced by repeated doses of endotoxin that will present even after the endotoxin insult is discontinued, which is a characteristic of the multisystem organ failure syndrome.