Cardiopulmonary changes with intermittent endotoxin administration in sheep.

Chronic sepsis was induced by administering endotoxin (lipopolysaccharide--LPS) at 12-hr intervals to sheep. The animals (n = 7) responded to the first dose of LPS with increased pulmonary arterial pressure (PAP), systemic vascular resistance, plasma and lymph thromboxane B2 (TxB2) concentrations, and lung lymph flow rate concurrent with a reduction in the cardiac index (CI). Subsequent doses of LPS produced an elevation of PAP and TxB2 which was progressively attenuated and eventually disappeared. With LPS the lung lymph flow was markedly elevated and CI increased. This latter was transient and associated with a reduction in systemic vascular resistance. Concomitant with the cardiopulmonary changes prekallikrein levels were not diminished, but there was a statistically significant reduction in C1-esterase inhibitor. The administration of LPS was discontinued after 5 days and the cardiopulmonary variables rapidly returned to baseline levels. Chronic endotoxemia appears to be associated with an elevated pulmonary microvascular permeability and a tendency toward a hyperdynamic circulation but with an appreciable degree of refractoriness associated with regional hemodynamics and eicosanoid biosynthesis.