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 CI-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.