Hemodynamic variables and plasma levels of PGI2, TXA2 and IL-6 in a porcine model of recurrent endotoxemia.

The pulmonary and systemic hemodynamic effects of recurrent endotoxemia were studied in pigs over a 48-hr period. Six pigs of the test group were given 0.5 micrograms/kg of an E. coli endotoxin (WO111: B4) over 60 min at the beginning and in the middle (22 hr) of the experiment. Three pigs given the same amount of physiological saline solution served as controls. The hemodynamic response to the first LPS injection was characterized by severe pulmonary hypertension, a significant increase in systemic vascular resistance, and a marked decrease in cardiac output. Circulating TxB2 levels were higher than those of 6-keto-PGF1 alpha levels, so that the first response to LPS is influenced by the vasoconstrictive actions of TxA2. With the second LPS application, the pulmonary response was attenuated, although a significant increase of pulmonary artery pressure and pulmonary vascular resistance occurred. Once again systemic vascular resistance rose and cardiac output decreased, but this time plasma levels of 6-keto-PGF1 alpha were greater than those of TxB2. Toward the end of the experiment, we noted the progressive onset of a hyperdynamic and hypotensive state. Systemic vascular resistant index decreased to 50% of the baseline value. IL-6, a cytokine of systemic importance during the course of septic shock, markedly and significantly peaked after each LPS injection. Circulating plasma levels in response to recurrent endotoxemia are described.