AN ASSOCIATION BETWEEN LUNG LYMPH ENDOTHELIN CONCENTRATION AND SURVIVAL DURING ENDOTOXEMIA IN AWAKE SHEEP

Endotoxin stimulates synthesis of endothelin which can cause pulmonary and systemic vasoconstriction and bronchoconstriction. Prolonged endo toxemia in sheep results in dramatic increases in pulmonary and system ic vascular resistances in nonsurvivors compared with survivors. Exper iments were conducted in 12 conscious sheep (seven survivors, five non survivors) to determine if synthesis of endothelin might contribute to the pathophysiology in nonsurvivors. Endotoxin was infused at 10 ng/m in/kg for 12 h followed by a 4 h recovery in survivors. Lung lymph end othelin concentration peaked at 38.7 +/- 5.8 pg/mL during the endotoxi n infusion in survivors compared with a peak of 128.7 +/- 33.0 pg/mL ( p <.05) in nonsurvivors. Cardiac output was lower, and systemic and pu lmonary vascular resistances and the Aa gradient in Po-2 were signific antly greater in nonsurvivors compared with survivors. These variables are those likely to be affected by increased circulating endothelin c oncentrations which suggests that endothelin contributes to early mort ality during prolonged endotoxemia.