OBJECTIVE: Cardiac surgery with cardiopulmonary bypass induces ischemia to the heart, hypoxemia to various tissues and release of endotoxins. The endothelial cell may suffer from hypoxia and trigger cascades of adverse reactions by activation of neutrophils through adhesion molecules. The authors measured expression of intercellular adhesion molecule-1 (ICAM-1), during hypoxia and normoxia and hypothesized that salicylate, which inhibits the nuclear factor-kappaB (NFkappaB), an hypoxia-dependent transmission factor, could reduce this expression. METHODS: Human umbilical vein endothelial cells were cultured and exposed to normoxia and hypoxia in the presence of lipopolysaccharide (LPS). The endothelial cells were thereafter treated with salicylate or indomethacin under the same conditions. The surface expression of ICAM-1 was measured by whole cell enzyme-linked immunosorbent assay (ELISA) and the NFkappaB expression by Western blotting. RESULTS: In the presence of LPS and under hypoxic conditions, the endothelial cells produced a 300 +/- 41% increased expression of ICAM-1 compared with normoxia. The addition of salicylate (0.02-20 mM) completely inhibited the enhanced expression of ICAM-1, the addition of indomethacin at equivalent concentrations did not reduce ICAM-1 expression under either condition. CONCLUSION: ICAM-1 expression is greatly enhanced by the hypoxic endothelial cell in the presence of circulating endotoxin. Pre-treatment with salicylate completely abolishes the enhanced expression. The study suggests that salicylate administered before cardiopulmonary bypass might protect the heart against ischemic/reperfusion injuries and reduce the load of the overall inflammatory reaction.
OBJECTIVE: Cardiac surgery with cardiopulmonary bypass induces ischemia to the heart, hypoxemia to various tissues and release of endotoxins. The endothelial cell may suffer from hypoxia and trigger cascades of adverse reactions by activation of neutrophils through adhesion molecules. The authors measured expression of intercellular adhesion molecule-1 (ICAM-1), during hypoxia and normoxia and hypothesized that salicylate, which inhibits the nuclear factor-kappaB (NFkappaB), an hypoxia-dependent transmission factor, could reduce this expression. METHODS:Human umbilical vein endothelial cells were cultured and exposed to normoxia and hypoxia in the presence of lipopolysaccharide (LPS). The endothelial cells were thereafter treated with salicylate or indomethacin under the same conditions. The surface expression of ICAM-1 was measured by whole cell enzyme-linked immunosorbent assay (ELISA) and the NFkappaB expression by Western blotting. RESULTS: In the presence of LPS and under hypoxic conditions, the endothelial cells produced a 300 +/- 41% increased expression of ICAM-1 compared with normoxia. The addition of salicylate (0.02-20 mM) completely inhibited the enhanced expression of ICAM-1, the addition of indomethacin at equivalent concentrations did not reduce ICAM-1 expression under either condition. CONCLUSION:ICAM-1 expression is greatly enhanced by the hypoxic endothelial cell in the presence of circulating endotoxin. Pre-treatment with salicylate completely abolishes the enhanced expression. The study suggests that salicylate administered before cardiopulmonary bypass might protect the heart against ischemic/reperfusion injuries and reduce the load of the overall inflammatory reaction.