Circulating endothelin and nitrate-nitrite relate to hemodynamic and metabolic variables in human septic shock

Activation of the nitric oxide (NO) pathway over that of endothelin in the vessel wall, as judged from circulating endothelin and nitrate-nitrite (NN) levels, may partly account for the hypotension associated with vasodilatio n, diminished catecholamine sensitiveness and O-2 extraction, and lactic ac idemia in human septic shock. In a prospective study, 14 consecutive patien ts with septic shock and a pulmonary artery catheter in place were included . For 3 days after admission, serial measurements of hemodynamic variables and plasma levels of endothelin and NN were done. The patients had a hyperd ynamic circulation. Except for a higher final blood lactate level and more treatment with vasoconstricting catecholamines in nonsurvivors, global hemo dynamic and O-2-related variables did not differ between outcome groups. On the day of admission, circulating endothelin and NN levels were elevated a nd related to elevated levels of tumor necrosis factor-alpha and interleuki n-6. The levels of endothelin increased in time in nonsurvivors as compared with survivors. The NN levels declined in survivors but not in nonsurvivor s. The systemic vascular resistance indices (SVRI), global O-2 extraction r atios, and blood lactate levels directly related to the endothelin levels. SVRI and global O-2 extraction ratios inversely, and the lactate blood leve ls directly, related to NN levels, and the hemodynamic and metabolic parame ters related directly to the ratio between endothelin and NN plasma levels on the days of the study. The vessel wall factors did not relate to the cre atinine levels. The results suggest that the hemodynamic and metabolic peri pheral abnormalities of human septic shock are mediated in part by cytokine -activated endothelin and NO systems in the vessel wall. They also suggest that increased production rather than diminished renal clearance accounts f or elevated levels of NN and endothelin and that the latter are associated with a poor outcome.