Perioperative plasma endothelin-1 and big endothelin-1 concentrations in elderly patients undergoing major surgical procedures

Plasma concentrations of the vasoconstrictor endothelin-1 (ET-1) increase d uring acute physiologic stress, but the role of ET-1 in the pathophysiology of stress remains largely undefined. Whether ET-1 mediates thermoregulator y changes in vasomotor tone is unknown. ET-1 and its more stable precursor, Big ET-1, were measured in plasma obtained at several perioperative time p oints from 95 consecutive elderly patients (mean age 70 +/- 1 yr) randomize d to receive either normothermic or hypothermic perioperative care while un dergoing major surgical procedures. In the postoperative period, there were no significant changes in plasma ET-1 concentrations, but Big ET-1 concent rations increased considerably (P < 0.0001). There were no significant diff erences in mean ET-1 or Big ET-1 levels in normothermic and hypothermic pat ients. Preoperative and postoperative ET-1 concentrations were significantl y higher in patients with a history of hypertension (P < 0.002) and in thos e requiring treatment for postoperative hypertension (P < 0.003). Patients with cancer and those undergoing abdominal surgery had significantly higher Big ET-1 concentrations (P < 0.0001 and P < 0.003, respectively). These da ta support the hypothesis that Big ET-1 is a more sensitive measure of endo thelin system activation after major surgery. Premorbid conditions and loca tion and type of surgery influence perioperative ET-1/Big ET-1 concentratio ns. Implications: The endothelin response seems to be significantly associa ted with perioperative hemodynamic aberrations. The endothelin-l (ET-1) pre cursor Big ET-1 is a more sensitive measure of the endothelin system activa tion in response to surgical stress than ET-1 alone. Thermoregulatory vasoc onstriction in response to mild perioperative hypothermia occurs independen tly of the endothelin system.