Endothelin-A Receptor Inhibition After Cardiopulmonary Bypass: Cytokines and Receptor Activation

Background Basic studies have suggested that cross-talk exists between the endothelin-A receptor (ET-AR) and tumor necrosis factor signaling pathway. This study tested the hypothesis that administration of an ET-AR antagonist at the separation from cardiopulmonary bypass would alter the tumor necrosis factor activation in the early postoperative period. Methods Patients (n = 44) were randomly allocated to receive bolus infusion of vehicle, 0.1, 0.5, 1, or 2 mg/kg of the ET-AR antagonist (sitaxsentan), at the separation from cardiopulmonary bypass (n = 9, 9, 9, 9, and 8, respectively). Plasma levels of tumor necrosis factor-α and soluble tumor necrosis factor receptor 1 and 2 were measured. Results Compared with the vehicle group at 24 hours, plasma levels of tumor necrosis factor-α and tumor necrosis factor receptor 2 (indicative of receptor activation) were reduced in the 1 mg/kg ET-AR antagonist group (by approximately 13 pg/mL and approximately 0.5 ng/mL, respectively; p p p Conclusions This study demonstrated a mechanistic relationship between the ET-AR and tumor necrosis factor receptor activation in the post–cardiac surgery period. Thus, in addition to the potential cardiovascular effects, a selective ET-AR antagonist can modify other biological processes relevant to the post–cardiac surgery setting.