Modulation of circulating endothelin-1 and big endothelin by nitric oxide inhalation following left ventricular assist device implantation.

BACKGROUND Inhaled nitric oxide (iNO) is an established therapy in the treatment of pulmonary hypertension and right ventricular dysfunction following left ventricular assist device implantation. Since it is known that endothelin-1 contributes to pulmonary hypertension, and nitric oxide modulates endothelin-1 synthesis in vitro, we investigated the effects of iNO on circulating endothelin-1 and big endothelin following left ventricular assist device implantation. METHODS AND RESULTS On weaning from cardiopulmonary bypass, 15 consecutive patients with secondary pulmonary hypertension after implantation of a left ventricular assist device were treated with iNO. Endothelin-1 and big endothelin plasma levels were measured preoperatively, on cardiopulmonary bypass prior to iNO, 12, 24, and 48 hour postoperatively, and 72 hour after cessation of iNO. Endothelin-1 levels were increased preoperatively (1.05+/-0.20 fmol/L), and were highest on cardiopulmonary bypass (1.65+/-0.27 fmol/L). During iNO therapy endothelin-1 and big endothelin decreased significantly (endothelin-1: 12 hour 1.24+/-0.18, 24 hour 0.93+/-0.20, and 48 hour 0.81+/-0.14 fmol/L); they were lowest 72 hour post-iNO (endothelin-1: 0.56+/-0.09 fmol/L). Plasma endothelin-1 concentrations and iNO dose were inversely correlated (r=-0.657, P<0.015). A significant correlation was also found between endothelin-1 versus PA pressures and PVR/SVR ratio, but not with CI and SVR. CONCLUSIONS Since it is known that endothelin-1 mediates pulmonary hypertension, we suggest a 2-fold effect of iNO therapy: firstly, a selective vasodilation of the pulmonary vasculature; and secondly, iNO mediated modulation of endothelin-1.