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

Abstract

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.