DIPYRIDAMOLE ATTENUATES REBOUND PULMONARY-HYPERTENSION AFTER INHALED NITRIC-OXIDE WITHDRAWAL IN POSTOPERATIVE CONGENITAL HEART-DISEASE

Objective: Inhaled nitric oxide therapy causes selective and sustained pulmonary vasodilation in patients with pulmonary hypertension; howev er, attempts to discontinue inhaled nitric oxide therapy may be compli cated by abrupt life-threatening events. Dipyridamole, a cyclic guanos ine monophosphate-specific phosphodiesterase inhibitor, blocks the hyd rolysis of cyclic guanosine monophosphate in vascular smooth muscle ce lls. Methods: We studied 23 consecutive children who were treated with inhaled nitric oxide because of clinically significant pulmonary hype rtension after surgery for congenital heart disease. Inhaled nitric ox ide therapy was withdrawn before and after dipyridamole treatment of c hildren in whom sustained elevations of pulmonary artery pressure deve loped for over 30 minutes. Results: In 7 of 23 children, inhaled nitri c oxide withdrawal caused a 40% increase in pulmonary artery pressure, a 17% decrease in systemic venous oxygen saturation, and a 46% increa se in the ratio of mean pulmonary artery pressure to aortic pressure. Compared with children who had no significant increase in pulmonary ar tery pressure, children who experienced the development of prolonged p ulmonary hypertension after inhaled nitric oxide therapy withdrawal ha d higher mean pulmonary artery pressure immediately before inhaled nit ric oxide, withdrawal (22 +/- 1 mm Hg versus 27 +/- 2 mm Hg; p = 0.04) and received inhaled nitric oxide for a longer duration (2 +/- 1 days versus 4 +/- 1 days; p = 0.01). Dipyridamole therapy attenuated the r ise in pulmonary artery pressure and fall in systemic venous oxygen sa turation in all six patients studied with rebound pulmonary hypertensi on after withdrawal of inhaled nitric oxide. Conclusion: We conclude t hat dipyridamole therapy acutely attenuates the adverse hemodynamic ef fects of rapid withdrawal of inhaled nitric oxide therapy. Children, w ith higher pulmonary artery pressure and who are treated with inhaled nitric oxide for a longer duration may be at increased risk for advers e hemodynamic effects of inhaled nitric oxide therapy withdrawal. We s peculate that dipyridamole therapy may sustain elevations of smooth mu scle cyclic guanosine monophosphate induced by inhaled nitric oxide an d that phosphodiesterase activity contributes to acute pulmonary hyper tension after inhaled nitric oxide withdrawal.