Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide withdrawal in postoperative congenital heart disease

J Thorac Cardiovasc Surg. 1998 Apr;115(4):875-82. doi: 10.1016/S0022-5223(98)70369-1.


Objective: Inhaled nitric oxide therapy causes selective and sustained pulmonary vasodilation in patients with pulmonary hypertension; however, attempts to discontinue inhaled nitric oxide therapy may be complicated by abrupt life-threatening events. Dipyridamole, a cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, blocks the hydrolysis of cyclic guanosine monophosphate in vascular smooth muscle cells.

Methods: We studied 23 consecutive children who were treated with inhaled nitric oxide because of clinically significant pulmonary hypertension after surgery for congenital heart disease. Inhaled nitric oxide therapy was withdrawn before and after dipyridamole treatment of children in whom sustained elevations of pulmonary artery pressure developed for over 30 minutes.

Results: In 7 of 23 children, inhaled nitric oxide withdrawal caused a 40% increase in pulmonary artery pressure, a 17% decrease in systemic venous oxygen saturation, and a 46% increase in the ratio of mean pulmonary artery pressure to aortic pressure. Compared with children who had no significant increase in pulmonary artery pressure, children who experienced the development of prolonged pulmonary hypertension after inhaled nitric oxide therapy withdrawal had higher mean pulmonary artery pressure immediately before inhaled nitric 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 rise in pulmonary artery pressure and fall in systemic venous oxygen saturation in all six patients studied with rebound pulmonary hypertension after withdrawal of inhaled nitric oxide.

Conclusion: We conclude that dipyridamole therapy acutely attenuates the adverse hemodynamic effects of rapid withdrawal of inhaled nitric oxide therapy. Children with higher pulmonary artery pressure and who are treated with inhaled nitric oxide for a longer duration may be at increased risk for adverse hemodynamic effects of inhaled nitric oxide therapy withdrawal. We speculate that dipyridamole therapy may sustain elevations of smooth muscle cyclic guanosine monophosphate induced by inhaled nitric oxide and that phosphodiesterase activity contributes to acute pulmonary hypertension after inhaled nitric oxide withdrawal.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-GMP Phosphodiesterases / physiology
  • Administration, Inhalation
  • Adolescent
  • Child, Preschool
  • Dipyridamole / therapeutic use*
  • Heart Defects, Congenital / surgery*
  • Humans
  • Hypertension, Pulmonary / chemically induced*
  • Hypertension, Pulmonary / prevention & control
  • Infant
  • Infant, Newborn
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / adverse effects*
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Postoperative Complications / chemically induced*
  • Postoperative Complications / prevention & control
  • Risk Factors
  • Substance Withdrawal Syndrome / prevention & control*
  • Time Factors


  • Phosphodiesterase Inhibitors
  • Nitric Oxide
  • Dipyridamole
  • 3',5'-Cyclic-GMP Phosphodiesterases