title: Hemodynamic effects of inhaled nitric oxide and phosphodiesterase inhibitor (dipyridamole) on secondary pulmonary hypertension following heart valve surgery in adults.
abstract: BACKGROUND
  Inhaled nitric oxide (iNO) is proposed in the management of pulmonary hypertension (PH) in patients undergoing cardiac surgery. Secondary PH related to a long-standing heart valve disease however may be refractory to iNO. Aim of this prospective study was to determine whether the combination of iNO plus dipyridamole (DP), a cyclic guanosine monophosphate-specific phosphodiesterase inhibitor (PDE5), may enhance and/or prolong the response to iNO in adult patients with secondary valve-related PH undergoing cardiac surgery, and attenuate rebound events related to its discontinuation.
  
  
  METHODS
  Responses in 27 patients, 11 male, mean age 72+/-11 years, with PH due to mitral and/or aortic valve disease, were studied in the Intensive Care Unit after cardiac surgery, during sedation and stable hemodynamic conditions. The effect of isolated iNO administration (40 ppm), iNO combined with DP (0.2 mg/kg i.v.), and DP alone (1 mg/kg/24 h) on pulmonary vascular resistance, mean pulmonary artery pressure, cardiac index, mixed venous O2Sat%, and mean arterial pressure were determined.
  
  
  RESULTS
  All patients showed at least a 10% decrease in pulmonary vascular resistance vs. baseline after administration of iNO [responders]. Inhaled NO and the combination of iNO/DP produced a reduction of pulmonary vascular resistance and mean pulmonary artery pressure (p<0.05). Cardiac index improved with a significant difference between iNO and the association iNO/DP versus baseline (p<0.05). This significant hemodynamic improvement versus baseline was maintained during isolated DP administration (p<0.05), but not during isolated iNO discontinuation. Mixed venous oxygen saturation showed an overall improvement of 17% (p<0.05).
  
  
  CONCLUSIONS
  Inhaled NO and DP infusion might represent a valuable association in the management of PH secondary to a heart valve disease in patients undergoing cardiac surgery. Their beneficial hemodynamic effects might be particularly valuable in the management of patients with associated right ventricular dysfunction.
authors.affiliation: Division of Cardiac Surgery and Anesthesiology, University of Verona, OCM Borgo Trento, Piazzale Stefani 1, 37126, Verona, Italy. fsant@yahoo.com
authors.forename: Francesco
authors.initials: F
authors.lastname: Santini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Casali
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Franchi
authors.forename: Stefano
authors.initials: S
authors.lastname: Auriemma
authors.forename: Mario
authors.initials: M
authors.lastname: Lusini
authors.forename: Luca
authors.initials: L
authors.lastname: Barozzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Favaro
authors.forename: Antonio
authors.initials: A
authors.lastname: Messina
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mazzucco
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000704:Analysis of Variance; D001021:Aortic Valve / Q000601:surgery; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002302:Cardiac Output / Q000187:drug effects; D004176:Dipyridamole / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006349:Heart Valve Diseases / Q000150:complications / Q000503:physiopathology / Q000601:surgery*; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000601:surgery; D009569:Nitric Oxide / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D009569:Nitric Oxide; D004176:Dipyridamole