title: The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension.
abstract: Selective pulmonary vasodilation is an advantageous therapeutic strategy for cardiac surgical patients with increased pulmonary vascular resistance (PVR) and right ventricular failure. We hypothesized that milrinone, an adenosine-3',5'-cyclic monophosphate (cAMP)-selective phosphodiesterase enzyme (PDE) inhibitor may, when nebulized and inhaled, cause selective pulmonary vasodilation and potentiate the vasodilation by inhaled prostacyclin (iPGI(2)). Consequently, we investigated the hemodynamic effects of inhaled milrinone or the combination iPGI(2) + inhaled milrinone in cardiac surgical patients with postoperative mean pulmonary arterial pressure (MPAP) >25 mm Hg and PVR >200 dynes. s(-1). cm(-5). During mechanical ventilation and using a conventional nebulizing system, 9 patients inhaled incremental concentrations of milrinone (0.25, 0.5 and 1 mg/mL) in subsequent 10-min periods (Study Part 1). In the same manner, 11 patients received iPGI(2) (10 microg/mL) followed by the combination of iPGI(2) (10 microg/mL) and inhaled milrinone (1 mg/mL) (Study Part 2). Inhaled milrinone reduced PVR with a maximal effect (-20%, P < 0.001) at the largest concentration. As compared with iPGI(2) alone, iPGI(2) + inhaled milrinone caused a further and prolonged reduction of PVR (-8%, P < 0.05) and increased stroke volume (+5%, P < 0.05). Systemic vascular resistance or mean arterial pressure was not affected by inhalation of either drug(s). The authors conclude that inhalation of the cAMP-selective PDE-inhibitor milrinone selectively dilates the pulmonary vasculature without systemic effects in cardiac surgical patients with pulmonary hypertension. Furthermore, inhaled milrinone appears to potentiate and prolong the pulmonary selective vasodilatory effect of iPGI(2). Inhaled milrinone alone or combined with iPGI(2) may be an important therapeutic option in the treatment of patients with pulmonary hypertension and right ventricular failure.
  
  
  CONCLUSIONS
  Pulmonary hypertension may cause or aggravate right heart failure. IV vasodilators reduce systemic blood pressure and might thereby further impair coronary perfusion and right heart performance. In the present study of cardiac surgical patients with pulmonary hypertension, selective pulmonary vasodilation without systemic effects was induced by nebulized, inhaled vasodilators.
authors.affiliation: Department of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Haraldsson s
authors.forename: N
authors.initials: N
authors.lastname: Kieler-Jensen
authors.forename: S E
authors.initials: SE
authors.lastname: Ricksten
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000008:administration & dosage*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage; D011652:Pulmonary Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000959:Antihypertensive Agents; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D011464:Epoprostenol; D020105:Milrinone