title: The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension.
abstract: OBJECTIVE
  This study evaluated the response to prostacyclin dose reduction in patients with primary pulmonary hypertension (PPH) who developed high cardiac outputs.
  
  
  BACKGROUND
  Patients on prostacyclin require chronic upward dose titration to overcome tolerance to the medication. No upper limit of effective dose has been described.
  
  
  METHODS
  We studied 12 patients with PPH treated with chronic prostacyclin therapy who presented in high cardiac output states. Each patient underwent prostacyclin dose reduction under hemodynamic guidance targeted to reduce the cardiac index to < or =4 liter/min/M2, unless rebound pulmonary hypertension occurred. Following dose reduction, patients were observed for changes in the effectiveness of the prostacyclin.
  
  
  RESULTS
  Patients were treated for 39 +/- 20 months, resulting in a 71% reduction in pulmonary vascular resistance compared to baseline. At the time of their most recent evaluation their cardiac outputs were increased to 10.1 +/- 2.3 liter/min. The patients underwent a 39% dose reduction (range 12% to 78%) resulting in a change of mean PAP from 45 to 46 mm Hg (p = NS), cardiac index from 7.4 +/- 1.4 to 4 +/- 0.74 liter/min/M2 (p = 0.01), and pulmonary vascular resistance from 3.7 +/- 1.7 to 4.7 +/- 1.5 units (p < 0.001). In no instance did rebound pulmonary hypertension occur. However, the patients all retained their clinical benefit without a return of tolerance.
  
  
  CONCLUSIONS
  Excessive prostacyclin in PPH can lead to a high cardiac output state, suggesting it has important positive inotropic effects. In this circumstance, reducing the dose can allow the cardiac output to return to normal without worsening the clinical state.
authors.affiliation: Department of Medicine, Rush University Medical College, Chicago, Illinois, USA. srich@rush.edu
authors.forename: S
authors.initials: S
authors.lastname: Rich
authors.forename: V V
authors.initials: VV
authors.lastname: McLaughlin
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002302:Cardiac Output / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D011464:Epoprostenol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D011464:Epoprostenol