title: Assessment of pulmonary endothelial function during invasive testing in children and adolescents with idiopathic pulmonary arterial hypertension.
abstract: OBJECTIVE
  The purpose of our study was to assess pulmonary endothelial function by vasodilator response to acetylcholine (Ach) administered in segmental pulmonary arteries in children with idiopathic pulmonary arterial hypertension (IPAH). We hypothesized that there was a relationship among pulmonary endothelial response to Ach, severity of the disease, and clinical outcome.
  
  
  BACKGROUND
  IPAH may be associated with pulmonary endothelial dysfunction; however, data regarding the impact of endothelial dysfunction on severity and prognosis of this disease are limited.
  
  
  METHODS
  Forty-three children and adolescents (mean age: 10.4 ± 5.5 years) with IPAH were included in the study. Changes in pulmonary blood flow in response to Ach were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values.
  
  
  RESULTS
  Mean PFR of all patients was 1.58 ± 0.67. Mean follow-up after catheterization was 55.7 ± 41.9 months. Freedom from serious cardiovascular events (lung transplantation or death) was 83% after 2 years, 76% after 3 years, and 57% after 5 years. PFR was related significantly to World Health Organization functional class. Receiver-operating characteristic curves revealed a PFR of 1.4 as the best cutoff value. Kaplan-Meier analysis demonstrated that a PFR of <1.4 was highly predictive for cardiovascular events (log-rank [Mantel Cox] chi-square: 12.49, p < 0.0001).
  
  
  CONCLUSIONS
  Our study demonstrates a strong relationship between pulmonary endothelial response to Ach and prognosis of children with IPAH. As an adjunct to the usual testing protocol, this method provides additional information for therapeutic guidance.
authors: Pediatric Heart Centre, Justus-Liebig-University, Giessen, Germany. capitz@aol.com
authors: Christian
authors: C
authors: Apitz
authors: Rainer
authors: R
authors: Zimmermann
authors: Joachim
authors: J
authors: Kreuder
authors: Christian
authors: C
authors: Jux
authors: Heiner
authors: H
authors: Latus
authors: Joern
authors: J
authors: Pons-Kühnemann
authors: Ines
authors: I
authors: Kock
authors: Peter
authors: P
authors: Bride
authors: Karsten Grosse
authors: KG
authors: Kreymborg
authors: Ina
authors: I
authors: Michel-Behnke
authors: Dietmar
authors: D
authors: Schranz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000503:physiopathology*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008168:Lung / Q000503:physiopathology*; D008297:Male; D011379:Prognosis; D011651:Pulmonary Artery / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D000109:Acetylcholine