title: Pulmonary microvessel density is a marker of angiogenesis in children after cavopulmonary anastomosis.
abstract: OBJECTIVE
  Pulmonary arteriovenous malformations cause progressive cyanosis in children after cavopulmonary anastomosis and may be due to abnormal angiogenesis. We determined the microvessel density, a marker of angiogenesis, in the lungs of children after cavopulmonary anastomosis.
  
  
  METHODS
  Lung biopsy specimens were obtained from 8 children after cavopulmonary anastomosis and from 4 control patients. Three of the 8 children undergoing cavopulmonary anastomosis had clinical and angiographic evidence of pulmonary arteriovenous malformations, whereas the other 5 were free of symptoms. Routine histologic and immunohistologic stains were performed with a primary antibody to von Willebrand factor. Microvessel staining for von Willebrand factor was determined for 10 fields (200x) per patient.
  
  
  RESULTS
  Patients with and without pulmonary arteriovenous malformations after cavopulmonary anastomosis demonstrated significantly increased microvessel density compared with control subjects (32.7 +/- 2.8 vs 9.3 +/- 4.6, P =.02, and 31.5 +/- 15.7 vs 9.3 +/- 4.6, P =.01, respectively). There was no difference in microvessel density in children with and without clinically apparent pulmonary arteriovenous malformations after cavopulmonary anastomosis (P =.9). The children with pulmonary arteriovenous malformations had numerous greatly dilated vessels that were absent in the asymptomatic children after cavopulmonary anastomosis.
  
  
  CONCLUSIONS
  After cavopulmonary anastomosis, pulmonary microvessel density is increased even in the absence of clinically apparent pulmonary arteriovenous malformations, supporting the presence of a constant angiogenic stimulus. Children with clinically apparent pulmonary arteriovenous malformations possess large numbers of greatly dilated pulmonary microvessels, which are absent in asymptomatic children after cavopulmonary anastomosis. These results suggest that the transition to clinically apparent pulmonary arteriovenous malformations may be due to mechanisms that lead to vessel dilation and remodeling.
authors.affiliation: Divisions of Cardiac Surgery and Cardiology, Children's Hospital and Regional Medical Center, Seattle, Washington, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Starnes
authors.forename: B W
authors.initials: BW
authors.lastname: Duncan
authors.forename: J M
authors.initials: JM
authors.lastname: Kneebone
authors.forename: C H
authors.initials: CH
authors.lastname: Fraga
authors.forename: S
authors.initials: S
authors.lastname: States
authors.forename: G L
authors.initials: GL
authors.lastname: Rosenthal
authors.forename: F M
authors.initials: FM
authors.lastname: Lupinetti
mesh_terms: D000704:Analysis of Variance; D000714:Anastomosis, Surgical / Q000009:adverse effects / Q000379:methods; D001165:Arteriovenous Malformations / Q000209:etiology*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D018729:Fontan Procedure / Q000009:adverse effects; D006330:Heart Defects, Congenital / Q000601:surgery; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D011183:Postoperative Complications; D011651:Pulmonary Artery / Q000601:surgery*; D016896:Treatment Outcome; D014683:Vena Cava, Superior / Q000601:surgery*