title: Hypoplasia of the small pulmonary arteries in hypoplastic left heart syndrome with restrictive atrial septal defect.
abstract: BACKGROUND
  Restrictive atrial septal defect (ASD) (including intact atrial septum [IAS]) has been reported to be a risk factor that negatively impacts survival in hypoplastic left heart syndrome (HLHS). Although lymphangiectasia and "arterialization" of the veins of the lung in HLHS with restrictive ASD have been reported, they cannot fully explain the high mortality. We have introduced a new method of evaluating the development of the pulmonary vasculature in histological sections and used it to assess patients' lungs. We tested the hypothesis that the small pulmonary arteries (SPA), which are pulmonary arteries in a histological section whose radii are approximately 25 microm to 250 microm, in HLHS with restrictive ASD are hypoplastic, but that the alveoli are not, to elucidate the mechanism underlying the poor outcome of these patients.
  
  
  RESULTS
  Fourteen HLHS patients between 1 day and 40 days of age were studied. In 8 cases, the ASD was restrictive [R(+) group], and in the other 6 cases it was not [R(-) group]. Specimens from 12 autopsies of cases with no congenital heart or pulmonary disease were examined as a control group (C group). As a novel histological parameter, we assessed the size of SPA in relation to the size of accompanying bronchioles to identify SPA underdevelopment. To evaluate the development of alveoli and interstitial tissue, radial alveolar counts (RAC), which reflect alveolar maturity and complexity, were also performed. Statistical comparisons between groups were made by analysis of covariance with age as a covariant factor. When the radius of the accompanying bronchiole was 100 microm, the radius of the SPA was 34.0+/-10.8 microm in the R(+) group, and significantly lower than the 46.6+/-8.5 microm in R(-) group (P=0.0022) and 70.5+/-8.4 microm in the C group (P<0.0001). The RAC was in 3.5+/-0.9 in the R(+) group, 3.4+/-0.6 in the R(-) group, and 3.7+/-0.9 in the C group (no significant differences between groups).
  
  
  CONCLUSIONS
  The SPA in HLHS with restrictive ASD were underdeveloped compared with the SPA in HLHS with nonrestrictive ASD and the controls, but their alveoli were not hypoplastic. Based on these results, it is speculated that SPA hypoplasia may be responsible for the poor outcome of HLHS with restrictive ASD.
authors.affiliation: Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. maedak-tky@umin.ac.jp
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Maeda
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yamaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kado
authors.forename: Toshihide
authors.initials: T
authors.lastname: Asou
authors.forename: Arata
authors.initials: A
authors.lastname: Murakami
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takamoto
mesh_terms: D000015:Abnormalities, Multiple / Q000473:pathology*; D000367:Age Factors; D000886:Anthropometry; D001980:Bronchi / Q000648:ultrastructure; D005260:Female; D005865:Gestational Age; D006344:Heart Septal Defects, Atrial / Q000473:pathology*; D006801:Humans; D006935:Hypercapnia / Q000401:mortality / Q000473:pathology; D006984:Hypertrophy; D018636:Hypoplastic Left Heart Syndrome / Q000473:pathology* / Q000601:surgery; D000860:Hypoxia / Q000401:mortality / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D008200:Lymphangiectasis / Q000473:pathology; D008297:Male; D010166:Palliative Care; D011183:Postoperative Complications / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011650:Pulmonary Alveoli / Q000648:ultrastructure; D011651:Pulmonary Artery / Q000002:abnormalities* / Q000648:ultrastructure; D017540:Tunica Media / Q000473:pathology