Possible role of adrenomedullin in the regulation of Fontan circulation: mature form of plasma adrenomedullin is extracted in the lung in patients with Fontan procedure.
OBJECTIVE
We investigated the pathophysiological significance of molecular forms of adrenomedullin (AM) in patients after the Fontan procedure.


METHODS
Plasma concentrations of mature AM (AM-m), an active form, glycine-extended AM (AM-Gly), an inactive form, and total AM (AM-T: AM-m+AM-Gly) were measured by specific immunoradiometric assay in the femoral vein, pulmonary artery and femoral artery of 29 consecutive patients after the Fontan procedure. The eleven patients who had history of Kawasaki disease and have normal coronary and hemodynamics served as control.


RESULTS
Patients who underwent Fontan procedure had significantly higher venous concentrations of AM-T, AM-Gly, and AM-m than age-matched normal controls (AM-T, 12.0+/-3.3 vs. 9.6+/-2.0; AM-Gly, 10.4+/-3.0 vs. 8.5+/-1.6; AM-m, 1.6+/-0.7 vs. 1.0+/-0.6 pmol/l, each p<0.05). In patients with Fontan procedure, there were no differences in plasma AM-T, AM-Gly or AM-m levels between the femoral vein and pulmonary artery, however, there was a significant step-down in the AM-m levels, but not in plasma AM-T or AM-Gly levels, between the pulmonary artery and femoral artery (1.3+/-0.6 to 1.0+/-0.6, p<0.05). The venous concentrations of AM-m correlated negatively with systemic blood flow (cardiac output) (r=-0.46, p<0.05).


CONCLUSIONS
Results suggest that in Fontan circulation plasma AM-m is increased in parallel with those of AM-T and AM-Gly and that AM-m is extracted in the lung. Extracted AM-m may be involved in the regulation of pulmonary arterial tonus, although further studies are necessary to elucidate the exact role of AM in Fontan circulation.
Watanabe
Ken
K
Department of Pediatrics, National Cardiovascular Center, Osaka, Japan.
Nishikimi
Toshio
T
Takamuro
Motoki
M
Yasuda
Kenji
K
Ishikawa
Yuichi
Y
Tanabe
Saori
S
Yamada
Osamu
O
Yagihara
Toshikatsu
T
Suga
Shinichi
S
Kangawa
Kenji
K
Matsuoka
Hiroaki
H
Echigo
Shigeyuki
S
D000293:Adolescent; D053607:Adrenomedullin / Q000097:blood*; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D018729:Fontan Procedure / Q000379:methods*; D006801:Humans; D015592:Immunoradiometric Assay; D007223:Infant; D008168:Lung / Q000098:blood supply* / Q000737:chemistry*; D008297:Male; D011652:Pulmonary Circulation / Q000502:physiology*
C507862:ADM protein, human; D053607:Adrenomedullin