Watanabe Ken, Nishikimi Toshio, Takamuro Motoki, Yasuda Kenji, Ishikawa Yuichi, Tanabe Saori, Yamada Osamu, Yagihara Toshikatsu, Suga Shinichi, Kangawa Kenji, Matsuoka Hiroaki, Echigo Shigeyuki
Department of Pediatrics, National Cardiovascular Center, Osaka, Japan.
Regul Pept. 2007 Jun 7;141(1-3):129-34. doi: 10.1016/j.regpep.2006.12.025. Epub 2007 Jan 12.
We investigated the pathophysiological significance of molecular forms of adrenomedullin (AM) in patients after the Fontan procedure.
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.
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).
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.
我们研究了Fontan手术患者中肾上腺髓质素（AM）分子形式的病理生理意义。
通过特异性免疫放射分析测定了29例连续接受Fontan手术后患者股静脉、肺动脉和股动脉中成熟AM（AM-m，一种活性形式）、甘氨酸延伸型AM（AM-Gly，一种非活性形式）以及总AM（AM-T：AM-m + AM-Gly）的血浆浓度。11例有川崎病病史且冠状动脉和血流动力学正常的患者作为对照。
接受Fontan手术的患者静脉血中AM-T、AM-Gly和AM-m的浓度显著高于年龄匹配的正常对照（AM-T，12.0±3.3对9.6±2.0；AM-Gly，10.4±3.0对8.5±1.6；AM-m，1.6±0.7对1.0±0.6 pmol/l，各p<0.05）。在接受Fontan手术的患者中，股静脉和肺动脉之间血浆AM-T、AM-Gly或AM-m水平无差异，然而，肺动脉和股动脉之间AM-m水平有显著下降，但血浆AM-T或AM-Gly水平无下降（1.3±0.6至1.0±0.6，p<0.05）。AM-m的静脉浓度与全身血流量（心输出量）呈负相关（r = -0.46，p<0.05）。
结果表明，在Fontan循环中，血浆AM-m与AM-T和AM-Gly平行升高，且AM-m在肺中被提取。尽管需要进一步研究以阐明AM在Fontan循环中的确切作用，但提取的AM-m可能参与肺动脉张力的调节。
