Dupuis J, Stewart D J, Cernacek P, Gosselin G
Department of Medicine, Montreal Heart Institute, St. Michael's Hospital, Toronto, Canada.
Circulation. 1996 Oct 1;94(7):1578-84. doi: 10.1161/01.cir.94.7.1578.
Animal studies suggest a major role of the pulmonary circulation in the clearance of circulating endothelin-1 (ET-1). The contribution of the human pulmonary circulation to plasma ET-1 clearance, however, has never been quantified. The absence of an AV gradient in plasma ET-1 has previously been interpreted as evidence that the lungs do not have a role in modulating circulating ET-1 levels. This study was designed to quantify and discern between pulmonary ET-1 clearance and production in humans.
We studied 13 subjects by combining the multiple indicator-dilution technique with the measurement of immunoreactive ET-1 (irET-1). All patients had normal left ventricular ejection fractions (61 +/- 7%, mean +/- SD) and baseline hemodynamics. Mean pulmonary ET-1 extraction was 47 +/- 7%. The ET-1 extracted does not return to circulation and can be characterized by a sequestration rate constant: Kseq = 0.048 +/- 0.019 s-1. There was no significant difference between irET-1 levels from the pulmonary artery and aorta (0.61 +/- 0.29 and 0.68 +/- 0.33 pg/mL, respectively; P = .22); the normal lung consequently produces an amount of ET-1 that is quantitatively similar to the amount that has been extracted.
The human lung is an important site for both clearance and production of ET-1. There is a normal physiological balance of ET-1 across the pulmonary circulation, which explains the absence of difference in AV ET-1 levels despite a 47 +/- 7% clearance. Reduced pulmonary clearance or increased production of this peptide may contribute to the increase in circulating levels found in various cardiovascular conditions.
动物研究表明肺循环在循环内皮素 -1（ET-1）清除中起主要作用。然而，人类肺循环对血浆 ET-1 清除的贡献从未被量化。血浆 ET-1 中不存在动静脉梯度以前被解释为肺在调节循环 ET-1 水平中不起作用的证据。本研究旨在量化并区分人类肺对 ET-1 的清除和产生。
我们通过将多指示剂稀释技术与免疫反应性 ET-1（irET-1）测量相结合，对 13 名受试者进行了研究。所有患者左心室射血分数正常（61±7%，平均值±标准差）且基线血流动力学正常。平均肺 ET-1 提取率为 47±7%。提取的 ET-1 不会再回到循环中，其特征可以用一个隔离速率常数来表示：Kseq = 0.048±0.019 s-1。肺动脉和主动脉的 irET-1 水平之间没有显著差异（分别为 0.61±0.29 和 0.
