Kirshbom P M, Page S O, Jacobs M T, Tsui S S, Bello E, Ungerleider R M, Schwinn D A, Gaynor J W
Department of Surgery, Duke University Medical Center, Durham, N.C., USA.
J Thorac Cardiovasc Surg. 1997 Apr;113(4):777-83. doi: 10.1016/s0022-5223(97)70237-x.
Endothelin-1 has been shown to be a mediator of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest. It is not known whether the mechanism is increased production of endothelin-1 or alterations in expression of endothelin-1 receptors in the lung. This study was designed to test the hypothesis that circulatory arrest increases endothelin-1 mRNA levels and endothelin-1 receptor expression in the lung.
Twenty-four piglets (7 to 30 days old) were studied randomly either at baseline (controls, n = 12) or after cardiopulmonary bypass with 30 minutes of circulatory arrest (deep hypothermic circulatory arrest, n = 12). Lungs and pulmonary arteries were harvested immediately after hemodynamic data collection. Deep hypothermic circulatory arrest significantly increased pulmonary vascular resistance (p < 0.01). Deep hypothermic circulatory arrest also produced a significant increase in endothelin-1 mRNA levels in the pulmonary arteries (149 +/- 55 pg vs 547 +/- 111 pg, p = 0.007). There was no significant change in the pulmonary parenchymal endothelin-1 mRNA levels (4102 +/- 379 pg vs 4623 +/- 308 pg, p = 0.32). Ligand binding studies of the lung parenchyma revealed a single specific endothelin-1 binding site with an EC50 value (effective concentration causing 50% of the maximum response) of about 1 x 10(-8) mol/L, consistent with the endothelin B subtype. Deep hypothermic circulatory arrest resulted in a significant increase in the number of endothelin-1 receptors in the lung (109 +/- 6 fmol/mg total protein to 135 +/- 9 fmol/mg total protein, p = 0.02).
Deep hypothermic circulatory arrest increases production of endothelin-1 by the pulmonary vascular endothelium. Endothelin-1 production in the pulmonary parenchyma does not change. Expression of endothelin B receptors in the pulmonary parenchyma also increases after cardiopulmonary bypass with deep hypothermic circulatory arrest. This study supports the hypothesis that deep hypothermic circulatory arrest results in pulmonary vascular endothelial activation with increased endothelin-1 mRNA production.
内皮素-1已被证明是体外循环和深低温循环停搏后肺动脉高压的介质。目前尚不清楚其机制是内皮素-1产生增加还是肺中内皮素-1受体表达改变。本研究旨在验证循环停搏会增加肺中内皮素-1 mRNA水平和内皮素-1受体表达这一假设。
24头仔猪（7至30日龄）被随机分为两组，一组为基线期（对照组，n = 12），另一组为体外循环并伴有30分钟循环停搏（深低温循环停搏，n = 12）。在收集血流动力学数据后立即采集肺和肺动脉。深低温循环停搏显著增加了肺血管阻力（p < 0.01）。深低温循环停搏还使肺动脉中内皮素-1 mRNA水平显著升高（149 ± 55 pg对547 ± 111 pg，p = 0.007）。肺实质中内皮素-1 mRNA水平无显著变化（4102 ± 379 pg对4623 ± 308 pg，p = 0.32）。肺实质的配体结合研究显示存在一个单一的特异性内皮素-1结合位点，其EC50值（引起最大反应50%的有效浓度）约为1×10⁻⁸ mol/L，与内皮素B亚型一致。深低温循环停搏导致肺中内皮素-1受体数量显著增加（从109 ± 6 fmol/mg总蛋白增至135 ± 9 fmol/mg总蛋白，p = 0.02）。
深低温循环停搏增加了肺血管内皮细胞内皮素-1的产生。肺实质中内皮素-1产生未改变。在深低温循环停搏的体外循环后，肺实质中内皮素B受体表达也增加。本研究支持深低温循环停搏导致肺血管内皮激活并伴有内皮素-1 mRNA产生增加这一假设。
