Malhotra S P, Riemer R K, Thelitz S, He Y P, Hanley F L, Reddy V M
Division of Cardiothoracic Surgery, University of California, San Francisco, Calif 94143-0118, USA.
J Thorac Cardiovasc Surg. 2001 Sep;122(3):464-9. doi: 10.1067/mtc.2001.115698.
Superior cavopulmonary anastomosis is widely used for palliation of various forms of univentricular heart defects. However, clinically significant pulmonary arteriovenous malformations develop in 15% to 25% of patients after surgery.
To assess altered regulation of pulmonary vascular tone caused by superior cavopulmonary anastomosis in an ovine model.
Lambs, aged 35 to 45 days, underwent an end-to-end anastomosis of the superior vena cava to the right pulmonary artery. In age-matched controls, a sham operation was performed. Arteriovenous malformations were detectable by contrast echocardiography by 8 weeks after surgery. Animals (n = 24) were studied at various time points after the operations. Expression of angiotensin-converting enzyme messenger RNA, protein levels, and enzyme activity were measured in lung homogenates. Levels of angiotensin II were measured by enzyme-linked immunosorbent assay.
Expression of angiotensin-converting enzyme messenger RNA and protein was significantly reduced at 1 to 5 weeks after superior cavopulmonary anastomosis. Angiotensin-converting enzyme activity in the right lung of animals subjected to superior cavopulmonary anastomosis was reduced 86% +/- 1% (standard deviation) compared with control values at 1 week (P =.003) and 77% +/- 8.5% at 2 weeks (P <.001) after surgery. This correlated with a 59% +/- 3.5% (P =.007) reduction in angiotensin II levels up to 5 weeks after cavopulmonary anastomosis. By 15 weeks after the operations, angiotensin II levels were equivalent to control levels (P =.19).
Superior cavopulmonary anastomosis causes an early reversible reduction in activity and expression of angiotensin-converting enzyme, resulting in decreased circulating levels of the vasoconstrictor angiotensin II. These results suggest that the ability of the pulmonary endothelium to regulate vascular tone is inhibited after superior cavopulmonary anastomosis. Dilation of the affected vasculature induced by cavopulmonary anastomosis may contribute to the disordered vascular remodeling observed in this setting.
上腔静脉肺动脉吻合术广泛用于各种形式的单心室心脏缺陷的姑息治疗。然而，术后15%至25%的患者会出现具有临床意义的肺动静脉畸形。
在绵羊模型中评估上腔静脉肺动脉吻合术引起的肺血管张力调节改变。
对35至45日龄的羔羊进行上腔静脉与右肺动脉的端端吻合术。在年龄匹配的对照组中进行假手术。术后8周通过对比超声心动图可检测到动静脉畸形。在术后不同时间点对动物（n = 24）进行研究。测量肺匀浆中血管紧张素转换酶信使核糖核酸的表达、蛋白质水平和酶活性。通过酶联免疫吸附测定法测量血管紧张素II的水平。
上腔静脉肺动脉吻合术后1至5周，血管紧张素转换酶信使核糖核酸和蛋白质的表达显著降低。与术后1周的对照值相比，接受上腔静脉肺动脉吻合术的动物右肺中的血管紧张素转换酶活性降低了86%±1%（标准差）（P = 0.003），术后2周降低了77%±8.5%（P < 0.001）。这与上腔静脉肺动脉吻合术后长达5周血管紧张素II水平降低59%±3.5%（P = 0.007）相关。术后15周时，血管紧张素II水平与对照水平相当（P = 0.19）。
上腔静脉肺动脉吻合术导致血管紧张素转换酶的活性和表达早期可逆性降低，导致血管收缩剂血管紧张素II的循环水平降低。这些结果表明，上腔静脉肺动脉吻合术后肺内皮调节血管张力的能力受到抑制。上腔静脉肺动脉吻合术引起的受影响血管系统的扩张可能导致在这种情况下观察到的血管重塑紊乱。
