Reddy V M, Hendricks-Munoz K D, Rajasinghe H A, Petrossian E, Hanley F L, Fineman J R
Department of Cardiothoracic Surgery, University of California, San Francisco 94143-0106, USA.
Circulation. 1997 Feb 18;95(4):1054-61. doi: 10.1161/01.cir.95.4.1054.
After cardiopulmonary bypass (CPB), pulmonary hypertension and its associated increased vascular reactivity are a major source of morbidity, particularly for children with increased pulmonary blood flow. Although post-CPB pulmonary hypertension is well described, its mechanisms remain incompletely understood. Plasma levels of endothelin 1. a potent vasoactive substance implicated in pulmonary hypertension, are increased after CPB. The purpose of the present study was threefold: to characterize the changes in pulmonary vascular resistance and vascular reactivity induced by hypothermic CPB; to investigate the effects of preexisting increased pulmonary blood flow on these changes; and to better define the role of endothelin 1 in the pathogenesis of post-CPB pulmonary hypertension.
Vascular pressures and blood flows were monitored in 14 1-month-old lambs with increased pulmonary blood flow (after in utero placement of an aortopulmonary shunt) and 6 age-matched control lambs. During the 2-hour study period after 105.3 +/- 20.6 minutes of hypothermic CPB the increase in pulmonary vascular resistance was significantly augmented in lambs with increased pulmonary blood flow compared with control lambs (P < .05). Pretreatment with PD 145065 (a nonselective endothelin receptor blocker; 50 micrograms.kg-1.min-1) completely blocked this increase in pulmonary vascular resistance and blocked the increase in pulmonary vascular resistance in response to acute alveolar hypoxia after CPB (96.3 +/- 88.5% versus -9.7 +/- 16.4%; P < .05). Plasma endothelin 1 levels increased after CPB in all lambs.
Preexisting increased pulmonary blood flow alters the response of the pulmonary circulation to hypothermic CPB; the increase in pulmonary vascular resistance induced by CPB is augmented in lambs with increased pulmonary blood flow. Pretreatment with endothelin 1 receptor blockers eliminated the increase in pulmonary vascular resistance and the pulmonary vasoconstricting response to alveolar hypoxia, suggesting a role for endothelin 1 in post-CPB pulmonary hypertension. Endothelin 1 receptor blockers may decrease morbidity in children at risk for pulmonary hypertension after surgical repair with CPB and warrants further study.
体外循环（CPB）后，肺动脉高压及其相关的血管反应性增加是发病的主要原因，尤其是对于肺血流量增加的儿童。虽然CPB后肺动脉高压已有充分描述，但其机制仍未完全明确。内皮素-1是一种与肺动脉高压有关的强效血管活性物质，CPB后其血浆水平升高。本研究的目的有三个：描述低温CPB诱导的肺血管阻力和血管反应性的变化；研究既往肺血流量增加对这些变化的影响；更好地确定内皮素-1在CPB后肺动脉高压发病机制中的作用。
监测14只1月龄肺血流量增加的羔羊（在子宫内放置主肺动脉分流后）和6只年龄匹配的对照羔羊的血管压力和血流量。在105.3±20.6分钟的低温CPB后的2小时研究期间，与对照羔羊相比，肺血流量增加的羔羊肺血管阻力的增加显著增强（P<.05）。用PD 145065（一种非选择性内皮素受体阻滞剂；50微克·千克-1·分钟-1）预处理可完全阻断肺血管阻力的这种增加，并阻断CPB后对急性肺泡缺氧的肺血管阻力增加（96.3±88.5%对-9.7±16.4%；P<.05）。所有羔羊CPB后血浆内皮素-1水平均升高。
既往肺血流量增加会改变肺循环对低温CPB的反应；CPB诱导的肺血管阻力增加在肺血流量增加的羔羊中更为明显。用内皮素-1受体阻滞剂预处理可消除肺血管阻力的增加和对肺泡缺氧的肺血管收缩反应，提示内皮素-1在CPB后肺动脉高压中起作用。内皮素-1受体阻滞剂可能降低CPB手术修复后有肺动脉高压风险儿童的发病率，值得进一步研究。
