Nagashima M, Stock U, Nollert G, Sperling J, Shum-Tim D, Hatsuoka S, Mayer J E
Department of Cardiovascular Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Ann Thorac Surg. 1999 Aug;68(2):499-504; discussion 504-5. doi: 10.1016/s0003-4975(99)00741-9.
Lung function is often impaired after cardiac surgery and cardiopulmonary bypass (CPB), particularly in chronically cyanotic patients. This study aimed to evaluate lung function in a surgically created chronic cyanotic neonatal lamb model after CPB and deep hypothermic circulatory arrest (DHCA) and to assess the role of nitric oxide (NO) in the pathogenesis of increased pulmonary vascular resistance.
A chronic cyanosis model was surgically created in 7 lambs (4.7+/-0.8 days old) by anastomosing the pulmonary artery (PA) to the left atrium (LA). Another 7 lambs underwent a sham operation (control). One week later, the animals underwent shunt takedown and CPB with 90 minutes of DHCA at 18 degrees C. Cardiac index (CI), pulmonary vascular resistance index (PVRI), lung dynamic compliance (Cdyn), alveolar-arterial oxygen difference (AaDO2), left atrial plasma nitrate/nitrite (NO metabolites) levels, and pulmonary cGMP production (concentration difference between LA and PA) were measured before CPB and at 1 and 2 hours after reperfusion.
The cyanosis model consistently produced significantly lower arterial oxygen tension (34.8+/-2.3 vs 93.1+/-8.8 torr in control, p < 0.001) and Qp/Qs (0.6+/-0.1 vs 1.0+/-0.0 in control, p < 0.001) than controls. Postoperative PVRI was significantly lower in the cyanosis group than in controls, although CPB with DHCA significantly elevated PVR in both cyanotic and control animals. There were no significant differences in AaDO2 and Cdyn after CPB between groups. The level of NO metabolites did not change before or after CPB in either cyanotic or acyanotic animals. NO metabolite levels tended to be higher in the cyanotic animals (p = 0.08). There was no significant difference in pulmonary cGMP production between both groups.
These findings suggest that CPB with DHCA, per se, does not affect NO production in cyanotic or acyanotic neonatal lambs but causes increased PVR in both groups. Chronic cyanosis does not result in reduced pulmonary function after CPB with DHCA, and is associated with lower PVR. The mechanism may involve an increased NO production in cyanotic animals.
心脏手术和体外循环(CPB)后肺功能常受损,尤其是在慢性发绀患者中。本研究旨在评估在手术创建的慢性发绀新生羔羊模型中,CPB和深低温循环停搏(DHCA)后的肺功能,并评估一氧化氮(NO)在肺血管阻力增加发病机制中的作用。
通过将肺动脉(PA)与左心房(LA)吻合,对7只羔羊(4.7±0.8日龄)进行手术创建慢性发绀模型。另外7只羔羊接受假手术(对照组)。一周后,动物接受分流拆除和在18℃下进行90分钟DHCA的CPB。在CPB前以及再灌注后1小时和2小时测量心脏指数(CI)、肺血管阻力指数(PVRI)、肺动态顺应性(Cdyn)、肺泡-动脉氧分压差(AaDO2)、左心房血浆硝酸盐/亚硝酸盐(NO代谢产物)水平以及肺cGMP生成(LA和PA之间的浓度差)。
与对照组相比,发绀模型始终产生显著更低的动脉氧分压(34.8±2.3 vs对照组的93.1±8.8 torr,p<0.001)和肺循环血流量与体循环血流量比值(Qp/Qs)(0.6±0.1 vs对照组的1.0±0.0,p<0.001)。尽管CPB联合DHCA使发绀组和对照组动物的肺血管阻力均显著升高,但发绀组术后的PVRI显著低于对照组。两组CPB后AaDO2和Cdyn无显著差异。发绀或非发绀动物CPB前后NO代谢产物水平均无变化。发绀动物中NO代谢产物水平有升高趋势(p = 0.08)。两组肺cGMP生成无显著差异。
这些发现表明,CPB联合DHCA本身并不影响发绀或非发绀新生羔羊的NO生成,但会导致两组肺血管阻力增加。慢性发绀在CPB联合DHCA后不会导致肺功能降低,且与较低的肺血管阻力相关。其机制可能涉及发绀动物中NO生成增加。