Myers J L, Domkowski P W, Wang Y, Hopkins R A
Georgetown University, Department of Surgery, Washington, DC 20007, USA.
Eur J Cardiothorac Surg. 1998 Mar;13(3):298-305. doi: 10.1016/s1010-7940(98)00007-4.
Hypercapnia has been implicated in the pathophysiology of pulmonary hypertensive disease in newborns. However, little has been done to determine how its vasoconstrictive actions are mediated. The purpose of this study is to define the role of the sympathetic nervous system in modulating the response of the newborn pulmonary circulation to hypercapnia. Specifically, we studied the effect of sympathetic blockade on mean and pulsatile pulmonary arterial hemodynamics in 48-h-old, intact, open-chest Yorkshire piglets during hypercapnic ventilation.
All animals were anesthetized and then instrumented for high fidelity measurement of pulmonary artery pressure (PAP), flow (PAF), aortic pressure and radius of the main pulmonary artery (Rmn). Baseline data were acquired in all animals. Control animals (n = 7) were subjected to 30 s intervals of hypercapnia (inspired CO2 fraction (FiCO2) = 0.20). Experimental animals (n = 7) were pre-treated with an intravenous bolus of the adrenergic blocking agent guanethidine (20 mg/kg) before being subjected to the hypercapnic stress. Characteristic impedance (Zo) and input mean impedance (Zm) were determined through application of a Fourier analysis of the PAP and PAF waveforms. The modulus of elasticity (Ey) was calculated from Zo and Rmn. Pulmonary vascular resistance (PVR) was calculated as (PAP - LAP/PAF).
Control animals underwent significant increases in PVR (4860 +/- 341 dyne cm s(-5) versus 8090 +/- 387 dyne cm s(-5), P < 0.01) and Zm (7215 +/- 495 dyne cm s(-5) versus 10228 +/- 993 dyne cm s(-5), P < 0.01) when exposed to hypercapnia. Pre-treatment with guanethidine attenuated this response (PVR, 5552 +/- 368 dyne cm s(-5) versus 7105 +/- 611 dyne cm s(-5), P = 0.31 and ZM, 7922 +/- 446 dyne cm s(-5) versus 9745 +/- 600 dyne cm s(-5), P = 0.31). Characteristic impedance, modulus of elasticity and the radius of the main pulmonary artery were unchanged in both groups.
These data indicate that vasoconstriction secondary to hypercapnia in the neonatal pulmonary arterial circulation occurs at the level of the distal arteriolar bed, rather than the more proximal pulmonary arteries. In addition, this response is partially modulated by the sympathetic nervous system and may therefore respond clinically to manipulation of sympathetic input to the pulmonary arterial circulation.
高碳酸血症与新生儿肺动脉高压疾病的病理生理学有关。然而，关于其血管收缩作用是如何介导的研究甚少。本研究的目的是确定交感神经系统在调节新生儿肺循环对高碳酸血症反应中的作用。具体而言，我们研究了在高碳酸血症通气期间，交感神经阻滞对48小时龄、完整、开胸的约克夏仔猪平均和搏动性肺动脉血流动力学的影响。
所有动物均麻醉后进行仪器安装，以高保真测量肺动脉压（PAP）、血流量（PAF）、主动脉压和主肺动脉半径（Rmn）。采集所有动物的基线数据。对照动物（n = 7）接受30秒间隔的高碳酸血症（吸入二氧化碳分数（FiCO2）= 0.20）。实验动物（n = 7）在遭受高碳酸血症应激前，静脉推注肾上腺素能阻滞剂胍乙啶（20 mg/kg）进行预处理。通过对PAP和PAF波形进行傅里叶分析来确定特征阻抗（Zo）和输入平均阻抗（Zm）。弹性模量（Ey）由Zo和Rmn计算得出。肺血管阻力（PVR）计算为（PAP - LAP/PAF）。
对照动物在暴露于高碳酸血症时，PVR（4860 +/- 341达因·厘米·秒（-5）对8090 +/- 387达因·厘米·秒（-5），P < 0.01）和Zm（7215 +/- 495达因·厘米·秒（-5）对10228 +/- 993达因·厘米·秒（-5），P < 0.01）显著增加。用胍乙啶预处理可减弱这种反应（PVR，5552 +/- 368达因·厘米·秒（-5）对7105 +/- 611达因·厘米·秒（-5），P = 0.31；ZM，7922 +/- 446达因·厘米·秒（-5）对9745 +/- 600达因·厘米·秒（-5），P = 0.31）。两组的特征阻抗、弹性模量和主肺动脉半径均无变化。
这些数据表明，新生儿肺动脉循环中高碳酸血症继发的血管收缩发生在远端小动脉床水平，而非更近端的肺动脉。此外，这种反应部分受交感神经系统调节，因此在临床上可能对调节肺动脉循环的交感神经输入有反应。
