Sympathetic blockade blunts hypercapnic pulmonary arterial vasoconstriction in newborn piglets.

Abstract

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.