SYMPATHETIC BLOCKADE BLUNTS HYPERCAPNIC PULMONARY ARTERIAL VASOCONTRICTION IN NEWBORN PIGLETS

Objective: Hypercapnia has been implicated in the pathophysiology of p ulmonary hypertensive disease in newborns. However, little has been do ne to determine how its vasoconstrictive actions are mediated. The pur pose of this study is to define the role of the sympathetic nervous sy stem in modulating the response of the newborn pulmonary circulation t o hypercapnia. Specifically, we studied the effect of sympathetic bloc kade on mean and pulsatile pulmonary arterial hemodynamics in 48-h-old , intact, open-chest Yorkshire piglets during hypercapnic ventilation. Methods: 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 (R-mn). Baseli ne data were acquired in all animals. Control animals (n = 7) were sub jected to 30 s intervals of hypercapnia (inspired CO2 fraction (FiCO(2 )) = 0.20). Experimental animals (n = 7) were pre-treated with an intr avenous bolus of the adrenergic blocking agent guanethidine (20 mg/kg) before being subjected to the hypercapnic stress. Characteristic impe dance (Z(o)) and input mean impedance (Z(m)) were determined through a pplication of a Fourier analysis of the PAP and PAF waveforms. The mod ulus of elasticity (E-y) was calculated From Z(o) and R-mn. Pulmonary vascular resistance (PVR) was calculated as (PAP - LAP/PAF). Results: Control animals underwent significant increases in PVR (4860 +/- 341 d yne cm s(-5) versus 8090 +/- 387 dyne cm s(-5), P < 0.01) and Z(m) (72 15 +/- 495 dyne cm s(-5) versus 10228 +/- 993 dyne cm s(-5), P < 0.01) when exposed to hypercapnia. Pre-treatment with guanethidine attenuat ed this response (PVR, 5552 +/- 368 dyne rm s(-5) versus 7105 +/- 611 dyne cm s(-5), P = 0.31 and Z(m), 7922 +/- 446 dyne cm s(-5) versus 97 45 +/- 600 dyne cm s(-5), P = 0.31). Characteristic impedance, modulus of elasticity and the radius of the main pulmonary artery were unchan ged in both groups. Conclusions: These data indicate that vasoconstric tion secondary to hypercapnia in the neonatal pulmonary arterial circu lation occurs at the level of the distal arteriolar bed, rather than t he more proximal pulmonary arteries. In addition, this response is par tially modulated by the sympathetic nervous system and may therefore r espond clinically to manipulation of sympathetic input to the pulmonar y arterial circulation. (C) 1998 Elsevier Science B.V. All rights rese rved.