CONTRACTILE PROPERTIES OF INTRALOBAR PULMONARY-ARTERIES AND VEINS IN THE FETAL LAMB MODEL OF CONGENITAL DIAPHRAGMATIC-HERNIA

Background/Purpose: Pulmonary hypertension plays a significant role in the pathophysiology of congenital diaphragmatic hernia (CDH). Althoug h there has been an intensive research effort directed at mediators th at may cause pulmonary vasoconstriction, no single agent has been iden tified. The authors hypothesize that there may be an alteration in the cGMP-nitric oxide (NO) pathway of vasodilatation contributing to the pulmonary hypertension observed in CDH. The purpose of these studies i s to begin to elucidate vasoactive properties of pulmonary vessels wit h particular attention to the cGMP-NO pathway of vasodilatation in fet al lambs with CDH. Methods: Fourth-generation pulmonary arteries and p ulmonary veins were dissected from both right and left lungs of eight, 139-day gestational fetuses with surgically created CDH. Vessels were studied with standard isolated tissue bath techniques. Experiments ex amined basal release of NO in endothelium-intact PVs and PAs of both r ight and left lungs by measuring the contractile force of vessels cons tricted with norepinephrine (NE) in the presence and absence of the ni tric oxide synthase (NOS) inhibitor N-omega-nitro-L-arginine (L-NA). C oncentration-response curves to the vasodilating agents zaprinast and A23187 were also obtained in vessels contracted by NE. Results: Left a nd right pulmonary artery responses to NE are en ha need over those of historic controls. Pretreatment of left pulmonary arteries with L-NA enhances the vasoconstrictor response to NE, whereas right PAs show no increased response. Relaxation responses to A23187 and zaprinast, in both left and right pulmonary arteries were not different from control lambs. Relaxation responses of both left and right pulmonary veins to A23187 and zaprinast are blunted compared with controls. This bluntin g is significantly more in left pulmonary veins than right. Further, r ight but not left pulmonary veins display enhanced vasoconstrictive re sponse to NE after L-NA pretreatment. Conclusions: The NO-cGMP pathway of vasodilatation is abnormal in the near term, fetal lamb with CDH. These abnormalities were most apparent in pulmonary veins and may refl ect abnormal NOS activity or content between left and right lungs of t he fetal lamb with CDH. Pulmonary arteries from CDH lambs have basal a nd stimulated NO release equal to that of historic controls but appear to be hypersensitive to exogenous vasoconstrictors. J Pediatr Surg 33 :921-928. Copyright (C) 1998 by W.B. Saunders Company.