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J Thorac Cardiovasc Surg 1995;110:1486-1492
© 1995 Mosby, Inc.
GENERAL THORACIC SURGERY |
-NITRO-L-ARGININE IN MODULATION OF PULMONARY VASCULAR TONE IN THE MATURING NEWBORN PIG
Washington, D.C.
Supported in part by an American Heart Association (Nation's Captial Affiliate) grant.
Address for reprints: Richard A. Hopkins, MD, Georgetown University Hospital, 3800 Reservoir Rd., N.W., Washington, DC 20027.
Abstract
Current therapeutic modalities for treatment of newborn pulmonary hypertensive crisis include but are not limited to the administration of nitric oxide (endothelium-derived relaxing factor). However, few data are available on the role of endogenously produced endothelium-derived relaxing factor in the modulation of pulmonary vascular tone in the neonate. In the current study, we investigated the acute effects of N
-nitro-L-arginine (a potent competitive inhibitor of endothelium-derived relaxing factor synthase) on the pulmonary vasculature of anesthetized open-chest 48-hour-old (n= 8) and 2-week-old (n= 7) Yorkshire pigs. After baseline data were acquired, all animals received a 10 mg/kg per minute infusion of N
-nitro-L-arginine for 10 minutes. To discern distal and proximal pulmonary arterial vessel changes, input mean and characteristic impedance were respectively determined. Pulmonary vascular resistance was also calculated (units determined in dyne
sec
cm -5 plus or minus the standard errorof the mean). Results showed N
-nitro-L-arginine infusion did not significantly alter baseline pulmonary arterial pressure (22,370±1473 dyne/cm2 ), pulmonary vascular resistance (5171±805 dyne
sec
cm -5 ), input impedance (6343±806 dyne
sec
cm -5 ), or characteristic impedance (2073±418 dyne
sec
cm -5 ) in 48-hour-old pigs. In 2-week-old pigs, infusion of N
-nitro-L-arginine elevated pulmonary arterial pressure (18,162±1415 dyne/cm 2 versus 23,838±1810 dyne/cm 2 , p= 0.015), pulmonary vascular resistance (810±137 dyne
sec
cm -5 versus 1519 dyne
sec
cm -5 , p= 0.030), and input impedance (2302±251 dyne
sec
cm -5 versus 2900±255 dyne
sec
cm -5 ,p= 0.018). Characteristic impedance was not altered in 2-week-old pigs. These data indicate that N
-nitro-L-arginine infusion resulted in pulmonary arteriolar vasoconstriction in 2-week-old pigs, but not in 48-hour-old pigs. This finding suggests that endothelium-derived relaxing factor does not modulate basal pulmonary arteriolar tone during the early newborn period, but does play a significant role in 2-week-old pigs. These data also suggest that the functional role for endothelium-derived relaxing factor is confined to the distal arteriolar pulmonary bed and does not extend to the larger proximal arterial vessels. (J THORAC CARDIOVASC SURG 1995;110:1486-92)
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