ENDOGENOUS NITRIC-OXIDE AND PULMONARY VASCULAR TONE IN THE NEONATE

Purpose: In newborns, inhaled nitric oxide (NO) has been shown to amel iorate increased pulmonary vascular resistance (PVR) precipitated by h ypoxia. The role of endogenous NO production in this response is not c lear. The contribution of endogenous NO to resting PVR in normoxic new borns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detrac tors in which endogenous NO could be selectively inhibited, to determi ne whether (1) endogenous NO plays a role in the maintenance of PVR wi th normoxia, (2) endogenous NO plays a role in the response to hypoxia , and (c) inhaled NO can reverse changes induced by inhibition of endo genous NO. Methods: Sixteen neonatal piglets underwent occlusive trach eostomy and pressure-cycled ventilation. After heparinization and liga tion of the ductus arteriosus, left atrial and pulmonary arterial cann ulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40% to 45%), pH (7.37 to 7.44), PCO2 (35 to 40 mm Hg), and peak inspiratory pressur es (20 mm Hg) were constant. Pulmonary artery pressure (P-PA), left at rial pressure (P-LA), and circuit flow (Q(PA)) were recorded continuou sly. PVR calculated as follows: PVR[(dynes x seconds x cm(-5)) x 1,000 ] = [(P-PA - P-LA)/(Q(PA) x 1,000/60)] x 1,332. The experimental anima ls were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two gro ups of eight animals each. One group remained normoxemic (FIO2, 0.21; SPAO2, 100%) while the other group was made hypoxemic by ventilation w ith hypoxic gas (FIO2, 0.07; SPAO2, 50%). Endogenous NO was suppressed with L-arginine-N-omega methyl ester (L-NAME) at 40 mg/kg in both gro ups. Inhaled NO was given at 40 ppm in both groups. Analysis of varian ce for repeated measures was used to test for statistical significance . Results: Baseline normoxic PVR (3,403 +/- 1,169) was increased signi ficantly by hypoxia (6,524 +/- 1,018, P < .01) and was fully restored to baseline by normoxia (3,497 +/- 1,079; P = NS). In normoxic animals , inhibition of endogenous NO production by L-NAME increased PVR to le vels similar to those seen during hypoxic stress (6,345 +/- 1,441, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to norm oxic baseline values (3,986 +/- 1,363, P = NS). In hypoxic animals, in hibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 +/- 1,642, P < .01). Replacement of endogenou s NO by inhaled NO reversed PVR to hypoxic baseline (6,450 +/- 1,796, P = NS). Conclusion: In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused b y inhibition of endogenous NO and may normalize PVR in diseases in whi ch the production of endogenous NO is compromised. Copyright (C) 1996 by W.B. Saunders Company.