Persistent pulmonary hypertension of the newborn

In low doses, inhaled NO may have a beneficial therapeutic effect, since NO in the inspired air leads to pulmonary vasodilation. In persistent pulmonary hypertension of the newborn, NO inhalation has already been used with some success. NO inhalation as the treatment for acute respiratory distress syndrome, however, has been disappointing. Only transient improvements of oxygenation were detected and the outcome of placebo-controlled trials did not show any improvement... 

Even though nitric oxide is the physiological mediator of a variety of responses, excess nitric oxide is toxic to many cells as a result of its role in the production of per-oxynitrite and resultant lipid oxidation. Inhibitors of the NOS enzyme are in clinical trials for the treatment of hypotension associated with septic shock. Administration of low concentrations of nitric oxide through respiratory ventilators has been implemented to treat persistent pulmonary hypertension of the newborn. 

Gaseous nitric oxide is a short-lived molecule that has been used in the treatment of patients with primary pulmonary hypertension and is used in subgroups of severely ill and hypoxic children with persistent pulmonary hypertension of the newborn, in preterm infants of less than 34 weeks gestation, and in adults with acute lung injury and adult respiratory distress syndrome. There are some reports of its use for intestinal ischemia, reperfusion injury, thrombotic disorders, and sickle cell crises. 

Roberts JD, Polaner DM, Lang P, Zapol WM. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992 340(8823) 818-19. 

Roberts JD Jr, Fineman JR, Morin FC 3rd, Shaul PW, Rimar S, Schreiber MD, Polin RA, Zwass MS, Zayek MM, Gross I, Heymann MA, Zapol WM. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group. N Engl J Med 1997 336(9) 605-10. 

Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, Roy BJ, Keszler M, KinseUa JP. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med 2000 342(7) 469-74. 

An ingenious therapy for pulmonary hypertension involves mixing low concentrations of gaseous NO with the air these patients breathe. The concentration is kept low enough that the oxidation of NO to toxic NO2 is negligible, and the vasodilatory effect is limited to the site of need—the pulmonary vascular bed. The procedure has been widely tested and is now approved by the FDA for treating hypoxic respiratory failure associated with persistent pulmonary hypertension of the newborn (19). 

PPH), heritable pulmonary hypertension, drug- and toxin-induced pulmonary hypertension, associated with known disease (APAH), persistent pulmonary hypertension of the newborn, and pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH). 

Kinsella, J. P., Neish, S. R., Ivy, D. D., Shaffer, E., and Abman, S. H. (1993). Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide./. Pediatr. 123, 103-108. 

Levin, D. L., Hyman, A. I., Heymann, M. A., and Rudolph, A. M. (1978). Fetal hypertension and the development of increased pulmonary vascular smooth muscle A possible mechanism for persistent pulmonary hypertension of the newborn infant.. Pediatr. 92, 265-269. 

FIGURE I Age analysis of 200 consecutive patients who received inhaled nitric oxide. The majority of the patients were less than 1 year old and had congenital heart disease (CHD) or persistent pulmonary hypertension of the newborn (PPHN). 

Vosatka, R., Kashyap, S., and Trifiletti, R. (1994). Arginine deficiency accompanies persistent pulmonary hypertension of the newborn. Biol. Neonate 66, 65-70. 

O Rourke, RR, et al. 1989. Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn A prospective randomized study. Pediatrics 84(6) 957-63. 

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