Persistent pulmonary hypertension

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... 

Inhaled NO has been used for treatment of persistent pulmonary hypertension of newborn infants, critical respiratory failure of preterm infants, and acute hypertension of adult cardiac surgery patients. PDE-5 inhibitors such as sildenafil are also effective for treatment of pulmonary hypertension. The combination of PDE-5 and NO inhalation yields additive beneficial effects on pulmonary hemodynamics. On the other hand, measurement of exhaled NO is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with bronchial asthma. 

No major teratogenic effects have been identified with the SSRIs or TCAs. However, evaluations to date suggest a possible association of fluoxetine with low birth weight and respiratory distress. Another study reported a sixfold greater likelihood of the occurrence of persistent pulmonary hypertension of newborn infants exposed to an SSRI after the twentieth week of gestation. 

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. 

There are concerns that the use of SSRIs in later pregnancy may be associated with persistent pulmonary hypertension in the newborn (86). 

Wilkinson AR, Aynsley-Green A, Mitchell MD. Persistent pulmonary hypertension and abnormal prostaglandin E levels in preterm infants after maternal treatment with naproxen. Arch Dis Child 1979 54(12) 942-5. 

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). 

Very few animal studies have addressed the question of whether addition of NO to inhaled gas has benefits in addition to improved gas exchange and/or central hemodynamics. Zayek et al. (1993) randomized newborn near-term lambs with experimentally induced persistent pulmonary hypertension by ductus ligation. They compared the effect of prolonged inhalation of 80 ppm NO to that of a control group, with both groups mechanically ventilated postnatally for 23 hr. A significant increase in the survival of lambs by inhaling NO was reported. 

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. 

Zayek, M., Wild, L., Roberts, J. D., and Morin, F. C. (1993). Effects of nitric oxide on the survival rate and incidence of lung injury in newborn lambs with persistent pulmonary hypertension. Pediatrics 123, 947-952. 

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. 

Morin, F. C. (1989). Ligating the ductus arteriosus before birth causes persistent pulmonary hypertension in the newborn lamb. Pediatr. Res. 25, 245-250. 

Walther, F. J., Benders, M. J., and Leighton, J. O. (1992). Persistent pulmonary hypertension in premature neonates with severe respiratory distress syndrome. Pediatrics 90, 899-904. 

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