Eight-epi-PGF2alpha: a possible marker of lipid peroxidation in term infants with severe pulmonary disease.

A prostaglandin F2-like compound, 8-epi-PGF2alpha, formed from oxidation of arachidonate, has been proposed as an indicator of lipid peroxidation. We determined whether tracheal aspirate or urinary 8-epi-PGF2alpha levels would differ over time or between infants in a control group and infants with severe respiratory failure. We correlated tracheal aspirate 8-epi-PGF2alpha levels with the fraction of inspired oxygen and with mean airway pressures at 24 and 48 hours of life. Levels in tracheal aspirates were in the range of 0 to 36 pg/microg of fSC of IgA and were higher in infants with severe pulmonary disorders compared with those in infants in the control group (p < 0.02). Urinary concentrations did not discriminate between sick infants and infants in the control group.

Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn.

BACKGROUND: Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed. METHODS: To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) ("other": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater. RESULTS: Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%). CONCLUSIONS: We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.

Airway muscle in preterm infants: changes during development.

OBJECTIVE: To quantitate airway muscle changes in infants born at 23 to 41 weeks' gestation (control subjects) and to compare the changes with those in infants with chronic lung disease. METHODS: Fifty-five human lungs (from infants born at 23 to 41 weeks' gestation) were studied: 46 from infants who died of various diseases within 72 hours of birth, and 9 from infants with CLD (infants born at 26.9 +/- 0.5 weeks' gestation, who lived 17 +/- 8 days). All the lungs were perfused via the trachea and pulmonary artery in a standardized protocol. Formalin-fixed tissues in paraffin blocks were cut 5 microns thick. Sections were immunohistochemically stained for alpha-smooth muscle actin. By using computerized image analysis to quantitate images digitized into the computer, we measured the area of muscle, epithelium, airway lumen, and length of basement membrane in 18 airways, from the smallest bronchioles to bronchi, in each infant. RESULTS: Muscle was present at 23 weeks' gestation at all levels of the bronchial tree, and from 25 weeks to term the control lungs had a similar quantity of muscle at any given airway circumference. Relative to airway size, there was more muscle in small airways, less than 1000 microns in circumference, than in larger airways. In airways greater than 1500 microns in circumference, infants with CLD had significantly more muscle than did control lungs. CONCLUSIONS: Airway muscle is present at 23 weeks' gestation at all levels of the conducting airways. The 25-week gestation infants had a quantity of airway muscle relative to airway circumference similar to that of term infants. Preterm infants with CLD who were aged 9 to 29 days have increased airway muscle in airways greater than 1500 microns in circumference. Bronchospasm in very low birth weight infants is possible within the first days of life.

Efficacy of thromboresistant umbilical artery catheters in reducing aortic thrombosis and related complications.

Previous in vitro and in vivo reports suggest that catheters constructed of polyurethane with heparin bonded to the surface (HB-PU) are less thrombogenic than catheters made of polyvinyl chloride (PVC). A randomized trial sufficiently large (power 80%) to detect a reduction in the incidence of umbilical artery (UA) catheter complications, including aortic thrombus formation, from 45% to 20% was conducted in 125 infants. The infants were monitored for complications possibly related to the use of a UA catheter, such as systemic hypertension and abnormalities of lower extremity perfusion. The presence of aortic thrombi was assessed by ultrasound study 3.5 +/- 1.2 (SD) days and 11.1 +/- 2.3 days after insertion of the catheter. The use of HB-PU umbilical catheters did not lead to a significant reduction in the incidence of complications and aortic thrombi compared with the use of PVC catheters. The lack of reduction may have been related to the prolonged duration of catheter use in both groups. A much larger study would have been required to detect a smaller, but perhaps clinically significant, reduction in catheter-associated complications.

Effects of PEEP and tolazoline infusion on respiratory and inert gas exchange in experimental meconium aspiration.

Meconium aspiration syndrome often produces respiratory failure in the neonate. We utilized the multiple inert gas elimination technique to study the effects on respiratory and inert gas exchange of the application of positive end expiratory pressure or continuous infusion of tolazoline HCl. The application of PEEP, with the optimal level of PEEP defined for each animal, produced a decrease in AaDO2 and pulmonary shunt, without an increase in blood flow to low VA/Q areas, or an increase in dead space. Tolazoline infusion, at 2 mg/kg/hour, had no apparent effect on AaDO2 or shunt, or magnitude of low VA/Q regions. Tolazoline therapy was associated with an increase in heart rate and a decrease in systemic blood pressure. We conclude that immediate postaspiration application of PEEP, but not of tolazoline, will diminish pulmonary shunt without creating low VA/Q areas, and therefore will improve gas exchange in MAS.

The immature monkey as a model for studies of bronchopulmonary dysplasia.

The monkey is a potential model for BPD since there is considerable background information on the normal-developing lung, the prematurely delivered infant is viable, HMD can be produced, the infant is large enough to permit physiologic measurements, and it should be possible to test the effects of positive pressure, oxygen, and pharmacologic agents. Clearly further information is needed on the cellular and subcellular changes occurring during the acute and recovery stages of HMD. The monkey has already proven to be of value in this inquiry. Studies on mechanisms of altered lung repair by various injurious agents are needed, and will require an animal model as well as in vitro systems. Basic understanding of the pathogenesis of bronchopulmonary dysplasia with establishment of the relative importance of the contributing factors should help in our efforts to prevent or minimize chronic lung disease in the newborn infant.

Unchanged incidence of bronchopulmonary dysplasia in survivors of hyaline membrane disease.

To test the hypothesis that decreased mortality from severe HMD will result in increased morbidity from BPD, chest films of 30-day survivors of severe HMD were reviewed for evidence of Northway's Stage IV BPD. During July, 1970 to June, 1971, 20 survivors of severe HMD were identified; one case of Stage IV BPD was found in this group. During July 1974-June 1975, 80 survivors of severe HMD were identified; five infants had BPD. In spite of more survivors of severe HMD, no increase in the incidence of BPD could be demonstrated.