Lung protective strategies of ventilation in the neonate: what are they?
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Cytokines↗
Biomedical subjects
D R Gerstmann
Publications and source records attributed to D R Gerstmann.
Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial.
BACKGROUND: Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease. METHODS: We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age. FINDINGS: The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%). INTERPRETATION: Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.
Administration, Inhalation↗
High-frequency oscillatory ventilation in neonatal RDS: initial volume optimization and respiratory mechanics.
To determine whether initial lung volume optimization influences respiratory mechanics, which could indicate the achievement of optimal volume, we studied 17 premature infants with respiratory distress syndrome (RDS) assisted by high-frequency oscillatory ventilation. The continuous distending pressure (CDP) was increased stepwise from 6-8 cmH2O up to optimal CDP (OCDP), i.e., that allowing good oxygenation with the lowest inspired O2 fraction. Respiratory system compliance (Crs) and resistance were concomitantly measured. Mean OCDP was 16.5 +/- 1.2 cmH2O. Inspired O2 fraction could be reduced from an initial level of 0.73 +/- 0.17 to 0.33 +/- 0.07. However, Crs (0.45 +/- 0.14 ml . cmH2O-1 . kg-1 at starting CDP point) remained unchanged through lung volume optimization but appeared inversely related to OCDP. Similarly, respiratory system resistance was not affected. We conclude that there is a marked dissociation between oxygenation improvement and Crs profile during the initial phase of lung recruitment by early high-frequency oscillatory ventilation in infants with RDS. Thus optimal lung volume cannot be defined by serial Crs measurement. At the most, low initial Crs suggests that higher CDP will be needed.
High-Frequency Ventilation↗
Controversies in high-frequency ventilation.
Clinical care of newborns with respiratory failure is constantly changing and improving. Thus, optimizing health care is a commitment to constant, but careful change. This article addresses five current controversies about high-frequency ventilation and provides a discussion on each debated question.
Extracorporeal Membrane Oxygenation↗
The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.
OBJECTIVE: To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support. DESIGN: A prospective randomized clinical trial. SETTING: Three community-based level III neonatal intensive care units. SUBJECTS: A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50. INTERVENTIONS: Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit. MEASUREMENTS AND MAIN RESULTS: No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants. CONCLUSIONS: When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.
Equipment Failure↗
Effect of ductal patency on organ blood flow and pulmonary function in the preterm baboon with hyaline membrane disease.
OBJECTIVE: To examine the effect of early ductal ligation vs. maintenance of ductal patency on vital organ perfusion and pulmonary function in premature baboons with hyaline membrane disease. DESIGN: Randomized, controlled interventional study to compare early ligation with formalin infiltration of the ductus arteriosus. SETTING: Animal care facility at a dedicated research foundation. SUBJECTS: Eighteen premature baboons delivered by hysterotomy at 140 +/- 2 day gestation. INTERVENTION: Nine premature baboons underwent formalin infiltration of the ductus arteriosus (group 1), and nine underwent ductal ligation (group 2). Surgical ligation or formalin infiltration was performed at 2 to 4 hrs of age. Animals were maintained on mechanical ventilation and ventilator parameters were adjusted to maintain PaO2 and PaCO2 within the physiologic range. MAIN OUTCOME MEASURES: Left ventricular output indexed to body weight and vital organ perfusion were measured at 24 hrs of age by the radiolabeled microsphere method. Lung mechanics, including lung wet/dry weight ratio, total lung water, static compliance and functional residual capacity were measured immediately following euthanasia. RESULTS: Total pulmonary blood flow was significantly lower (p = .0001) in group 2 (mean = 94 mL/min/kg), compared with group 1 (mean = 287 mL/min/kg). Systemic blood flow and effective pulmonary blood flow were higher in group 1 (p = .07). No significant difference between groups in absolute organ blood flow was noted, although flow as a percent of left ventricular index was significantly higher in all organs except the kidney in group 2. There was no difference in arterial blood gas values, parameters of mechanical ventilation, percent lung water, or postmortem measurement of lung mechanics between groups. CONCLUSION: Early ductal ligation did not result in improved cardiac output, increased organ blood flow, or improved pulmonary function. We postulate that gradual constriction of the ductus arteriosus may play an important role in successful cardiovascular adaptation in the premature infant. While it is clear that premature infants with symptomatic patent ductus arteriosus often benefit from ductal closure, we question the practice of prophylactic early ductal closure.
Adrenal Glands↗
Surfactant protein-A deficiency in a primate model of bronchopulmonary dysplasia.
Pathophysiologic and biochemical (surfactant protein and phospholipid) features were studied in a baboon model of hyperoxia-induced bronchopulmonary dysplasia (BPD) and superimposed infection. A total of 20 baboons were delivered by hysterotomy at 76% of gestation (140 d of gestational age) and were randomized into four groups, consisting of two control and two injury groups. Animals constituting a group that was managed on a pro re nata (PRN) basis were ventilated with clinically appropriate oxygen for the 16-d experimental period and served as ventilatory controls. They underwent an initial period of 42 h during which they demonstrated evidence of hyaline membrane disease (HMD), but began recovery at 42 h and by Day 6 appeared to have maximally recovered. At the time of these animals' killing, concentrations of surfactant proteins, messenger ribonucleic acids (mRNAs), and phospholipids were similar to those of normal adult baboons. Gestational control animals were delivered and killed without ventilation at 156 d gestational age. Surfactant protein-A (SP-A) and phospholipid concentrations in these animals' lavage fluids were about 10% of those in the PRN animals. Animals with BPD were subjected to positive-pressure ventilation and an FIO2 of 1.0 for 11 d, followed by 5 d of an FIO2 sufficient to maintain PaO2 at 40 to 50 mm Hg. The animals with BPD and infection were treated in the same way as the BPD group, except that 10(8) Escherichia coli were instilled intratracheally on Day 11, concomitantly with the reduction in FIO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Failure of acute perinatal asphyxia or meconium aspiration to produce persistent pulmonary hypertension in a neonatal baboon model.
OBJECTIVE: Our purpose was to determine whether perinatal asphyxia or meconium aspiration, or both, can produce the physiologic and histologic pulmonary vascular changes associated with the meconium aspiration syndrome. STUDY DESIGN: Twenty neonatal baboons were studied in four groups: 1, control; 2, meconium aspiration; 3, asphyxia (intermittent cord compression); and 4, asphyxia with meconium aspiration. Animals were ventilated for 24 hours under ketamine, diazepam, and pancuronium. Data were analyzed by means of mixed model analysis of measures. RESULTS: Meconium significantly impaired oxygenation (p < 0.001), whereas concurrent asphyxia moderated this effect (p < 0.034). Meconium also increased the need for ventilatory support (p < 0.002). No animal had persistent pulmonary hypertension; neither systemic nor pulmonary systolic pressures differed statistically between the groups. No animal showed evidence of abnormal pulmonary arteriolar muscularization. CONCLUSION: Sublethal perinatal asphyxia or meconium aspiration were insufficient to produce either the physiologic or histologic changes of severe meconium aspiration syndrome. It is unlikely that intrapartum fetal distress alone can produce this syndrome in human neonates.
Acute Disease↗
Total parenteral nutrition does not improve diaphragm development in premature baboons.
We hypothesized that total parenteral nutrition accelerates growth and development of diaphragm muscle (DPH) in prematurely delivered baboons (140 days gestation). For 10 days after delivery by cesarean section, we administered parenteral nutrition containing glucose, electrolytes, and water or total parenteral nutrition containing lipids, amino acids, glucose, vitamins, and electrolytes. After 10 days of care, dorsolateral and ventrolateral (VL) costal DPH were sampled for histochemically determined mean fiber area (MFA) and fiber type percentages. We determined isolated bundle isometric tension (normalized for cross-sectional area), time to peak tension, half-relaxation time, force-frequency relationship, and fatigability. Neither sex nor nutritional treatment affected contractile properties. Differences among sexes and muscle sites, but not among nutritional treatments, were observed for histochemical characteristics. In females, the VL DPH had a lower percentage of type IIo fibers and a greater MFA of type IIc fibers than the dorsolateral DPH and a lower percentage of type IIo fibers and greater MFA of type IIc and IIo fibers than the VL DPH in males. Mean fiber cross-sectional area of VL DPH was significantly greater in females than males. The larger fibers in females than males suggest a stronger DPH in females. Earlier growth of type II fibers in females could contribute to a better outcome for female than male premature infants with hyaline membrane disease.
Animals↗
Hormonal response of the premature primate to operative stress.
There are few data on the hormonal response to operation in the premature infant. Studies examining the response of newborn human infants have been performed on patients beyond the first few days of life, where some adaptation to postnatal life has occurred. This study evaluated the response of the newly born premature primate to surgical stress. Premature baboons (75% gestation) were intubated, mechanically ventilated and underwent thoracotomy at 2 hours of life with exposure of the ductus arteriosus (PDA). In group 1, formalin was infiltrated to keep the ductus patent. In group 2, the PDA was ligated. Controls had no operation. Blood was drawn at 0, 6, 24, 48, 72, and 96 hours of age. Echocardiograms were performed to confirm patency or closure of the ductus and to monitor cardiac function. Epinephrine, norepinephrine, renin, and cortisol levels were measured. Cortisol levels rose in all groups. Operation stimulated a marked increase in catecholamine and renin levels in both operative groups, which was more marked in the group with PDA ligation at 24 hours. These data reflect expected pathophysiology since early PDA ligation exerts additional hemodynamic demand on the heart. In conclusion, the premature primate is able to mount a significant and severity-dependent endocrine response to stress.
Animals↗
Rescue ventilation with high frequency oscillation in premature baboons with hyaline membrane disease.
We tested the hypothesis that high-frequency oscillatory ventilation can be efficacious in hyaline membrane disease (HMD) even after lung injury is established. We compared high frequency oscillatory ventilation (HFOV) rescue (n = 8; 15 Hz; I:E = 1:2) after 8 hours of positive pressure ventilation (PPV) with positive end-expiratory pressure, to continued PPV (control, n = 7) in premature baboons with HMD over a 24 hour period. Ventilator settings and physiologic parameters were recorded hourly. At necropsy (24 hours), lung status pressure-volume curves, alveolar phospholipids (PL), platelet activating factor-like activity (PAF), and lung water were determined. Roentgenographic and morphologic differences in lung inflation were quantified by standard techniques. No intergroup differences were found in heart rate, blood pressures, ventilator settings, FiO2, blood gases, or chest radiographs during the first 8 hours. Both groups had progressive physiologic disease. At 8 hours, HFOV-rescue animals, in contrast to controls, had immediate significant time-related improvements in Pa/AO2 (at the same Paw) and in oxygenation index (Pa/AO2/Paw) lasting for 16 hours. No significant intergroup differences in lung/body weight, lung water, lung mechanics, PL, PAF, or frequency of moderate to severe roentgenographic changes existed at 24 hours. Although all animals had morphologic evidence of HMD, saccular aeration was more uniform and airway dilatation less evident in HFOV rescue (P less than 0.0001). Based on the improved gas exchange, we conclude that HFOV rescue was efficacious in the "late' treatment of HMD, presumably because of the more uniform saccular aeration.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Frequency of chronic lung disease in infants with severe respiratory failure treated with high-frequency ventilation and/or extracorporeal membrane oxygenation.
OBJECTIVE: To assess the frequency of chronic lung disease and factors associated with its development in term infants with severe respiratory failure who receive high-frequency oscillatory ventilation, or high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective review of pulmonary outcome of all ECMO candidates admitted to Wilford Hall USAF Medical Center between July 1985 and September 1989. SETTING: A tertiary, level III, neonatal ICU accepting regional referrals for high-frequency ventilation and ECMO. PATIENTS: Ninety-four patients who were candidates for ECMO were studied. High-frequency oscillatory ventilation alone was used in 48 infants. Forty-six infants were treated with high-frequency oscillatory ventilation and ECMO. MAIN RESULTS: Twenty (24%) of 84 survivors developed chronic lung disease. There were no differences in gestational age, birth weight, or gender between those infants who developed chronic lung disease and those infants who did not. Arterial blood gas and ventilatory settings at initiation of high-frequency oscillatory ventilation were similar between those infants who did and those who did not develop chronic disease. Patients who developed chronic lung disease more often had lung hypoplasia (40% vs. 5%) and more often required ECMO (75% vs. 39%) than those patients who did not. In patients without lung hypoplasia, those patients who developed chronic lung disease were older at initiation of high-frequency oscillatory ventilation rescue than those patients who did not develop chronic lung disease (median 91 vs. 46 hrs). CONCLUSIONS: The frequency of chronic lung disease in ECMO candidates is clinically important. Factors associated with chronic lung disease in ECMO candidates are: the presence of lung hypoplasia, delayed referral, and the need for ECMO to support gas exchange.
Birth Weight↗
Pathophysiologic, morphometric, and biochemical studies of the premature baboon with bronchopulmonary dysplasia.
Pathophysiologic, morphometric, and biochemical (surfactant and coagulation-fibrinolytic parameters) features were studied in premature baboons with and without bronchopulmonary dysplasia (BPD). A total of 22 baboons were delivered by hysterotomy at 75% of gestation and randomized into two groups. Group 1 (PRN) animals were ventilated with high-frequency oscillation for 48 to 72 h and then changed to positive-pressure ventilation (PPV) while maintained on clinically appropriate oxygen for the 21-day experimental period. Group 2 (BPD) animals were ventilated with PPV and 1.0 FlO2 for 7 days followed by 0.8 FlO2 for 14 days. Group 3 (control) animals were delivered and immediately killed at 140 days gestation. Group 1 animals showed no significant airway or saccular lesions, and alveolarization of the saccules was present. Group 2 animals showed metaplastic or hyperplastic epithelial lesions in airways and an alternating pattern of atelectatic but more normal appearing saccules and alveoli interposed between foci of thickened overexpanded saccular walls with no alveolarization. Differences within and between the three study groups were analyzed morphometrically. When numerical densities were examined by comparing control, PRN, BPD-atelectatic areas, and BPD-overexpanded areas. Type II cells were significantly increased in the BPD-overexpanded sites above those of control and PRN values. The interstitial cells were significantly more numerous in the BPD-atelectatic blocks compared with control and BPD-overexpanded blocks. Endothelial cell numerical densities were significantly decreased in the overexpanded sites of the BPD animals compared with the control, PRN, and BPD-atelectatic values. Volume density data showed that the interstitial compartment of the BPD group was significantly larger than those of the control and PRN groups. This was seen as significant increases in the cellular, noncellular, and connective tissue fiber components. Vascular endothelium or lumen volume densities were not different between the BPD and PRN animals, but did differ from those of the 140-day gestation controls. Comparable levels of lavage plasminogen-dependent fibrinolytic activity, were detectable at the 21-day study interval. The phospholipid composition of pulmonary surfactant, including disaturated PC and total PG, was similar between BPD and PRN groups at 21 days. The pathologic, morphometric, and biochemical patterns in this study probably represent those seen in human neonates with mild to moderate clinical BPD who survive. At this time, it is not known if the destructive endothelial lesion and the lack of alveolarization in the overexpanded and fibrotic lesions will resolve over time in long-term BPD survivors.
Animals↗
The effect of extracorporeal membrane oxygenation on coronary perfusion and regional blood flow distribution.
We studied the distribution of systemic blood flow during venoarterial extracorporeal membrane oxygenation (ECMO) in newborn lambs. We used a three-compartment model that defined partitioning of blood flow to the heart, upper body (brachiocephalic trunk), and lower body (descending aorta). The method used concurrent left ventricular and arterial cannular injections of radiolabeled microspheres to calculate compartment flows and solve the system of equations that defined the partition model. Seven newborn lambs (1-8 d) were studied. A baseline microsphere injection (left ventricle) was performed and the animals were then placed on venoarterial ECMO using right carotid and jugular vein cannulation. The arterial cannula was placed 2-3.5 cm above the aortic valve. After stabilization on ECMO flow rates of 50 and 100 mL/min/kg, differently labeled microspheres were injected simultaneously into the left ventricle and arterial limb of the ECMO circuit. From the flow partition model, distribution of blood flow was calculated. We found that ECMO did not change the overall distribution of blood flow to the three compartments studied. However, blood flow from the ECMO circuit was preferentially directed to the upper body. Coronary arterial and abdominal organ blood flow was predominantly derived from the left ventricle at both ECMO flow rates. Coronary arterial blood flow did not significantly change on ECMO (253 +/- 45 mL/min/100 g at 50 mL/min/kg ECMO flow; 246 +/- 50 mL/min/100 g at 100 mL/min/kg ECMO flow) compared to baseline (186 +/- 31 mL/min/100 g).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Prospective randomized comparison of high-frequency oscillatory and conventional ventilation in respiratory distress syndrome.
A prospective randomized trial with a crossover design was conducted to compare the efficacy and safety of two distinct strategies of high-frequency oscillatory ventilation (HFOV) to conventional intermittent mandatory ventilation (CV) in the management of respiratory distress syndrome. Only premature neonates with a birth weight less than 1.751 kg were eligible for enrollment into the study. Of 83 patients studied, 26 patients were assigned to CV-only, 27 to HFOV for 72 hours followed by CV (HFOV/CV), and 30 to HFOV-only until extubation. There was no difference among the three groups with respect to the incidence of pulmonary airleak, intraventricular hemorrhage, or death. The highest incidence of chronic lung disease was in the CV-only group. Although both HFOV groups had a lower incidence of chronic lung disease assessed at 30 days and 36 weeks postconception age, the difference was statistically significant only between the CV-only and HFOV-only groups (65% vs 30% at 30 days; P = .008; 38% vs 10% at 36 weeks postconception age, P = .013). These results suggest that use of HFOV as the predominant mode of ventilation in the management of respiratory distress syndrome is as safe as CV and can contribute to a decreased incidence of chronic lung disease. Furthermore, a short (72-hour) period of HFOV support does not provide the same advantage as continuous HFOV.
Analysis of Variance↗
Cardiac output by Doppler echocardiography in the premature baboon: comparison with radiolabeled microspheres.
Pulsed-Doppler echocardiography (PDE) is a useful noninvasive method for determining left ventricular output (LVO). However, despite increasingly widespread use in neonatal intensive care units, validation studies in prematures with cardiopulmonary disease are lacking. The purpose of this study was to compare radiolabeled microsphere (RLM) and PDE measurements of LVO, using the critically ill premature baboon as a model of the human neonate. Twenty-two paired RLM and PDE measurements of LVO were obtained in 14 animals between 3 and 24 h of age. Average PDE LVO was 152 ml/min/kg (range, 40-258 ml/min/kg) compared to 158 ml/min/kg (range, 67-278 ml/min/kg) measured by RLM. Linear regression analysis of the paired measurements showed good correlation with a slope near unity (gamma = 0.94x + 4.20, r = 0.91, SEE = 25.7 ml). We conclude that PDE determinations of LVO compare well with those measured by RLM in the premature baboon. PDE appears to provide a valid estimate of LVO and should be useful in human prematures with cardiopulmonary distress.
Animals↗
Circulatory changes following premature delivery in a baboon model of hyaline membrane disease.
The premature baboon delivered by hysterotomy at 140 +/- 2 days (75%) gestation develops hyaline membrane disease (HMD) and left-to-right (L-R) shunting through the patent ductus arteriosus (PDA). To characterize hemodynamic changes that follow premature delivery, we measured systemic and organ blood flow, oxygen transport, and systemic vascular resistance over the first 96 h of life. We compared these measurements with those from more mature animals of the same species. Radiolabeled microspheres were used to measure organ blood flow (in ml.min-1.g-1) at 3 (n = 18), 23 (n = 17), and 96 h (n = 4) in the premature animals, and at 13 +/- 4 mo in the older animals (n = 5). Premature animals demonstrated over the first 96 h of life significant hemodynamic changes that included decreased systemic vascular resistance (P less than 0.001), increased systemic (P less than 0.05), intestinal (P less than 0.05), and hepatic blood flow (P less than 0.05), as well as resolution of L-R PDA shunting. These 96-h values were similar to those of the more mature infant baboons. Blood flow and oxygen transport to the kidneys and cerebrum did not significantly increase over the first 96 h in premature baboons and were significantly less than those of 13-mo-old animals (P less than 0.01, both). We speculate that low renal and cerebral blood flow in the 140-day premature baboon are manifestations of multisystem immaturity and, as such, may represent persistent physiological disturbances that are distinct from the severity of underlying lung disease in HMD.
Aging↗
Allopurinol-induced effects in premature baboons with respiratory distress syndrome.
To test the hypothesis that administration of allopurinol could modify the response to prolonged hyperoxia in premature baboons (140 days gestation) with respiratory distress syndrome, we evaluated physiological, pathological, and lung biochemical parameters in groups of premature baboons treated with mechanical ventilation and exposed to various amounts of oxygen for 6 days. Three groups of experimental animals were studied, including animals that received oxygen as needed to maintain arterial oxygen between 60 and 80 Torr [inspiratory O2 concentration- (FIO2) PRN], animals that received 100% oxygen continuously but also received allopurinol intravenously at a dose of 10 mg.kg-1.day-1 (FIO2-1.0 + allopurinol), and animals that received 100% oxygen continuously and the vehicle for allopurinol administration (FIO2-1.0). Pathological examinations of the experimental animals showed evidence of lung injury in both 100% oxygen-exposed groups, but the allopurinol-treated animals had findings more compatible with the FIO2-PRN group, with relatively few macrophages or polymorphonuclear lymphocytes being present in lung tissue. Lungs of animals treated with allopurinol were also more distensible and had a trend toward decreased lung water compared with the FIO2-1.0 group. Allopurinol-treated animals were able to induce lung glutathione concentrations and glutathione-related and antioxidant enzyme activities compared with the normoxic control (FIO2-PRN) group. Ventilator pressure requirements were also decreased in the allopurinol-treated animals compared with the FIO2-1.0 controls after 42 h. These data suggest that treatment of hyperoxia-exposed premature baboons with allopurinol for the first 6 days of life results in significant changes in lung responses and antioxidant defenses compared with vehicle-treated baboons exposed to 100% oxygen for the same time period.
Allopurinol↗