Abstract
The aim of the study was to evaluate pulmonary endogenous and
inhaled nitric oxide (NO) in neonates with severe respiratory failure.
Infant autopsy documents were reviewed for fulminant early-onset
bacterial pneumonia. 12 infants with the onset at < 72 h of age and
three control groups were identified. Immunohistochemistry revealed that
11 of the infants with early-onset pneumonia (92%) had no or faint
inducible nitric oxide synthase (NOS2) staining in their alveolar
macrophages (AM). All control infants, regardless of their postnatal age,
had NOS2-positive AM. The marker of NO-toxicity, nitrotyrosine, was low in
all specimens. To confirm this finding, airway specimens of 21 newborns
requiring mechanical ventilation were examined. Seven of them had
fulminant early-onset pneumonia with maternal ascending intra-uterine
infection (IUI). The controls had no infection at birth despite IUI or
neither infection nor IUI. In early-onset pneumonia, NOS2 and
nitrotyrosine immunoreactivity were low at birth and increased during the
recovery phase (p < 0.05). Analyses of interleukin-1 and
surfactant protein A showed the same pattern of age-dependent
change.
Of the autopsied infants, 12 had received inhaled NO (iNO) before
death. Each case was paired with a matched control. Additional five
infants without respiratory failure prior to death were also studied. The
iNO-treated ones tended to have more intensive NOS2 staining in the
bronchiolar epithelium and adjacent tissue than the controls. No
differences in other NOS isoforms or nitrotyrosine were detected.
A novel method for exhaled NO measurements of intubated infants was
developed. Six preterm and six term newborns were prospectively recruited
for expired and nasal NO measurements. During the first week of life, the
preterm infants showed a different pattern of exhaled NO excretion
compared to the term infants.
For the pilot intervention study on very early iNO, the eligible
patients had a birth weight < 1500 g and progressive, therapy-resistant
respiratory failure before five hours of age. Five infants received iNO,
showed immediately improved oxygenation and survived without deleterious
side effects.
Deficient production of NO in small premature infants is associated
with severe infection and respiratory failure. Very early iNO therapy may
be exceptionally effective in a select group of infants, and did not
appear to cause oxidation lung injury.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-6851-2 |
| Date | 01 November 2002 |
| Creators | Aikio, O. (Outi) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2002 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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