Vascular endothelial growth factor in the cerebrospinal fluid of infants who died of sudden infant death syndrome: evidence for antecedent hypoxia.

Abstract

OBJECTIVES:

Recurrent hypoxemia has been proposed as an important pathophysiological mechanism underlying sudden infant death syndrome (SIDS). However, conflicting results emerged when xanthines were used as markers for hypoxia. The vascular endothelial growth factor (VEGF) gene is highly sensitive to changes in tissue partial oxygen tension, and changes in genomic and protein expression occur even after changes in oxygenation within the physiologic range.

METHODS:

For determining whether hypoxia precedes SIDS, VEGF levels were measured using an enzyme-linked immunosorbent assay in the cerebrospinal fluid (CSF) of 51 SIDS infants and in 33 additional control infants who died of an identifiable cause. In addition, 6 rats that had a chronically implanted catheter in the lateral ventricle were exposed to a short hypoxic challenge, and VEGF concentrations were measured in CSF at various time points for 24 hours. Another set of 6 rats were killed with a pentobarbital overdose, and VEGF CSF levels were obtained at different time points after death.

RESULTS:

Mean VEGF concentrations in CSF were 308.2 +/- 299.1 pg/dL in the SIDS group and 85.1 +/- 82.9 pg/dL in those who died of known causes. Mean postmortem delay averaged 22 hours for both groups. In rat experiments, hypoxic exposures induced time-dependent increases in VEGF, peaking at 12 hours and returning to baseline at 24 hours. Postmortem duration in the animals was associated with gradual increases in VEGF that reached significance only at 36 hours.

CONCLUSIONS:

We conclude that VEGF CSF concentrations are significantly higher in infants who die of SIDS. We postulate that hypoxia is a frequent event that precedes the sudden and unexpected death of these infants.

• Authors: Kimberly L Jones, Henry F Krous, Julie Nadeau, Brian Blackbourne, H Ronald Zielke, David Gozal
• Journal: Pediatrics (Pediatrics) Vol. 111 Issue 2 Pg. 358-63 (Feb 2003) ISSN: 1098-4275 [Electronic] United States
• PMID: 12563064 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Validation Study)

Chemical References

• Endothelial Growth Factors
• Intercellular Signaling Peptides and Proteins
• Lymphokines
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• Oxygen

Topics

• Animals
• Body Fluids (chemistry)
• Cause of Death
• Disease Models, Animal
• Endothelial Growth Factors (blood, cerebrospinal fluid, immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Humans
• Hypoxia (blood, cerebrospinal fluid, complications)
• Infant
• Infant, Newborn
• Intercellular Signaling Peptides and Proteins (blood, cerebrospinal fluid, immunology, metabolism)
• Lymphokines (blood, cerebrospinal fluid, immunology, metabolism)
• Male
• Oxygen (blood)
• Rats
• Rats, Sprague-Dawley
• Sudden Infant Death (blood, cerebrospinal fluid, etiology)
• Time Factors
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• Vitreous Body (chemistry)