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Effect of indomethacin on cerebral oxidized cytochrome oxidase in preterm infants
D C McCormick1, A D Edwards, G C Brown
1Department of Paediatrics, University College and Middlesex School of Medicine, London, England.
Insights
Intravenous indomethacin significantly reduced cerebral intracellular oxygenation in preterm infants by affecting blood flow and volume. These changes in oxidized cytochrome oxidase suggest hemodynamic alterations, not direct mitochondrial effects.
Area of Science:
- Neonatal Medicine
- Neuroscience
- Pharmacology
Background:
- Patent ductus arteriosus (PDA) is common in preterm infants.
- Indomethacin is frequently used to close PDA.
- Cerebral oxygenation is critical for neurodevelopment in neonates.
Purpose of the Study:
- To investigate the impact of intravenous indomethacin on cerebral intracellular oxygenation.
- To assess changes in oxidized cytochrome oxidase concentration as an indicator of oxygenation.
- To explore the mechanism behind indomethacin's effect on cerebral oxygenation.
Main Methods:
- Near-infrared spectroscopy (NIRS) was used to monitor cerebral intracellular oxygenation.
- Studies were conducted on 15 preterm infants (23-29 wk gestation) treated with indomethacin for PDA.
- Parallel experiments were performed on rat brain synaptosomes to assess direct mitochondrial effects.
Main Results:
- Indomethacin significantly decreased cerebral blood flow, oxygen delivery, and blood volume (p < 0.01).
- A significant reduction in oxidized cytochrome oxidase concentration was observed in 11 of 15 infants (p < 0.01).
- Indomethacin showed minimal direct impact on mitochondrial respiration in synaptosome studies.
Conclusions:
- Indomethacin administration leads to reduced cerebral intracellular oxygenation in preterm infants.
- The observed decrease in oxidized cytochrome oxidase is likely due to indomethacin-induced hemodynamic changes.
- These findings suggest that hemodynamic perturbations, rather than direct mitochondrial toxicity, underlie the effect of indomethacin on neonatal cerebral oxygenation.
Abstract:
To determine the effect of i.v. indomethacin on cerebral intracellular oxygenation, as judged by changes in the concentration of oxidized cytochrome oxidase, studies were performed using near-infrared spectroscopy on 15 infants of 23 to 29 wk gestation, aged 8 to 30 d, who required the drug for closure of a patent ductus arteriosus. Indomethacin caused significant (p < 0.01) falls in cerebral blood flow, oxygen delivery, and blood volume and its reactivity to changes in arterial carbon dioxide tension, as previously reported. In 11 of the 15 infants, significant (p < 0.01) falls of 0.18 to 0.92 mumol.L-1 in the concentration of oxidized cytochrome oxidase were observed. Parallel experiments on synaptosomes derived from rat brain showed that indomethacin was most unlikely to have had a direct effect on mitochondrial respiration. These results are consistent with the hypothesis that the observed falls in the concentration of oxidized cytochrome oxidase resulted from hemodynamic perturbations that reduced cerebral intracellular oxygenation.