Propofol Compared with Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex
| Autor: | Masaki Kajimoto, Phil G. Morgan, Nancy G. Isern, Margaret M. Sedensky, Christine Des Rosiers, Dolena R. Ledee, Douglas B. Atkinson, Michael A. Portman, Ernst Bernhard Kayser |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Swine Anesthetics General Gas Chromatography-Mass Spectrometry chemistry.chemical_compound Leucine Internal medicine Administration Inhalation medicine Animals Glycolysis Infusions Intravenous Propofol Cerebral Cortex Isoflurane Glycogen Pyruvate dehydrogenase complex medicine.disease Mitochondria Glucose Propofol infusion syndrome medicine.anatomical_structure Endocrinology Animals Newborn Neurology chemistry Cerebral cortex Anesthesia Anesthetic Original Article Neurotoxicity Syndromes Neurology (clinical) Energy Metabolism Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 34:514-521 |
| ISSN: | 1559-7016 0271-678X |
| Popis: | Anesthetics used in infants and children are implicated in the development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in immature swine anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon-labeled glucose and leucine in the common carotid artery to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared spectroscopy. Compared with isoflurane, propofol depleted ATP and glycogen stores. Propofol decreased pools of the CAC intermediates, citrate, and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked lactate accumulation. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype that resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations that typically accompany propofol infusion syndrome. These metabolic abnormalities may have a role in the neurotoxity observed with propofol in the vulnerable immature brain. |
| Databáze: | OpenAIRE |
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