Imaging the Effects of Propofol on Human Cerebral Glucose Metabolism Using Positron Emission Tomography

Sun, Xishan; Zhang, H; Gao, Changjun; Zhang, G; Xu, Li; Lv, Miaomiao; Chai, Weidong

doi:10.1177/147323000803600618

Cited by 23 publications

(23 citation statements)

References 14 publications

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“…In a previous study, also using PET imaging, we observed in the subcortical regions, the decrease of glucose consumption in the thalamus was the largest, which is consistent with another PET study (Sun et al, 2008). In the present study, we showed that in 5 of 10 subjects, the signals of thalamus were decreased during propofol anesthesia although the changes were weak and significantly different compared with the changes in hypothalamus, frontal lobe, and temporal lobe.…”

Section: Discussionsupporting

confidence: 92%

The Action Sites of Propofol in the Normal Human Brain Revealed by Functional Magnetic Resonance Imaging

Zhang¹,

Wang²,

Zhao³

et al. 2010

The Anatomical Record

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Propofol has been used for many years but its functional target in the intact brain remains unclear. In the present study, we used functional magnetic resonance imaging to demonstrate blood oxygen level dependence signal changes in the normal human brain during propofol anesthesia and explored the possible action targets of propofol. Ten healthy subjects were enrolled in two experimental sessions. In session 1, the Observer's Assessment of Alertness/Sedation Scale was performed to evaluate asleep to awake/alert status. In session 2, images with blood oxygen level dependence contrast were obtained with echo-planar imaging on a 1.5-T Philips Gyroscan Magnetic Resonance System and analyzed. In both sessions, subjects were intravenously administered with saline (for 3 min) and then propofol (for 1.5 min) and saline again (for 10.5 min) with a constant speed infusion pump. Observer's Assessment of Alertness/Sedation Scale scoring showed that the subjects experienced conscious-sedative-unconscious-analepsia, which correlated well with the signal decreases in the anesthesia states. Propofol induced significant signal decreases in hypothalamus (18.2% AE 3.6%), frontal lobe (68.5% AE 11.2%), and temporal lobe (34.7% AE 6.1%). Additionally, the signals at these three sites were fulminant and changed synchronously. While in the thalamus, the signal decrease was observed in 5 of 10 of the subjects and the magnitude of decrease was 3.9% AE 1.6%. These results suggest that there is most significant inhibition in hypothalamus, frontal lobe, and temporal in propofol anesthesia and moderate inhibition in thalamus. These brain regions might be the targets of propofol anesthesia in human brain. Anat Rec, 293:1985Rec, 293: -1990

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Section: Discussionsupporting

confidence: 92%

The Action Sites of Propofol in the Normal Human Brain Revealed by Functional Magnetic Resonance Imaging

Zhang¹,

Wang²,

Zhao³

et al. 2010

The Anatomical Record

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show abstract

“…Further, in the human brain, isoflurane (0.5% expired) has been shown to reduce CMRglu by 46% (Alkire et al, 1997). Propofol administered in concentrations inducing unconsciousness in humans also reduced CMRglu by B50% (Sun et al, 2008). Although much information has been gained from positron emission tomography studies in the live brain, it is important to acknowledge, that CMRglu measured by 2-deoxy-2-( 18 F)fluoro-D-glucose is interpreted as an indirect measure of neuronal function, and only provides information on the rate of glycolysis under the assumption of oxidative phosphorylation (Fowler and Ido, 2002).…”

Section: Introductionmentioning

confidence: 96%

“…The effects of general anesthetics on traditional measures of brain function and metabolism, including the cerebral metabolic rate of glucose utilization (CMRglu), oxygen utilization, and neurotransmission, have been well characterized in humans and animals using jugular bulb oximetry, positron emission tomography, magnetic resonance imaging, or autoradiography (Alkire et al, 1995;Newberg et al, 1983;Olsen et al, 1992;Ori et al, 1986;Sun et al, 2008). For example, cortical oxidative metabolism and glutamate (Glu) flux have been shown to be stoichiometrically related, coupled to neuronal firing, and dependent on depth of barbiturate anesthesia (Shulman et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The metabolomic profile during isoflurane anesthesia differs from propofol anesthesia in the live rodent brain

Makaryus

Lee

et al. 2011

J Cereb Blood Flow Metab

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Development of noninvasive techniques to discover new biomarkers in the live brain is important to further understand the underlying metabolic pathways of significance for processes such as anesthesia-induced apoptosis and cognitive dysfunction observed in the undeveloped brain. We used in vivo proton magnetic resonance spectroscopy and two different signal processing approaches to test the hypothesis that volatile (isoflurane) and intravenous (propofol) anesthetics at equipotent doses produce distinct metabolomic profiles in the hippocampus and parietal cortex of the live rodent. For both brain regions, prolonged isoflurane anesthesia was characterized by higher levels of lactate (Lac) and glutamate compared with long-lasting propofol. In contrast, propofol anesthesia was characterized by very low concentrations of Lac ([lac]) as well as glucose. Quantitative analysis revealed that the [lac] was fivefold higher with isoflurane compared with propofol anesthesia and independent of [lac] in blood. The metabolomic profiling further demonstrated that for both brain regions, Lac was the most important metabolite for the observed differences, suggesting activation of distinct metabolic pathways that may impact mechanisms of action, background cellular functions, and possible agent-specific neurotoxicity.

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“…Positron emission tomography of adult human brains corroborated that propofol shifted central nervous system metabolism toward glycolysis. 10 However, those studies used 2-fluorodeoxyglucose uptake, and did not determine the actual fate of glucose. Similarly, other studies have used metabolic profiling by 1 H-nuclear magnetic resonance (NMR) to demonstrate differences between volatile anesthetics and propofol.…”

Section: Introductionmentioning

confidence: 99%

Propofol Compared with Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

Kajimoto

Atkinson

Ledee

et al. 2014

J Cereb Blood Flow Metab

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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 a-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.

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Imaging the Effects of Propofol on Human Cerebral Glucose Metabolism Using Positron Emission Tomography

Cited by 23 publications

References 14 publications

The Action Sites of Propofol in the Normal Human Brain Revealed by Functional Magnetic Resonance Imaging

The Action Sites of Propofol in the Normal Human Brain Revealed by Functional Magnetic Resonance Imaging

The metabolomic profile during isoflurane anesthesia differs from propofol anesthesia in the live rodent brain

Propofol Compared with Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

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