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• W4385402702 abstract "ABSTRACT Hypercapnia increases cerebral blood flow, but the effect on cerebral metabolism in humans remains incompletely understood. Either increased or reduced oxygen consumption has been predicted from Fick models incorporating cerebral oxygen extraction fraction and cerebral blood flow. Hypercapnia also results in oxidation of cytochrome c oxidase, complex IV of the mitochondrial respiratory chain, implicating a change in cellular metabolism. The aim of this study was to combine systems modelling with non-invasive measurements of cerebral tissue oxygenation, cerebral blood flow, and cytochrome c oxidase redox state to evaluate any metabolic effects of hypercapnia. Cerebral tissue oxygen saturation and cytochrome oxidase redox state were measured with broadband near infrared spectroscopy and cerebral blood flow velocity using transcranial Doppler ultrasound. Data collected during 5-minutes hypercapnia in human volunteers were analyzed using a Fick model to determine changes in brain oxygen consumption and a mathematical model of cerebral hemodynamics and metabolism (BrainSignals) to inform on the potential mechanisms of any observed changes. Systemic physiology - blood pressure, arterial oxygen saturations and end-tidal carbon dioxide - served as model inputs. The extent of the hypercapnic oxidation of cytochrome oxidase required modifications of the BrainSignals model; simulations compared two possible modifications that could cause this oxidation - a decrease in metabolic substrate supply or an increase in metabolic demand. Only the decrease in substrate supply was able to explain both the enzyme redox state changes and the Fick calculated drop in brain oxygen consumption. These modelled outputs are consistent with, but do not prove, previous reports of CO 2 inhibition of succinate dehydrogenase, complex II of the mitochondrial respiratory chain. These findings suggest that hypercapnia may have physiologically significant effects suppressing oxidative metabolism in humans and perturbing mitochondrial signaling pathways in health and disease." @default.
• W4385402702 created "2023-07-31" @default.
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• W4385402702 date "2023-07-26" @default.
• W4385402702 modified "2023-09-27" @default.
• W4385402702 title "The influence of carbon dioxide on cerebral metabolism and oxygen consumption: combining multimodal monitoring with dynamic systems modelling" @default.
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• W4385402702 doi "https://doi.org/10.1101/2023.07.24.550309" @default.
• W4385402702 hasPublicationYear "2023" @default.
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