The Roles of Cerebral Blood Flow, Capillary Transit Time Heterogeneity, and Oxygen Tension in Brain Oxygenation and Metabolism
Open Access
- 2 November 2011
- journal article
- research article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 32 (2), 264-277
- https://doi.org/10.1038/jcbfm.2011.153
Abstract
Normal brain function depends critically on moment-to-moment regulation of oxygen supply by the bloodstream to meet changing metabolic needs. Neurovascular coupling, a range of mechanisms that converge on arterioles to adjust local cerebral blood flow ( CBF), represents our current framework for understanding this regulation. We modeled the combined effects of CBF and capillary transit time heterogeneity (CTTH) on the maximum oxygen extraction fraction ( OEFmax) and metabolic rate of oxygen that can biophysically be supported, for a given tissue oxygen tension. Red blood cell velocity recordings in rat brain support close hemodynamic—metabolic coupling by means of CBF and CTTH across a range of physiological conditions. The CTTH reduction improves tissue oxygenation by counteracting inherent reductions in OEFmax as CBF increases, and seemingly secures sufficient oxygenation during episodes of hyperemia resulting from cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF, both lower oxygen tension and CTTH may secure tissue oxygenation. Our model predicts that disturbed capillary flows may cause a condition of malignant CTTH, in which states of higher CBF display lower oxygen availability. We propose that conditions with altered capillary morphology, such as amyloid, diabetic or hypertensive microangiopathy, and ischemia—reperfusion, may disturb CTTH and thereby flow-metabolism coupling and cerebral oxygen metabolism.Keywords
This publication has 58 references indexed in Scilit:
- Oxygen gradients in the microcirculationActa Physiologica, 2010
- Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brainProceedings of the National Academy of Sciences of the United States of America, 2010
- Glial and neuronal control of brain blood flowNature, 2010
- Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortexProceedings of the National Academy of Sciences of the United States of America, 2010
- Interpreting oxygenation-based neuroimaging signals: the importance and the challenge of understanding brain oxygen metabolismFrontiers in Neuroenergetics, 2010
- Pharmacological Uncoupling of Activation Induced Increases in CBF and CMRO2Journal of Cerebral Blood Flow & Metabolism, 2009
- Hemodynamic Changes after Visual Stimulation and Breath Holding Provide Evidence for an Uncoupling of Cerebral Blood Flow and Volume from Oxygen MetabolismJournal of Cerebral Blood Flow & Metabolism, 2008
- Functional Reactivity of Cerebral CapillariesJournal of Cerebral Blood Flow & Metabolism, 2007
- Bidirectional control of CNS capillary diameter by pericytesNature, 2006
- Simultaneous Blood–Tissue Exchange of Oxygen, Carbon Dioxide, Bicarbonate, and Hydrogen IonAnnals of Biomedical Engineering, 2006