The Roles of Cerebral Blood Flow, Capillary Transit Time Heterogeneity, and Oxygen Tension in Brain Oxygenation and Metabolism

• Published in: Journal of cerebral blood flow and metabolism 2012-02, Vol.32 (2), p.264-277
• Main Authors: Jespersen, Sune N, Østergaard, Leif
• Format: Article
• Language: English
• Subjects: Animals; Basal Metabolism; Biological and medical sciences; Biological Transport; Brain - blood supply; Brain - metabolism; Brain - physiology; Capillaries - physiology; Cerebrovascular Circulation; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hemodynamics; Humans; Hypercapnia - metabolism; Hypotension - metabolism; Hypoxia - metabolism; Kinetics; Medical sciences; Models, Biological; Nervous system (semeiology, syndromes); Neurology; Original; Oxygen - blood; Oxygen - metabolism; Rats; Vascular diseases and vascular malformations of the nervous system; Vasodilation
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2011.153

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.