title: Effect of electrical forepaw stimulation on capillary transit-time heterogeneity (CTH).
abstract: Functional hyperemia reduces oxygen extraction efficacy unless counteracted by a reduction of capillary transit-time heterogeneity of blood. We adapted a bolus tracking approach to capillary transit-time heterogeneity estimation for two-photon microscopy and then quantified changes in plasma mean transit time and capillary transit-time heterogeneity during forepaw stimulation in anesthetized mice (C57BL/6NTac). In addition, we analyzed transit time coefficient of variance = capillary transit-time heterogeneity/mean transit time, which we expect to remain constant in passive, compliant microvascular networks. Electrical forepaw stimulation reduced, both mean transit time (11.3% ± 1.3%) and capillary transit-time heterogeneity (24.1% ± 3.3%), consistent with earlier literature and model predictions. We observed a coefficient of variance reduction (14.3% ± 3.5%) during functional activation, especially for the arteriolar-to-venular passage. Such coefficient of variance reduction during functional activation suggests homogenization of capillary flows beyond that expected as a passive response to increased blood flow by other stimuli. This finding is consistent with an active neurocapillary coupling mechanism, for example via pericyte dilation. Mean transit time and capillary transit-time heterogeneity reductions were consistent with the relative change inferred from capillary hemodynamics (cell velocity and flux). Our findings support the important role of capillary transit-time heterogeneity in flow-metabolism coupling during functional activation.
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark eugenio@cfin.au.dk.
authors: Eugenio
authors: E
authors: Gutiérrez-Jiménez
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Changsi
authors: C
authors: Cai
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Irene Klærke
authors: IK
authors: Mikkelsen
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Peter Mondrup
authors: PM
authors: Rasmussen
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Hugo
authors: H
authors: Angleys
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Mads
authors: M
authors: Merrild
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Kim
authors: K
authors: Mouridsen
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark.
authors: Sune Nørhøj
authors: SN
authors: Jespersen
authors: Department of Radiology, Harvard Medical School, Boston, USA.
authors: Jonghwan
authors: J
authors: Lee
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Nina Kerting
authors: NK
authors: Iversen
authors: Department of Radiology, Harvard Medical School, Boston, USA.
authors: Sava
authors: S
authors: Sakadzic
authors: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Leif
authors: L
authors: Østergaard
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D002196:Capillaries / Q000502:physiology*; D004558:Electric Stimulation; D005528:Foot / Q000098:blood supply*; D006439:Hemodynamics; D006940:Hyperemia / Q000209:etiology; D000069416:Intravital Microscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological
keywords: Capillary transit-time heterogeneity; neurovascular coupling; perfusion; transit time; two-photon microscopy