Effect of electrical forepaw stimulation on capillary transit-time heterogeneity (CTH)

J Cereb Blood Flow Metab. 2016 Dec;36(12):2072-2086. doi: 10.1177/0271678X16631560. Epub 2016 Feb 8.

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.

Keywords: Capillary transit-time heterogeneity; neurovascular coupling; perfusion; transit time; two-photon microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Flow Velocity*
  • Capillaries / physiology*
  • Electric Stimulation*
  • Foot / blood supply*
  • Hemodynamics
  • Hyperemia / etiology
  • Intravital Microscopy
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological