Gutiérrez-Jiménez Eugenio, Cai Changsi, Mikkelsen Irene Klærke, Rasmussen Peter Mondrup, Angleys Hugo, Merrild Mads, Mouridsen Kim, Jespersen Sune Nørhøj, Lee Jonghwan, Iversen Nina Kerting, Sakadzic Sava, Østergaard Leif
Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
J Cereb Blood Flow Metab. 2016 Dec;36(12):2072-2086. doi: 10.1177/0271678X16631560. Epub 2016 Feb 8.
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.
功能性充血会降低氧提取效率，除非血液毛细血管通过时间异质性降低来抵消这种影响。我们采用团注追踪法估计双光子显微镜下的毛细血管通过时间异质性，然后量化麻醉小鼠（C57BL/6NTac）前爪刺激期间血浆平均通过时间和毛细血管通过时间异质性的变化。此外，我们分析了通过时间变异系数=毛细血管通过时间异质性/平均通过时间，我们预计在被动、顺应性微血管网络中该系数保持恒定。前爪电刺激降低了平均通过时间（11.3%±1.3%）和毛细血管通过时间异质性（24.1%±3.3%），这与早期文献和模型预测一致。我们观察到功能激活期间变异系数降低（14.3%±3.5%），尤其是在小动脉到小静脉段。功能激活期间这种变异系数降低表明，毛细血管血流的均匀化程度超过了对其他刺激引起的血流增加的被动反应预期。这一发现与一种主动的神经毛细血管耦合机制一致，例如通过周细胞扩张。平均通过时间和毛细血管通过时间异质性的降低与从毛细血管血流动力学（细胞速度和通量）推断出的相对变化一致。我们的研究结果支持了毛细血管通过时间异质性在功能激活期间血流-代谢耦合中的重要作用。
