Brief disruptions in capillary flow result in rapid onset of hypoxia

Capillaries are the critical site of vascular exchange with the local tissue, with continuous flow to meet the brain's unique and steep energetic demands. However, transient stalls in capillary flow have been observed and at elevated levels in preclinical models of disease. Systematic measurements have not been made to quantify the acute effects of individual capillary stalls on local oxygen.

We aim to quantify oxygen dynamics around capillary stalls as they occur in vivo.

We use high-resolution two-photon phosphorescent lifetime microscopy (2PLM) to monitor capillary flux and ${\mathrm{pO}}_2$ in the mouse cortex, allowing us to capture acute oxygen dynamics around capillary stalling.

All stalls cause rapid drops in intra-capillary oxygen that likely extend to local tissue based on estimates using the erythrocyte-associated transient (EAT). This includes a subset of capillaries, which reach critically hypoxic levels (<10 mmHg), which could not be predicted by the capillaries' normal flux and oxygen levels, nor local vessel density or proximity to diving arterioles and venules.

Our findings indicate that a subset of capillary stalls reach extremely low local oxygen, resulting in transient hypoxia in the surrounding tissue. This reveals a new potential pathological mechanism due to stalled capillary flow.