Influence of the endothelial glycocalyx on cerebral blood flow in mice

The endothelial surface layer (glycocalyx) of cerebral capillaries may incr ease resistance to blood flow. This hypothesis was investigated in mice by intravenous administration of heparinase (2500 IU/kg body weight in saline) , which cleaves proteoglycan junctions of the glycocalyx. Morphology was in vestigated by transmission electron microscopy. Cerebral perfusion velocity was recorded before and during heparinase or saline treatment using laser- Doppler flowmetry. In addition, cerebral blood flow (CBF) was measured 10 m inutes after heparinase or saline treatment using the iodo[C-14]antipyrine method. Laser-Doppler flowmetry and CBF measurements were performed during normocapnia and severe hypercapnia (Pco(2): 120 mm Hg). After heparinase, m orphology showed a reduced thickness of the glycocalyx in cortical microves sels by 43% (P < 0.05) compared with saline-treated controls. Under normoca pnic conditions, a 15% (P < 0.05) transient increase of cerebral flow veloc ity occurred 2.5 to 5 minutes after heparinase injection. Laser-Doppler flo w and CBF returned to control values ten minutes after the injection. Howev er, during severe hypercapnia, heparinase treatment resulted in a persistin g increase in laser-Doppler flow (6%, P < 0.05) and CBF (30%, P < 0.05). Th ese observations indicate the existence of a flow resistance in cerebral ca pillaries exerted by the glycocalyx. The transient nature of the CBF increa se during normocapnia may be explained by a vascular compensation that is e xhausted during severe hypercapnia.