Cerebral capillary oxygen diffusion: exploring the concept of intracapillary hemoglobin conformational changes.

The mechanisms of oxygen diffusion in brain capillaries have not been fully clarified to date. According to the laws of physics, the well-documented phenomenon of hyperoxemia-induced excessive increases in brain tissue oxygen pressure (PbtO2) contradicts traditional models of cerebral capillary oxygen diffusion. Circulating models predict a significant drop in oxygen pressure (PO2), and some of them foresee the presence of hypoxic or anoxic corners near the capillary end, regardless of high PbtO2 levels. We propose that the cerebral intracapillary transformation of hemoglobin from the relaxed (R) to the tense (T) quaternary conformational state, driven by deoxygenation and an overload of negative allosteric effectors, and characterized by a lower, more hyperbolic dissociation curve, mitigates the oxygen pressure difference across cerebral capillaries, ensuring a homogeneous pericapillary distribution of oxygen. The hemoglobin R to T state transition is responsible for the high PbtO2 levels observed in viable cerebral tissue during hyperoxemia.