Capillary blood volume increase in already perfused capillaries: role for glycocalyx modulation.

To the editor. The viewpoints put forward by both Point (1) and Counterpoint (4) presenters clearly illustrate that there is a potential for recruitment of capillary reserve in muscle during exercise and in response to insulin administration. The question at hand that arises from the Point/Counterpoint discussion is how capillary blood volume can be increased by muscle contractions or insulin (1) when the vast majority of capillaries are supporting blood flow in the resting condition already (4). In line with the original suggestions of Duling and co-workers (e.g., (2)) on how to explain a threeto fourfold increase in capillary tube hematocrit in cremaster tissue during muscle contractions and adenosine superfusion, we are proposing a role for agonist-induced recruitment of glycocalyx volume in mediating increases in capillary blood content in muscle (5). Experimental data has been provided showing that robust exclusion of circulating red blood cells and plasma by the glycocalyx layer causes functionally perfused capillary volume to be greatly reduced in resting muscle (6), but that the exclusion properties of the glycocalyx are greatly diminished in the presence of adenosine, resulting in a recruitment of blood accessible capillary volume upon administration of this vasodilator (2, 5). Modulation of the level of blood exclusion by the glycocalyx might provide a way by which vasoactive substances (e.g., those released during exercise, insulin) can increase functionally perfused capillary volume: the potential impact of glycocalyx volume modulation for capillary blood filling is illustrated by recent estimations of a blood-excluding glycocalyx volume of about 1.5 L in the systemic circulation of healthy human subjects (3).