The authors reply
RBCs have a key impact on local mechanisms involved in hemorheology. RBCs contribute to microcirculatory hypoxic vasodilation by regulated nitric oxide (NO)-dependent vasodilation, thereby facilitating delivery of oxygen to oxygen-deprived tissue. As mentioned by Morel et al (1), RBCs can induce a rise in wall shear stress (WSS) on the endothelial cells that triggers dilation. The WSS is the frictional force generated by blood flow. It is the product of the viscosity and the flow velocity gradient. The proposed mechanosensors on the luminal surface of the endothelium include components of the glycocalyx (glycoproteins and proteoglycans), stretch-activated ion channels, cytoskeletal rearrangements, cell-cell and cell-extracellular matrix connections. RBCs influence the WSS by changes in blood viscosity as a function of both number and deformability. RBCs could also be mobile sensors of oxygen, detecting point-to-point variations in arteriolar oxygen content, and capable of immediate modulation of vascular tone through liberation of adenosine triphosphate (ATP) that interacts with endothelium inducing a microcirculatory vasodilatation by the liberation of NO and non-NO mediators.
Stored RBCs have time-dependent metabolic and biochemical alterations including diminished intracellular ATP and 2,3-diphosphoglycerate and a loss of bioactive nitric NO derivatives. Functionally, longer banked RBCs are less deformable, adhere excessively to blood vessel walls and alter the WSS signals that determine NO production (2). Thus, transfusion of stored cell disrupts the balance between NO formation and NO scavenging resulting in increased rates for NO scavenging and inhibition of NO-dependent signaling. However, despite these storage lesions, our results indicate that transfusion of RBC significantly increased microvascular perfusion and density with capillary recruitment associated with a decrease in microcirculation heterogeneity. This change in microvascular perfusion after transfusion correlated negatively with baseline microvascular perfusion. The positive impact of RBCs transfusion on microcirculation was not eliminated by storage lesions. In addition, a recent randomized trial failed to demonstrate any differences in mortality among patients who underwent transfusion with the freshest available blood (mean storage duration, 13 d) and those who underwent transfusion according to the standard practice of transfusing the oldest available blood (mean storage duration, 24 d) (3).
It is reassuring to establish that transfusion of stored RBCs has a positive impact on microcirculation.