Influence of red blood cell aggregation on perfusion of an artificial microvascular network

Abstract

Red blood cells (RBCs) suspended in plasma form multicellular aggregates under low flow conditions, increasing apparent blood viscosity at low shear rates. It has previously been unclear, however, if RBC aggregation affects microvascular perfusion. Here we analyzed the impact of RBC aggregation on perfusion and ‘capillary’ hematocrit in an artificial microvascular network (AMVN) at driving pressures ranging from 5 to 60 cmH2O to determine if aggregation could improve tissue oxygenation. RBCs were suspended at 30% hematocrit in either 46.5 g/L dextran 40 (D40, non-aggregating medium) or 35 g/L dextran 70 (D70, aggregating medium) solutions with equal viscosity. Aggregation was readily observed in the AMVN for RBCs suspended in D70 at driving pressures ≤ 40 cmH2O. The AMVN perfusion rate was the same for RBCs suspended in aggregating and non-aggregating medium, at both ‘venular’ and ‘capillary’ level. Estimated ‘capillary’ hematocrit was higher for D70 suspensions than for D40 suspensions at intermediate driving pressures (5 – 40 cm H2O). We conclude that although RBC aggregation did not affect the AMVN perfusion rate independently of the driving pressure, a higher hematocrit in the ‘capillaries’ of the network for D70 suspensions suggested a better oxygen transport capacity in the presence of RBC aggregation.

Influence of feeding hematocrit and perfusion pressure on hematocrit reduction (Fåhræus effect) in an artificial microvascular network

“…Measurement of Hct in the AMVN microchannels was performed as described previously in detail . In brief, the use of the band‐pass blue filter for imaging the flow of blood in the AMVN enabled us to apply the basic principles of densitometric spectrophotometry to estimate the Hct in each capillary microchannel.…”

“…The design and fabrication of the AMVN device have been described previously in detail. 19,20,[22][23][24][25][26][27][28] In brief, each AMVN device contained three identical, parallel networks of "capillary" microchannels (widths 5-51 μm) with architecture inspired by rat mesentery microvasculature ( Figure 1). Each network had an independent inlet port (4 mm diameter) connected to the "capillary" network via a 70μm-wide "arteriole" microchannel and all networks converged to a common outlet port (1.5 mm diameter) via a 70μm-wide "venule" microchannel.…”

“…Measurement of V RBC in the AMVN microchannels was performed as described previously in detail. 19,20,[22][23][24][25][26][27][28] In brief, to perform the V RBC measurement, an AMVN device was secured to the stage of an in-…”

“…[19][20][21][22] The AMVN consists of a complex network of interconnected microchannels (with the layout inspired by the microvasculature of rat mesentery) 21,22 of uniform height (5 μm) and widths ranging from 70 μm ("arteriole" and "venule") down to 5 μm ("capillaries"). 19 We have previously used the AMVN microfluidic device to study the effect of RBC shape, 23,24 aggregation, 25 and deformability 19,22,[26][27][28] on the overall perfusion of the microvascular network. Additionally, we have used the AMVN to prove that the dynamic interplay between plasma skimming and the dependence of blood viscosity on vessel Hct (known as the Fåhraeus-Lindqvist effect 29 ) could produce spontaneous, self-sustaining oscillations of capillary blood flow and Hct in microvascular networks.…”

Microfluidics Technologies and Approaches for Studying the Microcirculation

“…4 The next group of articles emphasizes the use of microfluidics for evaluating blood cell deformability and aggregation during network perfusion with a focus on gaining insights into the effects of sickle cell disease on altered red blood cell stiffness and function. [5][6][7][8][9] Collectively, the articles in this issue exemplify the value of applying microfluidic fabrication techniques for microvascular research and, more broadly, the potential for incorporating emergent technologies to learn more about the complex and dynamic physiology of the microcirculation.…”