Local vs. Global Blood Flow Modulation in Artificial Microvascular Networks: Effects on Red Blood Cell Distribution and Partitioning

Abstract

Our understanding of cerebral blood flow (CBF) regulation during functional activation is still limited. Alongside with the accepted role of smooth muscle cells in controlling the arteriolar diameter, a new hypothesis has been recently formulated suggesting that CBF may be modulated by capillary diameter changes mediated by pericytes. In this study, we developed in vitro microvascular network models featuring a valve enabling the dilation of a specific micro-channel. This allowed us to investigate the non-uniform red blood cell (RBC) partitioning at microvascular bifurcations ( phase separation ) and the hematocrit distribution at rest and for two scenarios modeling capillary and arteriolar dilation. RBC partitioning showed similar phase separation behavior during baseline and activation. Results indicated that the RBCs at diverging bifurcations generally enter the high-flow branch ( classical partitioning ). Inverse behavior ( reverse partitioning ) was observed for skewed hematocrit profiles in the parent vessel of bifurcations, especially for high RBC velocity (i.e., arteriolar activation). Moreover, results revealed that a local capillary dilation, as it may be mediated in vivo by pericytes, led to a localized increase of RBC flow and a heterogeneous hematocrit redistribution within the whole network. In case of a global increase of the blood flow, as it may be achieved by dilating an arteriole, a homogeneous increase of RBC flow was observed in the whole network and the RBCs were concentrated along preferential pathways. In conclusion, overall increase of RBC flow could be obtained by arteriolar and capillary dilation, but only capillary dilation was found to alter the perfusion locally and heterogeneously.

Physiologic flow-conditioning limits vascular dysfunction in engineered human capillaries

“…For example, the fluid is considered Newtonian (an acceptable assumption for cell culture media) and vessel walls are considered to be inelastic with no remodeling. Future work will focus on incorporating the active remodeling of vessels, and complex 2-phase effects caused by the inclusion of red blood cells into these simulations, which will undoubtedly alter the flow velocity profiles and shear rates within the vessels, as has also been recently shown by capillary dilation in situ [47]. The WSS and shear rates at the 90 th percentile distribution of our simulation demonstrate values similar to those reported for post-capillary venules (2 Pa or 20 dynes/cm 2 ), as measured previously in vivo for similarly sized vessels [48].…”

Influence of storage and buffer composition on the mechanical behavior of flowing red blood cells

“…• PBS tablet dissolved in 200 mL of a mixture of 68.5 % water and 31.5 % Optiprep from Axis Shield (v/v) + 2 g/L BSA, named Iodixanol-1 hereafter, as used in (16,21,22,25,48,(50)(51)(52)55).…”

“…Running experiments in microgravity conditions is one of them ( 14), yet it poses issues in terms of access, cost and compatibility between the allotted microgravity time and the needed experimental time. The much more accessible technique of density matching was introduced in the community in (50), then used in several studies (16,21,22,25,48,(51)(52)(53)(54)(55). By using iodixanol solutions, agreement between the mean density of RBCs and the carrying fluid can be reached, while the viscosity remains in an acceptable range (around 1.5 to 1.6 mPa.s at room temperature, see Section Viscosimetry)…”

Lingering Dynamics in Microvascular Blood Flow

“…Currently, in vitro experiments on a scale %10 mm addressing network effects are rare because of the complexity of the fabrication procedure. Nonetheless, there has been significant progress in mimicking realistic microvascular networks in vitro and addressing partitioning of RBCs in subsequent bifurcations (31) and dilating vessels (32,33). Albeit most results from FIGURE 5 Probability density functions of scaled void durations for all branches if only lingering events are taken into account.…”