Alteration of Blood Flow in a Venular Network by Infusion of Dextran 500: Evaluation with a Laser Speckle Contrast Imaging System

October Alteration of Blood Flow in a Venular Network by Infusion of Dextran 500: Evaluation with a Laser Speckle Contrast Imaging System Bumseok Namgung 0 1 2 3 Yan Cheng Ng 0 1 2 3 Jeonghun Nam 0 1 2 3 Hwa Liang Leo 0 1 2 3 Sangho Kim 0 1 2 3 0 Funding: This work was supported by National Medical Research Council (NMRC)/Cooperative Basic Research Grant (CBRG)/0019/2012 1 Received: July 3 , 2015 2 Editor: Philippe Connes , Université Claude Bernard Lyon 1, FRANCE 3 1 Department of Biomedical Engineering, National University of Singapore, Singapore, 2 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 3 Department of Surgery, National University of Singapore , Singapore This study examined the effect of dextran-induced RBC aggregation on the venular flow in microvasculature. We utilized the laser speckle contrast imaging (LSCI) as a wide-field imaging technique to visualize the flow distribution in venules influenced by abnormally elevated levels of RBC aggregation at a network-scale level, which was unprecedented in previous studies. RBC aggregation in rats was induced by infusing Dextran 500. To elucidate the impact of RBC aggregation on microvascular perfusion, blood flow in the venular network of a rat cremaster muscle was analyzed with a stepwise reduction of the arterial pressure (100 ! 30 mmHg). The LSCI analysis revealed a substantial decrease in the functional vascular density after the infusion of dextran. The relative decrease in flow velocity after dextran infusion was notably pronounced at low arterial pressures. Whole blood viscosity measurements implied that the reduction in venular flow with dextran infusion could be due to the elevation of medium viscosity in high shear conditions (> 45 s-1). In contrast, further augmentation to the flow reduction at low arterial pressures could be attributed to the formation of RBC aggregates (< 45 s-1). This study confirmed that RBC aggregation could play a dominant role in modulating microvascular perfusion, particularly in the venular networks. - Competing Interests: The authors have declared that no competing interests exist. function. Accordingly, impaired tissue perfusion can potentially result from abnormal alteration in the rheological properties including red blood cell (RBC) aggregation, deformability and hematocrit. Among these factors, RBC aggregation has gathered great attention [1–5] due to its clinical relevance to various disease conditions [6–9]. Thus, it is important to understand the relation between RBC aggregation and flow resistance in the microvascular network since the latter is inversely proportional to the perfusion. In many previous in vivo and in vitro studies, Dextran 500 has been used to induce RBC aggregation. Previous in vitro studies performed in a vertical glass tube reported that the formation of near-wall cell-free layer resulted in a reduction in the apparent viscosity [10,11]. In contrast, flow resistance could increase with RBC aggregation at low shear rates in a horizontal tube due mainly to sedimentation of RBCs [12]. Unlike the in vitro micro-tube experiments, the microvascular network has a complex geometry with multiple branches. Therefore, the effect of RBC aggregation on vascular resistance may not be adequately examined from the findings obtained in in vitro studies [13,14]. Moreover, a previous in vivo study highlighted that the tissue perfusion could decrease with RBC aggregation [3]. The increase in flow resistance due to RBC aggregation is prominent in venules due to their low shear condition which is favorable for the formation of RBC aggregates. Tissue perfusion was found to be significantly modulated at reduced arterial pressures (50 and 25 mmHg) with RBC aggregation when evaluated by the functional capillary density (FCD) [3]. However, most previous studies relied only on data obtained from a single-vessel or capillary-based analysis, thus greatly limiting the ability to highlight the effect of RBC aggregation on microvascular network flows. Recently, in vivo studies have adopted the laser speckle contrast imaging (LSCI) technique to visualize the microvascular remodeling and hemodynamic changes [15,16]. LSCI provides high-resolution perfusion images in a relatively wide field by analyzing laser speckle patterns with time. Owing to the great advantages of LSCI including low-cost, ease of setup, and noninvasive measurement, it has been widely used in various studies on cerebral blood flow [17,18], retinal blood flow [19,20], liver microcirculation [21], and wound healing angiogenesis [15]. In addition, a recent study proposed the use of speckle contrast imaging to quantify the functional vascular density (FVD) [22] which has been used to examine changes in blood flow. In the present study, we adopted the LSCI to visualize the microvasculature of the rat cremaster muscle to obtain quantitative flow information at a network scale. Particularly (...truncated)