Movement of ions (Ca²⁺, K⁺, Na⁺ and Cl^-) and second messenger molecules like inositol 1, 4, 5-trisphosphate inside and in between different cells is the basis of many signaling mechanisms in the microcirculation. In spite of the vast experimental efforts directed towards evaluation of these fluxes, it has been a challenge to establish their roles in many essential microcirculatory phenomena. Recently, detailed theoretical models of calcium dynamics and plasma membrane electrophysiology have emerged to assist in the quantification of these intra and intercellular fluxes and enhance understanding of their physiological importance. This perspective reviews selected models relevant to estimation of such intra and intercellular ionic and second messenger fluxes and prediction of their relative significance to a variety of vascular phenomena such as myoendothelial feedback, conducted responses and vasomotion.

© 2012 John Wiley & Sons Ltd

In this paper, we describe the histological and contractile properties of the thoracodorsal artery (TDA), which indirectly feeds the spinotrapezius muscle. Our results demonstrate that the TDA is composed of approximately one-two layers of smooth muscle cells, is highly innervated with adrenergic nerves, and develops spontaneous tone at intraluminal pressures above 80 mmHg. The reactivity of the TDA in response to various contractile agonists such as phenylephrine, noradrenaline, angiotensin II, serotonin, endothelin 1 and ATP as well as vasodilators show that the TDA exhibits a remarkably comparable reactivity to what has been observed in mesenteric arteries. We further studied the different components of the TDA response to acetylcholine and found that the TDA was sensitive to TRAM 34, a blocker of the intermediate conductance potassium channel, which is highly suggestive of an endothelium-dependent hyperpolarization. We conclude that the TDA exhibits comparable characteristics to other current vascular models, with the additional advantage of being easily manipulated for molecular and ex vivo vasoreactivity studies.

© 2012 John Wiley & Sons Ltd

Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate whether increasing concentrations of noradrenaline (NA, 1.8-59 μmol/L) and vasopressin (VP, 1-100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate). We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose-response model. Urea in the dialysate increased from a baseline of 7.9 ± 1.7 to 10.9 ± 0.9 mmol/L for the highest concentration of NA (p<0.001) and from 8.1 ± 1.4 to 10.0 ± 1.7 mmol/L for the highest concentration of VP (p=0.037). Glucose decreased from 2.3 ± 0.7 to 0.41 ± 0.18 mmol/L for NA (p=0.001) and from 2.7 ± 0.6 to 1.3 ± 0.5 mmol/L for VP (p<0.001). Lactate increased from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for NA (p=0.005) and from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for VP (p=0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters. Microdialysis in the skin, either with a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects.

© 2012 John Wiley & Sons Ltd

Visualising the molecular strands making up the glycocalyx in the lumen of small blood vessels has proved to be difficult using conventional transmission electron microscopy techniques. Images obtained from tissue stained in a variety of ways have revealed a regularity in the organisation of the proteoglycan components of the glycocalyx layer (fundamental spacing about 20 nm), but require a large sample number. Attempts to visualise the glycocalyx face-on (i.e. in a direction perpendicular to the endothelial cell layer in the lumen and directly applicable for permeability modelling) has had limited success (e.g. freeze fracture). A new approach is therefore needed. Here we demonstrate the effectiveness of using the relatively novel electron microscopy technique of 3D electron tomography ontwo differently stained preparations to reveal details of the architecture of the glycocalyx just above the endothelial cell layer. One preparation uses the novel staining technique using Lanthanum Dysprosium Glycosamino Glycan adhesion (the LaDy GAGa method).

© 2012 John Wiley & Sons Ltd

Objective:  Endothelial dysfunction, associated with reduced nitric oxide bioavailability and oxidative stress, is a common feature of vascular-related diseases. Sirtuin 1 (SIRT1) is a protein deacetylase that has been shown to target endothelial nitric oxide synthase in large arteries and is protective during oxidative stress. However within resistance-sized vessels, the expression and functional effects of SIRT1 remain unknown.

Methods:  Immunoblotting and immunohistochemistry were used to determine SIRT1 expression and localization in cultured brain endothelial cells and intact rat middle cerebral artery. The influence of SIRT1 on vascular function was then studied in intact middle cerebral arteries using pressure myography.

Results:  We report for the first time that SIRT1 is expressed in the resistance-sized vessels in the brain and is present in both the endothelium and smooth muscle. Pharmacological inhibition of SIRT1 demonstrated reduced endothelium-dependent dilations mediated by nitric oxide. However endothelium-independent dilations were comparable in the presence and absence of SIRT1 block.

Conclusions:  Our results support a role for SIRT1 in endothelium-dependent relaxation in the cerebral vasculature and reveal a potential for SIRT1 as a therapeutic target in vascular-related diseases by restoring endothelial function.

© 2012 John Wiley & Sons Ltd

The mechanism enabling coordination of the resistance of feed arteries with microcirculatory arterioles in order to rapidly regulate tissue blood flow in line with changes in metabolic demand has preoccupied scientists for a quarter of a century. As experiments uncovered the underlying electrical events, it was frequently questioned how vasodilation could conduct over long distances without appreciable attenuation. This perspective reviews the data pertinent to this phenomenon and provides evidence that this remarkable response could be made possible by a simple mechanism based on the steep relationship between membrane potential and calcium entry demonstrated by the voltage dependent calcium channels which mediate the control of vascular tone in vivo.

© 2012 John Wiley & Sons Ltd

Objective  Damage in the capillaries supplying the myenteric plexus has been proposed as a critical factor in the development of diabetic enteric neuropathy. We therefore investigated connections between streptozotocin-induced diabetes and the basement membrane morphology, the size of caveolar compartments, the width of tight junctions, the transport of albumin, and the quantitative features of caveolin-1 and endothelial nitric oxide synthase (eNOS) expression in these microvessels.

Methods  Gut segments from diabetic rats were compared with those from insulin-treated diabetics and those from controls. The effects of diabetes on the basement membrane, the caveolar compartments and the tight junctions were evaluated morphometrically. The quantitative features of the albumin transport were investigated by post-embedding immunohistochemistry. The diabetes-related changes in caveolin-1 and eNOS expression were assessed by post-embedding immunohistochemistry and molecular method.

Results  Thickening of the basement membrane, enlargement of the caveolar compartments, opening of the junctions, enhanced transport of albumin, and overexpression of caveolin-1 and eNOS were documented in diabetic animals. Insulin replacement in certain gut segments prevented the development of these alterations.

Conclusions  These data provide morphological, functional and molecular evidence that the endothelial cells in capillaries adjacent to the myenteric plexus is a target of diabetic damage in a regional manner.

Objectives:  1) Develop a valid experimental method for quantifying blood flow in continuously branching skeletal muscle arterioles, and 2) derive an empirical relationship between velocity ratio (V_Max/V_Mean) and arteriolar diameter.

Methods:  We evaluated arteriolar trees using intravital video microscopy of rat gluteus maximus muscle and developed a method to acquire single fluorescent-labelled red blood cell velocities across arteriolar lumens to create velocity profiles. These data were used to calculate blood flow for 37 vessel segments (diameters: 21-115 μm).

Results:  Mass balance at arteriolar bifurcations had 0.6 ± 3.2% error. Velocity ratios ranged from 1.35 to 1.98, were positively correlated with diameter (P < 0.0001), and V_RBC profiles were blunted with decreasing diameter.

Conclusions:  We present a means for quantifying blood flow in continuously branching skeletal muscle arterioles. Further, we provide an equation for calculating velocity ratios based on arteriolar diameter, which may be used by others for blood flow calculations.

This spotlight issue of Microcirculation contains four state-of-the-art review articles on the role of microRNAs (miRNAs), a class of endogenous, highly conserved, small, non-coding RNAs that regulate gene expression at the post transcriptional level, and can act as key regulators of cellular mechanisms within the microcirculation. The expert reviews address issues such as the role of miRNAs in determining endothelial cell differentiation and lineage commitment, the physiological role of miRNAs as critical modulators of endothelial cell proliferation, apoptosis and in angiogenesis, and their aberrant expression in different vascular disorders. The reviews also explore the prognostic value of miRNAs in cardiovascular disease and how they may serve both as a therapeutic target and clinical biomarker in the future. This cutting edge edition of the journal Microcirculation highlights the progress that has been made in this new and challenging research area.

Objective:  Regional blood flow to the diaphragm muscle varies with the workload of inspiration. To provide anatomical insight into coupling between muscle fiber recruitment and oxygen supply, we tested whether arterioles are physically associated with motor nerve branches of the diaphragm.

Methods:  Following vascular casting, intact diaphragm muscles of C57BL/6 and CD-1 mice were stained for motor innervation. Arteriolar networks and nerve networks were mapped (∼2 μm resolution) to evaluate their physical proximity.

Results:  Neurovascular proximity was similar between muscle regions and mouse strains. Of total mapped nerve lengths (C57BL/6, 70±15 mm; CD-1, 87±13 mm), 80±14% and 67±10% were ≤250 μm from the nearest arteriole and associated predominantly with arterioles ≤45 μm in diameter. Distances to the nearest arteriole encompassing 50% of total nerve length (D₅₀) were consistently within 200 μm. With nerve networks repositioned randomly within muscle borders, D₅₀ values nearly doubled (P<0.05). Reference lines within anatomical boundaries reduced proximity to arterioles (P<0.05) as they deviated from the original location of motor nerves.

Conclusion:  Across 2 strains of mice, motor nerves and arterioles of the diaphragm muscle are more closely associated than can be explained by chance. We hypothesize that neurovascular proximity facilitates local perfusion upon muscle fiber recruitment.

Vascular endothelial cells derived from human pluripotent stem cells have substantial potential for the development of novel vascular therapeutics and cell based therapies for the repair of ischemic damage. To gain maximum benefit from this source of cells a complete understanding of the changes in gene expression and how they are regulated is required. microRNAs have been demonstrated to play a critical roles in controlling stem cell pluripotency and differentiation and are important for mature endothelial cell function. Specific microRNAs which determine stem cell fate have been identified for a number of different cell lineages, however in the case of differentiation and specification of vascular endothelial cells this is yet to be fully elucidated.

Objective:  Vascular-disrupting agents like combretastatin (CA-4-P), used to attenuate tumour blood flow in vivo, exert anti-mitotic and anti-migratory effects on endothelial cells in vitro. We tested whether anti-vascular or anti-angiogenic effects of CA-4-P are evident with physiological angiogenesis in skeletal muscle (EDL) due to sustained hyperaemia (intraluminal splitting) and chronic muscle overload (abluminal sprouting).

Methods:  CA-4-P was given i.v. (25 mg^.kg⁻¹ on alternate days for 14 d) to mice subjected to angiogenic stimuli (prazosin or synergist extirpation). The responses of femoral artery blood flow as well as capillarity, capillary ultrastructure, and levels of Rho GTPase were measured.

Results:  Blood flow was unaffected in the sprouting angiotype, but decreased in the splitting angiotype, by CA-4-P. In contrast, CA-4-P attenuated the capillarity increase in both models, associated with reduced lamellipodia and filopodia formation. Muscle overload, but not hyperaemia was accompanied by an increase in Rho GTPase with CA-4-P.

Conclusion:  CA-4-P impaired the angiogenic response in both experimental models. This inhibitory effect was associated with a lower increase in femoral blood flow in splitting, while sprouting angiogenesis was accompanied by higher Rho activity consistent with interruption of actin polymerisation. Thus, CA-4-P may exert context-dependent anti-vascular and anti-angiogenic effects in vivo under physiological conditions.

Objective:  Homocysteine (Hcy) is an independent risk factor for cerebrovascular disease and cognitive impairment. The purpose of this study was to elucidate the role of metabotropic glutamate receptor5 (mGluR5) in Hcy-mediated impairment of cerebral endothelial wound repair.

Methods:  Mouse cerebral microvascular endothelial cells (bEnd.3) were used in conjunction with directed pharmacology and shRNA. Autodock was used to simulate docking of ligand-receptor interactions.

Results:  Hcy (20 μM) significantly increased phosphorylation of connexin43 at S368 (Cx43-pS368) by mGluR5- and protein kinase C-dependent mechanisms. Hcy attenuated wound repair by an mGluR5-dependent mechanism over the 6-day study period but did not alter cell proliferation in a proliferation assay, suggesting that attenuation of wound repair may be due to dysfunctional migration in hyperhomocysteinemia (HHcy). Hcy increased the expression of Cx43 and Cx43-pS368 at the wound edge by activating mGluR5. Direct activation of mGluR5, using the specific agonist CHPG, was sufficient to reproduce the results while knockout of mGluR5 with shRNA, or inhibition with MPEP, blocked the response to Hcy.

Conclusions:  Inhibition of mGluR5 activation could be a novel strategy for promoting endothelial wound repair in patients with HHcy. Activation of mGluR5 may be a viable strategy for disrupting angiogenesis.

In complex organisms, both intracellular and intercellular communication is critical for the appropriate regulation of the distribution of perfusion to assure optimal oxygen (O₂) delivery and organ function. The mobile erythrocyte is in a unique position in the circulation since it both senses and responds to a reduction in O₂ tension in its environment. When erythrocytes enter a region of the microcirculation in which O₂ tension is reduced, they release both O₂ and the vasodilator, adenosine triphosphate (ATP) via activation of a specific and dedicated signaling pathway that requires increases in cAMP, that are regulated by phosphodiesterase 3B. The ATP released initiates a conducted vasodilation that results in alterations in the distribution of perfusion to meet the tissue’s metabolic needs. This delivery mechanism is modulated by both positive and negative feedback regulators. Importantly, defects in low O₂-induced ATP release from erythrocytes have been observed in several human disease states in which impaired vascular function is present. Understanding of the role of erythrocytes in controlling perfusion distribution and the signaling pathways that are responsible for ATP release from these cells makes the erythrocyte a novel therapeutic target for the development of new approaches for the treatment of vascular dysfunction.

Purpose:  The study describes the use of intra-vital microscopy (IVM) to assess the behaviour of ultrasound contrast agents (UCAs), including targeted UCAs, in the microcirculation of rodents.

Materials and Methods:  IVM was performed on various exteriorized organs: hamster cheek pouch, rat mesentery, liver, spinotrapezius muscle and mouse cremaster muscle. A dorsal skin-fold chamber with MatBIII tumor cells was also implanted in rats. Non-targeted UCAs (SonoVue® and BR14) and targeted UCAs (BR55 and P-selectin targeted microbubbles) were tested. IVM was used to measure microbubble size, determine their persistence and observe their behaviour in the blood circulation.

Results:  Intravenous and intra-arterial injections of high doses of UCAs did not modify the local microvascular haemodynamics. No microbubble coalescence and no size increased were observed. Adhesion of some microbubbles to leukocytes was observed in various microcirculation models. Microbubbles are captured by Kupffer cells in the liver. Targeted microbubbles were shown to adhere specifically to endothelial receptors without compromising local blood flow.

Conclusion:  These results support the safety of both targeted and non-targeted UCAs since no microvascular flow alteration or plugging of microvessels were observed. They confirm that binding observed with targeted microbubbles are due to the binding of these microbubbles to specific endothelial receptors.

Chronic wounds represent a rising health and economic burden to our society. Emerging studies indicate that miRNAs play a key role in regulating several hubs that orchestrate the wound inflammation and angiogenesis processes. Of interest to wound inflammation are the regulatory loops where inflammatory mediators elicited following injury, are regulated by miRNAs as well as regulate miRNA expression. Adequate angiogenesis is a key determinant of success in ischemic wound repair. Hypoxia and cellular redox state are among the key factors that drive wound angiogenesis. We provided first evidence demonstrating that miRNAs regulate cellular redox environment via a NADPH oxidase dependent mechanism in human microvascular endothelial cells (HMECs). We further demonstrated that hypoxia-sensitive miR-200b is involved in induction of angiogenesis by directly targeting Ets-1 in HMECs. These studies points towards a potential role of miRNA in wound angiogenesis. miRNA-based therapeutics represents one of the major commercial hot spots in today’s biotechnology market space. Understanding the significance of miRs in wound inflammation and angiogenesis may help design therapeutic strategies for management of chronic non-healing wounds.

Introduction:  Microvascular function has been proposed to link body fatness to CVD and DM2. Current knowledge of these relationships is mainly based on studies in selected populations of extreme phenotypes. Whether these findings can be translated to the general population remains to be investigated.

Aim:  To assess the relationship of body fatness and body fat distribution with microvascular function in a healthy population-based cohort.

Methods:  Body fatness parameters were obtained by anthropometry and whole-body dual-X-ray absoptiometry (DEXA) in 2000 and 2006. Microvascular recruitment (i.e. absolute increase in perfused capillaries after arterial occlusion, using nailfold capillaroscopy) was measured in 2006. Linear regression analysis was used to examine the relationship of (changes in) body fatness and body fat distribution with microvascular recruitment.

Results:  Data were available for 259 participants (116 men). Capillary density was higher in women than in men (difference 7.3/mm²; p<.05). In the total population, the relationship between total body fatness and microvascular recruitment was positive (β=.43; p=.002), whereas a central pattern of fat distribution (trunk-over-total fatness) showed a negative relationship (β=-26.2; p=.032) with microvascular recruitment. However no association remained apparent after adjustment for gender. Additionally, there was no relationship between 6-year changes in body fatness or fat distribution and microvascular recruitment.

Conclusion:  Women show higher capillary recruitment values than men. This study does not support a linear relationship between microvascular function and body fatness or body fat distribution within a population-based normal range.

Objective:  The purpose of the present study was to explore the protective effects of Cerebralcare Granule® (CG) on rat cerebral injury after focal cerebral ischemia and reperfusion (I/R).

Methods:  Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 60 min followed by reperfusion for 60 min or 24 hours. CG (0.4 g/kg or 0.8 g/kg) was administrated 90 min before ischemia. Brian edema was evaluated by Evan’s blue dye extravasations and brain water content, leukocyte adhesion and albumin leakage were determined with an upright fluorescence microscope, and neuron damage was assessed by 2, 3, 5-triphenyltetrazolium chloride staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunohistochemistry of Caspase-3, p53, p53 up-regulated modulator of apoptosis.

Results:  Focal cerebral I/R elicited a prominent brain edema, an increase in leukocyte adhesion and albumin leakage, as well as neuron damage. All the insults after focal cerebral I/R were significantly attenuated by pretreatment with CG.

Conclusions:  Pretreatment with CG significantly reduced focal cerebral I/R-induced brain edema, cerebral microcirculatory disturbance and neuron damage, suggesting the potential of CG as a prophylactic strategy for patients in danger of stroke.

MicroRNAs (miRs) are small non-coding RNAs implicated mainly in post-transcriptional gene silencing by interacting with the unstranslated region of the transcript. miR-210 represents a major hypoxia-inducible miRs, also known as hypoxamirs, which is ubiquitously expressed in a wide range of cells, serving versatile functions. This review article summarizes the current progress on biogenesis of miR-210 and its physiological roles including arrest of cell proliferation, repression of mitochondrial respiration, arrest of DNA repair, vascular biology, and angiogenesis. Given the fact that miR-210 is aberrantly expressed in a number of diseases such as tumor progression, myocardial infarction and cutaneous ischemic wounds, miR-210 could serve as an excellent candidate for prognostic purposes and therapeutic intervention. With the advancement of computational prediction, high-throughput target validation methodology, sequencing, proteomic analysis and microarray, it is anticipated that more down-stream targets of miR-210 and its-associated biological consequences under hypoxia will be unveiled establishing miR-210 as a major hub in the biology of hypoxia-response.

Objective:  To investigate the effects and possible mechanisms of caffeic acid (CA) on acute hyperhomocysteinemia (HHcy)-induced leukocyte rolling and adhesion in mouse cerebral venules.

Methods:  Male C57 BL/6J mice were injected with DL-homocysteine (50 mg/kg) and CA (10 mg/kg). The effect of CA on HHcy-induced leukocyte rolling and adhesion in cerebral vessels was accessed using intravital microscopy. Plasma cytokines and chemokines were evaluated by cytometric bead array. Reactive oxygen species (ROS) production in human umbilical vein endothelial cells (HUVECs) and adhesion molecules expression on leukocyte were determined by flow cytometry. E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression in cerebrovascular endothelium were detected by immunohistochemistry. CD18 phosphorylation and Src/PI3K/Akt pathway in leukocyte were determined by confocal microscopy and western blot.

Results:  CA inhibited HHcy-elicited leukocyte rolling and adhesion, decreased ROS production in HUVECs, and reduced plasma keratinocyte-derived chemokine, macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 levels. CA reduced the E-selectin and ICAM-1 expression on cerebrovascular endothelium and CD11b/CD18 on leukocyte caused by HHcy. Of notice, CA depressed CD18 phosphorylation and Src/PI3K/Akt pathway in leukocyte.

Conclusions:  CA inhibited HHcy-provoked leukocyte rolling and adhesion in cerebral venules, ameliorating adhesion molecule expression and activation, which is related to suppression of Src/PI3K/Akt pathway in leukocyte.

MicroRNAs (miRNAs) are a class of highly conserved, non-coding short RNA molecules that regulate gene expression on the post-transcriptional level. MiRNAs are involved in a variety of processes such as proliferation, differentiation and apoptosis. Deregulated expression of miRNAs has been linked to the development of diseases including cardiovascular disorders. Recently, the miR-23/24/27 cluster has been shown to be involved in angiogenesis and endothelial apoptosis in cardiac ischemia and retinal vascular development. In the present review we summarize and discuss the role and importance of the miRNA-23/27/24 cluster during cardiovascular angiogenesis. Moreover, we illustrate a novel therapeutic application of the miRNA-23/27/24 cluster in vascular disorders and ischemic heart disease.

In the renal vasculature of humans, rats and mice at least 4 isoforms of connexins (Cx), Cxs 37, 40, 43, and 45 are expressed. In the endothelial cells Cx40 is the predominantly expressed connexin whereas Cx45 is suggested to be expressed in the vascular smooth muscle cells. The preglomerular vasculature has a higher expression of connexins than the postglomerular vasculature. Connexins form gap junctions between neighboring cells and as in other organ systems, the major function of connexins in the kidney appears to be mediation of intercellular communication. Connexins may also form hemichannels that allow cellular secretion of signaling molecules like ATP and thereby mediate paracrine signaling. Renal connexins facilitate vascular conduction, juxtaglomerlar apparatus calcium signaling, and enable endothelial cells and vascular smooth muscle cells to communicate. Thus, current research suggests multiple roles for connexins in important regulatory mechanisms within the kidney including the renin-angiotensin system, tubuloglomerular feedback, and salt and water homeostasis. Interestingly, changes in the activity of the renin-angiotensin system or changes in blood pressure seem to affect the expression of the renal vascular connexins. At the systemic level, renal connexins may be involved in blood pressure regulation and possibly in the pathogenesis of hypertension and diabetes.

In several species and in many vascular beds, ultrastructural studies describe close contact sites between the endothelium and smooth muscle of <∼20 nm. Such sites are thought to facilitate the local action of signalling molecules and/or the passage of current, as metabolic and electrical coupling conduits between the arterial endothelium and smooth muscle. These sites have the potential for bidirectional communication between the endothelium and smooth muscle, as a key pathway for coordinating vascular function. The aim of this brief review is to summarise the literature on the ultrastuctural anatomy and distribution of key components of myoendothelial close contact sites in arteries. In addition to their traditional role of facilitating electrical coupling between the two cell layers, data on the role of myoendothelial close contact sites in arteries, as signalling microdomains involving a spatial localization of channels, receptors and calcium stores is highlighted. Diversity in the density and specific characteristics of myoendothelial close contact sites as signalling microdomains, suggests considerable potential for functional diversity within and between arteries in health and disease.

Please cite this paper as: Davis MJ. Perspective: Physiological Role(s) of the Vascular Myogenic Response. Microcirculation 19: 99–114, 2012.

Please cite this paper as: Young RJ and Reed MWR. Anti-angiogenic Therapy: Concept to Clinic. Microcirculation 19: 115–125, 2012.

Please cite this paper as: Stapleton PA, Minarchick VC, McCawley M, Knuckles TL and Nurkiewicz TR. Xenobiotic Particle Exposure and Microvascular Endpoints: A Call to Arms. Microcirculation 19: 126–142, 2012.

Please cite this paper as: Bruce AC and Peirce SM. Exogenous Thrombin Delivery Promotes Collateral Capillary Arterialization and Tissue Reperfusion in the Murine Spinotrapezius Muscle Ischemia Model. Microcirculation 19: 143–154, 2012.

Please cite this paper as: Chaitanya GV, Cromer W, Wells S, Jennings M, Mathis JM, Minagar A and Alexander JS. Metabolic Modulation of Cytokine-Induced Brain Endothelial Adhesion Molecule Expression. Microcirculation 19: 155–165, 2012.

Please cite this paper as: Unekawa M, Tomita M, Tomita Y, Toriumi H and Suzuki N. Sustained Decrease and Remarkable Increase in Red Blood Cell Velocity in Intraparenchymal Capillaries Associated With Potassium-Induced Cortical Spreading Depression. Microcirculation 19: 166–174, 2012.

Please cite this paper as: Su S-W, Catherall M and Payne S. The Influence of Network Structure on the Transport of Blood in the Human Cerebral Microvasculature. Microcirculation 19: 175–187, 2012.