The majority of low- and intermediate-risk recipients who had received IL-2Ra induction therapy were Caucasian, male and had received kidneys from deceased donors. Low- and intermediate-risk recipients receiving pre-emptive grafts (31% and 40%, respectively) were more likely to have had received IL-2Ra compared with recipients with non-pre-emptive grafts (16% and 27%, respectively). Low- and intermediate-risk recipients initiated on tacrolimus (27% and 46%, respectively) were more likely to have been given IL-2Ra compared with recipients receiving cyclosporine (16% and 22%,

respectively). Less than 5% of all transplant recipients received IL-2Ra prior Ku-0059436 datasheet to 2001. Figure 1 shows the unadjusted Kaplan–Meier survival analyses of overall graft failure by IL-2Ra

in low-risk (Fig. 1A) and intermediate-risk (Fig. 1B) recipients. In the low-risk recipients, there was no relationship between the use of IL-2Ra and overall graft failure in the adjusted model. In the intermediate-risk recipients, the use of IL-2Ra was associated with an increased risk of overall graft failure in the adjusted model (hazard ratio 1.32, 95% CI 1.04, 1.69; Tables 2,3). There was a significant ZVADFMK interaction between IL-2Ra and transplanting states so that the effect of IL-2Ra on the hazard of graft failure differed by which state the transplant was performed. Donor and recipient characteristics associated with higher risk of overall graft failure in both low- and intermediate-risk models include older and deceased donor grafts, younger recipients, presence of cardiovascular disease and diabetes. In addition, indigenous recipients and longer time on dialysis were associated with increased risk of graft failure in intermediate-risk recipients. There was no relationship between the use of IL-2Ra and DCGF in both low- and intermediate-risk transplant recipients in the adjusted Cox proportional hazard model (Tables 2,3).

For low-risk recipients, donor and recipient characteristics associated with increased risk of DCGF include live-donor transplants, Caucasian and younger recipients, whereas for intermediate-risk recipients, older donor grafts and younger recipients were associated with increased risk of DCGF. Similarly, there was no association between the use of IL-2Ra and DFG in low- and intermediate-risk transplant Ureohydrolase recipients. For low-risk recipients, donor and recipient characteristics associated with increased risk of DFG include deceased-donor transplants, older recipients, diabetes and current smoker, whereas for intermediate-risk recipients, older donors, older recipients, longer duration on dialysis and diabetes were associated with increased risk of DFG. Figure 2 shows the cumulative incidences of DCGF and DFG by use of IL-2Ra induction in low-risk (Fig. 2A) and intermediate-risk (Fig. 2B) recipients, considering the two as competing events.

These previous studies in BALB/c mice suggested that the initial constraints regulating CDR-H3 content reflected germline sequence content; i.e. the product of natural selection. Superimposed upon these germline restrictions in diversity

were a series of somatic, presumably Tofacitinib nmr clonal, selective events that sequentially produced a CDR-H3 repertoire that had undergone “trimming” of apparently “disfavored” sequence content. This process included a reduction in the use of a specific VH gene segment, VH81X; a reduction in the use of very short CDR-H3s; enhanced use of reading frame 1; enhanced use of tyrosine and glycine in the CDR-H3 loop; and a sequential elimination of highly charged or heavily hydrophobic CDR-H3s with development. The present analysis of immunoglobulin repertoire development in the bone marrow of C57BL/6 mice again demonstrates the effects of germline-imposed restrictions on the range of initial diversity in the H-chain repertoire; but would point to significant differences in either the efficiency, the ability, or the direction of the late-stage somatic, clonal selective events in the bone marrow and the periphery. The end result is a mature, recirculating B-cell repertoire characterized by including IgM BCRs that bear antigen-binding sites that seemed to be not just “disfavored”,

but commonly “discarded” by the mature, recirculating learn more B cells in BALB/c mice. At the progenitor B-cell stage, the influence of the germline on the C57BL/6 repertoire is obvious. VH, DH, and JH usage in C57BL/6 H-chain transcripts appears to differ from BALB/c H-chain transcripts both due to changes in number as well as the sequence of homologous gene segments. Germline variation appeared to be associated with changes in VDJ rearrangement frequency, although this latter point needs to be confirmed through the analysis of nonfunctional sequences. Among the features

of the C57BL/6 repertoire that most closely matched the BALB/c repertoire were similarities in the initial distribution Thiamine-diphosphate kinase of N addition, lengths, charge, and the usage of 18 of the 20 different potential amino acids. One of the features that varied between the two strains reflected the diminished number of functional VH gene segments, including the absence of the most commonly used VH in the BALB/c genome, VH7183.10. Others included the enhanced use of serine-enriched DFL16.1; the presence of a DSP2.11 homologue, DSP2.x, that encodes serine in RF1; and an increased use of JH1 in place of JH4. Of these changes, the most apparent effect in early B-cell progenitors was on VH content, again due to the absence of many of the VH7183 variant sequences available to BALB/c mice.

Samples (~10 ng μL−1) were dissolved in a 50 : 50 : 0.001 (v/v/v) mixture of 2-propanol, water, and triethylamine and sprayed at a flow rate of 2 μL min−1. Capillary entrance

and exit voltage were set to 3.8 kV and −100 V, respectively; the drying gas temperature was 150 °C. The spectra that showed several charge states for each component were charge-deconvoluted using Bruker xmass 6.0.0 software, and mass numbers given refer to monoisotopic molecular masses. Preparation of rabbit O-antiserum against P. alcalfaciens O40 (Bartodziejska et al., 1998) and enzyme-immunosorbent assay (Torzewska et al., 2001) were performed as described selleck earlier. Chromosomal DNA was prepared as described (Bastin & Reeves, 1995). Primers wl-35627 (5′-CAA TTT TCT GGT TTA CCC TCG CAC T-3′) and wl-35631 (5′-TCT GGA CCA AAC ATT AAA TAA TCA TCT T-3′) based on the cpxA and yibK genes, respectively, were used to amplify the P. alcalifaciens O40 O-antigen gene cluster with the Expand click here Long Template PCR system (TaKaRa Biotechnology). Each PCR cycle consisted of denaturation at 95 °C for 30 s, annealing at 55 °C for 45 s and extension at 68 °C for 15 min. The PCR products were sheared at speed code 8 (20 cycles) to the desired molecular mass 1000–2000  using a HydroShear apparatus (GeneMachines, CA). The resulting DNA fragments were cloned into pUC18 vector to produce a shotgun bank. Sequencing was carried out with an ABI 3730 automated DNA sequencer by the Tianjin Biochip Corporation.

Sequence data were assembled using the Staden package (Staden, 1996), and the program Artemis (Rutherford et al., 2000) was used for annotation. CD-Search (Marchler-Bauer & Bryant, 2004) was performed to search conserved

motifs. blast (Altschul et al., 1997) was used to search databases for possible gene functions. The program tmhmm 2.0 (http://www.cbs.dtu.dk/services/TMHMM/) was used for identification of potential transmembrane segments. The DNA sequence of the O-antigen gene cluster of P. alcalifaciens O40 has been deposited in the GenBank database under the accession number HM583640. The LPS was isolated from dry cells of P. alcalifaciens O40 by the phenol–water extraction. Mild acid degradation of the LPS followed by gel-permeation chromatography of the carbohydrate portion on Sephadex G-50 resulted in a high-molecular-mass O-polysaccharide and Baricitinib two oligosaccharide fractions A and B. Sugar analysis of the polysaccharide by GLC of the acetylated alditols revealed galactose, 3-amino-3,6-dideoxyglucose (3-amino-3-deoxyquinovose, Qui3N), and 2-amino-2-deoxygalactose (GalN) in the ratio ~ 1.0 : 1.0 : 0.7. In addition, glucuronic acid (GlcA) was identified by GLC of the acetylated methyl glycosides. The d configuration of all monosaccharides was determined by GLC of the acetylated (S)-2-octyl glycosides. The 13C NMR spectrum of the polysaccharide (Fig. 1) showed signals for four anomeric carbons at δ 100.5–105.7, two nitrogen-bearing carbons at δ 56.0 and 52.

Nevertheless, the findings raised here with respect to atherosclerosis are not without precedent in the cancer literature. Recent work has shown, for example, that dendritic cells with high lipid content are less effective at presenting tumor-associated antigens; this appears to be due to a selective defect in antigen processing while the cells continue to take up soluble proteins 33. Several other studies have also supported a role for nuclear receptors 34 and the NLRP3 inflammasome 35–37 in cancer progression. Many questions remain, however. What is the role of the cholesterol efflux pathways in the macrophage cancer response? Do lipid-loaded monocytes/macrophages traffic to tumor sites and influence

cancer progression? Is atherosclerosis-associated Selleck Pexidartinib leukocytosis a major mechanism by which myeloid-derived suppressor cells (MDSCs, discussed in the next section)

arise? Harnessing some Alisertib in vivo of these atherosclerosis-related studies to better understand how metabolism and inflammation converge in cancer may provide unexpected insights and strengthen common threads between these two pathologies. Ly6Chigh CCR2high (but not Ly6Clow CCR2−) mouse monocytes represent a sizeable fraction of a heterogeneous population of cells called Gr-1+ CD11b+ MDSCs, which are defined operationally by their capacity to regulate T-cell responses 38. MDSCs are widely talked about in the context of cancer and have CHIR-99021 mouse been also shown to control immune responses during pathogen infection, transplantation and trauma 39, 40. Whether they participate during atherosclerosis remains largely unknown. MDSCs produce immunosuppressive factors, such as nitric oxide and reactive oxygen species, that suppress anti-tumor effector

T-cell activity 41, enhance regulatory T-cell responses 42 and collectively support tumor progression. Accumulating evidence also supports a key role for T cells in atherosclerosis 6. In this context, however, effector T cells exert proatherogenic effects, whereas regulatory T cells dampen inflammation and are antiatherogenic. Consequently, when merely considering their impact on T cells, Ly6Chigh monocytes/MDSCs might exert antiatherogenic functions. This notion is unexplored because Ly6Chigh monocytes are well-known precursors of macrophages and lipid-rich foam cells in atheromata. Future studies should define the spectrum of MDSC-mediated functions (beside modulation of T-cell responses) and the relative importance of these activities in distinct disease settings. MDSCs (and TAMs) also often activate STAT3 upon recruitment to tumors. This transcription factor, by triggering the NF-κB and JAK pathways, typically activates the production of enzymes (metalloproteinases), cytokines (IL-6, IL-10, IL-17, IL-23) and growth factors (VEGF, FGF) that elicit and sustain angiogenic and metastatic programs 43, 44.

The paraffin-embedded tissues were sliced and stained with hematoxylin and eosin (H&E). Each frozen tissue was randomly sliced into

8-μm-thick specimens, and three specimens from each mouse were obtained, followed by immunohistological analysis as described below or H&E staining. The number and major axis size of clearly identified gastric lymphoid follicles in the specimens were determined using a microscope in a blinded manner. A fluorescence Selumetinib ic50 immunohistological examination was carried out using frozen sections as described above. The sections were air-dried, fixed in acetone for 5 min, and blocked with 10% goat serum for 30 min. After being washed with phosphate-buffered saline, the sections were incubated with appropriate antibodies for 2 h at room temperature and then reacted with the corresponding secondary antibodies for 30 min at room temperature. These sections were observed using a confocal laser scanning microscope (LSM 5 PASCAL, Carl Zeiss Co. Ltd, Germany), and the number of infiltrating immune https://www.selleckchem.com/products/kpt-330.html cell clusters in the gastric mucosa of the specimens was counted

in a blinded manner. The cluster was defined as >20 of B220-positive cells gathering together in the microscopic view. The following antibodies were used: polyclonal rabbit anti-H. pylori antibody (DAKO, Glostrup, Denmark), Alexa488-conjugated polyclonal goat anti-rabbit IgG antibody (Invitrogen, Eugene, OR), fluorescein isothiocyanate-conjugated monoclonal

hamster anti-mouse CD11c antibody (BD, Franklin Lakes, NJ), purified monoclonal rat anti-mouse B220 antibody (BD), Alexa546-conjugated polyclonal goat anti-rat IgG antibody (Invitrogen), and PE-conjugated monoclonal rat anti-mouse CD4 antibody (BD). DNA ligase The nuclei and F-actin in the sections were stained with Alexa642-conjugated topro (Invitrogen) and Alexa546-conjugated phalloidin (Invitrogen) or Alexa647-conjugated phalloidin (Invitrogen), respectively. The gastric mucosa was carefully scraped off the stomach using microscopic slides, and the mucosal samples were obtained. Then, the samples were homogenized with 1 mL of Trizol Regent (Invitrogen). RNA and DNA were extracted from the homogenates according to the manufacturer’s instructions. RNA was subjected to the reverse transcription reaction using a High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA) according to the manufacturer’s protocols, and quantitative real-time PCR was performed using Power SYBR Green PCR Master Mix (Applied Biosystems) and the ABI Prism 7500 Real Time PCR system (Applied Biosystems) according to the manufacturer’s instructions. The following primers were used: β-actin: 5′-AAGGCCAACCGTGAAAAGAT-3′ and 5′-GTGGTACGACCAGAGGCATAC-3′; H.

Lastly, targeting different specificities on the same DC subset can result in different immune outcomes. For example, CD8+ cDCs induced a strong antibody response without adjuvant when targeted via the 10B4 anti-Clec9a (DNGR1) antibody but not via CD205 [54] or the 7H11 Clec9a antibody [55]. Similarly, CD8+ cDCs induced strong CD8+ T cell responses when targeted via CD207, CD205 or Clec9a [51, 54], whereas a weaker response was observed when targeting Clec12a [54]. These distinctions may reflect differences in the expression or signalling properties of the targeted molecule [56] and/or the properties of the targeting antibody itself, including Selleckchem ABT 263 its lifespan in vivo

[54]. Thus, targeting experiments, while crucial in determining the therapeutic potential of particular antigen–antibody complexes, may not add substantially to our understanding of the function of DC subsets in vivo. DC ablation models have been used to test whether a DC subset is required for a particular T cell response. DC ablation models generally rely upon expression of diphtheria toxin or its receptor to delete DCs either constitutively

or inducibly (reviewed in [57]). In addition to killing DCs, ablation may have significant secondary effects due to changes in the immune Cilomilast solubility dmso microenvironment, interference with feedback loops involving other cell types, and so on. Constitutive removal of the entire DC compartment not only prevented immune responses to immunization, but also resulted in gross secondary syndromes ranging from myeloproliferative Buspirone HCl disorders to spontaneous fatal multi-organ autoimmunity [58, 59]. Inducible ablation of individual DC subsets, which would be predicted to have fewer unforseen secondary effects, has been achieved by administration of

diphtheria toxin into mice expressing the high-affinity diphtheria toxin receptor (DTR) under appropriate promoters, or by means of treatment with horse cytochrome c. When CD11c-DTR mice were treated with diphtheria toxin, T cell responses to bacterial, viral and parasitic infections were reduced dramatically [57]. However, a range of CD11c-negative/low macrophage and monocyte subsets were also depleted [60], while the majority of the mDC subsets were unaffected [57]. CD11c-DTR mice also developed a chemokine-dependent neutrophilia after dendritic cell ablation [61]. An alternative CD11c-Cre DTR model has been developed recently. In this model, Cre recombinase-mediated excision of a floxed-stop codon allows for constitutive DTR expression in CD11c-Cre-positive cells [62]. Langerin-DTR models have been used to assess the role of LCs in the immune response, but the results from these experiments have been heavily model-dependent.

Overall, the DNA vaccine pVAX1–TgCyP induced a significantly higher level of humoral response and splenocyte Bcl-2 inhibitor proliferation in BALB/c mice. A higher survival rate was attained in the pVAX1–TgCyP vaccinated group compared with the control groups. From these results, we believe that TgCyP can be an alternative vaccine

antigen for preventing T. gondii infection. In recent years, vaccine studies have predominated in the quest to prevent toxoplasmosis. Specific immune responses and efficient production have been induced in mice by DNA vaccines that have been constructed with different T. gondii antigens, including SAG1, AMA1, IMP1, ADF and MIC3 [10-13]. Cyclophilins are known to be molecular chaperones, suggesting that TgCyP and certain parasite peptides or other molecules may together engage the chemokine receptor CCR5 and a TLR molecule to trigger high production of IL-12 [17, 23-25]. Recombinant TgCyP has also been shown to have potent PPIase and IL-12-inducing activities,

thus promoting the stabilization of the T. gondii life cycle and preventing T. gondii from overwhelming its intermediate click here hosts [17]. Furthermore, NcCyP has been shown to enhance IL-12 and IFN-γ production in dendritic cells [18]. IFN-γ, which produced by T cells and NK cells, is up-regulated by IL-12, and it is one of the most critical cytokines that mediates host protection against infection by T. gondii. In this study, the parasite antigen TgCyP was investigated as an initiation immunoregulatory molecule and was expected to trigger an antigen-specific

immune response to T. gondii by inducing IL-12 and IFN-γ. A TgCyP-specific antibody was detected in mice immunized with pVAX1–TgCyP. The survival rate after challenge with tachyzoites increased, suggesting that there is a correlation between a high anti-TgCyP antibody level and protection. Splenocytes consist of a variety of cell populations, such as B cells, T cells, dendritic cells and macrophages, all of which Tangeritin take part in several immune responses to intracellular parasite infection. Due to the high similarity between TgCyP and NcCyP, the high splenocyte proliferation in the pVAX1–TgCyP-vaccinated mice suggest that TgCyP could increase the proliferation of dendritic cells and antigen-specific CD4+ T cells, which has been previously verified for NcCyP antigen[19]. To further characterize the polarization of the immune response, we evaluated IL-2, IL-4, IL-10 and IFN-γ as indications of the Th1 and Th2 responses. IL-2 is produced primarily by T cells that express the surface antigen CD4 following allogenic activation. IL-2 is also a growth factor for all subpopulations of T-lymphocytes. T. gondii is a protozoan that is susceptible to the T-cell immunosuppressive agent cyclosporin A (CsA), and the activity of TgCyP and IL-2 synthesis in vitro has been shown to be suppressed by CsA [16].

To further support our hypothesis that proteolytic cleavage of the proteins might be the relevant mechanism for elimination from CSF we performed an additional experiment. After fungal growth for 1, 2, 3 and 5 days, the hyphae of the Pseudallescheria and Scedosporium isolates were removed from their

culture supernatants by filtration and the sterile supernatants enriched with secreted fungal protease but free from any fungal surfaces were supplemented with purified C1q or C3 protein. Again, a time-dependent elimination of the purified complement proteins could be observed for the fast-degrading isolates with appearance of larger fragments after 1–2 days which then progressively disappear over time (data not shown). In addition, HIF inhibitor review when the fungi were grown in nutrient-rich LY2606368 culture media such as Sabouraud medium that do not favour secretion of proteolytic enzymes as shown for Aspergillus species27 the corresponding supernatants did not induce any decrease in the concentration of supplemented complement proteins (data not shown). The phylogenetical analysis shown in Fig. 4, reveals a clear bipartition between P. boydii and P. apiosperma. The strains isolated from CNS are not specifically clustered in a branch. Within P. apiosperma, no particular groups concerning the ability for degradation of C3 or C1q were found. Two strains (CBS

122085 and CS 330.93), which were efficiently clearing C1q and C3 from CSF, had identical Cyclin-dependent kinase 3 ITS-sequences even though they were isolated in geographical distance

and with approximately 15 years difference. Pseudallescheria strains cause a broad spectrum of clinical symptoms after infection and vary in their resistance against antimycotic drugs. This variability was found to be based partly on a poor understanding of the taxonomy. New data have completely revised the systematic, and new species have been described. It is now an intriguing question whether or not this revised taxonomy correlates with any infection parameters in vivo and in vitro. As the CNS was reported to be one of the major loci of infection,2,17,18 the ability of the fungus to gain nutrients in this specific environment and to cope with the local innate immune system is of particular interest. The preference of Pseudallescheria and Scedosporium for the CNS and the high lethality of the cerebral infections despite the presence of complement indicate that these species have developed appropriate mechanisms. In general, fungi have developed a broad armamentarium of mechanisms either to avoid recognition by the immune system or to eliminate the antifungal immune weapons. This arsenal of skills represents important virulence factors of the fungi that enable their survival in the host.

Post-translational regulation of T-cell fitness, as occurs in lymphoreplete conditions, allows for the most rapid response to changing homeostatic conditions, while transcriptional changes as occur in lymphopenia permit more sustained and robust homeostatic responses by T cells. We identified a key role for IL-7 in regulating T-cell fitness. It will be interesting in future studies to determine whether other signals known to be important for T-cell homeostasis, such as TCR signalling induced by spMHC, also influences T-cell fitness and by what

mechanism. F5Il7r−/− TreIL-7R rtTAhuCD2 tetracycline-inducible mice (TetIL-7R) have been described previously 24. Breeders and weaned pups were fed doxycycline (dox) in food (3 mg/g) to induce IL-7Rα expression. (F5Rag1−/−×C57BL/6J Ly5.1)F1 mice were used as controls throughout. Doxorubicin mw These strains

and F5 Rag1−/− BadhuCD232, Rag1−/−, Il7r−/− and F5 Rag1−/− mice were bred in a conventional colony free of pathogens at the NIMR, London. All lines used were of the H-2b haplotype. Animal experiments were performed according to the institutional guidelines and Home Office regulations under project license 80/2092. Flow cytometry was carried out using thymus, spleen cells, or peripheral blood lymphocytes (PBLs). Cell concentrations were determined using a Scharfe Instruments STA-9090 clinical trial Casy Counter (Scharfe System, Reutlingen, Germany). Cells were incubated with saturating concentrations of antibodies in 200 μL PBS-bovine serum albumin (0.1%)-azide (1 mM) for 30 mins at 4°C followed by two washes in PBS-bovine serum albumin-azide. Monoclonal antibodies used in this study were as follows: Pacific blue-CD4 (RM4-5; eBioscience, San Diego, CA, USA), PE-CD8α (53-6.7, BD Biosciences, PharMingen), FITC, PE Cy5, allophycocyanin-CD8α (eBioscience), PE, PE Cy5, allophycocyanin-CD127 (A7R34, eBioscience), allophycocyanin-TCRβ (H57-597; eBioscience), FITC-TCRβ (BD Biosciences), FITC, AF-780-CD44 (IM7; eBioscience), PE-Ly5.1 (BD Biosciences). Cell viability Thalidomide was determined by 7-AAD

(Sigma, St. Louis, MO, USA) exclusion and labelling at 10 μg/mL. Four- and six-colour cytometric staining was analysed on a FACSCalibur (Becton Dickinson, San Jose, CA, USA) and a Cyan (Dako Cytomation), respectively. Data were analysed using the Flowjo software v8.1 (Tree Star, Ashland, OR, USA). Cells were labelled with 2 μM carboxyfluorescein diacetate succinimidyl ester (CFSE; Molecular Probes) in Dulbecco PBS (Invitrogen) for 10 min at 37°C and washed twice. Analysis of total active caspases was performed by adding 1× carboxyfluorescein-labelled VAD-fluoromethylketone (FMK) FLICA (Chemicon) reagent to surface-stained cells and incubated for 60 min at 37°C with 5% CO2 in the dark prior to acquisition. PE-Bcl2 (BD Biosciences) and active PE-caspase 3 (BD Biosciences) staining of IC fix buffer (eBioscience) fixed samples was carried out according to manufacturer’s instructions.

A variety of studies now indicate that retinal vasodilation during flicker light simulation is reduced in diabetes, hypertension, hyperlipidemia and obesity, and may be influenced by age and race/ethnicity. These data suggest that flicker light-induced retinal vasodilation may be a unique and non-invasive measure of endothelial dysfunction. This review focuses recent studies on systemic associations of flicker light-induced retinal vasodilation, and discusses the potential for future research in this area. “
“Refractory angina is the occurrence

of clinical symptoms despite maximal therapy. We investigated associations between microvascular function, atherosclerotic burden, and clinical symptoms in subjects with CAD. Skin microvascular response see more to heating and ischemia was assessed in 167 male volunteers by laser Doppler fluximetry; 82 with CAD on maximal selleck chemicals llc therapy

and 85 with no known CAD (noCAD). CAC scores, carotid IMT, and femoral IMT were measured and symptoms were scored using the Rose angina questionnaire. Patients with CAD had poorer microvascular response to heating (114[95% CI 106–122]au CAD vs. 143[134–153]au no CAD; p < 0.0001) and ischemia (42[38–46]au CAD vs. 53[78–58]au. noCAD; p = 0.001). Thirty-eight percent of the noCAD group had elevated CAC scores. There were no associations between markers of atherosclerosis and microvascular function. Forty-two percent of the CAD group had refractory angina. This was associated with impaired microvascular function compared to those with elevated CAC scores but no symptoms (109 [95–124]au vs. 131[122–140]au; p = 0.008). Men with symptomatic CAD have poorer microvascular function compared to individuals without CAD. Microvascular function does not correlate with atherosclerosis, but is impaired in individuals with refractory angina. Microvascular dysfunction may play a role in the symptomatology of angina. "
“Please cite this paper as: Bierbach B, Scheewe J, Derfuss mafosfamide T, Krug A, Schramm R, Dahm M, Kuroczynski W, Kempski O, Horstick G. Continuous regional myocardial blood flow measurement: validation of a near-infrared laser Doppler device in a porcine

model. Microcirculation 19: 485–493, 2012. Objective:  RMBF measurement is a major concern in various clinical and experimental settings, but no validated device for RMBF is currently available. Methods:  An LVP-triggered laser Doppler to measure RMBF was validated by simultaneous fluorescent MS RMBF in a porcine LAD flow reduction model (n = 10 pigs). The laser probe was positioned on the left ventricle’s anterior wall. LAD blood flow reduction was achieved by a shaft-driven occluder positioned proximal to the transit-time flow meter measuring coronary blood flow. RMBF was measured at baseline; after the reduction of LAD blood flow to 70% and 30% of baseline; at 20 and 120 minutes of reperfusion; and, finally, 15 minutes after LAD occlusion.