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Sample records for hind limb ischemia

  1. Treatment of hind limb ischemia using angiogenic peptide nanofibers.

    PubMed

    Kumar, Vivek A; Liu, Qi; Wickremasinghe, Navindee C; Shi, Siyu; Cornwright, Toya T; Deng, Yuxiao; Azares, Alon; Moore, Amanda N; Acevedo-Jake, Amanda M; Agudo, Noel R; Pan, Su; Woodside, Darren G; Vanderslice, Peter; Willerson, James T; Dixon, Richard A; Hartgerink, Jeffrey D

    2016-08-01

    For a proangiogenic therapy to be successful, it must promote the development of mature vasculature for rapid reperfusion of ischemic tissue. Whole growth factor, stem cell, and gene therapies have yet to achieve the clinical success needed to become FDA-approved revascularization therapies. Herein, we characterize a biodegradable peptide-based scaffold engineered to mimic VEGF and self-assemble into a nanofibrous, thixotropic hydrogel, SLanc. We found that this injectable hydrogel was rapidly infiltrated by host cells and could be degraded while promoting the generation of neovessels. In mice with induced hind limb ischemia, this synthetic peptide scaffold promoted angiogenesis and ischemic tissue recovery, as shown by Doppler-quantified limb perfusion and a treadmill endurance test. Thirteen-month-old mice showed significant recovery within 7 days of treatment. Biodistribution studies in healthy mice showed that the hydrogel is safe when administered intramuscularly, subcutaneously, or intravenously. These preclinical studies help establish the efficacy of this treatment for peripheral artery disease due to diminished microvascular perfusion, a necessary step before clinical translation. This peptide-based approach eliminates the need for cell transplantation or viral gene transfection (therapies currently being assessed in clinical trials) and could be a more effective regenerative medicine approach to microvascular tissue engineering.

  2. Imaging receptor for advanced glycation end product expression in mouse model of hind limb ischemia

    PubMed Central

    2013-01-01

    Background The purpose of this study is to image the effect of diabetes on expression of receptor for advanced glycation endproducts (RAGE) in limb ischemia in live animals. Methods Male wild-type C57BL/6 mice were either made diabetic or left as control. Two months later, diabetic and non-diabetic mice underwent left femoral artery ligation. The right leg served as lesion control. Five days later, mice were injected with 15.1 ± 4.4 MBq 99mTc-anti-RAGE F(ab’)2 and 4 to 5 h later (blood pool clearance) underwent SPECT/CT imaging. At the completion of imaging, mice were euthanized, hind limbs counted and sectioned, and scans reconstructed. Regions of interest were drawn on serial transverse sections comprising the hind limbs and activity in millicuries summed and divided by the injected dose (ID). Quantitative histology was performed for RAGE staining and angiogenesis. Results Uptake of 99mTc-anti-RAGE F(ab')2 as %ID × 10−3 was higher in the left (ischemic) limbs for the diabetic mice (n = 8) compared to non-diabetic mice (n = 8) (1.20 ± 0.44% vs. 0.49 ± 0.40%; P = 0.0007) and corresponded to less angiogenesis in the diabetic mice. Uptake was also higher in the right limbs of diabetic compared to non-diabetic animals (0.82 ± 0.33% vs. 0.40 ± 0.14%; P = 0.0004). Conclusions These data show the feasibility of imaging and quantifying the effect of diabetes on RAGE expression in limb ischemia. PMID:23663412

  3. p66(ShcA) and oxidative stress modulate myogenic differentiation and skeletal muscle regeneration after hind limb ischemia.

    PubMed

    Zaccagnini, Germana; Martelli, Fabio; Magenta, Alessandra; Cencioni, Chiara; Fasanaro, Pasquale; Nicoletti, Carmine; Biglioli, Paolo; Pelicci, Pier Giuseppe; Capogrossi, Maurizio C

    2007-10-26

    Oxidative stress plays a pivotal role in ischemic injury, and p66(ShcA)ko mice exhibit both lower oxidative stress and decreased tissue damage following hind limb ischemia. Thus, it was investigated whether tissue regeneration following acute hind limb ischemia was altered in p66(ShcA)ko mice. Upon femoral artery dissection, muscle regeneration started earlier and was completed faster than in wild-type (WT) control. Moreover, faster regeneration was associated with decreased oxidative stress. Unlike ischemia, cardiotoxin injury induced similar skeletal muscle damage in both genotypes. However, p66(ShcA)ko mice regenerated faster, in agreement with the regenerative advantage upon ischemia. Since no difference between p66(ShcA)wt and knock-out (ko) mice was found in blood perfusion recovery after ischemia, satellite cells (SCs), a resident population of myogenic progenitors, were examined. Similar SCs numbers were present in WT and ko mice. However, in vitro cultured p66(ShcA)ko SCs displayed lower oxidative stress levels and higher proliferation rate and differentiated faster than WT. Furthermore, when exposed to sublethal H(2)O(2) doses, p66(ShcA)ko SCs were resistant to H(2)O(2)-induced inhibition of differentiation. Finally, myogenic conversion induced by MyoD overexpression was more efficient in p66(ShcA)ko fibroblasts compared with WT. The present work demonstrates that oxidative stress and p66(ShcA) play a crucial role in the regenerative pathways activated by acute ischemia.

  4. Curcumin and dexmedetomidine prevents oxidative stress and renal injury in hind limb ischemia/reperfusion injury in a rat model.

    PubMed

    Karahan, M A; Yalcin, S; Aydogan, H; Büyükfirat, E; Kücük, A; Kocarslan, S; Yüce, H H; Taskın, A; Aksoy, N

    2016-06-01

    Curcumin and dexmedetomidine have been shown to have protective effects in ischemia-reperfusion injury on various organs. However, their protective effects on kidney tissue against ischemia-reperfusion injury remain unclear. We aimed to determine whether curcumin or dexmedetomidine prevents renal tissue from injury that was induced by hind limb ischemia-reperfusion in rats. Fifty rats were divided into five groups: sham, control, curcumin (CUR) group (200 mg/kg curcumin, n = 10), dexmedetomidine (DEX) group (25 μg/kg dexmedetomidine, n = 10), and curcumin-dexmedetomidine (CUR-DEX) group (200 mg/kg curcumin and 25 μg/kg dexmedetomidine). Curcumin and dexmedetomidine were administered intraperitoneally immediately after the end of 4 h ischemia, just 5 min before reperfusion. The extremity re-perfused for 2 h and then blood samples were taken and total antioxidant capacity (TAC), total oxidative status (TOS) levels, and oxidative stress index (OSI) were measured, and renal tissue samples were histopathologically examined. The TAC activity levels in blood samples were significantly lower in the control than the other groups (p < 0.01 for all comparisons). The TOS activity levels in blood samples were significantly higher in Control group and than the other groups (p <  0.01 for all comparison). The OSI were found to be significantly increased in the control group compared to others groups (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in the sham, CUR, DEX, and CUR-DEX groups, compared with the control group (p < 0.01). Rat hind limb ischemia-reperfusion causes histopathological changes in the kidneys. Curcumin and dexmedetomidine administered intraperitoneally was effective in reducing oxidative stress and renal histopathologic injury in an acute hind limb I/R rat model.

  5. In Vivo Detection of Macrophage Recruitment in Hind-Limb Ischemia Using a Targeted Near-Infrared Fluorophore

    PubMed Central

    Yoo, Jung Sun; Das, Raj Kumar; Jow, Zhi Yen; Chang, Young-Tae

    2014-01-01

    Macrophages are an essential component of the immune system and have protective and pathogenic functions in various diseases. Imaging of macrophages in vivo could furnish new tools to advance evaluation of disease and therapies. Critical limb ischemia is a disease in which macrophages have considerable pathogenic roles, and are potential targets for cell-based immunotherapy. We sought to develop a new near-infrared fluorescence (NIRF) imaging probe to target macrophages specifically in vivo in various pathological states, including hind-limb ischemia. We rapidly screened the photostable cyanine-based NIRF library against different blood cell lines. The identified monocyte/macrophage-selective hit was tested in vitro in live-cell labeling assay. Non-invasive NIRF imaging was performed with murine models of paw inflammation by lipopolysaccharide challenge and hind-limb ischemia with femoral artery ligation. in vivo macrophage targeting was further evaluated using intravital microscopy with Csf1r-EGFP transgenic mice and immunofluorescent staining with macrophage-specific markers. We discovered MF800, a Macrophage-specific near-infrared Fluorophore, which showed selective live-cell imaging performance in a panel of cell lines and primary human blood samples. MF800 outperforms the clinically-available NIRF contrast agent ICG for in vivo specificity in paw inflammation and hind-limb ischemia models. We observed a marked overlap of MF800-labeled cells and EGFP-expressing macrophages in intravital imaging of Csf1r-EGFP transgenic mice. In the histologic analysis, MF800-positive cells also expressed the macrophage markers CD68 and CD169. NIRF imaging showcased the potential of using MF800 to understand macrophage behavior in vivo, characterize macrophage-associated diseases, and may help in assessing therapeutic responses in the clinic. PMID:25072508

  6. Fucoidan improves bioactivity and vasculogenic potential of mesenchymal stem cells in murine hind limb ischemia associated with chronic kidney disease.

    PubMed

    Lee, Jun Hee; Ryu, Jung Min; Han, Yong-Seok; Zia, Mohammad Farid; Kwon, Hyog Young; Noh, Hyunjin; Han, Ho Jae; Lee, Sang Hun

    2016-08-01

    Chronic kidney disease (CKD) is a significant risk factor for cardiovascular and peripheral vascular disease. Although mesenchymal stem cell (MSC)-based therapy is a promising strategy for treatment of ischemic diseases associated with CKD, the associated pathophysiological conditions lead to low survival and proliferation of transplanted MSCs. To address these limitations, we investigated the effects of fucoidan, a sulfated polysaccharide, on the bioactivity of adipose tissue-derived MSCs and the potential of fucoidan-treated MSCs to improve neovascularization in ischemic tissues of CKD mice. Treatment of MSCs with fucoidan increased their proliferative potential and the expression of cell cycle-associated proteins, such as cyclin E, cyclin dependent kinase (CDK) 2, cyclin D1, and CDK4, via focal adhesion kinase and the phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt axis. Moreover, fucoidan enhanced the immunomodulatory activity of MSCs through the ERK-IDO-1 signal cascade. Fucoidan was found to augment the proliferation, incorporation, and endothelial differentiation of transplanted MSCs at ischemic sites in CKD mice hind limbs. In addition, transplantation of fucoidan-treated MSCs enhanced the ratio of blood flow and limb salvage in CKD mice with hind limb ischemia. To our knowledge, our findings are the first to reveal that fucoidan enhances the bioactivity of MSCs and improves their neovascularization in ischemic injured tissues of CKD. In conclusion, fucoidan-treated MSCs may provide an important pathway toward therapeutic neovascularization in patients with CKD.

  7. TLR4 Accessory Molecule RP105 (CD180) Regulates Monocyte-Driven Arteriogenesis in a Murine Hind Limb Ischemia Model

    PubMed Central

    Bastiaansen, Antonius J. N. M.; Karper, Jacco C.; Wezel, Anouk; de Boer, Hetty C.; Welten, Sabine M. J.; de Jong, Rob C. M.; Peters, Erna A. B.; de Vries, Margreet R.; van Oeveren-Rietdijk, Annemarie M.; van Zonneveld, Anton Jan; Hamming, Jaap F.

    2014-01-01

    Aims We investigated the role of the TLR4-accessory molecule RP105 (CD180) in post-ischemic neovascularization, i.e. arteriogenesis and angiogenesis. TLR4-mediated activation of pro-inflammatory Ly6Chi monocytes is crucial for effective neovascularization. Immunohistochemical analyses revealed that RP105+ monocytes are present in the perivascular space of remodeling collateral arterioles. As RP105 inhibits TLR4 signaling, we hypothesized that RP105 deficiency would lead to an unrestrained TLR4-mediated inflammatory response and hence to enhanced blood flow recovery after ischemia. Methods and Results RP105−/− and wild type (WT) mice were subjected to hind limb ischemia and blood flow recovery was followed by Laser Doppler Perfusion Imaging. Surprisingly, we found that blood flow recovery was severely impaired in RP105−/− mice. Immunohistochemistry showed that arteriogenesis was reduced in these mice compared to the WT. However, both in vivo and ex vivo analyses showed that circulatory pro-arteriogenic Ly6Chi monocytes were more readily activated in RP105−/− mice. FACS analyses showed that Ly6Chi monocytes became activated and migrated to the affected muscle tissues in WT mice following induction of hind limb ischemia. Although Ly6Chi monocytes were readily activated in RP105−/− mice, migration into the ischemic tissues was hampered and instead, Ly6Chi monocytes accumulated in their storage compartments, bone marrow and spleen, in RP105−/− mice. Conclusions RP105 deficiency results in an unrestrained inflammatory response and monocyte over-activation, most likely due to the lack of TLR4 regulation. Inappropriate, premature systemic activation of pro-inflammatory Ly6Chi monocytes results in reduced infiltration of Ly6Chi monocytes in ischemic tissues and in impaired blood flow recovery. PMID:24945347

  8. FACS-purified myoblasts producing controlled VEGF levels induce safe and stable angiogenesis in chronic hind limb ischemia.

    PubMed

    Wolff, Thomas; Mujagic, Edin; Gianni-Barrera, Roberto; Fueglistaler, Philipp; Helmrich, Uta; Misteli, Heidi; Gurke, Lorenz; Heberer, Michael; Banfi, Andrea

    2012-01-01

    We recently developed a method to control the in vivo distribution of vascular endothelial growth factor (VEGF) by high throughput Fluorescence-Activated Cell Sorting (FACS) purification of transduced progenitors such that they homogeneously express specific VEGF levels. Here we investigated the long-term safety of this method in chronic hind limb ischemia in nude rats. Primary myoblasts were transduced to co-express rat VEGF-A(164) (rVEGF) and truncated ratCD8a, the latter serving as a FACS-quantifiable surface marker. Based on the CD8 fluorescence of a reference clonal population, which expressed the desired VEGF level, cells producing similar VEGF levels were sorted from the primary population, which contained cells with very heterogeneous VEGF levels. One week after ischemia induction, 12 × 10(6) cells were implanted in the thigh muscles. Unsorted myoblasts caused angioma-like structures, whereas purified cells only induced normal capillaries that were stable after 3 months. Vessel density was doubled in engrafted areas, but only approximately 0.1% of muscle volume showed cell engraftment, explaining why no increase in total blood flow was observed. In conclusion, the use of FACS-purified myoblasts granted the cell-by-cell control of VEGF expression levels, which ensured long-term safety in a model of chronic ischemia. Based on these results, the total number of implanted cells required to achieve efficacy will need to be determined before a clinical application.

  9. Effect of picroside II on erythrocyte deformability and lipid peroxidation in rats subjected to hind limb ischemia reperfusion injury

    PubMed Central

    Çomu, Faruk Metin; Kılıç, Yiğit; Özer, Abdullah; Kirişçi, Mehmet; Dursun, Ali Doğan; Tatar, Tolga; Zor, Mustafa Hakan; Kartal, Hakan; Küçük, Ayşegül; Boyunağa, Hakan; Arslan, Mustafa

    2016-01-01

    Background Ischemia reperfusion injury (I/R) in hind limb is a frequent and important clinical phenomenon. Many structural and functional damages are observed in cells and tissues in these kinds of injuries. In this study, we aimed to evaluate the effect of picroside II on lipid peroxidation and erythrocyte deformability during I/R in rats. Methods Rats were randomly divided into four groups – each containing six animals (sham, I/R, sham + picroside II, and I/R + picroside II). The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R groups. The clamp was removed after 120 minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg·kg−1) was administered intraperitoneally to the animals in the appropriate groups (sham + picroside II, I/R + picroside II groups). All rats were euthanized by intraperitoneal administration of ketamine (100 mg·kg−1) and taking blood from the abdominal aorta. Erythrocytes were extracted from heparinized complete blood samples. Buffer (PT) and then erythrocytes (PE) were passed through the filtration system and the changes in pressure were measured to investigate the role of serum malondialdehyde and nitric oxide (NO) in lipid peroxidation and erythrocyte deformability index. Results Deformability index was significantly increased in the I/R group compared to groups sham, sham + picroside-II, and I/R + picroside-II (P<0.0001, P<0.0001, and P=0.007). Malondialdehyde (MDA) and NO levels were evaluated. MDA level and NO activity were also higher in the I/R group than in the other groups. Picroside II treatment before hind limb I/R prevented these changes. Conclusion These results support that deformability of erythrocytes is decreased in I/R injury and picroside II plays a critical role to prevent these alterations. Further experimental and clinical studies are needed to evaluate and clarify the molecular mechanisms of action and clinical importance of these

  10. The Impact of Prophylactic Fasciotomy Following Porcine (Sus scrofa) Hind Limb Ischemia/Reperfusion Injury

    DTIC Science & Technology

    2012-03-23

    the 14-day survival period to calculate the composite physiologic model of recovery ( PMR ). Necropsy was performed for evaluation of nerve and...muscle histology. Results: In hemorrhage alone, according to the PMR the recovery was 94+/-28%, 63+/- 37% and 55+/-44% at 0, 3 and 6 hours of ischemia...hours. , , . v w and compared to baseline to create the Physiologic Model of Recovery ( PMR ). On day 14, necropsy was performed and

  11. Calcium-dependent signalling is essential during collateral growth in the pig hind limb-ischemia model.

    PubMed

    Troidl, C; Nef, H; Voss, S; Schilp, A; Kostin, S; Troidl, K; Szardien, S; Rolf, A; Schmitz-Rixen, T; Schaper, W; Hamm, C W; Elsässer, A; Möllmann, H

    2010-07-01

    We investigated the effect of pharmacological activation of the Ca(2+)-channel transient receptor potential cation channel, subfamily V, member 4 (TRPV4) on collateral growth in a pig hind limb-ischemia model thereby identifying subcellular mechanisms. Domestic pigs received femoral artery ligature and were randomly assigned to one of the following groups (each n=6): (1) 4alpha-phorbol 12,13-didecanoate (4alphaPDD) treatment; (2) treatment with an arterio-venous shunt (AV-shunt) distal to the occlusion; or (3) implantation of NaCl-filled minipump. Six sham-operated pigs acted as controls. Aortic and peripheral mean arterial pressure (MAP) measurements were performed to assess the collateral flow index (CFI). Tissue was isolated from M. quadriceps for immunohistochemistry and from isolated collateral arteries for quantitative real time PCR (qRT-PCR). Shortly after ligature the CFI dropped from 0.96+/-0.02 to 0.21+/-0.02 in all ligature-treated groups. In ligature-only-treated pigs CFI increased to 0.56+/-0.03 after 7days. Treatment with 4alphaPDD led to an enhancement of CFI compared with ligature alone (0.73+/-0.03). CD31-staining showed improved arteriolar density. Increased Ki67 staining in collaterals indicated proliferation. qRT-PCR and Western blot analysis showed upregulation or modulation of Ca(2+)-dependent transcription factors nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), Kv channel interacting protein 3, calsenilin (KCNIP3/CSEN/DREAM), and myocyte enhancer factor 2C (MEF2C) in 4alphaPDD- and AV-shunt-treated pigs compared with controls. Improved CFI after 4alphaPDD treatment identifies TRPV4 as an initial fluid shear-stress sensor and collateral remodelling and growth trigger. Subcellularly, modulation of Ca(2+)-dependent transcription factors indicates a pivotal role for Ca(2+)-signalling during arteriogenesis.

  12. GM-CSF treated F4/80+ BMCs improve murine hind limb ischemia similar to M-CSF differentiated macrophages.

    PubMed

    Kuwahara, Go; Nishinakamura, Hitomi; Kojima, Daibo; Tashiro, Tadashi; Kodama, Shohta

    2014-01-01

    Novel cell therapy is required to treat critical limb ischemia (CLI) as many current approaches require repeated aspiration of bone marrow cells (BMCs). The use of cultured BMCs can reduce the total number of injections required and were shown to induce therapeutic angiogenesis in a murine model of hind limb ischemia. Blood flow recovery was significantly improved in mice treated with granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent BMCs that secreted inflammatory cytokines. Angiogenesis, lymphangiogenesis, and blood flow recovery ratio were significantly higher in the GM-CSF-cultured F4/80+ macrophage (GM-Mø)-treated group compared with controls. Furthermore, Foxp3+ cell numbers and tissue IL-10 concentrations were significantly increased compared with controls. There was no significant difference in blood flow recovery between GM-Mø and M-CSF-cultured F4/80+ macrophages (M-Mø). Thus, GM-Mø were associated with improved blood flow in hind limb ischemia similar to M-Mø. The selective methods of culturing and treating GM-Mø cells similar to M-Mø cells could be used clinically to help resolve the large number of cells required for BMC treatment of CLI. This study demonstrates a novel cell therapy for CLI that can be used in conjunction with conventional therapy including percutaneous intervention and surgical bypass.

  13. Effects of N-acetylcysteine and pentoxifylline on remote lung injury in a rat model of hind-limb ischemia/reperfusion injury

    PubMed Central

    Takhtfooladi, Hamed Ashrafzadeh; Hesaraki, Saeed; Razmara, Foad; Takhtfooladi, Mohammad Ashrafzadeh; Hajizadeh, Hadi

    2016-01-01

    Objective : To investigate the effects of N-acetylcysteine (NAC) and pentoxifylline in a model of remote organ injury after hind-limb ischemia/reperfusion (I/R) in rats, the lungs being the remote organ system. Methods : Thirty-five male Wistar rats were assigned to one of five conditions (n = 7/group), as follows: sham operation (control group); hind-limb ischemia, induced by clamping the left femoral artery, for 2 h, followed by 24 h of reperfusion (I/R group); and hind-limb ischemia, as above, followed by intraperitoneal injection (prior to reperfusion) of 150 mg/kg of NAC (I/R+NAC group), 40 mg/kg of pentoxifylline (I/R+PTX group), or both (I/R+NAC+PTX group). At the end of the trial, lung tissues were removed for histological analysis and assessment of oxidative stress. Results : In comparison with the rats in the other groups, those in the I/R group showed lower superoxide dismutase activity and glutathione levels, together with higher malondialdehyde levels and lung injury scores (p < 0.05 for all). Interstitial inflammatory cell infiltration of the lungs was also markedly greater in the I/R group than in the other groups. In addition, I/R group rats showed various signs of interstitial edema and hemorrhage. In the I/R+NAC, I/R+PTX, and I/R+NAC+PTX groups, superoxide dismutase activity, glutathione levels, malondialdehyde levels, and lung injury scores were preserved (p < 0.05 for all). The differences between the administration of NAC or pentoxifylline alone and the administration of the two together were not significant for any of those parameters (p > 0.05 for all). Conclusions : Our results suggest that NAC and pentoxifylline both protect lung tissue from the effects of skeletal muscle I/R. However, their combined use does not appear to increase the level of that protection. PMID:26982035

  14. Transfection of VEGF(165) genes into endothelial progenitor cells and in vivo imaging using quantum dots in an ischemia hind limb model.

    PubMed

    Yang, Han Na; Park, Ji Sun; Woo, Dae Gyun; Jeon, Su Yeon; Park, Keun-Hong

    2012-11-01

    Endothelial progenitor cells (EPCs) were transfected with fluorescently labeled quantum dot nanoparticles (QD NPs) with or without VEGF(165) plasmid DNA (pDNA) to probe the EPCs after in vivo transplantation and to test whether they presented as differentiated endothelial cells (ECs). Bare QD NPs and QD NPs coated with PEI or PEI + VEGF(165) genes were characterized by dynamic light scattering, scanning electron microscopy, and atomic force microscopy. Transfection of EPCs with VEGF(165) led to the expression of specific genes and proteins for mature ECs. A hind limb ischemia model was generated in nude mice, and VEGF(165) gene-transfected EPCs were transplanted intramuscularly into the ischemic limbs. At 28 days after transplantation, the VEGF(165) gene-transfected EPCs significantly increased the number of differentiated ECs compared with the injection of medium or bare EPCs without VEGF(165) genes. Laser Doppler imaging revealed that blood perfusion levels were increased significantly by VEGF(165) gene-transfected EPCs compared to EPCs without VEGF(165). Moreover, the transplantation of VEGF(165) gene-transfected EPCs increased the specific gene and protein expression levels of mature EC markers and angiogenic factors in the animal model.

  15. Critical Limb Ischemia (CLI)

    MedlinePlus

    ... High blood pressure Family history of vascular disease Warning Signs You may have critical limb ischemia if ... blood flow to the limb. Other treatments include laser atherectomy, where small bits of plaque are vaporized ...

  16. Protective effects of erdosteine and vitamins C and E combination on ischemia-reperfusion-induced lung oxidative stress and plasma copper and zinc levels in a rat hind limb model.

    PubMed

    Sirmali, Mehmet; Uz, Efkan; Sirmali, Rana; Kilbaş, Aynur; Yilmaz, H Ramazan; Altuntaş, Irfan; Naziroğlu, Mustafa; Delibaş, Namik; Vural, Hüseyin

    2007-07-01

    The aim of this study was to investigate the protective effects of erdosteine and vitamins C and E (VCE) on the lungs after performing hind limb ischemia-reperfusion (I/R) by assessing oxidative stress, plasma copper (Cu), and zinc (Zn) analysis. The animals were divided randomly into four groups as nine rats each as follows: control, I/R, I/R plus erdosteine, and I/R plus VCE combination. I/R period for 60 min was performed on the both hind limbs of all the rats in the groups of I/R, erdosteine with I/R, VCE with I/R allowing 120 min of reperfusion. The animals received orally erdosteine one time in a day and 3 days before I/R in the erdosteine group. In the VCE group, the animals VCE combination received one time in a day and 3 days before I/R, although placebo was given to control and I/R group animals. Lung lipid peroxidation (malondialdehyde [MDA]) level, superoxide dismutase (SOD), and catalase activities were increased, although lung glutathione (GSH) and plasma Zn levels decreased in I/R group in lung tissue compared with the control group. Serum MDA level, creatine kinase, and lactate dehydrogenase activities were increased in I/R group compared with the control. Lung MDA and plasma Zn levels and lung SOD activity were decreased by erdosteine administration, whereas lung GSH levels after I/R increased. The plasma Zn levels and lung SOD activity were decreased by VCE administration, although the plasma Cu and lung GSH levels increased after I/R. In conclusion, erdosteine has an antioxidant role on the values in the rat model, and it has more protective affect than in VCE in attenuating I/R-induced lung injury in rats.

  17. Vasospastic Limb Ischemia Presenting Acute and Chronic Limb Ischemia

    PubMed Central

    2014-01-01

    Vasospastic limb ischemia might have been underappreciated compared to vasospasm in other territories such as heart and brain. However, an increasing awareness of this vascular disorder can be translated to an improved patients’ care. Herein, we report a case of vasospasm presenting acute and chronic limb ischemia in four extremities. PMID:24995065

  18. Scaling and functional morphology in strigiform hind limbs

    PubMed Central

    Madan, Meena A.; Rayfield, Emily J.; Bright, Jen A.

    2017-01-01

    Strigiformes are an order of raptorial birds consisting exclusively of owls: the Tytonidae (barn owls) and the Strigidae (true owls), united by a suite of adaptations aiding a keen predatory lifestyle, including robust hind limb elements modified for grip strength. To assess variation in hind limb morphology, we analysed how the dimensions of the major hind limb elements in subfossil and modern species scaled with body mass. Comparing hind limb element length, midshaft width, and robusticity index (RI: ratio of midshaft width to maximum length) to body mass revealed that femoral and tibiotarsal width scale with isometry, whilst length scales with negative allometry, and close to elastic similarity in the tibiotarsus. In contrast, tarsometatarsus width shows strong positive allometry with body mass, whilst length shows strong negative allometry. Furthermore, the tarsometatarsi RI scales allometrically to mass0.028, whilst a weak relationship exists in femora (mass0.004) and tibiotarsi (mass0.004). Our results suggest that tarsometatarsi play a more substantial functional role than tibiotarsi and femora. Given the scaling relationship between tarsometatarsal width and robusticity to body mass, it may be possible to infer the body mass of prehistoric owls by analysing tarsometatarsi, an element that is frequently preserved in the fossil record of owls. PMID:28327549

  19. Investigating the involvement of TRPV1 ion channels in remote hind limb preconditioning-induced cardioprotection in rats.

    PubMed

    Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

    2017-02-01

    Remote ischemic preconditioning (RIPC) treatment strategy is a breakthrough in the field of cardiovascular pharmacology as it has the potential to attenuate myocardial ischemia-reperfusion injury. However, the underlying intracellular pathways have not been widely explored. The present study intends to explore the possible role of TRPV1 channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 cycles in succession) was delivered by tying the blood pressure cuff at the inguinal level of the rat. The Langendorff system was used to perfuse the isolated heart and afterward was subjected to 30 min of global ischemia and 120 min of reperfusion. Sustained ischemia and, thereafter, reperfusion led to cardiac injury that was assessed in terms of infarct size, lactate dehydrogenase (LDH) release, creatine kinase (CK) release, left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), +dp/dtmax, -dp/dtmin, heart rate, rate pressure product, and coronary flow rate. The pharmacological modulators employed included capsaicin as TRPV1 agonist and capsazepine as TRPV1 antagonist. Remote hind limb preconditioning stimulus and capsaicin preconditioning (5 and 10 mg/kg) led to significant reduction in infarct size, LVEDP, LDH release, CK release, and significant improvement in LVDP, +dp/dtmax, -dp/dtmin, heart rate, rate pressure product, and coronary flow rate. However, remote hind limb preconditioning-induced cardioprotective effects were considerably abolished in the presence of capsazepine (2.5 and 5 mg/kg). This indicates that remote hind limb preconditioning stimulus possibly activates TRPV1 channels to produce cardioprotective effects.

  20. Pelvic and hind limb musculature of Staurikosaurus pricei (Dinosauria: Saurischia).

    PubMed

    Grillo, Orlando N; Azevedo, Sergio A K

    2011-03-01

    The study of pelvic and hind limb bones and muscles in basal dinosaurs is important for understanding the early evolution of bipedal locomotion in the group. The use of data from both extant and extinct taxa placed into a phylogenetic context allowed to make well-supported inferences concerning most of the hind limb musculature of the basal saurischian Staurikosaurus pricei Colbert, 1970 (Santa Maria Formation, Late Triassic of Rio Grande do Sul, Brazil). Two large concavities in the lateral surface of the ilium represent the origin of the muscles iliotrochantericus caudalis plus iliofemoralis externus (in the anterior concavity) and iliofibularis (in the posterior concavity). Muscle ambiens has only one head and originates from the pubic tubercle. The origin of puboischiofemoralis internus 1 possibly corresponds to a fossa in the ventral margin of the pré-acetabular iliac process. This could represent an intermediate stage prior to the origin of a true pré-acetabular fossa. Muscles caudofemorales longus et brevis were likely well developed, and Staurikosaurus is unique in bearing a posteriorly projected surface for the origin of caudofemoralis brevis.

  1. Exploring the Role of TRPV and CGRP in Adenosine Preconditioning and Remote Hind Limb Preconditioning-Induced Cardioprotection in Rats.

    PubMed

    Singh, Amritpal; Randhawa, Puneet Kaur; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2017-02-14

    The cardioprotective effects of remote hind limb preconditioning (RIPC) are well known, but mechanisms by which protection occurs still remain to be explored. Therefore, the present study was designed to investigate the role of TRPV and CGRP in adenosine and remote preconditioning-induced cardioprotection, using sumatriptan, a CGRP release inhibitor and ruthenium red, a TRPV inhibitor, in rats. For remote preconditioning, a pressure cuff was tied around the hind limb of the rat and was inflated with air up to 150 mmHg to produce ischemia in the hind limb and during reperfusion pressure was released. Four cycles of ischemia and reperfusion, each consisting of 5 min of inflation and 5 min of deflation of pressure cuff were used to produce remote limb preconditioning. An ex vivo Langendorff's isolated rat heart model was used to induce ischemia reperfusion injury by 30 min of global ischemia followed by 120 min of reperfusion. RIPC demonstrated a significant decrease in ischemia reperfusion-induced significant myocardial injury in terms of increase in LDH, CK, infarct size and decrease in LVDP, +dp/dtmax and -dp/dtmin. Moreover, pharmacological preconditioning with adenosine produced cardioprotective effects in a similar manner to RIPC. Pretreatment with sumatriptan, a CGRP release blocker, abolished RIPC and adenosine preconditioning-induced cardioprotective effects. Administration of ruthenium red, a TRPV inhibitor, also abolished adenosine preconditioning-induced cardioprotection. It may be proposed that the cardioprotective effects of adenosine and remote preconditioning are possibly mediated through activation of a TRPV channels and consequent, release of CGRP.

  2. Hind-limb vascular-capacitance responses in anaesthetized dogs.

    PubMed Central

    Hainsworth, R; Karim, F; McGregor, K H; Wood, L M

    1983-01-01

    In anaesthetized dogs a hind limb was vascularly isolated, perfused through the femoral artery at either constant flow or constant pressure and drained from the femoral vein at constant pressure. Inflow and outflow were recorded. Vascular-resistance changes were calculated from changes in pressure or flow and volume changes from the differences between inflow and outflow. During constant-flow perfusion, both changes in carotid sinus pressure and direct stimulation of efferent sympathetic nerves resulted in large resistance responses. However, changes in carotid sinus pressure did not result in changes in limb blood volume and only small decreases were obtained in response to direct stimulation. During constant-pressure perfusion, both reflex and direct stimulation resulted not only in significant changes in resistance but also in significant volume changes which were much larger than those obtained during constant-flow perfusion. Similar responses were obtained when the flow rate was changed by altering the pump speed. These results indicate that changes in pressure to carotid baroreceptors do not result in active capacitance responses in the limb circulation and that only very small responses are obtained even to electrical stimulation of sympathetic nerves. The larger responses occurring during constant-pressure perfusion are thought to be secondary to changes in blood flow. PMID:6875939

  3. Bone morphology of the hind limbs in two caviomorph rodents.

    PubMed

    de Araújo, F A P; Sesoko, N F; Rahal, S C; Teixeira, C R; Müller, T R; Machado, M R F

    2013-04-01

    In order to evaluate the hind limbs of caviomorph rodents a descriptive analysis of the Cuniculus paca (Linnaeus, 1766) and Hydrochoerus hydrochaeris (Linnaeus, 1766) was performed using anatomical specimens, radiography, computed tomography (CT) and full-coloured prototype models to generate bone anatomy data. The appendicular skeleton of the two largest rodents of Neotropical America was compared with the previously reported anatomical features of Rattus norvegicus (Berkenhout, 1769) and domestic Cavia porcellus (Linnaeus, 1758). The structures were analyzed macroscopically and particular findings of each species reported. Features including the presence of articular fibular projection and lunulae were observed in the stifle joint of all rodents. Imaging aided in anatomical description and, specifically in the identification of bone structures in Cuniculus paca and Hydrochoerus hydrochaeris. The imaging findings were correlated with the anatomical structures observed. The data may be used in future studies comparing these animals to other rodents and mammalian species.

  4. New Australovenator hind limb elements pertaining to the holotype reveal the most complete Neovenatorid leg.

    PubMed

    White, Matt A; Benson, Roger B J; Tischler, Travis R; Hocknull, Scott A; Cook, Alex G; Barnes, David G; Poropat, Stephen F; Wooldridge, Sarah J; Sloan, Trish; Sinapius, George H K; Elliott, David A

    2013-01-01

    We report new skeletal elements pertaining to the same individual which represents the holotype of Australovenator wintonensis, from the 'Matilda Site' in the Winton Formation (Upper Cretaceous) of western Queensland. The discovery of these new elements means that the hind limb of Australovenator is now the most completely understood hind limb among Neovenatoridae. The new hind limb elements include: the left fibula; left metatarsal IV; left pedal phalanges I-2, II-1, III-4, IV-2, IV-3; and right pedal phalanges, II-2 and III-1. The detailed descriptions are supported with three dimensional figures. These coupled with the completeness of the hind limb will increase the utility of Australovenator in comparisons with less complete neovenatorid genera. These specimens and the previously described hind limb elements of Australovenator are compared with other theropods classified as neovenatorids (including Neovenator, Chilantaisaurus, Fukuiraptor, Orkoraptor and Megaraptor). Hind limb length proportion comparisons indicate that the smaller neovenatorids Australovenator and Fukuiraptor possess more elongate and gracile hind limb elements than the larger Neovenator and Chilantaisaurus. Greater stride lengths to body size exist in both Fukuiraptor and Australovenator with the femur discovered to be proportionally shorter the rest of the hind limb length. Additionally Australovenator is identified as possessing the most elongate metatarsus. The metatarsus morphology varies with body size. The larger neoventorids possess a metatarsus with greater width but shorter length compared to smaller forms.

  5. New Australovenator Hind Limb Elements Pertaining to the Holotype Reveal the Most Complete Neovenatorid Leg

    PubMed Central

    White, Matt A.; Benson, Roger B. J.; Tischler, Travis R.; Hocknull, Scott A.; Cook, Alex G.; Barnes, David G.; Poropat, Stephen F.; Wooldridge, Sarah J.; Sloan, Trish; Sinapius, George H. K.; Elliott, David A.

    2013-01-01

    We report new skeletal elements pertaining to the same individual which represents the holotype of Australovenator wintonensis, from the ‘Matilda Site’ in the Winton Formation (Upper Cretaceous) of western Queensland. The discovery of these new elements means that the hind limb of Australovenator is now the most completely understood hind limb among Neovenatoridae. The new hind limb elements include: the left fibula; left metatarsal IV; left pedal phalanges I-2, II-1, III-4, IV-2, IV-3; and right pedal phalanges, II-2 and III-1. The detailed descriptions are supported with three dimensional figures. These coupled with the completeness of the hind limb will increase the utility of Australovenator in comparisons with less complete neovenatorid genera. These specimens and the previously described hind limb elements of Australovenator are compared with other theropods classified as neovenatorids (including Neovenator, Chilantaisaurus, Fukuiraptor, Orkoraptor and Megaraptor). Hind limb length proportion comparisons indicate that the smaller neovenatorids Australovenator and Fukuiraptor possess more elongate and gracile hind limb elements than the larger Neovenator and Chilantaisaurus. Greater stride lengths to body size exist in both Fukuiraptor and Australovenator with the femur discovered to be proportionally shorter the rest of the hind limb length. Additionally Australovenator is identified as possessing the most elongate metatarsus. The metatarsus morphology varies with body size. The larger neoventorids possess a metatarsus with greater width but shorter length compared to smaller forms. PMID:23894328

  6. Recipient twin limb ischemia with postnatal onset.

    PubMed

    Broadbent, Roland Spencer

    2007-02-01

    After the occurrence of 3 local cases of limb ischemia in newborn twins, we reviewed the literature to investigate this combination systematically. This review reveals a distinct condition: postnatal onset limb ischemia affecting recipient twins in twin-twin transfusion syndrome.

  7. [Critical limb ischemia--update].

    PubMed

    Melamed, Eitan; Kotyba, Baydousi; Galili, Offer; Karmeli, Ron

    2010-12-01

    Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery occlusive disease. Without timely diagnosis and revascularization, patients with CLI are at risk of devastating complications including loss of limb and life. Therapeutic goals in treating patients with CLI include reducing cardiovascular risk factors, relieving ischemic pain, heating ulcers, preventing major amputation, improving quality of life and increasing survival. These aims may be achieved through medical therapy, revascularization or amputation. The past decade has seen substantial growth in endovascular therapies and options now exist for treating long segment occlusive disease, but surgical bypass may still yield more durable results. Patients who are younger, more active, and at low risk for surgery, may have better outcomes undergoing an operation. This is also indicated for endovascular failures, which may include technical failures or late occlusions after stents or other procedures. In contrast, frail patients with a limited life expectancy may experience better outcomes with endovascular therapy. For patients who are non-ambulatory, demented, or unfit to undergo revascularization, an amputation should be considered.

  8. Management of Critical Limb Ischemia

    PubMed Central

    Kinlay, Scott

    2016-01-01

    Critical limb ischemia (CLI) is a clinical syndrome of ischemic pain at rest or tissue loss, such as non-healing ulcers or gangrene, related to peripheral artery disease. CLI has a high short-term risk of limb loss and cardiovascular events. Non-invasive or invasive angiography help determine the feasibility and approach to arterial revascularization. An “endovascular-first” approach is often advocated based on a lower procedural risk, however, specific patterns of disease may be best treated by open surgical revascularization. Balloon angioplasty and stenting form the backbone of endovascular techniques, with drug-eluting stents and drug-coated balloons offering low rates of repeat revascularization. Combined antegrade and retrograde approaches can increase success in long total occlusions. Below the knee, angiosome-directed angioplasty may lead to greater wound healing, but failing this, any straight line flow into the foot is pursued. Hybrid surgical techniques such as iliac stenting and common femoral endarterectomy are commonly used to reduce operative risk. Lower extremity bypass grafting is most successful with a good quality, long, single-segment autogenous vein of at least 3.5mm diameter. Minor amputations are often required for tissue loss as part of the treatment strategy. Major amputations (at or above the ankle) limit functional independence and their prevention is a key goal of CLI therapy. Medical therapy after revascularization targets risk factors for atherosclerosis and assesses wound healing and new or recurrent flow limiting disease. The ongoing NIH sponsored BEST-CLI study is a randomized trial of the contemporary endovascular versus open surgical techniques in patients with CLI. PMID:26858079

  9. A case report of partial bilateral hind limb adactyly in a male lamb.

    PubMed

    Rajabioun, Masoud; Kazemi Mehrjerdi, Hossein; Ghasemi, Samaneh

    2016-01-01

    Hemimelia as a congenital anomaly is a failure of development of extremities formation in embryonic period. This anomaly is defined as complete absence of the part of extremities and different forms were explained for hemimelia. Adactyly is an alternative name for transverse hemimelia and is a rare disorder in the most of animal species. A two months old male lamb with normal vital signs was referred to clinic due to both hind limbs shortness and absence of hooves from the birth day. Clinical and radiological examinations were performed and partial hemimelia was confirmed radiographically in both hind limbs. In left hind limb, total absence of the toe indicated presence of adactyly in this limb. No other congenital deformities were diagnosed in skeletal system based on clinical and radiological examinations. According to our knowledge, this is the first report of such rare conditions in a lamb. Clinical findings and radiological signs of this rare anomaly in a lamb were described in this report.

  10. Dynamic imaging of allogeneic adipose-derived regenerative cells transplanted in ischemic hind limb of apolipoprotein E mouse model

    PubMed Central

    Zheng, Yi; Qin, Jinbao; Wang, Xin; Peng, Zhiyou; Hou, Peiyong; Lu, Xinwu

    2017-01-01

    Background Transplantation of allogeneic adipose-derived regenerative cells (ADRCs) is a promising treatment modality for severe ischemic diseases. However, minimal information is available on the in vivo effects, fate, and migration of ADRCs, as well as the mechanisms of their therapeutic angiogenesis. Materials and methods In this study, green fluorescent protein-expressing ADRCs (GFP-ADRCs) were obtained, labeled with acetylated 3-aminopropyltrimethoxysilane (APTS)-coated iron oxide nanoparticles (APTS NPs), and injected into an old apolipoprotein E knockout (ApoE-KO) mouse model with hind limb ischemia. Then, 3.0 T magnetic resonance imaging (MRI) was performed to dynamically trace the role of ADRCs targeting hind limb ischemia in the ApoE-KO mice model. Results Labeled cells were visualized as large hypointense spots in ischemic muscles by serial 3.0 T MRI scans during a 4-week follow-up. The presence of labeled GFP-ADRCs was confirmed by Prussian blue staining and fluorescence microscopy on postmortem specimens. Conclusion This study showed that allogeneic ADRCs offer great potential application for therapeutic angiogenesis in severe ischemic disease based on the efficacy and feasibility of ADRC transplantation and on the available amounts of tissue. PMID:28053524

  11. Endovascular management of acute limb ischemia.

    PubMed

    Peeters, P; Verbist, J; Keirse, K; Deloose, K; Bosiers, M

    2010-06-01

    Acute limb ischemia (ALI) refers to a rapid worsening of limb perfusion resulting in rest pain, ischemic ulcers or gangrene. With an estimated incidence of 140 million/year, ALI is serious limb-threatening and life-threatening medical emergency demanding prompt action. Three prospective, randomized clinical trials provide data on trombolytic therapy versus surgical intervention in patients with acute lower extremity ischemia. Although they did not give us the final answer, satisfactory results are reported for percutaneous thrombolysis compared with surgery. Moreover, they suggest an important advantage of thrombolysis in acute bypass graft occlusions. Therefore, we believe thrombolytic therapy should be a part of the vascular surgeon's armamentarium to safely and successfully treat ALI patients.

  12. Acute limb ischemia due to ergotism.

    PubMed

    Naz, Iram; Sophie, Ziad

    2006-08-01

    Acute ischemia of an extremity potentially threatens limb loss and occasionally the life of the patient. We are reporting two cases of extremity ischemia secondary to ergot poisoning. The first patient was a 60 years old woman, who presented with a 15 days history of ischemia of the left arm with gangrene of the fingers and pain in the resting right hand for one day. Right brachial artery catheterization showed severe spasm of the artery which was resolved by passage of the inflated balloon catheter. She underwent amputation for gangrene of the left hand. The second patient presented with bilateral symmetrical ischemia of the lower extremities which improved upon withdrawal of the ergot containing medicine. She responded to nifedipine.

  13. The role of hind limb flexor muscles during swimming in the toad, Bufo marinus.

    PubMed

    Gillis, Gary B

    2007-01-01

    Most work examining muscle function during anuran locomotion has focused largely on the roles of major hind limb extensors during jumping and swimming. Nevertheless, the recovery phase of anuran locomotion likely plays a critical role in locomotor performance, especially in the aquatic environment, where flexing limbs can increase drag on the swimming animal. In this study, I use kinematic and electromyographic analyses to explore the roles of four anatomical flexor muscles in the hind limb of Bufo marinus during swimming: m. iliacus externus, a hip flexor; mm. iliofibularis and semitendinosus, knee flexors; and m. tibialis anticus longus, an ankle flexor. Two general questions are addressed: (1) What role, if any, do these flexors play during limb extension? and (2) How do limb flexors control limb flexion? Musculus iliacus externus exhibits a large burst of EMG activity early in limb extension and shows low levels of activity during recovery. Both m. iliofibularis and m. semitendinosus are biphasically active, with relatively short but intense bursts during limb extension followed by longer and typically weaker secondary bursts during recovery. Musculus tibialis anticus longus becomes active mid way through recovery and remains active through the start of extension in the next stroke. In conclusion, flexors at all three joints exhibit some activity during limb extension, indicating that they play a role in mediating limb movements during propulsion. Further, recovery is controlled by a complex pattern of flexor activation timing, but muscle intensities are generally lower, suggesting relatively low force requirements during this phase of swimming.

  14. Comparative anatomy and muscle architecture of selected hind limb muscles in the Quarter Horse and Arab.

    PubMed

    Crook, T C; Cruickshank, S E; McGowan, C M; Stubbs, N; Wakeling, J M; Wilson, A M; Payne, R C

    2008-02-01

    The Quarter Horse (bred for acceleration) and the Arab (bred for endurance) are situated at either end of the equine athletic spectrum. Studies into the form and function of the leg muscles in human sprint and endurance runners have demonstrated that differences exist in their muscle architecture. It is not known whether similar differences exist in the horse. Six Quarter Horse and six Arab fresh hind limb cadavers were dissected to gain information on the muscle mass and architecture of the following muscles: gluteus medius; biceps femoris; semitendinosus; vastus lateralis; gastrocnemius; tibialis cranialis and extensor digitorum longus. Specifically, muscle mass, fascicle length and pennation angle were quantified and physiological cross-sectional area (PCSA) and maximum isometric force were estimated. The hind limb muscles of the Quarter Horse were of a significantly greater mass, but had similar fascicle lengths and pennation angles when compared with those of the Arab; this resulted in the Quarter Horse hind limb muscles having greater PCSAs and hence greater isometric force potential. This study suggests that Quarter Horses as a breed inherently possess large strong hind limb muscles, with the potential to accelerate their body mass more rapidly than those of the Arab.

  15. Hind-limb paresis in a dog with paralumbar solitary T-cell lymphoma.

    PubMed

    Ortega, Maria; Castillo-Alcala, Fernanda

    2010-05-01

    A 2-year-old, neutered, male golden retriever was referred to the Ontario Veterinary College, with a 6-week history of hind limb weakness and back pain. Magnetic resonance imaging of the lumbar vertebral column, and histopathology and immunohistochemistry following euthanasia identified an uncommon solitary T-cell lymphoma in the paralumbar area.

  16. Effects of immobilization on rat hind limb muscles under non-weight-bearing conditions

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Fagan, Julie M.; Satarug, Soisungwan; Cook, Paul H.; Tischler, Marc E.

    1988-01-01

    The effect of stretched and unstretched immobilization of a hind limb on the concentration and the metabolism of proteins in the hind-limb muscles of rats was investigated. The animals were divided into three groups: (1) weight-bearing controls, (2) tail-cast-suspended, and (3) suspended, with one hind limb immobilized with the ankle in dorsiflexion (30-40 deg angle) and the other freely moving. It was found that unloading the hind limbs for 6 days by tail cast suspension caused soleus to atrophy and reduced growth of the gastrocnemius and plantaris muscles; unloading resulted in a higher degradation rate and lower synthesis rate in both in vitro and in vivo. Chronic stretch of the unloaded soleus not only prevented its atrophy but led to significant hypertrophy, relative to weight-bearing controls, with increases in both the sarcoplasmic and myofibrillar protein fractions. Immobilizing one ankle in dorsiflexion prevented the inhibition of growth in the plantaris and gastrocnemius muscles due to unloading.

  17. A Modified Heterotopic Swine Hind Limb Transplant Model for Translational Vascularized Composite Allotransplantation (VCA) Research

    PubMed Central

    Ibrahim, Zuhaib; Cooney, Damon S.; Shores, Jaimie T.; Sacks, Justin M.; Wimmers, Eric G.; Bonawitz, Steven C.; Gordon, Chad; Ruben, Dawn; Schneeberger, Stefan; Lee, W. P. Andrew; Brandacher, Gerald

    2013-01-01

    Vascularized Composite Allotransplantation (VCA) such as hand and face transplants represent a viable treatment option for complex musculoskeletal trauma and devastating tissue loss. Despite favorable and highly encouraging early and intermediate functional outcomes, rejection of the highly immunogenic skin component of a VCA and potential adverse effects of chronic multi-drug immunosuppression continue to hamper widespread clinical application of VCA. Therefore, research in this novel field needs to focus on translational studies related to unique immunologic features of VCA and to develop novel immunomodulatory strategies for immunomodulation and tolerance induction following VCA without the need for long term immunosuppression. This article describes a reliable and reproducible translational large animal model of VCA that is comprised of an osteomyocutaneous flap in a MHC-defined swine heterotopic hind limb allotransplantation. Briefly, a well-vascularized skin paddle is identified in the anteromedial thigh region using near infrared laser angiography. The underlying muscles, knee joint, distal femur, and proximal tibia are harvested on a femoral vascular pedicle. This allograft can be considered both a VCA and a vascularized bone marrow transplant with its unique immune privileged features. The graft is transplanted to a subcutaneous abdominal pocket in the recipient animal with a skin component exteriorized to the dorsolateral region for immune monitoring. Three surgical teams work simultaneously in a well-coordinated manner to reduce anesthesia and ischemia times, thereby improving efficiency of this model and reducing potential confounders in experimental protocols. This model serves as the groundwork for future therapeutic strategies aimed at reducing and potentially eliminating the need for chronic multi-drug immunosuppression in VCA. PMID:24145603

  18. A case report of partial bilateral hind limb adactyly in a male lamb

    PubMed Central

    Rajabioun, Masoud; Kazemi Mehrjerdi, Hossein; Ghasemi, Samaneh

    2016-01-01

    Hemimelia as a congenital anomaly is a failure of development of extremities formation in embryonic period. This anomaly is defined as complete absence of the part of extremities and different forms were explained for hemimelia. Adactyly is an alternative name for transverse hemimelia and is a rare disorder in the most of animal species. A two months old male lamb with normal vital signs was referred to clinic due to both hind limbs shortness and absence of hooves from the birth day. Clinical and radiological examinations were performed and partial hemimelia was confirmed radiographically in both hind limbs. In left hind limb, total absence of the toe indicated presence of adactyly in this limb. No other congenital deformities were diagnosed in skeletal system based on clinical and radiological examinations. According to our knowledge, this is the first report of such rare conditions in a lamb. Clinical findings and radiological signs of this rare anomaly in a lamb were described in this report. PMID:28144430

  19. Hind limb malformations in free-living northern leopard frogs (Rana pipiens) from Maine, Minnesota, and Vermont suggest multiple etiologies

    USGS Publications Warehouse

    Meteyer, C.U.; Loeffler, I.K.; Fallon, J.F.; Converse, K.A.; Green, E.; Helgen, J.C.; Kersten, S.; Levey, R.; Eaton-Poole, L.; Burkhart, J.G.

    2000-01-01

    Background Reports of malformed frogs have increased throughout the North American continent in recent years. Most of the observed malformations have involved the hind limbs. The goal of this study was to accurately characterize the hind limb malformations in wild frogs as an important step toward understanding the possible etiologies. Methods During 1997 and 1998, 182 recently metamorphosed northern leopard frogs (Rana pipiens) were collected from Minnesota, Vermont, and Maine. Malformed hind limbs were present in 157 (86%) of these frogs, which underwent necropsy and radiographic evaluation at the National Wildlife Health Center. These malformations are described in detail and classified into four major categories: (1) no limb (amelia); (2) multiple limbs or limb elements (polymelia, polydactyly, polyphalangy); (3) reduced limb segments or elements (phocomelia, ectromelia, ectrodactyly, and brachydactyly; and (4) distally complete but malformed limb (bone rotations, bridging, skin webbing, and micromelia). Results Amelia and reduced segments and/or elements were the most common finding. Frogs with bilateral hind limb malformations were not common, and in only eight of these 22 frogs were the malformations symmetrical. Malformations of a given type tended to occur in frogs collected from the same site, but the types of malformations varied widely among all three states, and between study sites within Minnesota. Conclusions Clustering of malformation type suggests that developmental events may produce a variety of phenotypes depending on the timing, sequence, and severity of the environmental insult. Hind limb malformations in free-living frogs transcend current mechanistic explanations of tetrapod limb development.

  20. Reinnervation of hind limb extremity after lumbar dorsal root ganglion injury.

    PubMed

    Liu, Song; Bréjot, Thomas; Cressant, Arnaud; Bacci, Josette; Saïd, Gérard; Tadié, Marc; Heard, Jean Michel

    2005-12-01

    Loss of dorsal root ganglion neuron, or injury to dorsal roots, induces permanent somatosensory defect without therapeutic option. We explored an approach to restoring hind limb somatosensory innervation after elimination of L4, L5 and L6 dorsal root ganglion neurons in rats. Somatosensory pathways were reconstructed by connecting L4, L5 and L6 lumbar dorsal roots to T10, T11 and T12 intercostal nerves, respectively, thus allowing elongation of thoracic ganglion neuron peripheral axons into the sciatic nerve. Connection of thoracic dorsal root ganglion neurons to peripheral tissues was documented 4 and 7 months after injury. Myelinated and unmyelinated fibers regrew in the sciatic nerve. Nerve terminations expressing calcitonin-gene-related-peptide colonized the footpad skin. Retrograde tracing showed that T10, T11 and T12 dorsal root ganglion neurons expressing calcitonin-gene-related-peptide or the neurofilament RT97 projected axons to the sciatic nerve and the footpad skin. Recording of somatosensory evoked potentials in the upper spinal cord indicated connection between the sciatic nerve and the central nervous system. Hind limb retraction in response to nociceptive stimulation of the reinnervated footpads and reversion of skin lesions suggested partial recovery of sensory function. Proprioceptive defects persisted. Delayed somatosensory reinnervation of the hind limb after destruction of lumbar dorsal root neurons in rats indicates potential approaches to reduce chronic disability after severe injury to somatosensory pathways.

  1. Identifying risk factors for poor hind limb cleanliness in Danish loose-housed dairy cows.

    PubMed

    Nielsen, B H; Thomsen, P T; Sørensen, J T

    2011-08-01

    The objective of this study was to identify possible risk factors for poor cow hind limb cleanliness in Danish loose-housed, lactating dairy cows. The study was conducted as a cross-sectional study of 1315 cows in 42 commercial Danish dairy herds with primarily Danish Holstein cows. The effect of four cow-level factors (parity, days in milk, daily lying time and lameness) and eight herd-level factors (herd size, milk production, milking system, floor type, access to pasture grazing, floor scraping frequency, hoof bathing frequency and hoof washing frequency) on the risk of having dirtier hind limbs were analysed using ordinal logistic regression fitting a proportional odds model. Cow hind limb cleanliness was scored using an ordinal score from 1 to 4: 1 being clean and 4 being covered in dirt. The odds ratios (ORs) estimated from the proportional odds model depict the effect of a risk factor on the odds of having a higher rather than a lower cleanliness score. First parity cows had an increased risk of being dirtier compared with third parity or older cows (OR=1.70). Compared with late lactation, early and mid lactation were associated with an increased risk of being dirtier (OR=2.07 and 1.33, respectively). Decreasing the daily time lying by 30 min was associated with an increased risk of being dirtier (OR=1.05). Furthermore, an increased risk of being dirtier was found in herds with no pasture access (OR=3.75).

  2. Ontogenetic Scaling of Fore- and Hind Limb Posture in Wild Chacma Baboons (Papio hamadryas ursinus)

    PubMed Central

    Patel, Biren A.; Horner, Angela M.; Thompson, Nathan E.; Barrett, Louise; Henzi, S. Peter

    2013-01-01

    Large-scale interspecific studies of mammals ranging between 0.04–280 kg have shown that larger animals walk with more extended limb joints. Within a taxon or clade, however, the relationship between body size and joint posture is less straightforward. Factors that may affect the lack of congruence between broad and narrow phylogenetic analyses of limb kinematics include limited sampling of (1) ranges of body size, and/or (2) numbers of individuals. Unfortunately, both issues are inherent in laboratory-based or zoo locomotion research. In this study, we examined the relationship between body mass and elbow and knee joint angles (our proxies of fore- and hind limb posture, respectively) in a cross-sectional ontogenetic sample of wild chacma baboons (Papio hamadryas ursinus) habituated in the De Hoop Nature Reserve, South Africa. Videos were obtained from 33 individuals of known age (12 to ≥108 months) and body mass (2–29.5 kg) during walking trials. Results show that older, heavier baboons walk with significantly more extended knee joints but not elbow joints. This pattern is consistent when examining only males, but not within the female sample. Heavier, older baboons also display significantly less variation in their hind limb posture compared to lighter, young animals. Thus, within this ontogenetic sample of a single primate species spanning an order of magnitude in body mass, hind limb posture exhibited a postural scaling phenomenon while the forelimbs did not. These findings may further help explain 1) why younger mammals (including baboons) tend to have relatively stronger bones than adults, and 2) why humeri appear relatively weaker than femora (in at least baboons). Finally, this study demonstrates how field-acquired kinematics can help answer fundamental biomechanical questions usually addressed only in animal gait laboratories. PMID:23923046

  3. Ontogenetic scaling of fore- and hind limb posture in wild chacma baboons (Papio hamadryas ursinus).

    PubMed

    Patel, Biren A; Horner, Angela M; Thompson, Nathan E; Barrett, Louise; Henzi, S Peter

    2013-01-01

    Large-scale interspecific studies of mammals ranging between 0.04-280 kg have shown that larger animals walk with more extended limb joints. Within a taxon or clade, however, the relationship between body size and joint posture is less straightforward. Factors that may affect the lack of congruence between broad and narrow phylogenetic analyses of limb kinematics include limited sampling of (1) ranges of body size, and/or (2) numbers of individuals. Unfortunately, both issues are inherent in laboratory-based or zoo locomotion research. In this study, we examined the relationship between body mass and elbow and knee joint angles (our proxies of fore- and hind limb posture, respectively) in a cross-sectional ontogenetic sample of wild chacma baboons (Papio hamadryas ursinus) habituated in the De Hoop Nature Reserve, South Africa. Videos were obtained from 33 individuals of known age (12 to ≥ 108 months) and body mass (2-29.5 kg) during walking trials. Results show that older, heavier baboons walk with significantly more extended knee joints but not elbow joints. This pattern is consistent when examining only males, but not within the female sample. Heavier, older baboons also display significantly less variation in their hind limb posture compared to lighter, young animals. Thus, within this ontogenetic sample of a single primate species spanning an order of magnitude in body mass, hind limb posture exhibited a postural scaling phenomenon while the forelimbs did not. These findings may further help explain 1) why younger mammals (including baboons) tend to have relatively stronger bones than adults, and 2) why humeri appear relatively weaker than femora (in at least baboons). Finally, this study demonstrates how field-acquired kinematics can help answer fundamental biomechanical questions usually addressed only in animal gait laboratories.

  4. Noninvasive Multimodal Imaging to Predict Recovery of Locomotion after Extended Limb Ischemia.

    PubMed

    Radowsky, Jason S; Caruso, Joseph D; Luthra, Rajiv; Bradley, Matthew J; Elster, Eric A; Forsberg, Jonathan A; Crane, Nicole J

    2015-01-01

    Acute limb ischemia is a common cause of morbidity and mortality following trauma both in civilian centers and in combat related injuries. Rapid determination of tissue viability and surgical restoration of blood flow are desirable, but not always possible. We sought to characterize the response to increasing periods of hind limb ischemia in a porcine model such that we could define a period of critical ischemia (the point after which irreversible neuromuscular injury occurs), evaluate non-invasive methods for characterizing that ischemia, and establish a model by which we could predict whether or not the animal's locomotion would return to baselines levels post-operatively. Ischemia was induced by either application of a pneumatic tourniquet or vessel occlusion (performed by clamping the proximal iliac artery and vein at the level of the inguinal ligament). The limb was monitored for the duration of the procedure with both 3-charge coupled device (3CCD) and infrared (IR) imaging for tissue oxygenation and perfusion, respectively. The experimental arms of this model are effective at inducing histologically evident muscle injury with some evidence of expected secondary organ damage, particularly in animals with longer ischemia times. Noninvasive imaging data shows excellent correlation with post-operative functional outcomes, validating its use as a non-invasive means of viability assessment, and directly monitors post-occlusive reactive hyperemia. A classification model, based on partial-least squares discriminant analysis (PLSDA) of imaging variables only, successfully classified animals as "returned to normal locomotion" or "did not return to normal locomotion" with 87.5% sensitivity and 66.7% specificity after cross-validation. PLSDA models generated from non-imaging data were not as accurate (AUC of 0.53) compared the PLSDA model generated from only imaging data (AUC of 0.76). With some modification, this limb ischemia model could also serve as a means on which

  5. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.

  6. Disparate Igf1 expression and growth in the fore- and hind limbs of a marsupial mammal (Monodelphis domestica).

    PubMed

    Sears, Karen E; Patel, Ankit; Hübler, Merla; Cao, Xiaoyi; Vandeberg, John L; Zhong, Sheng

    2012-06-01

    Proper regulation of growth is essential to all stages of life, from development of the egg into an embryo to the maintenance of normal cell cycle progression in adults. However, despite growth's importance to basic biology and health, little is known about how mammalian growth is regulated. In this study, we investigated the molecular basis of the highly disparate growth of opossum fore- and hind limbs in utero. We first used a novel, opossum-specific microarray to identify several growth-related genes that are differentially expressed in opossum fore- and hind limbs of comparable developmental stages. These genes included Igf1. Given Igf1's role in the growth of other systems, we further investigated the role of Igf1 in opossum limb growth. Supporting the microarray results, RT-PCR indicated that Igf1 levels are approximately two times higher in opossum fore- than hind limbs. Consistent with this, while Igf1 transcripts were readily detectable in opossum forelimbs using whole-mount in situ hybridization, they were not detectable in opossum hind limbs. Furthermore, opossum limbs treated with exogenous Igf1 protein experienced significantly greater cellular proliferation and growth than control limbs in vitro. Taken together, results suggest that the differential expression of Igf1 in developing opossum limbs contributes to their divergent rate of growth, and the unique limb phenotype of opossum newborns. This study establishes the opossum limb as a new mammalian model system for study of organ growth.

  7. Critical limb ischemia: medical and surgical management.

    PubMed

    Slovut, David Paul; Sullivan, Timothy M

    2008-08-01

    Chronic critical limb ischemia (CLI), defined as > 2 weeks of rest pain, ulcers, or tissue loss attributed to arterial occlusive disease, is associated with great loss of both limb and life. Therapeutic goals in treating patients with CLI include reducing cardiovascular risk factors, relieving ischemic pain, healing ulcers, preventing major amputation, improving quality of life and increasing survival. These aims may be achieved through medical therapy, revascularization, or amputation. Medical therapy includes administration of analgesics, local wound care and pressure relief, treatment of infection, and aggressive therapy to modify atherosclerotic risk factors. For patients who are not candidates for revascularization, and who are unwilling or unable to undergo amputation, treatments such as intermittent pneumatic compression or spinal cord stimulation may offer symptom relief and promote wound healing. Revascularization offers the best option for limb salvage. The decision to perform surgery, endovascular therapy, or a combination of the two modalities ('hybrid' therapy) must be individualized. Patients who are relatively fit and able to withstand the rigors of an open procedure may benefit from the long-term durability of surgical repair. In contrast, frail patients with a limited life expectancy may experience better outcomes with endovascular reconstruction. Hybrid therapy is an attractive option for patients with limited autologous conduit, as it permits complete revascularization with a less extensive procedure, shorter duration of operation, and decreased risk of peri-operative complications. Amputation should be considered for patients who are non-ambulatory, demented, or unfit to undergo revascularization.

  8. Therapeutic angiogenesis for critical limb ischemia.

    PubMed

    Ko, Sae Hee; Bandyk, Dennis F

    2014-03-01

    The application of gene- and cell-based therapies to promote angiogenesis is a novel concept to treat lower-limb critical limb ischemia (CLI) and may provide an unmet need for patients with no options for revascularization. Proof of concept was demonstrated in animal models resulting in clinical trials that have confirmed the feasibility and short-term efficacy of intramuscular injection of angiogenetic tissue growth factors or bone marrow stem cells. The safety of these biologic therapies has been demonstrated in randomized clinical trials with no "off-target" angiogenesis, growth of occult tumors, or progression of diabetic retinopathy. Current phase III randomized clinical trials using a DNA plasmid with the hepatocyte growth factor gene or bone marrow aspirate concentrate of mesenchymal cells are designed to address several crucial issues, including proper patient selection criteria, relevant clinical endpoints, and long-term efficacy. Because effectiveness of these novel therapies remains to be established, ongoing and future randomized clinical trials should be placebo-controlled, investigator-blinded, and have amputation-free survival as the primary endpoint. Further development of efficient gene transfer techniques and keeping transplanted stem cells healthy have the potential to make biologic therapies more robust in promoting angiogenesis, tissue regeneration, and resolution of CLI symptoms. If sustained efficacy can be demonstrated, new therapeutic strategies for patients with CLI will be available for clinicians, ie, limb revascularization using angiogenic gene or stem cell therapy alone, or in conjunction with endovascular intervention.

  9. Mechanical constraints on the functional morphology of the gibbon hind limb.

    PubMed

    Channon, Anthony J; Günther, Michael M; Crompton, Robin H; Vereecke, Evie E

    2009-10-01

    Gibbons utilize a number of locomotor modes in the wild, including bipedalism, leaping and, most of all, brachiation. Each locomotor mode puts specific constraints on the morphology of the animal; in some cases these may be complementary, whereas in others they may conflict. Despite several studies of the locomotor biomechanics of gibbons, very little is known about the musculoskeletal architecture of the limbs. In this study, we present quantitative anatomical data of the hind limb for four species of gibbon (Hylobates lar, H. moloch, H. pileatus and Symphalangus syndactylus). Muscle mass and fascicle lengths were obtained from all of the major hind limb muscles and the physiological cross-sectional area was calculated and scaled to remove the effect of body size. The results clearly indicate that, for all of the species studied, the major hip, knee and ankle extensors are short-fascicled and pennate. The major hip and knee flexors, however, are long-fascicled, parallel muscles with relatively small physiological cross-sectional areas. We hypothesize that the short-fascicled muscles could be coupled with a power-amplifying mechanism and are predominantly useful in leaping. The long-fascicled knee and hip flexors are adapted for a wide range of joint postures and can play a role in flexing the legs during brachiation.

  10. Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging.

    PubMed

    Lescale, Chloé; Schenten, Véronique; Djeghloul, Dounia; Bennabi, Meriem; Gaignier, Fanny; Vandamme, Katleen; Strazielle, Catherine; Kuzniak, Isabelle; Petite, Hervé; Dosquet, Christine; Frippiat, Jean-Pol; Goodhardt, Michele

    2015-02-01

    Within the bone marrow, the endosteal niche plays a crucial role in B-cell differentiation. Because spaceflight is associated with osteoporosis, we investigated whether changes in bone microstructure induced by a ground-based model of spaceflight, hind limb unloading (HU), could affect B lymphopoiesis. To this end, we analyzed both bone parameters and the frequency of early hematopoietic precursors and cells of the B lineage after 3, 6, 13, and 21 d of HU. We found that limb disuse leads to a decrease in both bone microstructure and the frequency of B-cell progenitors in the bone marrow. Although multipotent hematopoietic progenitors were not affected by HU, a decrease in B lymphopoiesis was observed as of the common lymphoid progenitor (CLP) stage with a major block at the progenitor B (pro-B) to precursor B (pre-B) cell transition (5- to 10-fold decrease). The modifications in B lymphopoiesis were similar to those observed in aged mice and, as with aging, decreased B-cell generation in HU mice was associated with reduced expression of B-cell transcription factors, early B-cell factor (EBF) and Pax5, and an alteration in STAT5-mediated IL-7 signaling. These findings demonstrate that mechanical unloading of hind limbs results in a decrease in early B-cell differentiation resembling age-related modifications in B lymphopoiesis.

  11. Therapeutic Angiogenesis in Critical Limb Ischemia

    PubMed Central

    Ouma, Geoffrey O.; Zafrir, Barak; Mohler, Emile R.; Flugelman, Moshe Y.

    2013-01-01

    Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis. PMID:23129733

  12. COORDINATED, MULTI-JOINT, FATIGUE-RESISTANT FELINE STANCE PRODUCED WITH INTRAFASCICULAR HIND LIMB NERVE STIMULATION

    PubMed Central

    Normann, R A; Dowden, B R; Frankel, M A; Wilder, A M; Hiatt, S D; Ledbetter, N M; Warren, D A; Clark, G A

    2012-01-01

    The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are bi-articular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve, and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes 1) that activated motor units in the extensor muscles of the hip, knee, and ankle joints, 2) that were able to evoke large extension forces, and 3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee, and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke, or disease. PMID

  13. Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation

    NASA Astrophysics Data System (ADS)

    Normann, R. A.; Dowden, B. R.; Frankel, M. A.; Wilder, A. M.; Hiatt, S. D.; Ledbetter, N. M.; Warren, D. A.; Clark, G. A.

    2012-04-01

    The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

  14. Muscular reconstruction and functional morphology of the hind limb of santacrucian (Early Miocene) sloths (Xenarthra, Folivora) of Patagonia.

    PubMed

    Toledo, Néstor; Bargo, M Susana; Vizcaíno, Sergio F

    2015-05-01

    This article presents a morphofunctional analysis of the hind limb of Santacrucian (Early Miocene) sloths from southernmost Patagonia (Argentina). These fossil sloths were mid sized to large animals, ranging from 40 to 120 kg, and their postcranial skeleton was markedly different in shape compared with that of extant tree sloths, which vary from 2 to 10 kg. The functional anatomy of the hind limb of Santacrucian sloths was compared with that of living xenarthrans (tree sloths, anteaters, and armadillos), which involved reconstruction of the hind limb musculature and comparative and qualitative morphofunctional analyses, and hypotheses on the biological role of the hind limb in terms of preferences in substrate, posture, and strategies of locomotion were formulated. The hind limb of Santacrucian sloths bears strong resemblances to that of living South American anteaters in stoutness of skeletal elements, form of the characteristics related to muscular and ligamentous attachments, and conservative, pentadactylous strong-clawed pes. The musculature was very well developed, allowing powerful forces, principally in entire limb adduction, crus flexion and extension, pes extension, and toe prehension. These functional features, together with those of the forelimb, are congruent with climbing behavior, and support the hypothesis that Santacrucian sloths were good but slow climbing mammals. However, their climbing strategies were limited, owing principally to their comparatively large body size, and they relied to a large extent on their powerful musculature and curved manual and pedal unguals for both moving and standing on the arboreal supports.

  15. The effect of baclofen on the hind limb flexor reflex of the spinal rat.

    PubMed

    Sypniewska, M

    1979-01-01

    The effect of baclofen on the hind limb flexor reflex of the spinal rat was studied. Baclofen inhibited the flexor reflex, this effect not being antagonized by picrotoxin and bicuculline. Baclofen reduced the stimulating action of quipazine and LSD, had no effect on the clonidine-induced reflex stimulation, but inhibited the flexor reflex stimulation induced by amphetamine and fenfluramine. The results obtained bring forth some doubts as to the GABA-mimetic action of baclofen. The action of baclofen on the spinal cord seems to be directed mainly to the presynaptic part of the noradrenergic and serotonergic systems.

  16. Combined effects of soy isoflavones and milk basic protein on bone mineral density in hind-limb unloaded mice

    PubMed Central

    Matsumoto, Yu; Tousen, Yuko; Nishide, Yoriko; Tadaishi, Miki; Kato, Ken; Ishimi, Yoshiko

    2016-01-01

    We examined whether the combination of isoflavone and milk basic protein both are reported to be effective for bone metabolism, prevents bone loss induced by skeletal hind-limb unloading in mice. Female ddY strain mice, aged 8 weeks, were divided into six groups (n = 6–8 each): (1) normally housed group, (2) loading group, (3) hind-limb unloading group fed a control diet, (4) hind-limb unloading group fed a 0.2% isoflavone conjugates diet, (5) hind-limb unloading group fed a 1.0% milk basic protein diet, and (6) hind-limb unloading group fed a 0.2% isoflavone conjugates and 1.0% milk basic protein diet. After 3 weeks, femoral bone mineral density was markedly reduced in unloading mice. The combination of isoflavone and milk basic protein showed cooperative effects in preventing bone loss and milk basic protein inhibited the increased expression of osteogenic genes in bone marrow cells in unloading mice. These results suggest that the combination of soy isoflavone and milk basic protein may be useful for bone health in subjects with disabling conditions as well as astronauts. PMID:27013781

  17. Outpatient follow-up for critical limb ischemia.

    PubMed

    Watch, Libby

    2014-09-01

    Outpatient follow-Up for critical limb ischemia offers the clinician the opportunity to monitor the patient for risk factor modification and wound healing. Routine surveillance following intervention will improve long-term patency.

  18. Treatment effect with anti-RAGE F(ab')2 antibody improves hind limb angiogenesis and blood flow in Type 1 diabetic mice with left femoral artery ligation.

    PubMed

    Tekabe, Yared; Anthony, Tamykah; Li, Qing; Ray, Rashmi; Rai, Vivek; Zhang, Geping; Schmidt, Ann Marie; Johnson, Lynne L

    2015-06-01

    We investigated treatment with a receptor for advanced glycation endproduct (RAGE) blocking antibody on angiogenic response to hind limb ischemia in diabetic mice. Streptozotocin treated C57BL/6 mice received either murine monoclonal anti-RAGE F(ab')2 intraperitoneally (n=10) or saline (n=9) for 9 weeks. Diabetic plus 10 non-diabetic C57BL/6 mice underwent left femoral artery ligation and 5 days later angiogenesis imaging with (99m)Tc-Arg-Gly-Asp (RGD) nanoSPECT/CT. Twenty-four days later, hind limb blood flow was measured with ultrasound, the mice were euthanized, and tissue was taken for immunohistochemistry. The angiogenic imaging signal in ischemic limbs was higher in RAGE-ab treated versus saline treated mice at day 5 (3.1±1.4 vs 1.68±0.35, p=0.02) and blood flow was higher at day 24 (1.49±0.5 vs 0.61±0.39, p=0.04). Immunohistochemistry of ischemic muscles showed greater capillary density in the RAGE-ab treated group versus the vehicle-treated group (p<0.001) (NS from non-diabetic mice). In conclusion, treatment with anti-RAGE F(ab')2 in diabetic mice improves neovascularization in the ischemic leg.

  19. One of the most urgent vascular circumstances: Acute limb ischemia

    PubMed Central

    Sahin, Muslum; Kirma, Cevat

    2013-01-01

    Acute limb ischemia is a sudden decrease in limb perfusion that threatens limb viability and requires urgent evaluation and management. Most of the causes of acute limb ischemia are thrombosis of a limb artery or bypass graft, embolism from the heart or a disease artery, dissection, and trauma. Assessment determines whether the limb is viable or irreversibly damaged. Prompt diagnosis and revascularization by means of catheter-based thrombolysis or thrombectomy and by surgery reduce the risk of limb loss and mortality. Amputation is performed in patients with irreversible damage. Despite urgent revascularization, amputation rate is 10%–15% in patients during hospitalization, mostly above the knee, and mortality within 1 year is 10%–15% due to the coexisting conditions. PMID:26770694

  20. Perivertebral B-cell lymphoma in a Queensland koala (Phascolarctos cinereus adustus) with paralytic symptoms in the hind limbs.

    PubMed

    Kido, Nobuhide; Edamura, Kazuya; Inoue, Naomi; Shibuya, Hisashi; Sato, Tsuneo; Kondo, Masako; Shindo, Izumi

    2012-08-01

    A male Queensland koala (Phascolarctos cinereus adustus) at Kanazawa Zoological Gardens (Kanagawa, Japan) exhibited paralytic symptoms in the hind limbs. Computed tomography and magnetic resonance imaging revealed a mass on the left ventral side of the 11th to 13th thoracic vertebrae, and the presence of myelitis or edema in the spinal cord. The koala was under anesthesia during the examination and suddenly developed ventricular fibrillation and died. Necropsy revealed a firm flat ovoid hemorrhagic mass on the vertebrae. Following a microscopic examination including immunohistochemistry, the perivertebral mass was diagnosed as B cell lymphoma. Therefore, neoplastic cell infiltration into the spinal cord may cause paralytic symptoms in the hind limbs.

  1. The development of functional innervation in the hind limb of the chick embryo.

    PubMed Central

    Landmesser, L; Morris, D G

    1975-01-01

    1. The development of functional motor innervation was studied in the hind limb of chick embryos from Stages 25 to 43 by observing contraction of individual muscles and by recording the resultant tension when individual spinal nerves were electrically stimulated. 2. At later developmental stages (35-43) a given muscle always received functional innervation from specific spinal nerves. This pattern, with respect to the craniocaudal position of motoneurones, was similar to those described for amphibians and mammals. 3. The observed pattern was similar throughout development from the time that movement could first be elicited at Stages 27-28. There was no indication that motoneurones form initial synapses with inappropriate muscles. 4. Recordings from muscle nerves during excitation of individual spinal nerves gave results similar to the tension recordings, showing that even at early developmental stages muscle nerves did not contain substantial numbers of inappropriate axons. 5. Most limb muscles or primitive muscle masses became functionally innervated at the same time with no clearly defined proximo-distal sequence of limb innervation. 6. It appears that chick motoneurones are initially specified with respect to their peripheral destination and grow out selectively to synapse with appropriate muscles from the outset. PMID:1177095

  2. FACS-based Satellite Cell Isolation From Mouse Hind Limb Muscles.

    PubMed

    Gromova, Anastasia; Tierney, Matthew T; Sacco, Alessandra

    2015-08-20

    Fluorescence Activated Cell Sorting (FACS) is a sensitive and accurate method for purifying satellite cells, or muscle stem cells, from adult mouse skeletal muscle (Liu et al., 2013; Sacco et al., 2008; Tierney et al., 2014). Mechanical and enzymatic digestion of hind limb muscles releases mononuclear muscle cells into suspension. This protocol employs fractionation strategies to deplete cells expressing the cell surface markers CD45, CD31, CD11b and Ly-6A/E-Sca1, both by magnetic separation and FACS-based exclusion, and positively select for cells expressing a7-integrin and CD34. This enables the researcher to successfully enrich satellite cells that uniformly express the paired-box transcription factor Pax7 and are capable of long-term self-renewal, skeletal muscle repair and muscle stem cell pool repopulation.

  3. Effect of demedullation on freezing injury in hind limbs of rats

    NASA Astrophysics Data System (ADS)

    Dhingra, Shashi; Bhatia, B.; Chhina, G. S.; Singh, Baldev

    1987-09-01

    Freezing incidence and tissue loss on exposure of hind limbs of female Wistar rats to freezing mixture was reduced by demedullation 6 days prior to cold exposure (p<0.01 and p<0.001 respectively); demedullation 1 h after freezing injury had no effect on tissue loss. Noradrenaline (1 mg/kg i.p.) 5 min before exposure increased the freezing incidence in intact (p<0.05) as well as in demedullated rats (p<0.01), with no effect on tissue loss. Adrenaline (500 mg/kg i.p.) had no effect on either. A sustained fall in plasma adrenaline after demedullation leading to reduced reactivity of the blood vessels to some vasoactive agents is postulated.

  4. 3D reconstruction of digitized histological sections for vasculature quantification in the mouse hind limb

    NASA Astrophysics Data System (ADS)

    Xu, Yiwen; Pickering, J. Geoffrey; Nong, Zengxuan; Gibson, Eli; Ward, Aaron D.

    2014-03-01

    In contrast to imaging modalities such as magnetic resonance imaging and micro computed tomography, digital histology reveals multiple stained tissue features at high resolution (0.25μm/pixel). However, the two-dimensional (2D) nature of histology challenges three-dimensional (3D) quantification and visualization of the different tissue components, cellular structures, and subcellular elements. This limitation is particularly relevant to the vasculature, which has a complex and variable structure within tissues. The objective of this study was to perform a fully automated 3D reconstruction of histology tissue in the mouse hind limb preserving the accurate systemic orientation of the tissues, stained with hematoxylin and immunostained for smooth muscle α actin. We performed a 3D reconstruction using pairwise rigid registrations of 5μm thick, paraffin-embedded serial sections, digitized at 0.25μm/pixel. Each registration was performed using the iterative closest points algorithm on blood vessel landmarks. Landmarks were vessel centroids, determined according to a signed distance map of each pixel to a decision boundary in hue-saturation-value color space; this decision boundary was determined based on manual annotation of a separate training set. Cell nuclei were then automatically extracted and corresponded to refine the vessel landmark registration. Homologous nucleus landmark pairs appearing on not more than two adjacent slides were chosen to avoid registrations which force curved or non-sectionorthogonal structures to be straight and section-orthogonal. The median accumulated target registration errors ± interquartile ranges for the vessel landmark registration, and the nucleus landmark refinement were 43.4+/-42.8μm and 2.9+/-1.7μm, respectively (p<0.0001). Fully automatic and accurate 3D rigid reconstruction of mouse hind limb histology imaging is feasible based on extracted vasculature and nuclei.

  5. Outcomes of lower extremity bypass performed for acute limb ischemia

    PubMed Central

    Baril, Donald T.; Patel, Virendra I.; Judelson, Dejah R.; Goodney, Philip P.; McPhee, James T.; Hevelone, Nathanael D.; Cronenwett, Jack L.; Schanzer, Andres

    2013-01-01

    Objective Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. Methods All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Results Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation

  6. The development of motor projection patterns in the chick hind limb.

    PubMed Central

    Landmesser, L

    1978-01-01

    1. Retrograde transport of horseradish peroxidase was used to map the initial projection patterns of lumbosacral motoneurones to the embryonic chick hind limb. 2. The stage 28 segmental projection pattern to each of the four primary muscle masses was characteristic and indistinguishable from the stage 36 projection pattern to the sum of the muscles derived from that mass. In addition, the adductor motoneurone pool was found to be similar in position (both rostro-caudal and mediolateral) at stages 29, 30, 32, 33 1/2 and 36. 3. Therefore axons from lumbosacral motoneurones project for the most part only to appropriate regions from early times shortly after they grow into the limb bud. Furthermore, the attainment of the segmental projection pattern occurs prior to the normal time of, and therefore without the aid of, cell death. This conclusion was supported by electrophysiological recordings made from muscle nerves. 4. A regionalization of the projection patterns within a single muscle mass could be shown both anatomically and physiologically prior to the cleavage of the mass into individual muscles and the projections were in a general way appropriate for the muscles derived from those regions. 5. Therefore the process of muscle cleavage does not in itself create the specific projection patterns observed, and motoneurone axons appear to grow to and to ramify and make synapses only within regions which correspond to their adult muscles. 6. Finally, the termination site of each motoneurone axon in the early limb was found to be tightly correlated in a somatotopic fashion with the position occupied by its soma in the cord. This suggests that some feature of the motoneurone related to its position may be of importance in achieving the specific projection patterns observed. Images Plate 1 PMID:731552

  7. A Reproducible Radiation Delivery Method for Unanesthetized Rodents during Periods of Hind Limb Unloading

    PubMed Central

    Walb, M.C.; Black, P.J.; Payne, V.S.; Munley, M.T.; Willey, J.S.

    2015-01-01

    Exposure to the spaceflight environment has long been known to be a health challenge concerning many body systems. Both microgravity and/or ionizing radiation can cause acute and chronic effects in multiple body systems. The hind limb unloaded (HLU) rodent model is a ground-based analogue for microgravity that can be used to simulate and study the combined biologic effects of reduced loading with spaceflight radiation exposure. However, studies delivering radiation to rodents during periods of HLU are rare. Herein we report the development of an irradiation protocol using a clinical linear accelerator that can be used with hind limb unloaded, unanesthetized rodents that is capable of being performed at most academic medical centers. A 30.5 cm × 30.5 cm × 40.6 cm rectangular chamber was constructed out of polymethyl methacrylate (PMMA) sheets (0.64 cm thickness). Five cm of water-equivalent material were placed outside of two PMMA inserts on either side of the rodent that permitted the desired radiation dose buildup (electronic equilibrium) and helped to achieve a flatter dose profile. Perforated aluminum strips permitted the suspension dowel to be placed at varying heights depending on the rodent size. Radiation was delivered using a medical linear accelerator at an accelerating potential of 10 MV. A calibrated PTW Farmer ionization chamber, wrapped in appropriately thick tissue-equivalent bolus material to simulate the volume of the rodent, was used to verify a uniform dose distribution at various regions of the chamber. The dosimetry measurements confirmed variances typically within 3%, with maximum variance <10% indicated through optically stimulated luminescent dosimeter (OSLD) measurements, thus delivering reliable spaceflight-relevant total body doses and ensuring a uniform dose regardless of its location within the chamber. Due to the relative abundance of LINAC’s at academic medical centers and the reliability of their dosimetry properties, this method

  8. A reproducible radiation delivery method for unanesthetized rodents during periods of hind limb unloading

    NASA Astrophysics Data System (ADS)

    Walb, M. C.; Black, P. J.; Payne, V. S.; Munley, M. T.; Willey, J. S.

    2015-07-01

    Exposure to the spaceflight environment has long been known to be a health challenge concerning many body systems. Both microgravity and/or ionizing radiation can cause acute and chronic effects in multiple body systems. The hind limb unloaded (HLU) rodent model is a ground-based analogue for microgravity that can be used to simulate and study the combined biologic effects of reduced loading with spaceflight radiation exposure. However, studies delivering radiation to rodents during periods of HLU are rare. Herein we report the development of an irradiation protocol using a clinical linear accelerator that can be used with hind limb unloaded, unanesthetized rodents that is capable of being performed at most academic medical centers. A 30.5 cm × 30.5 cm × 40.6 cm rectangular chamber was constructed out of polymethyl methacrylate (PMMA) sheets (0.64 cm thickness). Five centimeters of water-equivalent material were placed outside of two PMMA inserts on either side of the rodent that permitted the desired radiation dose buildup (electronic equilibrium) and helped to achieve a flatter dose profile. Perforated aluminum strips permitted the suspension dowel to be placed at varying heights depending on the rodent size. Radiation was delivered using a medical linear accelerator at an accelerating potential of 10 MV. A calibrated PTW Farmer ionization chamber, wrapped in appropriately thick tissue-equivalent bolus material to simulate the volume of the rodent, was used to verify a uniform dose distribution at various regions of the chamber. The dosimetry measurements confirmed variances typically within 3%, with maximum variance <10% indicated through optically stimulated luminescent dosimeter (OSLD) measurements, thus delivering reliable spaceflight-relevant total body doses and ensuring a uniform dose regardless of its location within the chamber. Due to the relative abundance of LINACs at academic medical centers and the reliability of their dosimetry properties, this

  9. Effects of Hind Limb Unloading on Pharmacokinetics of Procainamide in Mice

    NASA Technical Reports Server (NTRS)

    Risin, Semyon A.; Dasgupta, Amitava; Ramesh, Govindarajan T.; Risin, Diana

    2007-01-01

    The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in space. It is prudent to expect that low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration. Among the medications of special interest are the cardiovascular drugs, especially the antiarrhythmic agents. In this study we used hind limb unloaded (HLU) mice as a model to investigate possible changes in the PK of a common antiarrhythmic drug procainamide (PA). Prior to drug administration the experimental animals were tail suspended for 24 hours and the control animals were kept free. PA (150-250 mg per kg) was given orally by a gavage procedure. After that the experimental mice were kept suspended for additional 1, 2, 3 and 6 hours. At these time points the serum concentration of PA and N-acetyl-procainamide (NAPA), an active metabolite which is formed by N-acetyltransferase in the liver, were measured by the fluorescence polarization immunoassay (FPIA) on the AxSYM autoanalyzer (Abbott Laboratories, Abbott Park, IL). The serum level of PA in HLU mice at 1 hour after administration was almost 40% lower than in controls. At 2-3 hours the difference still maintained, however, it was not statistically significant; at 6 hours no difference was detected. The level of NAPA in HLU mice was slightly lower at 1 and 2 hours but the difference did not reach statistical significance. The estimated PA half-life time in HLU mice was almost 55% longer than in control animals. These results confirm that hind limb unloading and related hemodynamic changes significantly alter the PK of PA. The effects are most likely primarily associated with a decrease in the drug absorption, especially within the first two hours after administration. At the same time prolongation of the PA half

  10. A reproducible radiation delivery method for unanesthetized rodents during periods of hind limb unloading.

    PubMed

    Walb, M C; Black, P J; Payne, V S; Munley, M T; Willey, J S

    2015-07-01

    Exposure to the spaceflight environment has long been known to be a health challenge concerning many body systems. Both microgravity and/or ionizing radiation can cause acute and chronic effects in multiple body systems. The hind limb unloaded (HLU) rodent model is a ground-based analogue for microgravity that can be used to simulate and study the combined biologic effects of reduced loading with spaceflight radiation exposure. However, studies delivering radiation to rodents during periods of HLU are rare. Herein we report the development of an irradiation protocol using a clinical linear accelerator that can be used with hind limb unloaded, unanesthetized rodents that is capable of being performed at most academic medical centers. A 30.5 cm×30.5 cm×40.6 cm30.5 cm×30.5 cm×40.6 cm rectangular chamber was constructed out of polymethyl methacrylate (PMMA) sheets (0.64 cm thickness). Five centimeters of water-equivalent material were placed outside of two PMMA inserts on either side of the rodent that permitted the desired radiation dose buildup (electronic equilibrium) and helped to achieve a flatter dose profile. Perforated aluminum strips permitted the suspension dowel to be placed at varying heights depending on the rodent size. Radiation was delivered using a medical linear accelerator at an accelerating potential of 10 MV. A calibrated PTW Farmer ionization chamber, wrapped in appropriately thick tissue-equivalent bolus material to simulate the volume of the rodent, was used to verify a uniform dose distribution at various regions of the chamber. The dosimetry measurements confirmed variances typically within 3%, with maximum variance <10% indicated through optically stimulated luminescent dosimeter (OSLD) measurements, thus delivering reliable spaceflight-relevant total body doses and ensuring a uniform dose regardless of its location within the chamber. Due to the relative abundance of LINACs at academic medical centers and the reliability of their

  11. Critical Limb Ischemia: Reporting Outcomes and Quality

    PubMed Central

    2012-01-01

    The impetus to pursue quality in limb salvage is high in the current economic environment. This has been spurred on by the diffusion of multiple technologies, the lack of well-defined cost-effectiveness benchmarks, and the paucity of process and structure benchmarks. Furthermore, no national database exists to capture current activity and trends, and lead structure and process changes that could analyze outcomes and improve standards in peripheral interventions for limb salvage. This manuscript examines the challenges in measuring outcomes and quality in limb salvage and explores the components necessary for ensuring quality in limb salvage interventions. PMID:23342183

  12. Three-dimensional kinematics of the pelvis and hind limbs in chimpanzee (Pan troglodytes) and human bipedal walking.

    PubMed

    O'Neill, Matthew C; Lee, Leng-Feng; Demes, Brigitte; Thompson, Nathan E; Larson, Susan G; Stern, Jack T; Umberger, Brian R

    2015-09-01

    The common chimpanzee (Pan troglodytes) is a facultative biped and our closest living relative. As such, the musculoskeletal anatomies of their pelvis and hind limbs have long provided a comparative context for studies of human and fossil hominin locomotion. Yet, how the chimpanzee pelvis and hind limb actually move during bipedal walking is still not well defined. Here, we describe the three-dimensional (3-D) kinematics of the pelvis, hip, knee and ankle during bipedal walking and compare those values to humans walking at the same dimensionless and dimensional velocities. The stride-to-stride and intraspecific variations in 3-D kinematics were calculated using the adjusted coefficient of multiple correlation. Our results indicate that humans walk with a more stable pelvis than chimpanzees, especially in tilt and rotation. Both species exhibit similar magnitudes of pelvis list, but with segment motion that is opposite in phasing. In the hind limb, chimpanzees walk with a more flexed and abducted limb posture, and substantially exceed humans in the magnitude of hip rotation during a stride. The average stride-to-stride variation in joint and segment motion was greater in chimpanzees than humans, while the intraspecific variation was similar on average. These results demonstrate substantial differences between human and chimpanzee bipedal walking, in both the sagittal and non-sagittal planes. These new 3-D kinematic data are fundamental to a comprehensive understanding of the mechanics, energetics and control of chimpanzee bipedalism.

  13. Angiogenesis effect of therapeutic ultrasound on ischemic hind limb in mice

    PubMed Central

    Huang, Jing-Juan; Shi, Yi-Qin; Li, Rui-Lin; Hu, An; Zhou, Hong-Sheng; Cheng, Qian; Xu, Zheng; Yang, Zhi-Ming; Hao, Chang-Ning; Duan, Jun-Li

    2014-01-01

    Although significant progress in bypass surgery and catheter intervention against peripheral artery disease, the number of severe critical limb ischemia (CLI) patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. The purpose of this study was to determine the mechanism of therapeutic ultrasound (TUS) on ischemic angiogenesis using mouse model of hindlimb ischemia and the cellular/molecular mechanisms underlying TUS-related neovascularization. The hindlimb ischemic mice were exposed to extracorporeal TUS for 3, 6, 9 minute per day (1 MHz, 0.3 W/cm2) until day 14 after left femoral artery ligation. Increased blood perfusion and capillary density were determined following 9 min of TUS compared with ischemic group. Moreover, TUS treatment increased the protein levels of vascular endothelial growth factor (VEGF), hypoxic inducible factor-1α (HIF-1α), endothelial nitric oxide synthase (eNOS) and p-Akt in vivo. TUS promoted capillary-like tube formation, migration and motility of human umbilical venous endothelial cells (HUVECs). Furthermore, the protein expressions of VEGF, eNOS and p-Akt were increased after TUS treatment. In conclusion, TUS therapy promotes postnatal neovascularization through multiple angiogenic pathways in mice model of ischemic hindlimb. PMID:25628781

  14. Influence of 14-day hind limb unloading on isolated muscle spindle activity in rats.

    PubMed

    Zhao, Xue Hong; Fan, Xiao Li; Song, Xin Ai; Wu, Su Di; Ren, Jun Chan; Chen, Ming Xia

    2010-09-01

    During hind limb unloading (HU), the soleus is often in a shortened position and the natural physiological stimulus of muscle spindles is altered, such that muscle spindle activity also changes. Using isolated spindle conditions, the present study investigates the electrophysiological activity and ultrastructure of muscle spindles following HU. Results show that muscle spindle discharges fall into either of two main patterns, single spikes or spike clusters in shortened positions, with a steady frequency of 18-38 spikes/s (mean 29.08 +/- 2.45) in an extended position. Following 14-day HU, afferent discharge activity was significantly altered in soleus muscle spindles. Duration of individual spikes was significantly prolonged, from 0.54 +/- 0.05 ms for control rats to 1.53 +/- 0.25 ms for rats in the HU group. In a shortened position, regular rhythm afferent discharges were obviously depressed, and the majority of muscle spindles became silent, while in an extended position, the discharges remained continuous but with decreased frequency. Results also show that the ultrastructure of muscle spindles experience degenerative changes during HU. Altered muscle spindle afference could possibly modify the activity of motor neurons and further affect the activity of extrafusal fibers.

  15. Du-zhong (Eucommia ulmoides) prevents disuse-induced osteoporosis in hind limb suspension rats.

    PubMed

    Pan, Yalei; Niu, Yinbo; Li, Chenrui; Zhai, Yuankun; Zhang, Rong; Guo, Xin; Mei, Qibing

    2014-01-01

    Du-Zhong has a long history of being used in traditional Chinese formulas to treat bone related diseases. The objective of the present study is to systematically investigate the effects of Du-Zhong cortex extract (DZCE) on disuse-induced osteoporosis. Rats were randomly divided into four groups, and three groups were treated with hind limb suspension (HLS). Control and HLS group received deionized distilled water, while the other two groups received alendronate (2.0 mg/kg/day) and DZCE (300 mg/kg/day) respectively by intragastric gavage for six weeks (two weeks prior to and during the four weeks of HLS). Dual-energy X-ray absorptiometry, assay of biochemical markers, and three-point bending test were employed to determine the effect of various treatments on bone mass, turnover, and strength. The trabecular bone microarchitecture was assessed by microCT analysis. DZCE could effectively prevent the bone loss induced by HLS, which was indicated by decreased levels of bone turnover markers as well as the changes in urinary calcium and phosphorus. The DZCE treatment also enhanced the biomechanical strength of bone and prevented the deterioration of trabecular bone microarchitecture. DZCE administration was able to prevent disuse-induced osteoporosis by regulating the bone metabolism, suggesting that DZCE could be used as an alternative therapy for the prevention of disuse-induced osteoporosis.

  16. Muscle moment arms of the gibbon hind limb: implications for hylobatid locomotion.

    PubMed

    Channon, Anthony J; Crompton, Robin H; Günther, Michael M; Vereecke, Evie E

    2010-04-01

    Muscles facilitate skeletal movement via the production of a torque or moment about a joint. The magnitude of the moment produced depends on both the force of muscular contraction and the size of the moment arm used to rotate the joint. Hence, larger muscle moment arms generate larger joint torques and forces at the point of application. The moment arms of a number of gibbon hind limb muscles were measured on four cadaveric specimens (one Hylobates lar, one H. moloch and two H. syndactylus). The tendon travel technique was used, utilizing an electro-goniometer and a linear voltage displacement transducer. The data were analysed using a technique based on a differentiated cubic spline and normalized to remove the effect of body size. The data demonstrated a functional differentiation between voluminous muscles with short fascicles having small muscle moment arms and muscles with longer fascicles and comparatively smaller physiological cross-sectional area having longer muscle moment arms. The functional implications of these particular configurations were simulated using a simple geometric fascicle strain model that predicts that the rectus femoris and gastrocnemius muscles are more likely to act primarily at their distal joints (knee and ankle, respectively) because they have short fascicles. The data also show that the main hip and knee extensors maintain a very small moment arm throughout the range of joint angles seen in the locomotion of gibbons, which (coupled to voluminous, short-fascicled muscles) might help facilitate rapid joint rotation during powerful movements.

  17. Segmentation of digitized histological sections for quantification of the muscularized vasculature in the mouse hind limb.

    PubMed

    Xu, Yiwen; Pickering, J Geoffrey; Nong, Zengxuan; Ward, Aaron D

    2017-04-01

    Immunohistochemical tissue staining enhances microvasculature characteristics, including the smooth muscle in the medial layer of the vessel walls that is responsible for regulation of blood flow. The vasculature can be imaged in a comprehensive fashion using whole-slide scanning. However, since each such image potentially contains hundreds of small vessels, manual vessel delineation and quantification is not practically feasible. In this work, we present a fully automatic segmentation and vasculature quantification algorithm for whole-slide images. We evaluated its performance on tissue samples drawn from the hind limbs of wild-type mice, stained for smooth muscle using 3,3'-Diaminobenzidine (DAB) immunostain. The algorithm was designed to be robust to vessel fragmentation due to staining irregularity, and artefactual staining of nonvessel objects. Colour deconvolution was used to isolate the DAB stain for detection of vessel wall fragments. Complete vessels were reconstructed from the fragments by joining endpoints of topological skeletons. Automatic measures of vessel density, perimeter, wall area and local wall thickness were taken. The segmentation algorithm was validated against manual measures, resulting in a Dice similarity coefficient of 89%. The relationships observed between these measures were as expected from a biological standpoint, providing further reinforcement of the accuracy of this system. This system provides a fully automated and accurate means of measuring the arteriolar and venular morphology of vascular smooth muscle.

  18. Stem cell use in critical limb ischemia.

    PubMed

    Kolvenbach, R; Kreissig, C; Ludwig, E; Cagiannos, C

    2007-02-01

    The following paper gives an overview of the current status of stem cell use in vascular medicine. The role of endothelial progenitor cells (EPCs) is discussed. Different approaches to use cellular based concepts are outlined: among these are the treatment of patients with critical ischemia with bone marrow derived mononuclear cells as well as our own experience with purified and highly selected CD133 and CD34 cells. The pro and cons of these different treatment regimens are discussed. An outlook is given discussing a combination of gene therapy and stem cell injections. The clinical and laboratory results of 15 patients with end-stage critical ischemia are discussed with implications for future clinical trials. We conclude that, despite all open questions, the outlook for EPC-based therapies for tissue ischemia and blood vessel repair appears promising.

  19. 2014 JAPAN Critical Limb Ischemia Database (JCLIMB) Annual Report

    PubMed Central

    2016-01-01

    Since 2013, the Japanese Society for Vascular Surgery (JSVS) has started the project of nationwide registration and a tracking database for patients with critical limb ischemia (CLI) who are treated by vascular surgeons. The purpose of this project is to clarify the current status of the medical practice for patients with CLI to contribute to the improvement of the quality of medical care. This database, called JAPAN Critical Limb Ischemia Database (JCLIMB), is created on the National Clinical Database (NCD) and collects data of patients’ background, therapeutic measures, early results, and long-term prognosis as long as 5 years after the initial treatment. The limbs managed conservatively are also registered in JCLIMB, together with those treated by surgery and/or endovascular treatment (EVT). In 2014, 1347 CLI limbs (male 936 limbs: 69%) were registered by 95 facilities. Arteriosclerosis obliterans (ASO) has accounted for 97% of the pathogenesis of these limbs. In this manuscript, the background data and the early prognosis of the registered limbs are reported. (This is a translation of Jpn J Vasc Surg 2016;25:293–310.) PMID:28018516

  20. 2013 JAPAN Critical Limb Ischemia Database (JCLIMB) Annual Report

    PubMed Central

    2016-01-01

    Since 2013, the Japanese Society for Vascular Surgery (JSVS) has started the project of nationwide registration and a tracking database for patients with critical limb ischemia (CLI) who are treated by vascular surgeons. The purpose of this project is to clarify the current status of the medical practice for patients with CLI to contribute to the improvement of the quality of medical care. This database, called JAPAN Critical Limb Ischemia Database (JCLIMB), is created on the National Clinical Database (NCD) and collects data of patients’ background, therapeutic measures, early results, and long term prognosis as long as five years after the initial treatment. The limbs managed conservatively are also registered in JCLIMB, together with those treated by surgery and/or EVT. In 2013, 1207 CLI limbs (male 874 limbs: 72%) were registered by 87 facilities. ASO has accounted for 98% of the pathogenesis of these limbs. In this manuscript, the background data and the early prognosis of the registered limbs are reported. (This is a translation of Jpn J Vasc Surg 2016; 25: 215–232.) PMID:28018515

  1. Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection

    PubMed Central

    Onody, Peter; Aranyi, Peter; Turoczi, Zsolt; Stangl, Rita; Fulop, Andras; Dudas, Emese; Lotz, Gabor; Szijarto, Attila

    2016-01-01

    Aims and Objectives Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction. Methods Male Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2μg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected. Results Systemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-α levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion. Conclusion The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications. PMID:27684548

  2. A three-dimensional analysis of the morphological evolution and locomotor behaviour of the carnivoran hind limb

    PubMed Central

    2014-01-01

    Background The shape of the appendicular bones in mammals usually reflects adaptations towards different locomotor abilities. However, other aspects such as body size and phylogeny also play an important role in shaping bone design. We used 3D landmark-based geometric morphometrics to analyse the shape of the hind limb bones (i.e., femur, tibia, and pelvic girdle bones) of living and extinct terrestrial carnivorans (Mammalia, Carnivora) to quantitatively investigate the influence of body size, phylogeny, and locomotor behaviour in shaping the morphology of these bones. We also investigated the main patterns of morphological variation within a phylogenetic context. Results Size and phylogeny strongly influence the shape of the hind limb bones. In contrast, adaptations towards different modes of locomotion seem to have little influence. Principal Components Analysis and the study of phylomorphospaces suggest that the main source of variation in bone shape is a gradient of slenderness-robustness. Conclusion The shape of the hind limb bones is strongly influenced by body size and phylogeny, but not to a similar degree by locomotor behaviour. The slender-robust “morphological bipolarity” found in bone shape variability is probably related to a trade-off between maintaining energetic efficiency and withstanding resistance to stresses. The balance involved in this trade-off impedes the evolution of high phenotypic variability. In fact, both morphological extremes (slender/robust) are adaptive in different selective contexts and lead to a convergence in shape among taxa with extremely different ecologies but with similar biomechanical demands. Strikingly, this “one-to-many mapping” pattern of evolution between morphology and ecology in hind limb bones is in complete contrast to the “many-to-one mapping” pattern found in the evolution of carnivoran skull shape. The results suggest that there are more constraints in the evolution of the shape of the appendicular

  3. Impact of neonatal asphyxia and hind limb immobilization on musculoskeletal tissues and S1 map organization: implications for cerebral palsy.

    PubMed

    Coq, Jacques-Olivier; Strata, Fabrizio; Russier, Michaël; Safadi, Fayez F; Merzenich, Michael M; Byl, Nancy N; Barbe, Mary F

    2008-03-01

    Cerebral palsy (CP) is a complex disorder of locomotion, posture and movements resulting from pre-, peri- or postnatal damage to the developing brain. In a previous study (Strata, F., Coq, J.O., Byl, N.N., Merzenich, M.M., 2004. Comparison between sensorimotor restriction and anoxia on gait and motor cortex organization: implications for a rodent model of cerebral palsy. Neuroscience 129, 141-156.), CP-like movement disorders were more reliably reproduced in rats by hind limb sensorimotor restriction (disuse) during development rather than perinatal asphyxia (PA). To gain new insights into the underpinning mechanisms of CP symptoms we investigated the long-term effects of PA and disuse on the hind limb musculoskeletal histology and topographical organization in the primary somatosensory cortex (S1) of adult rats. Developmental disuse (i.e. hind limb immobilization) associated with PA induced muscle fiber atrophy, extracellular matrix changes in the muscle, and mild to moderate ankle and knee joint degeneration at levels greater than disuse alone. Sensorimotor restricted rats with or without PA exhibited a topographical disorganization of the S1 cortical hind limb representation with abnormally large, multiple and overlapping receptive fields. This disorganization was enhanced when disuse and PA were associated. Altered cortical neuronal properties included increased cortical responsiveness and a decrease in neuronal selectivity to afferent inputs. These data support previous observations that asphyxia per se can generate the substrate for peripheral tissue and brain damage, which are worsened by aberrant sensorimotor experience during maturation, and could explain the disabling movement disorders observed in children with CP.

  4. [Epidemiology of critical ischemia of the limbs].

    PubMed

    Estevan, J M; Valle, A; Pacho, J

    1993-01-01

    Authors report their results from a study made during 1991. The study was made in order to analyze the clinical complications (morbidity and mortality) and the socioeconomic consequences that are related to the cure of patients with highly developed ischemic diseases (critical ischemia). Economic expenses mean a 1.5% from the total budget of the Public Sanity into the Asturian Autonomic Community.

  5. Osteology and radiographic anatomy of the pelvis and hind limb of healthy ring-tailed lemurs (Lemur catta).

    PubMed

    Makungu, M; Groenewald, H B; du Plessis, W M; Barrows, M; Koeppel, K N

    2014-06-01

    In family Lemuridae, anatomical variations exist. Considering its conservation status (near threatened) and presence of similarities between strepsirrhines and primitive animals, it was thought to be beneficial to describe the gross osteology and radiographic anatomy of the pelvis and hind limb of ring-tailed lemurs (Lemur catta) as a reference for clinical use and species identification. Radiography was performed in 14 captive adult ring-tailed lemurs. The radiographic findings were correlated with bone specimens from two adult animals. Additionally, computed tomography of the hind limbs was performed in one animal. The pelvic bone has a well-developed caudal ventral iliac spine. The patella has a prominent tuberosity on the cranial surface. The first metatarsal bone and digit 1 are markedly stouter than the other metatarsal bones and digits with medial divergence from the rest of the metatarsal bones and digits. Ossicles were seen in the lateral meniscus, inter-phalangeal joint of digit 1 and in the infrapatellar fat pad. Areas of mineral opacity were seen within the external genitalia, which are believed to be the os penis and os clitoris. Variations exist in the normal osteology and radiographic appearance of the pelvis and hind limb of different animal species. The use of only atlases from domestic cats and dogs for interpretative purposes may be misleading.

  6. Effect of recovery mode following hind-limb suspension on soleus muscle composition in the rat

    NASA Technical Reports Server (NTRS)

    McNulty, A. L.; Otto, A. J.; Kasper, C. E.; Thomas, D. P.

    1992-01-01

    The purpose of this study was to compare the effects of two different recovery modes from hind-limb suspension-induced hypodynamia on whole body and muscle (soleus) growth as well as soleus composition and size changes of different fiber types within this same muscle. Following 28 days of tail-suspension, rats were returned to their cages and sedentarily recovered (HS), or were exercised by running on a treadmill 5 days/wk, at progressively increasing workloads (HR) for one month. Sedentary and running control groups of animals (CS, CR) were also evaluated for comparative purposes. The exercise program, which was identical for CR and HR groups, had no effect on body wt., soleus wt., soleus muscle composition or fiber size in CR rats. Atrophied soleus muscle and reduced soleus wt./body wt. ratio (both 60% of control) had returned to control values by day 7 of recovery in both suspended groups despite the fact that whole body wt. gain was significantly reduced (p less than 0.05) in HR as compared to HS rats. Atrophied soleus Type I fiber mean cross-sectional area in both HR and HS groups demonstrated similar and significant (p less than 0.01) increases during recovery. Increases in Type IIa and IIc fiber area during this same period were significant only in the HR group. While the percentage area of muscle composed of Type I fibers increased in both hypodynamic groups during recovery, the reduction in area percentage of muscle made up of Type IIa fibers was again only significant in the HR group.(ABSTRACT TRUNCATED AT 250 WORDS).

  7. Muscle growth and fiber type composition in hind limb muscles during postnatal development in pigs.

    PubMed

    Wank, Veit; Fischer, Martin S; Walter, Bernd; Bauer, Reinhard

    2006-01-01

    Rapid postnatal development in pigs is reflected by differentiation in skeletal muscle. This process depends on muscle function and demands, but a comprehensive overview of individual developmental characteristics of quickly growing leg muscles in pigs is still missing. This study focused on the development of 10 hind limb muscles in pigs. To determine these changes in mass, fiber type patterns and fiber diameters were analyzed 0, 2, 4, 7, 14, 28, 42, 56 and 400 days after birth. Generally, the proportion of slow fibers increased from birth to 8 weeks. Thereafter, only minor changes in muscle fiber type composition were observed. The majority of the muscles contained less then 10% slow-twitch fibers at birth, increasing to between 12 (Musculus vastus lateralis) and 38% (M. gastrocnemius medialis) in adult pigs. By contrast, postural muscles already had 20-30% slow fibers at birth, and this contribution increased up to 65% in adults (i.e. M. vastus intermedius). From birth to the 2nd week, only in slow fibers could activity of oxidative enzymes be detected. A differentiation of fast-twitch fibers into subtypes with high (comparable to type IIA) and low oxidative metabolism (equivalent to type IIB) occurred between the 2nd and 4th week of life. The ratio between type II fibers with high and low oxidative enzyme activity did not change markedly through development in any muscle, although there was a trend towards an increasing proportion of type IIA fibers in the soleus. In the majority of the muscles investigated, the fast-twitch fibers with low oxidative metabolism (IIB) obtained the largest cross-sectional area. In contrast, at birth no remarkable differences in the diameter of fast and slow fibers were found. The rapid increase in muscle mass compared to body mass reflects the high performance in meat production of the cross pig investigated.

  8. A three-dimensional musculoskeletal model of the chimpanzee (Pan troglodytes) pelvis and hind limb.

    PubMed

    O'Neill, Matthew C; Lee, Leng-Feng; Larson, Susan G; Demes, Brigitte; Stern, Jack T; Umberger, Brian R

    2013-10-01

    Musculoskeletal models have become important tools for studying a range of muscle-driven movements. However, most work has been in modern humans, with few applications in other species. Chimpanzees are facultative bipeds and our closest living relatives, and have provided numerous important insights into our own evolution. A chimpanzee musculoskeletal model would allow integration across a wide range of laboratory-based experimental data, providing new insights into the determinants of their locomotor performance capabilities, as well as the origins and evolution of human bipedalism. Here, we described a detailed three-dimensional (3D) musculoskeletal model of the chimpanzee pelvis and hind limb. The model includes geometric representations of bones and joints, as well as 35 muscle-tendon units that were represented using 44 Hill-type muscle models. Muscle architecture data, such as muscle masses, fascicle lengths and pennation angles, were drawn from literature sources. The model permits calculation of 3D muscle moment arms, muscle-tendon lengths and isometric muscle forces over a wide range of joint positions. Muscle-tendon moment arms predicted by the model were generally in good agreement with tendon-excursion estimates from cadaveric specimens. Sensitivity analyses provided information on the parameters that model predictions are most and least sensitive to, which offers important context for interpreting future results obtained with the model. Comparisons with a similar human musculoskeletal model indicate that chimpanzees are better suited for force production over a larger range of joint positions than humans. This study represents an important step in understanding the integrated function of the neuromusculoskeletal systems in chimpanzee locomotion.

  9. Dynamics of goat distal hind limb muscle–tendon function in response to locomotor grade

    PubMed Central

    McGuigan, M. Polly; Yoo, Edwin; Lee, David V.; Biewener, Andrew A.

    2009-01-01

    Summary The functional roles of the lateral gastrocnemius (LG), medial gastrocnemius (MG) and superficial digital flexor (SDF) muscle–tendon units (MTUs) in domestic goats (N=6) were studied as a function of locomotor grade, testing the hypothesis that changes in distal limb muscle work would reflect changes in mechanical work requirements while goats walked or trotted on the level, 15 deg. decline and 15 deg. incline. As steep terrain-adapted animals, changes in muscle work output are expected to be particularly important for goats. In vivo muscle–tendon forces, fascicle length changes and muscle activation were recorded via tendon force buckles, sonomicrometry and electromyography to evaluate the work performance and elastic energy recovery of the three distal MTUs. These recordings confirmed that fascicle strain and force within goat distal hind limb muscles are adjusted in response to changes in mechanical work demand associated with locomotor grade. In general, muscle work was modulated most consistently by changes in fascicle strain, with increased net shortening (P<0.001) observed as goats switched from decline to level to incline locomotion. Peak muscle stresses increased as goats increased speed from a walk to a trot within each grade condition (P<0.05), and also increased significantly with grade (P<0.05 to P<0.01). Due to the increase in net fascicle shortening and muscle force, net muscle work per cycle also increased significantly (P<0.05 to P<0.005) as goats switched from decline to level to incline conditions (LG work: 20 mJ to 56 mJ to 209 mJ; MG work: –7 mJ to 34 mJ to 179 mJ; SDF work: –42 mJ to 14 mJ to 71 mJ, at a 2.5 ms–1 trot). Although muscle work was modulated in response to changes in grade, the amount of work produced by these three distal pennate muscles was small (being <3%) in comparison with the change in mechanical energy required of the limb as a whole. Elastic energy recovery in the SDF and gastrocnemius (GA) tendons was

  10. Contemporary Outcomes of Endovascular Intervention for Critical Limb Ischemia.

    PubMed

    Dalal, Pratik K; Prasad, Anand

    2017-04-01

    Critical limb ischemia (CLI) remains a significant cause of morbidity and mortality in patients with peripheral arterial disease. Optimal treatment strategies for CLI remain controversial. The only randomized trial comparing surgical with endovascular revascularization suggests no significant difference in limb salvage between open surgical bypass and angioplasty. Although novel endovascular strategies are now available, their efficacies remain largely untested in a randomized fashion. This review provides an overview of the data surrounding contemporary outcomes of endovascular therapy with an emphasis on current knowledge gaps.

  11. Characteristics of physical activity in patients with critical limb ischemia

    PubMed Central

    Sakaki, Satoko; Takahashi, Tetsuya; Matsumoto, Junichi; Kubo, Kasuya; Matsumoto, Takuya; Hishinuma, Ryo; Terabe, Yuuta; Ando, Hiroshi

    2016-01-01

    [Purpose] The purpose of this study was to evaluate the amount of physical activity of the patients with critical limb ischemia consecutively in order to clarify the characteristics of physical activity of critical limb ischemia. [Subjects and Methods] Twelve patients who were eligible for the 2 months of consecutive evaluation of the amount of physical activity were enrolled in the study (men: 11; woman: 1; mean age: 64.4 [range: 44–80]). A pedometer with an accelerometer was used for the measurement of the number of steps walked as an index of the amount of physical activity. Participants were asked to lead a regular life and no instruction was given as to the number of steps. [Results] The average number of daily steps walked was 2,323 steps (range: 404–6,505). There was no clear tendency in the number of amputation site-specific steps walked. There was also no correlation between the number of steps walked and age as well as the maximum strength of the knee-extension muscle, skin perfusion pressure of the sole and the dorsum, and QOL scores. [Conclusion] The number of steps walked of the patients with critical limb ischemia was remarkably low and no significant association with health-related QOL. PMID:28174472

  12. The response of the hind-limb vascular bed of the rabbit to sympathetic stimulation and its modification by pregnancy.

    PubMed Central

    Humphreys, P W; Joels, N

    1982-01-01

    1. Pressure-flow relationships in the hind limb, perfused with blood at a series of constant flows, have been compared in primigravid and virgin rabbits following section of the lumbar sympathetic chain. 2. In the absence of sympathetic stimulation perfusion pressure was lower (P less than 0.05) in the pregnant rabbits at all levels of flow to the leg. 3. It is concluded that pregnancy leads to a reduction in the vascular resistance of the acutely sympathectomized hind limb. 4. The pressure-flow curves of hind limbs from pregnant and non-pregnant rabbits in which the cutaneous circulation had been excluded by skinning the leg and ligating the ankle were also compared. Again, perfusion pressure at each flow level was lower in the limbs from the pregnant animals (P less than 0.05). 5. The sympathetic supply was stimulated at frequencies of 0.3, 1, 3, 7, 15 and 30 Hz. Irrespective of whether the cutaneous circulation was excluded, the pressure-flow curves for the hind limbs of pregnant and non-pregnant rabbits were different at the lower frequencies. As stimulus frequency rose this difference became smaller, and at a stimulus frequency of 7-15 Hz or more there was little difference in the position of the curves in pregnant and non-pregnant rabbits. 6. Examination of the pressure-flow curves suggests that when, as in these experiments, flow is held constant, the ability of sympathetic stimulation to increase the resistance to blood flow is reduced in pregnancy. However, if these pressure-flow curves are used to predict the change of flow that would occur at a constant perfusion pressure, the response to sympathetic stimulation appears to be greater in pregnancy. 7. Further analysis of the findings, based on certain assumptions, suggests that differences between the pressure-flow curves of pregnant and non-pregnant animals during sympathetic stimulation are due in the main to either a differing size of the unstimulated vascular beds or a differing compliance of their

  13. Increased androgenic sensitivity in the hind limb muscular system marks the evolution of a derived gestural display

    PubMed Central

    Mangiamele, Lisa A.; Fuxjager, Matthew J.; Schuppe, Eric R.; Taylor, Rebecca S.; Hödl, Walter; Preininger, Doris

    2016-01-01

    Physical gestures are prominent features of many species’ multimodal displays, yet how evolution incorporates body and leg movements into animal signaling repertoires is unclear. Androgenic hormones modulate the production of reproductive signals and sexual motor skills in many vertebrates; therefore, one possibility is that selection for physical signals drives the evolution of androgenic sensitivity in select neuromotor pathways. We examined this issue in the Bornean rock frog (Staurois parvus, family: Ranidae). Males court females and compete with rivals by performing both vocalizations and hind limb gestural signals, called “foot flags.” Foot flagging is a derived display that emerged in the ranids after vocal signaling. Here, we show that administration of testosterone (T) increases foot flagging behavior under seminatural conditions. Moreover, using quantitative PCR, we also find that adult male S. parvus maintain a unique androgenic phenotype, in which androgen receptor (AR) in the hind limb musculature is expressed at levels ∼10× greater than in two other anuran species, which do not produce foot flags (Rana pipiens and Xenopus laevis). Finally, because males of all three of these species solicit mates with calls, we accordingly detect no differences in AR expression in the vocal apparatus (larynx) among taxa. The results show that foot flagging is an androgen-dependent gestural signal, and its emergence is associated with increased androgenic sensitivity within the hind limb musculature. Selection for this novel gestural signal may therefore drive the evolution of increased AR expression in key muscles that control signal production to support adaptive motor performance. PMID:27143723

  14. Activation patterns of embryonic chick hind limb muscles recorded in ovo and in an isolated spinal cord preparation.

    PubMed

    Landmesser, L T; O'Donovan, M J

    1984-02-01

    Muscle activation patterns of embryonic chick hind limb muscles were determined from electromyographic (e.m.g.) recordings in an isolated spinal cord/hind limb preparation of stage 34-36 embryos, and were compared with in ovo e.m.g. activity from similarly staged embryos. Muscle activity in ovo consisted of periodically recurring sequences of bursts during which antagonistic muscles often alternated and synergistic muscles were co-active, as compatible with their mature function. However, more variable behaviour was also observed. Burst sequences in ovo were often initiated by a short-duration, high-amplitude discharge that occurred synchronously in all muscles studied, and which was followed by a period of electrical silence that was longest in the flexor muscles. This type of activity has not been described previously in mature animals. In ovo movement sequences were generally initiated by extensor activity which progressively declined in duration and intensity throughout the sequence, while flexor activity progressively intensified. The onset of activity in extensor muscles was accompanied by an abrupt decrease in flexor activity, whereas the converse was not observed. Spontaneous movement sequences also occurred when the spinal cord and hind limb were isolated and maintained in oxygenated Tyrode solution for several hours. Deafferentation experiments indicated that the motor pattern in this preparation was generated centrally by circuits within the spinal cord. Activity from the isolated cord was less variable than that occurring in ovo, consisting of sequences of highly regular recurring bursts. Each burst began with a brief high-amplitude discharge that occurred synchronously in all muscles and which was similar to that observed in ovo. This was followed by a silent period, which was longest in the flexors, and then by a more prolonged burst. Although its behaviour differs from that in ovo in some respects, it is concluded that the isolated cord maintained in

  15. Activation patterns of embryonic chick hind limb muscles recorded in ovo and in an isolated spinal cord preparation.

    PubMed Central

    Landmesser, L T; O'Donovan, M J

    1984-01-01

    Muscle activation patterns of embryonic chick hind limb muscles were determined from electromyographic (e.m.g.) recordings in an isolated spinal cord/hind limb preparation of stage 34-36 embryos, and were compared with in ovo e.m.g. activity from similarly staged embryos. Muscle activity in ovo consisted of periodically recurring sequences of bursts during which antagonistic muscles often alternated and synergistic muscles were co-active, as compatible with their mature function. However, more variable behaviour was also observed. Burst sequences in ovo were often initiated by a short-duration, high-amplitude discharge that occurred synchronously in all muscles studied, and which was followed by a period of electrical silence that was longest in the flexor muscles. This type of activity has not been described previously in mature animals. In ovo movement sequences were generally initiated by extensor activity which progressively declined in duration and intensity throughout the sequence, while flexor activity progressively intensified. The onset of activity in extensor muscles was accompanied by an abrupt decrease in flexor activity, whereas the converse was not observed. Spontaneous movement sequences also occurred when the spinal cord and hind limb were isolated and maintained in oxygenated Tyrode solution for several hours. Deafferentation experiments indicated that the motor pattern in this preparation was generated centrally by circuits within the spinal cord. Activity from the isolated cord was less variable than that occurring in ovo, consisting of sequences of highly regular recurring bursts. Each burst began with a brief high-amplitude discharge that occurred synchronously in all muscles and which was similar to that observed in ovo. This was followed by a silent period, which was longest in the flexors, and then by a more prolonged burst. Although its behaviour differs from that in ovo in some respects, it is concluded that the isolated cord maintained in

  16. Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning.

    PubMed

    Ren, C; Gao, X; Steinberg, G K; Zhao, H

    2008-02-19

    Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 min occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 min occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for two or three cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with three cycles of 15 min performed immediately before stroke reduced infarct size from 47.7+/-7.6% of control ischemia to 9.8+/-8.6%; at two cycles of 15 min, infarct was reduced to 24.7+/-7.3%; at two cycles of 5 min, infarct was not reduced. Delayed preconditioning with three cycles of 15 min conducted 2 days before stroke also reduced infarct to 23.0+/-10.9%, but with two cycles of 15 min it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with three cycles of 15 min performed 12 h before stroke also reduced infarct to 24.7+/-4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia.

  17. Morphology of the pelvis and hind limb of the red panda (Ailurus fulgens) evidenced by gross osteology, radiography and computed tomography.

    PubMed

    Makungu, M; du Plessis, W M; Groenewald, H B; Barrows, M; Koeppel, K N

    2015-12-01

    The red panda (Ailurus fulgens) is a quadrupedal arboreal animal primarily distributed in the Himalayas and southern China. It is a species commonly kept in zoological collections. This study was carried out to describe the morphology of the pelvis and hind limb of the red panda evidenced by gross osteology, radiography and computed tomography as a reference for clinical use and identification of skeletons. Radiography of the pelvis and right hind limb was performed in nine and seven animals, respectively. Radiographic findings were correlated with bone specimens from three adult animals. Computed tomography of the torso and hind limb was performed in one animal. The pelvic bone had a wide ventromedial surface of the ilium. The trochlea of the femur was wide and shallow. The patella was similar to that seen in feline species. The medial fabella was not seen radiographically in any animal. The cochlea grooves of the tibia were shallow with a poorly defined intermediate ridge. The trochlea of the talus was shallow and presented with an almost flattened medial ridge. The tarsal sesamoid bone was always present. The lateral process of the base of the fifth metatarsal (MT) bone was directed laterally. The MT bones were widely spaced. The morphology of the pelvis and hind limb of the red panda indicated flexibility of the pelvis and hind limb joints as an adaptation to an arboreal quadrupedal lifestyle.

  18. AB296. SPR-23 Aberrant bladder reflexes can drive hind limb locomotor activity following complete suprasacral spinal cord injury

    PubMed Central

    Inouye, Brian M.; Brooks, Jillene M.; Degoski, Danielle J.; Hughes, Francis M.; Purves, J. Todd; Fraser, Matthew O.

    2016-01-01

    Objective Many rats with chronic suprasacral spinal cord injury (SCI) demonstrate hind limb locomotor activity (HLLA) in response to external crede or high pressure contractions during cystometry. We propose that this aberrant, pressure-driven bladder reflex pathway may be harnessed to facilitate walking in SCI patients. As a first step in exploring this possibility, we examined the relationship between intravesical pressure (IVP) and HLLA in chronic suprasacral SCI rats. Methods Female rats (4 weeks post-SCI at T9-10, n=16) were anesthetized with isoflurane and fitted with transvesical catheters and right quadriceps EMG electrodes to monitor bladder and hind limb locomotor activities, respectively. The animals were mounted in Ballman restraint cages to which they had been previously acclimated. The catheter was connected to a pressure transducer, an infusion pump, and a saline-filled reservoir mounted on a metered vertical pole (pressure clamp). After 30 min of recovery from anesthesia, the bladder was filled at 0.1 mL/min with saline to verify bladder-to-bladder reflex activity for 30 min. IVP was then increased in an interrupted stepwise fashion from 0–120 cmH2O at 10 cmH2O increments. Each step consisted of five minutes: 3 minutes at the new pressure followed by 2 minutes at 0 cmH2O. IVP and the number of HLLA events (as defined by rhythmic EMG discharges of 3–10 cycles/event) were recorded for each pressure step. This process was repeated for two more trials for each rat to assess the durability of the reflex. Data were analyzed using ANOVA with repeated measures both within and across pressure escalation trials. P<0.05 was considered significant. Results ANOVA revealed that locomotor events increased with increasing IVP and decreased with the number of escalation trials (P<0.0001 for both effects). The increase in the number of locomotor events with increasing IVP appeared to plateau at ~50–60 cmH2O (P<0.05 for all). The average of the maximal number of

  19. Accuracy and precision of hind limb foot contact timings of horses determined using a pelvis-mounted inertial measurement unit.

    PubMed

    Starke, Sandra D; Witte, Thomas H; May, Stephen A; Pfau, Thilo

    2012-05-11

    Gait analysis using small sensor units is becoming increasingly popular in the clinical context. In order to segment continuous movement from a defined point of the stride cycle, knowledge about footfall timings is essential. We evaluated the accuracy and precision of foot contact timings of a defined limb determined using an inertial sensor mounted on the pelvis of ten horses during walk and trot at different speeds and in different directions. Foot contact was estimated from vertical velocity events occurring before maximum sensor roll towards the contralateral limb. Foot contact timings matched data from a synchronised hoof mounted accelerometer well when velocity minimum was used for walk (mean (SD) difference of 15 (18)ms across horses) and velocity zero-crossing for trot (mean (SD) difference from -4 (14) to 12 (7)ms depending on the condition). The stride segmentation method also remained robust when applied to movement data of hind limb lame horses. In future, this method may find application in segmenting overground sensor data of various species.

  20. Niacin promotes revascularization and recovery of limb function in diet-induced obese mice with peripheral ischemia.

    PubMed

    Pang, Dominic K T; Nong, Zengxuan; Sutherland, Brian G; Sawyez, Cynthia G; Robson, Debra L; Toma, Jelena; Pickering, J Geoffrey; Borradaile, Nica M

    2016-06-01

    Niacin can reduce vascular disease risk in individuals with metabolic syndrome, but in light of recent large randomized controlled trials outcomes, its biological actions and clinical utility remain controversial. Niacin can improve endothelial function, vascular inflammation, and vascular regeneration, independent of correcting dyslipidemia, in various lean rodent models of vascular injury. Here, we tested whether niacin could directly improve endothelial cell angiogenic function during combined exposure to excess fatty acids and hypoxia, and whether intervention with niacin during continued feeding of western diet could improve revascularization and functional recovery in obese, hyperlipidemic mice with peripheral ischemia. Treatment with niacin (10 μmol/L) increased human microvascular endothelial cell angiogenic function during exposure to high fatty acids and hypoxia (2% oxygen), as determined by tube formation on Matrigel. To assess revascularization in vivo, we used western diet-induced obese mice with unilateral hind limb femoral artery ligation and excision. Treatment for 14 days postinjury with once daily i.p. injections of a low dose of niacin (50 mg/kg) improved recovery of hind limb use, in association with enhanced revascularization and decreased inflammation of the tibialis anterior muscle. These effects were concomitant with decreased plasma triglycerides, but not increased plasma apoAI. Thus, niacin improves endothelial tube formation under lipotoxic and hypoxic conditions, and moreover, promotes revascularization and functional hind limb recovery following ischemic injury in diet-induced obese mice with hyperlipidemia. These data may have implications for niacin therapy in the treatment of peripheral ischemic vascular disease associated with metabolic syndrome.

  1. Understanding objective performance goals for critical limb ischemia trials.

    PubMed

    Conte, Michael S

    2010-09-01

    Critical limb ischemia (CLI), the most advanced form of peripheral arterial disease, is associated with a high rate of limb loss and substantial mortality. Revascularization remains the cornerstone of limb salvage in the CLI patient, and surgical bypass is the established standard. Endovascular therapies, such as angioplasty, atherectomy, and stenting offer a less-invasive option, but evidence of efficacy is lacking, and no devices are currently approved specifically for CLI. Design and execution of clinical trials in the CLI population are challenging, in part because of the lack of consensus on cohort definitions and relevant endpoints. Recently, the Society for Vascular Surgery undertook an initiative to define therapeutic benchmarks, objective performance goals (OPGs), for CLI. Using surgical bypass with autogenous vein as the standard for comparison, OPGs were developed for nine safety and efficacy measures that could be utilized in the premarket assessment of new devices in CLI. Data from three large randomized controlled trials of surgical bypass for CLI were analyzed. We defined a major adverse limb event (MALE) as a key endpoint for revascularization therapies in CLI--inclusive of amputation (transtibial or above) or any major vascular reintervention (thrombectomy, thrombolysis, or major surgical procedure [new bypass graft, jump/interposition graft revision]) in the index limb. Freedom from perioperative (30-day) death or any MALE (MALE + POD) was suggested as the primary efficacy endpoint for a single-arm trial design in CLI, with an observed rate of 76.9% for the surgical bypass controls at 1 year. Specific high-risk subgroups were also defined from the surgical dataset--based on clinical (age older than 80 years and tissue loss), arterial anatomy (infrapopliteal disease), and conduit quality (inadequate saphenous vein) characteristics. Risk-adjusted OPG were developed for these subgroups of interest. These OPGs define a new set of benchmarks for

  2. Vasomotor responses in the hind limbs of foetal and new-born lambs to asphyxia and aortic chemoreceptor stimulation

    PubMed Central

    Dawes, G. S.; Lewis, B. V.; Milligan, J. E.; Roach, Margot R.; Talner, N. S.

    1968-01-01

    1. Hind limb blood flow was measured in lambs of from 91 days gestation (delivered by Caesarean section) to 1 month after birth (term is about 147 days), under chloralose anaesthesia. Vascular resistance/100 g wet wt. increased progressively with age. There was reflex femoral vascular tone from the earliest age studied, as shown by vasodilatation on cutting the sciatic nerve. 2. On asphyxia by cord occlusion reflex femoral vasoconstriction began earlier and was somewhat greater in older foetal lambs. At all ages, and after denervation of the hind limb, there was vasodilatation after local ischaemia, and a vasoconstriction of delayed onset during asphyxia attributed to release of noradrenaline into the circulation. The vasoconstrictor effect of noradrenaline in immature lambs was at least as great as at term or in the new-born. 3. Injections of minimal effective doses of cyanide were used to localize possible chemoreceptor sites in foetal lambs. Injection into the left atrium caused a rise of arterial pressure, femoral vasoconstriction and a complex change in heart rate (usually bradycardia) but rarely any respiratory movement. After atropine, cyanide caused a large tachycardia. All responses were much reduced or abolished by cervical vagotomy. 4. Injection of the same doses of cyanide into a jugular vein, the right ventricle, pulmonary or common carotid arteries of foetal lambs caused negligible cardiovascular or respiratory effects, whereas injection into the carotids of new-born lambs caused a profound hyperpnoea. 5. It is concluded that the aortic chemoreceptors are active in the foetus, are supplied from the left heart, and that they probably represent the primary defence in blood gas homeostasis by their effects on the circulation. PMID:4295757

  3. Arboreal Day Geckos (Phelsuma madagascariensis) Differentially Modulate Fore- and Hind Limb Kinematics in Response to Changes in Habitat Structure

    PubMed Central

    Zhuang, Mingna V.; Higham, Timothy E.

    2016-01-01

    By using adhesion, geckos can move through incredibly challenging habitats. However, continually changing terrain may necessitate modulation of the adhesive apparatus in order to maximize its effectiveness over a range of challenges. Behaviorally modulating how the adhesive system is applied can occur by altering the alignment of the foot relative to the long axis of the body and/or the angles between the digits (interdigital angle). Given the directionality of the adhesive system, geckos likely vary the application of the system via these mechanisms as they run. We quantified 3D movements (using high-speed video) of the day gecko, Phelsuma madagascariensis, running on a range of ecologically relevant inclines (0°, 45°, 90°) and perch diameters (1.5 cm, 10 cm and broad). We measured the instantaneous sum of interdigital angles and foot alignment relative to the body, as well as other kinematic variables, throughout each stride and across treatments. Modulation of foot alignment at 45° and 90° was similar between the forelimb and hind limb, but differed at 0°, suggesting that P. madagascariensis is able to exert an adhesive force using multiple strategies. Both the sum of interdigital angles and alignment in the fore- and hind foot were modulated. Differences in modulation between the limbs are likely related to the underlying morphology. The modulation of interdigital angle and foot alignment suggests that aspects other than the mechanism of adhesion, such as joint morphology, are important for arboreal movement in geckos. Our study of foot usage in arboreal locomotion reveals patterns that may be widespread across pad-bearing lizards. In addition to understanding the constraints exerted by the adhesive apparatus, we highlight how biomechanical traits may respond to the evolution of novel adaptations and morphologies. PMID:27145027

  4. Vasomotor responses in the hind limbs of foetal and new-born lambs to asphyxia and aortic chemoreceptor stimulation.

    PubMed

    Dawes, G S; Lewis, B V; Milligan, J E; Roach, M R; Talner, N S

    1968-03-01

    1. Hind limb blood flow was measured in lambs of from 91 days gestation (delivered by Caesarean section) to 1 month after birth (term is about 147 days), under chloralose anaesthesia. Vascular resistance/100 g wet wt. increased progressively with age. There was reflex femoral vascular tone from the earliest age studied, as shown by vasodilatation on cutting the sciatic nerve.2. On asphyxia by cord occlusion reflex femoral vasoconstriction began earlier and was somewhat greater in older foetal lambs. At all ages, and after denervation of the hind limb, there was vasodilatation after local ischaemia, and a vasoconstriction of delayed onset during asphyxia attributed to release of noradrenaline into the circulation. The vasoconstrictor effect of noradrenaline in immature lambs was at least as great as at term or in the new-born.3. Injections of minimal effective doses of cyanide were used to localize possible chemoreceptor sites in foetal lambs. Injection into the left atrium caused a rise of arterial pressure, femoral vasoconstriction and a complex change in heart rate (usually bradycardia) but rarely any respiratory movement. After atropine, cyanide caused a large tachycardia. All responses were much reduced or abolished by cervical vagotomy.4. Injection of the same doses of cyanide into a jugular vein, the right ventricle, pulmonary or common carotid arteries of foetal lambs caused negligible cardiovascular or respiratory effects, whereas injection into the carotids of new-born lambs caused a profound hyperpnoea.5. It is concluded that the aortic chemoreceptors are active in the foetus, are supplied from the left heart, and that they probably represent the primary defence in blood gas homeostasis by their effects on the circulation.

  5. Critical appraisal of surgical revascularization for critical limb ischemia.

    PubMed

    Conte, Michael S

    2013-02-01

    Peripheral artery disease is growing in global prevalence and is estimated to afflict between 8 and 12 million Americans. Its most severe form, critical limb ischemia (CLI), is associated with high rates of limb loss, morbidity, and mortality. Revascularization is the cornerstone of limb preservation in CLI, and has traditionally been accomplished with open surgical bypass. Advances in catheter-based technologies, coupled with their broad dissemination among specialists, have led to major shifts in practice patterns in CLI. There is scant high-quality evidence to guide surgical decision making in this arena, and market forces have exerted profound influences. Despite this, available data suggest that the expected outcomes for both endovascular and open surgery in CLI are strongly dependent on definable patient factors such as anatomic distribution of disease, vein quality, and comorbidities. Optimal patient selection is paramount for maximizing benefit with each technique. This review summarizes some of the existing data and suggests a selective approach to revascularization in CLI, which continues to rely on vein bypass surgery as a primary option in appropriately selected patients.

  6. Cell Therapy in Patients with Critical Limb Ischemia

    PubMed Central

    Compagna, Rita; Amato, Bruno; Massa, Salvatore; Amato, Maurizio; Grande, Raffaele; Butrico, Lucia; de Franciscis, Stefano; Serra, Raffaele

    2015-01-01

    Critical limb ischemia (CLI) represents the most advanced stage of peripheral arterial obstructive disease (PAOD) with a severe obstruction of the arteries which markedly reduces blood flow to the extremities and has progressed to the point of severe rest pain and/or even tissue loss. Recent therapeutic strategies have focused on restoring this balance in favor of tissue survival using exogenous molecular and cellular agents to promote regeneration of the vasculature. These are based on stimulation of angiogenesis by extracellular and cellular components. This review article carries out a systematic analysis of the most recent scientific literature on the application of stem cells in patients with CLI. The results obtained from the detailed analysis of the recent literature data have confirmed the beneficial role of cell therapy in reducing the rate of major amputations in patients with CLI and improving their quality of life. PMID:26300924

  7. [Management of a patient with critical limb ischemia].

    PubMed

    Bura-Rivière, Alessandra; Julia, Pierre; Sapoval, Marc

    2005-06-15

    The severity of the prognostic of critical limb ischemia imposes a multidisciplinary approach, done by a highly specialised centre. A delay in managing this condition increases significantly the risk of amputation. For most patients, a revascularisation procedure, surgical or endovascular, can be considered, since the aim of the treatment is to restore an arterial flux to permit cicatrisation and relieve pain. When the choice is possible, endovascular techniques are preferred, because more simple, done without anaesthesia and charged of less complications rate. The choice between two techniques is never simple and imposes the intervention of a multidisciplinary staff composed by vascular specialist, vascular surgeons and interventional radiologists. The aim of the medical treatment, waiting for the revascularisation, is to control the pain and the infection, prevent progression of the lesions and to optimise respiratory and cardiac functions.

  8. Critical limb ischemia in association with Charcot neuroarthropathy: complex endovascular therapy for limb salvage.

    PubMed

    Palena, Luis Mariano; Brocco, Enrico; Manzi, Marco

    2014-02-01

    Charcot neuroarthropathy is a low-incidence complication of diabetic foot and is associated with ankle and hind foot deformity. Patients who have not developed deep ulcers are managed with offloading and supportive bracing or orthopedic arthrodesis. In patients who have developed ulcers and severe ankle instability and deformity, below-the-knee amputation is often indicated, especially when deformity and cutaneous involvement result in osteomyelitis. Ischemic association has not been described but can be present as a part of peripheral arterial disease in the diabetic population. In this extreme and advanced stage of combined neuroischemic diabetic foot disease, revascularization strategies can support surgical and orthopedic therapy, thus preventing osteomyelitis and leading to limb and foot salvage.

  9. Critical Limb Ischemia in Association with Charcot Neuroarthropathy: Complex Endovascular Therapy for Limb Salvage

    SciTech Connect

    Palena, Luis Mariano; Brocco, Enrico; Manzi, Marco

    2013-05-09

    Charcot neuroarthropathy is a low-incidence complication of diabetic foot and is associated with ankle and hind foot deformity. Patients who have not developed deep ulcers are managed with offloading and supportive bracing or orthopedic arthrodesis. In patients who have developed ulcers and severe ankle instability and deformity, below-the-knee amputation is often indicated, especially when deformity and cutaneous involvement result in osteomyelitis. Ischemic association has not been described but can be present as a part of peripheral arterial disease in the diabetic population. In this extreme and advanced stage of combined neuroischemic diabetic foot disease, revascularization strategies can support surgical and orthopedic therapy, thus preventing osteomyelitis and leading to limb and foot salvage.

  10. A system identification analysis of neural adaptation dynamics and nonlinear responses in the local reflex control of locust hind limbs.

    PubMed

    Dewhirst, Oliver P; Angarita-Jaimes, Natalia; Simpson, David M; Allen, Robert; Newland, Philip L

    2013-02-01

    Nonlinear type system identification models coupled with white noise stimulation provide an experimentally convenient and quick way to investigate the often complex and nonlinear interactions between the mechanical and neural elements of reflex limb control systems. Previous steady state analysis has allowed the neurons in such systems to be categorised by their sensitivity to position, velocity or acceleration (dynamics) and has improved our understanding of network function. These neurons, however, are known to adapt their output amplitude or spike firing rate during repetitive stimulation and this transient response may be more important than the steady state response for reflex control. In the current study previously used system identification methods are developed and applied to investigate both steady state and transient dynamic and nonlinear changes in the neural circuit responsible for controlling reflex movements of the locust hind limbs. Through the use of a parsimonious model structure and Monte Carlo simulations we conclude that key system dynamics remain relatively unchanged during repetitive stimulation while output amplitude adaptation is occurring. Whilst some evidence of a significant change was found in parts of the systems nonlinear response, the effect was small and probably of little physiological relevance. Analysis using biologically more realistic stimulation reinforces this conclusion.

  11. Response of lymphatics of canine hind limb to sympathetic nerve stimulation.

    PubMed

    Browse, N L

    1968-07-01

    1. The changes in lymphatic pressure in a limb whose circulation was temporarily arrested with a pneumatic cuff have been studied.2. Stimulation of the lumbar sympathetic chain caused an increase in lymphatic pressure. It has been shown that this is a primary not a secondary phenomenon, due to an active lymphomotor mechanism.3. The increase of lymphatic tone is proportional to the rate of stimulation; peak values are reached between 5 and 9 impulses/sec.

  12. Mitochondrial Regulation of the Muscle Microenvironment in Critical Limb Ischemia

    PubMed Central

    Ryan, Terence E.; Schmidt, Cameron A.; Green, Tom D.; Brown, David A.; Neufer, P. Darrell; McClung, Joseph M.

    2015-01-01

    Critical limb ischemia (CLI) is the most severe clinical presentation of peripheral arterial disease and manifests as chronic limb pain at rest and/or tissue necrosis. Current clinical interventions are largely ineffective and therapeutic angiogenesis based trials have shown little efficacy, highlighting the dire need for new ideas and novel therapeutic approaches. Despite a decade of research related to skeletal muscle as a determinant of morbidity and mortality outcomes in CLI, very little progress has been made toward an effective therapy aimed directly at the muscle myopathies of this disease. Within the muscle cell, mitochondria are well positioned to modulate the ischemic cellular response, as they are the principal sites of cellular energy production and the major regulators of cellular redox charge and cell death. In this mini review, we update the crucial importance of skeletal muscle to CLI pathology and examine the evolving influence of muscle and endothelial cell mitochondria in the complex ischemic microenvironment. Finally, we discuss the novelty of muscle mitochondria as a therapeutic target for ischemic pathology in the context of the complex co-morbidities often associated with CLI. PMID:26635622

  13. Perioperative evaluation and outcomes of major limb replantations with ischemia periods of more than 6 hours.

    PubMed

    Tantry, Thrivikrama Padur; Kadam, Dinesh; Shenoy, Sunil P; Bhandary, Sanath; Adappa, Karunakara K

    2013-03-01

    Early revascularization is cardinal for successful replantation of proximal limb amputations. Prolonged ischemia time potentially leads to reperfusion syndrome and morbidity. The dilemma persists regarding safe duration of cold ischemia time for replantation. The study was conducted to evaluate retrospectively the outcomes of major replantation in terms of limb survival, reperfusion events, morbidity, and potential mortality with respect to the ischemia time and level of amputations. Fourteen patients with proximal amputations at the arm, elbow, and forearm with total ischemia time beyond 6 hours were replanted. All had warm ischemia time of less than 2 hours and were closely monitored to record and correct reperfusion events. Nine out of 14 limbs survived. Five patients had reperfusion events. Proximal limb amputations with larger muscle mass were at higher risk of developing reperfusion syndrome and such events had higher chances of limb loss. Major limb amputations within 2 hours of warm ischemia time even with prolonged cold ischemia can be successfully replanted with closed perioperative monitoring.

  14. Study of Hind Limb Tissue Gas Phase Formation in Response to Suspended Adynamia and Hypokinesia

    NASA Technical Reports Server (NTRS)

    Butler, Bruce D.

    1996-01-01

    The purpose of this study was to investigate the hypothesis that reduced joint/muscle activity (hypo kinesia) as well as reduced or null loading of limbs (adynamia) in gravity would result in reduced decompression-induced gas phase and symptoms of decompression sickness (DCS). Finding a correlation between the two phenomena would correspond to the proposed reduction in tissue gas phase formation in astronauts undergoing decompression during extravehicular activity (EVA) in microgravity. The observation may further explain the reported low incidence of DCS in space.

  15. Effects of stretching and disuse on amino acids in muscles of rat hind limbs

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Henriksen, Erik J.; Satarug, Soisungwan; Tischler, Marc E.

    1989-01-01

    The effects of disuse and passive stretch on the concentrations of amino acids and ammonia in the unloaded soleus muscle was investigated in hindquarter-suspended (for six days by casting one foot in dorsiflexion) tail-casted rats. For a comparison with the condition of unloading, amino acids and ammonia were also measured in shortened extensor digitorum longus in the same casted limb and in denervated leg muscles. The results obtained suggest that passive stretch diminishes some of the characteristic alterations of amino acid concentrations due to unloading. This effect of stretch is considered to be due to the maintenance of muscle tension.

  16. Young's modulus and SEM analysis of leg bones exposed to simulated microgravity by hind limb suspension (HLS)

    SciTech Connect

    Patel, Niravkumar D.; Mehta, Rahul; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal

    2013-04-19

    The aim of this study was to determine composition of the leg bone tissue of rats that were exposed to simulated microgravity by Hind-Limb Suspension (HLS) by tail for one week. The leg bones were cross sectioned, cleaned of soft tissues, dried and sputter coated, and then placed horizontally on the stage of a Scanning Electron Microscope (SEM) for analysis. Interaction of a 17.5 keV electron beam, incident from the vertical direction on the sample, generated images using two detectors. X-rays emitted from the sample during electron bombardment were measured with an Energy Dispersive Spectroscopy (EDS) feature of SEM using a liquid-nitrogen cooled Si(Li) detector with a resolution of 144 eV at 5.9 keV ({sub 25}Mn K{sub {alpha}} x-ray). K{sub {alpha}}- x-rays from carbon, oxygen, phosphorus and calcium formed the major peaks in the spectrum. Relative percentages of these elements were determined using a software that could also correct for ZAF factors namely Z(atomic number), A(X-ray absorption) and F(characteristic fluorescence). The x-rays from the control groups and from the experimental (HLS) groups were analyzed on well-defined parts (femur, tibia and knee) of the leg bone. The SEM analysis shows that there are definite changes in the hydroxyl or phosphate group of the main component of the bone structure, hydroxyapatite [Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2}], due to hind limb suspension. In a separate experiment, entire leg bones (both from HLS and control rats) were subjected to mechanical stress by mean of a variable force. The stress vs. strain graph was fitted with linear and polynomial function, and the parameters reflecting the mechanical strength of the bone, under increasing stress, were calculated. From the slope of the linear part of the graph the Young's modulus for HLS bones were calculated and found to be 2.49 times smaller than those for control bones.

  17. Quantitative evaluation of bone development of the distal phalanx of the cow hind limb using computed tomography.

    PubMed

    Tsuka, T; Ooshita, K; Sugiyama, A; Osaki, T; Okamoto, Y; Minami, S; Imagawa, T

    2012-01-01

    Computed tomography (CT) was performed on 400 claws (200 inner and 200 outer claws) of 100 pairs of bovine hind limbs to investigate the etiological theory that an exacerbating factor for ulceration is exostosis of the tuberculum flexorium within the distal phalanx. A variety of morphological changes of the tuberculum flexorium of bovine hind limb claws was visualized by 3-dimensional CT, and the geometry of these claws suggested a growth pattern of bone development with respect to the assumed daily loading patterns. This growth occurs initially at the abaxial caudal aspect of the distal phalanx and is followed by horizontal progression toward the axial aspect. The length of downward bone development on the solar face of the distal phalanx was 2.73±1.32 mm in the outer claws, significantly greater than in the inner claws (2.38±0.96 mm). Ratios of downward (vertical) bone development to the thickness of the subcutis and the corium (VerBD ratios) did not differ between the outer and inner claws (36.7 vs. 38.3%, respectively). Ratios of horizontal bone development to the axial-to-abaxial line of the tuberculum flexorium (HorBD ratios) were approximately 60% for both outer and inner claws. These quantitative measures regarding horizontal and vertical bone development within the distal phalanx were positively correlated with age and VerBD ratios (r=0.53 and r=0.36 for the inner and outer claws, respectively). Correlations between claw width of the outer claw and length of vertical bone development (r=0.43), the HorBD ratio (r=0.51), and the VerBD ratio (r=0.42) suggested that the relative size difference between the inner and outer claws enhances bone development in the outer claw. Correlation coefficients between VerBD and HorBD ratios (r=0.52 and 0.63 for the inner and outer claws, respectively) suggested that horizontal and vertical bone development occurs as a synchronized process within the tuberculum flexorium. This age-related progress of bone development

  18. Young's modulus and SEM analysis of leg bones exposed to simulated microgravity by hind limb suspension (HLS)

    NASA Astrophysics Data System (ADS)

    Patel, Niravkumar D.; Mehta, Rahul; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal

    2013-04-01

    The aim of this study was to determine composition of the leg bone tissue of rats that were exposed to simulated microgravity by Hind-Limb Suspension (HLS) by tail for one week. The leg bones were cross sectioned, cleaned of soft tissues, dried and sputter coated, and then placed horizontally on the stage of a Scanning Electron Microscope (SEM) for analysis. Interaction of a 17.5 keV electron beam, incident from the vertical direction on the sample, generated images using two detectors. X-rays emitted from the sample during electron bombardment were measured with an Energy Dispersive Spectroscopy (EDS) feature of SEM using a liquid-nitrogen cooled Si(Li) detector with a resolution of 144 eV at 5.9 keV (25Mn Kα x-ray). Kα- x-rays from carbon, oxygen, phosphorus and calcium formed the major peaks in the spectrum. Relative percentages of these elements were determined using a software that could also correct for ZAF factors namely Z(atomic number), A(X-ray absorption) and F(characteristic fluorescence). The x-rays from the control groups and from the experimental (HLS) groups were analyzed on well-defined parts (femur, tibia and knee) of the leg bone. The SEM analysis shows that there are definite changes in the hydroxyl or phosphate group of the main component of the bone structure, hydroxyapatite [Ca10(PO4)6(OH)2], due to hind limb suspension. In a separate experiment, entire leg bones (both from HLS and control rats) were subjected to mechanical stress by mean of a variable force. The stress vs. strain graph was fitted with linear and polynomial function, and the parameters reflecting the mechanical strength of the bone, under increasing stress, were calculated. From the slope of the linear part of the graph the Young's modulus for HLS bones were calculated and found to be 2.49 times smaller than those for control bones.

  19. Actions on gamma-motoneurones elicited by electrical stimulation of cutaneous afferent fibres in the hind limb of the cat.

    PubMed

    Johansson, H; Sojka, P

    1985-09-01

    The reflex actions elicited by graded electrical stimulation of hind-limb cutaneous (sural, superficial peroneal and tibial) nerves were investigated with intra- and extracellular micro-electrode recordings in gamma-motoneurones projecting to hind-limb muscles in twenty-four cats anaesthetized with alpha-chloralose. In total, reflex responses of 100 gamma-motoneurones were analysed. 82 of the gamma-cells were classified as dynamic (43) or static (39) using the method of mesencephalic stimulation (Appelberg, Hulliger, Johansson & Sojka, 1982). The general responsiveness (i.e. number of input nerves with effect/number of input nerves tested) of the whole sample of gamma-cells to stimulation of skin nerves was extremely high (94.8%). All negative observations were encountered among static and non-classified gamma-cells. Generally, the stimulation strengths needed for evoking effects in the gamma-cells were very low. A majority of the excitatory effects in the dynamic cells appeared with stimulation intensities below 1.5 threshold (T), while most static cells were excited with stimulation strengths between 1.5 and 2 T. Also a statistical comparison of the populations of stimulation strength thresholds for the excitatory effects revealed a significant difference (P less than 0.0009) between dynamic and static gamma-cells. By contrast, the thresholds for inhibitory effects in dynamic cells were slightly higher than for excitatory effects (P less than 0.0009). As regards excitation of static cells, inhibition of dynamic cells and inhibition of static cells, no statistically significant threshold differences were found. A strong dominance of excitation over inhibition was found in both dynamic and static flexor (posterior biceps and semitendinosus) gamma-motoneurones from all input nerves. In comparison to flexor gamma-motoneurones, there was a much higher incidence of inhibitory and mixed (excitatory and inhibitory) responses in extensor (triceps) gamma-motoneurones, from

  20. Segment and joint angles of hind limb during bipedal and quadrupedal walking of the bonobo (Pan paniscus).

    PubMed

    D'Août, Kristiaan; Aerts, Peter; De Clercq, Dirk; De Meester, Koen; Van Elsacker, Linda

    2002-09-01

    We describe segment angles (trunk, thigh, shank, and foot) and joint angles (hip, knee, and ankle) for the hind limbs of bonobos walking bipedally ("bent-hip bent-knee walking," 17 sequences) and quadrupedally (33 sequences). Data were based on video recordings (50 Hz) of nine subjects in a lateral view, walking at voluntary speed. The major differences between bipedal and quadrupedal walking are found in the trunk, thigh, and hip angles. During bipedal walking, the trunk is approximately 33-41 degrees more erect than during quadrupedal locomotion, although it is considerably more bent forward than in normal human locomotion. Moreover, during bipedal walking, the hip has a smaller range of motion (by 12 degrees ) and is more extended (by 20-35 degrees ) than during quadrupedal walking. In general, angle profiles in bonobos are much more variable than in humans. Intralimb phase relationships of subsequent joint angles show that hip-knee coordination is similar for bipedal and quadrupedal walking, and resembles the human pattern. The coordination between knee and ankle differs much more from the human pattern. Based on joint angles observed throughout stance phase and on the estimation of functional leg length, an efficient inverted pendulum mechanism is not expected in bonobos.

  1. RIP2-mediated LKB1 deletion causes axon degeneration in the spinal cord and hind-limb paralysis.

    PubMed

    Sun, Gao; Reynolds, Richard; Leclerc, Isabelle; Rutter, Guy A

    2011-03-01

    Axon degeneration is observed in neurodegenerative diseases and neuroinflammatory disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. The molecular basis of this process remains largely unknown. Here, we show that mice deleted for the tumour suppressor LKB1 (also called STK11) in the spinal cord, some parts of the brain and in the endocrine pancreas (βLKB1KO mice) develop hind-limb dysfunction and axon degeneration at about 7 weeks. Demyelination and macrophage infiltration are observed in the white matter of these mice, predominantly in the bilateral and anterior funiculi of the thoracic segment of the spinal cord, suggesting damage to the ascending sensory signalling pathway owing to LKB1 deletion in the brain. Microtubule structures were also affected in the degenerated foci, with diminished neurofilament and tubulin expression. Deletion of both PRKAA1 genes, whose products AMPKα1 and AMPKα2 are also downstream targets of LKB1, with the same strategy was without effect. We thus define LKB1 as an intrinsic suppressor of axon degeneration and a possible target for strategies that can reverse this process.

  2. Real-time control of hind limb functional electrical stimulation using feedback from dorsal root ganglia recordings

    PubMed Central

    Bruns, Tim M; Wagenaar, Joost B; Bauman, Matthew J; Gaunt, Robert A; Weber, Douglas J

    2013-01-01

    Objective Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability. PMID:23503062

  3. Real-time control of hind limb functional electrical stimulation using feedback from dorsal root ganglia recordings

    NASA Astrophysics Data System (ADS)

    Bruns, Tim M.; Wagenaar, Joost B.; Bauman, Matthew J.; Gaunt, Robert A.; Weber, Douglas J.

    2013-04-01

    Objective. Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach. We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results. Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance. This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability.

  4. Expression of nestin, desmin and vimentin in intact and regenerating muscle spindles of rat hind limb skeletal muscles.

    PubMed

    Cízková, Dana; Soukup, Tomás; Mokrý, Jaroslav

    2009-02-01

    We describe the expression and distribution patterns of nestin, desmin and vimentin in intact and regenerating muscle spindles of the rat hind limb skeletal muscles. Regeneration was induced by intramuscular isotransplantation of extensor digitorum longus (EDL) or soleus muscles from 15-day-old rats into the EDL muscle of adult female inbred Lewis rats. The host muscles with grafts were excised after 7-, 16-, 21- and 29-day survival and immunohistochemically stained. Nestin expression in intact spindles in host muscles was restricted to Schwann cells of sensory and motor nerves. In transplanted muscles, however, nestin expression was also found in regenerating "spindle fibers", 7 and 16 days after grafting. From the 21st day onwards, the regenerated spindle fibers were devoid of nestin immunoreactivity. Desmin was detected in spindle fibers at all developmental stages in regenerating as well as in intact spindles. Vimentin was expressed in cells of the outer and inner capsules of all muscle spindles and in newly formed myoblasts and myotubes of regenerating spindles 7 days after grafting. Our results show that the expression pattern of these intermediate filaments in regenerating spindle fibers corresponds to that found in regenerating extrafusal fibers, which supports our earlier suggestion that they resemble small-diameter extrafusal fibers.

  5. Implanting iodine-125 seeds into rat dorsal root ganglion for neuropathic pain: neuronal microdamage without impacting hind limb motion.

    PubMed

    Jiao, Ling; Zhang, Tengda; Wang, Huixing; Zhang, Wenyi; Fan, Saijun; Huo, Xiaodong; Zheng, Baosen; Ma, Wenting

    2014-06-15

    The use of iodine-125 ((125)I) in cancer treatment has been shown to relieve patients' pain. Considering dorsal root ganglia are critical for neural transmission between the peripheral and central nervous systems, we assumed that (125)I could be implanted into rat dorsal root ganglia to provide relief for neuropathic pain. (125)I seeds with different radioactivity (0, 14.8, 29.6 MBq) were implanted separately through L4-5 and L5-6 intervertebral foramen into the vicinity of the L5 dorsal root ganglion. von Frey hair results demonstrated the mechanical pain threshold was elevated after implanting (125)I seeds from the high radioactivity group. Transmission electron microscopy revealed that nuclear membrane shrinkage, nucleolar margination, widespread mitochondrial swelling, partial vacuolization, lysosome increase, and partial endoplasmic reticulum dilation were visible at 1,440 hours in the low radioactivity group and at 336 hours in the high radioactivity group. Abundant nuclear membrane shrinkage, partial fuzzy nuclear membrane and endoplasmic reticulum necrosis were observed at 1,440 hours in the high radioactivity group. No significant difference in combined behavioral scores was detected between preoperation and postoperation in the low and high radioactivity groups. These results suggested that the mechanical pain threshold was elevated after implanting (125)I seeds without influencing motor functions of the hind limb, although cell injury was present.

  6. Fasting increases palmitic acid incorporation into rat hind-limb intramuscular acylglycerols while short-term cold exposure has no effect.

    PubMed

    Synak, M; Zarzeczny, R; Górecka, M; Langfort, J; Kaciuba-Uściłko, H; Zernicka, Ewa

    2011-09-01

    The aim of the study was to investigate the palmitic acid incorporation into intramuscular acylglycerols in perfused hind-limb skeletal muscles of different fibre types in rats either fasted for 48 h or exposed to cold (6 °C) for 12 h. Hind-limb preparations of fasted and cold exposed rats were perfused with buffers containing tritium labelled and cold palmitic acid. Palmitic acid incorporation into intracellular lipid pools in the soleus, plantaris, red and white gastrocnemius and red and white quadriceps was measured. It was found that fasting increased approximately 2-fold palmitic acid incorporation in all muscles examined regardless of the fibre type composition of the muscle. On the other hand, exposure to cold had no effect on the palmitic acid incorporation into intramuscular acylglycerols regardless the muscle fibre type. The increased incorporation of palmitic acid into acylglycerols in fasted animals is in line with data showing that 48 h fasting stimulates the expression of plasma membrane proteins putatively facilitating fatty acid uptake. It appears that although 12 h cold exposure increases the use of fatty acids as energy substrates it does not alter the incorporation of palmitic acid into intramuscular acylglycerols in the perfused rat hind-limb.

  7. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    SciTech Connect

    Madaric, Juraj; Klepanec, Andrej; Mistrik, Martin; Altaner, Cestmir; Vulev, Ivan

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  8. Femorofemoral grafts for lower limb ischemia caused by intra-aortic balloon pump.

    PubMed

    Friedell, M L; Alpert, J; Parsonnet, V; Brief, D K; Brener, B J; Goldenkranz, R J; Nozick, J

    1987-01-01

    From January 1975 to December 1985, 1454 patients had an intra-aortic balloon inserted for cardiac assistance. Eighty balloon-dependent patients had severe limb ischemia and required a femorofemoral graft (FFG) (5% of the total group of patients). Twenty-nine of the 80 patients with grafts (or 36%) left the hospital and 28 were followed up for an average of 40 months to determine late complications associated with the crossover grafts. All grafts remained patent. The 28 patients were classified into five groups according to the degree and type of lower limb ischemia. Group I consisted of 13 asymptomatic patients (46%); group II had four (14%) patients with mild claudication caused by preexisting peripheral arteriosclerosis; group III comprised four patients (14%) without preexisting disease but claudication subsequent to the FFG; group IV had five patients with irreversible ischemic sequelae before grafting ending in amputation, foot drop, or persistent paresthesia; and group V consisted of two patients with graft infection (7%). The perioperative mortality rate of the balloon-dependent patients with an FFG (64%) reflects the gravity of the cardiac condition. Placement of an FFG to relieve limb ischemia in these patients is followed by few immediate or late complications in the survivors and any persistent limb changes were related to the prolonged ischemia present before revascularization. Our data suggest that in balloon-dependent patients with limb-threatening ischemia, aggressive use of the FFG is limb-saving, durable, and allows continuation of balloon support.

  9. Longitudinal evaluation of mouse hind limb bone loss after spinal cord injury using novel, in vivo, methodology.

    PubMed

    McManus, Madonna M; Grill, Raymond J

    2011-12-07

    Spinal cord injury (SCI) is often accompanied by osteoporosis in the sublesional regions of the pelvis and lower extremities, leading to a higher frequency of fractures. As these fractures often occur in regions that have lost normal sensory function, the patient is at a greater risk of fracture-dependent pathologies, including death. SCI-dependent loss in both bone mineral density (BMD, grams/cm2) and bone mineral content (BMC, grams) has been attributed to mechanical disuse, aberrant neuronal signaling and hormonal changes. The use of rodent models of SCI-induced osteoporosis can provide invaluable information regarding the mechanisms underlying the development of osteoporosis following SCI as well as a test environment for the generation of new therapies. Mouse models of SCI are of great interest as they permit a reductionist approach to mechanism-based assessment through the use of null and transgenic mice. While such models have provided important data, there is still a need for minimally-invasive, reliable, reproducible, and quantifiable methods in determining the extent of bone loss following SCI, particularly over time and within the same cohort of experimental animals, to improve diagnosis, treatment methods, and/or prevention of SCI-induced osteoporosis. An ideal method for measuring bone density in rodents would allow multiple, sequential (over time) exposures to low-levels of X-ray radiation. This study describes the use of a new whole-animal scanner, the IVIS Lumina XR (Caliper Instruments) that can be used to provide low-energy (1-3 milligray (mGy)) high-resolution, high-magnification X-ray images of mouse hind limb bones over time following SCI. Significant bone density loss was seen in the tibiae of mice by 10 days post-spinal transection when compared to uninjured, age-matched control (naïve) mice (13% decrease, p < 0.0005). Loss of bone density in the distal femur was also detectable by day 10 post-SCI, while a loss of density in the proximal

  10. Scaling factor relating conduction velocity and diameter for myelinated afferent nerve fibres in the cat hind limb.

    PubMed Central

    Boyd, I A; Kalu, K U

    1979-01-01

    1. Compound action potentials were recorded from certain muscle and cutaneous nerves in normal and chronically de-efferentated hind limbs of cats during stimulation of the appropriate dorsal spinal roots, 2. The peaks for groups I, II and III in the compound action potential were correlated with the corresponding peaks in the fibre-diameter histograms of the same de-efferentated nerve after processing it for light microscopy. 3. The scaling factor (ratio of conduction velocity in m/sec to total diameter in micrometer) was not constant for all sizes of fibre nor did it increase progressively with fibre size. Evidence is presented that a logarithmic relation between conduction velocity and fibre diameter is not appropriate. 4. In muscle nerves the scaling factor for fibres fixed by glutaraldehyde perfusion and embedded in Epon was 5.7 for group I afferent fibres and 4.6 for myelinated fibres in both group II and group III. 5. In cutaneous nerves the scaling factor was 5.6 for large fibres (group I or Abeta) and 4.6 for small fibres (group III or Adelta). 6. The scaling factor for group I fibres is the same as was found previously for alpha-efferent fibres, and that for groups II and III is the same as for gamma-efferent fibres (Boyd & Davey, 1968). 7. The possibility that there is a clear discontinuity in scaling factor between fibres in groups I and alpha, and those in other functional groups, is discussed. 8. It is concluded that there must be some structural feature of alpha and group I fibres which differs from that of smaller myelinated fibres. It is likely that a difference in the relative thickness of the myelin sheath is involved and possibly also in the conductances responsible for generating the action potential. Images Plate 1 PMID:458657

  11. Prognosis of critical limb ischemia: Major vs. minor amputation comparison.

    PubMed

    Matsuzaki, Kyoichi; Hayashi, Ruka; Okabe, Keisuke; Aramaki-Hattori, Noriko; Kishi, Kazuo

    2015-09-01

    Healthcare providers treating wounds have difficulties assessing the prognosis of patients with critical limb ischemia who had been discharged after complete healing of major amputation wounds. The word "major" in "major amputation" gives the impression of "being more severe" than "minor amputation." Therefore, even if wounds are healed after major amputation, they imagine that prognosis after major amputation would be poorer than that after minor amputation. We investigated the prognosis of diabetic nephropathy patients 2 years after amputations. Those patients underwent dialysis as well as amputation following percutaneous transluminal angioplasty for their foot wounds. They were ambulatory prior to these surgeries. Among 56 cases of minor amputation, 45 were males and 11 were females, and mortality was 41.1%. The mortality of cases with and without a coronary intervention history was 53.1% and 25.0%, respectively (p = 0.034). Among 10 cases of major amputation, 9 were males and 1 was female, and mortality was 60%. The mortality of cases with and without a coronary intervention history was 75.0% and 0%, respectively. Although we predicted poor prognosis in cases with major amputation, there was no significant difference in mortality 2 years after amputations (p = 0.267). Thus far poor prognosis has been reported for major amputation. It might be due to inclusion of the following patients: patients with wounds proximal to ankle joints, patients with extensive gangrene spreading to the lower legs, patients with septicemia from wound infection and who died around the time of operation, and patients with malnutrition. The results of our present study showed that the outcomes at 2 years postoperatively were similar between patients with major amputations and those with minor amputations, if surgical wounds were able to heal. We should not estimate the prognosis by the level of amputation, rather we should consider the effect of coronary intervention history on

  12. A flexible electrode array for muscle impedance measurements in the mouse hind limb: A tool to speed research in neuromuscular disease

    NASA Astrophysics Data System (ADS)

    Li, J.; Rutkove, S. B.

    2013-04-01

    Electrical impedance myography (EIM) is a bioelectrical impedance technique focused on the assessment of neuromuscular diseases using tetrapolar surface arrays. Recently, we have shown that reproducible and sensitive EIM measurements can be made on the gastrocnemius muscle of the mouse hind limb and that these are sensitive to disease alterations. A dedicated array would help speed data acquisition and provide additional sensitivity to disease-induced alterations. A flexible electrode array was developed with electrode sizes of 1mm × 1mm by Parlex, Inc. Tetrapolar electrode sets were arranged both parallel to (longitudinal) and orthogonally to (transverse) the major muscle fiber direction of the gastrocnemius muscle. Measurements were made with a dedicated EIM system. A total of 11 healthy animals and 7 animals with spinal muscular atrophy (a form of motor neuron disease) were evaluated after the fur was completely removed with a depilatory agent from the hind limb. Standard electrophysiologic testing (compound motor action potential amplitude and motor unit number estimation) was also performed. The flexible electrode array demonstrated high repeatability in both the longitudinal and transverse directions in the healthy and diseased animals (with intraclass correlation coefficients of 0.94 and 0.89, respectively, for phase angle measured transversely). In addition, differences between healthy and diseased animals were identifiable. For example, the 50 kHz transverse phase angle was higher in the healthy as compared to the SMA animals (16.8° ± 0.5 vs. 14.3° ± 0.7, respectively) at 21 weeks of age (p = 0.01). Differences in anisotropy were also identifiable. Correlations to several standard neurophysiologic parameters also appeared promising. This novel flexible tetrapolar electrode array can be used on the mouse hind limb and provides multidirectional data that can be used to assess muscle health. This technique has the potential of finding widespread use in

  13. Type B Dissection Resulting in Acute Limb Ischemia in a Patient With a History of EVAR.

    PubMed

    Jayakumar, Lalithapriya; Lombardi, Joseph V; Caputo, Francis J

    2017-02-01

    Type B aortic dissection (TBAD) can be complicated due to visceral and limb malperfusion. We present the case of a patient with a TBAD 5 months after endovascular aneurysm repair (EVAR) for an infrarenal aortic aneurysm, which resulted in a right leg acute limb ischemia due to impingement of the EVAR from to the dissection. In the following discussion, we will review the literature and describe our technique for the treatment of this infrequent problem.

  14. Epidural electrical stimulation in severe limb ischemia. Pain relief, increased blood flow, and a possible limb-saving effect.

    PubMed Central

    Augustinsson, L E; Carlsson, C A; Holm, J; Jivegård, L

    1985-01-01

    Peripheral vascular disease of the extremities causes ischemic pain and, at times, skin ulcerations and gangrene. It has been suggested that epidural spinal electrical stimulation (ESES) could improve peripheral circulation. Since 1978 we have used ESES in 34 patients with severe limb ischemia; all had resting pain and most had ischemic ulcers. Arterial surgery was technically impossible. Twenty-six patients had arteriosclerotic disease, one had Buerger's disease, and seven had severe vasospastic disorders. Ninety-four per cent of the patients experienced pain relief. ESES healed ulcers in 50% of those with preoperative nonhealing skin ulcerations. Seventy per cent of the patients showed improved skin temperature recordings. Only 38% of the stimulated arteriosclerotic patients underwent amputations during a mean followup period of 16 months, as compared to 90% of a comparable group of unstimulated patients. ESES is very promising in severe limb ischemia where reconstructive surgery is impossible or has failed. PMID:3874610

  15. Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

    NASA Astrophysics Data System (ADS)

    Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

    2014-03-01

    Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

  16. Transient Hemi-Lower Limb Ischemia in the Newborn: Arterial Thrombosis or Persistent Sciatic Artery?

    PubMed Central

    Kirino, Makiko; Ochiai, Masayuki; Ichiyama, Masako; Inoue, Hirosuke; Kusuda, Takeshi; Kinjo, Tadamune; Ishimura, Masataka; Ohga, Shouichi

    2017-01-01

    Neonatal thromboembolism occurs with various predispositions and triggers. Early diagnosis of the thrombosis is challenging and essential for the therapeutic interventions. We herein report two newborns who presented with transient hemi-lower limb ischemia due to (1) arterial thrombosis or (2) a persistent sciatic artery (PSA). The patient with arterial thrombosis showed elevations of fibrin degradation product and D-dimer and received antithrombin and heparin intravenously. The patient with PSA was immediately assessed by a contrast-enhanced computed tomography because of a transient ischemic episode with no evidence of hypercoagulability. Newborns suspected of having arterial thrombosis may need urgent surgical intervention along with thrombolytic and anticoagulant therapy to prevent organ ischemia and amputation of extremities. Conversely, some PSA cases have reportedly been treated conservatively. This vascular anomaly was previously reported as a cause of lower limb ischemia only in a newborn. PSA is a critical differential diagnosis of neonatal arterial thrombosis that needs urgent therapeutic intervention. PMID:28228977

  17. Endovascular therapy as the primary approach for limb salvage in patients with critical limb ischemia: experience with 443 infrapopliteal procedures.

    PubMed

    Bosiers, Marc; Hart, Joseph P; Deloose, Koen; Verbist, Jurgen; Peeters, Patrick

    2006-01-01

    Endovascular strategies for the treatment of critical infrageniculate peripheral arterial occlusive disease exist and are becoming the primary methodology for such lesions at many centers. Although technically feasible for experienced operators, the evidence to support this strategy for below the knee (BTK) interventions is still evolving. We studied the 6-month and 1-year outcomes of percutaneous transluminal angioplasty (PTA) alone, PTA with stenting, and excimer laser recanalization for BTK lesions in patients with critical limb ischemia. Between September 2002 and June 2005, 443 patients (355 Rutherford category 4, 82 category 5, 6 category 6) underwent intervention for 681 BTK lesions. Follow-up was performed at 6-month intervals after index intervention: limb salvage data were recorded and duplex ultrasonography was performed to measure the patency of treated areas. The primary patency and limb salvage rates of the entire population were 85.2% and 97.0% and 74.2% and 96.6% at 6 months and 1 year, respectively. Stratified for the treatment strategy (PTA alone in 79, PTA with stenting in 300 patients, and excimer laser in 64), 1-year primary patency rates were 68.6%, 75.5%, and 75.4%, whereas the limb salvage rates were 96.7%, 98.6%, and 87.9% for each modality, respectively. Endovascular intervention will become the primary treatment for BTK lesions in patients with critical limb ischemia, with 1-year primary patency and limb salvage rates that compare favorably with published surgical data. Prospective, randomized, multicenter trials will be needed to further establish the role of endovascular intervention in this challenging patient group.

  18. Inhalation anesthesia of rats: influence of the fraction of inspired oxygen on limb ischemia/reperfusion injury.

    PubMed

    Zhang, S; Duehrkop, C; Plock, J A; Rieben, R

    2016-06-01

    Inhalation anesthesia with isoflurane is a well-established and safe method used in small laboratory animals. In most cases oxygen is used as a carrier gas for isoflurane, but room air or mixtures of oxygen with air or nitrous oxide are also being used. Anesthesia is therefore administered using different fractions of inspired oxygen (FiO2), and this may have consequences for the outcome of experiments. The aim of the present study was to investigate the influence of FiO2 on rat hind limb ischemia/reperfusion injury and to refine the used inhalation anesthesia. Male Wistar rats were subjected to 3.5 h of ischemia and 2 h of reperfusion, and divided into three groups according to FiO2 in the O2/air/isoflurane anesthesia gas mixture: 40%, 60%, and 100% O2 Normal, healthy rats were used as controls. Muscle edema and creatine kinase MM, a marker for myocyte necrosis, were significantly increased with 40% FiO2 as compared with 100% FiO2 (P < 0.05). Partial pressure of oxygen, oxygen saturation, and oxyhemoglobin were significantly higher in the 100% O2 group as compared with 40% O2 No significant differences were detected for other parameters, such as the oxidative stress markers malondialdehyde and superoxide dismutase. We conclude that a refined inhalation anesthesia setting using 40% FiO2, reflecting more or less the clinical situation, leads to a more severe and more physiologically relevant reperfusion injury than higher FiO2. Oxidative stress did not correlate with FiO2 and seemed to have no influence on reperfusion injury.

  19. The Effects of Inclination (Up and Down) of the Treadmill on the Electromyogram Activities of the Forelimb and Hind limb Muscles at a Walk and a Trot in Thoroughbred Horses

    PubMed Central

    TAKAHASHI, Toshiyuki; MATSUI, Akira; MUKAI, Kazutaka; OHMURA, Hajime; HIRAGA, Atsushi; AIDA, Hiroko

    2014-01-01

    ABSTRACT It is important to know the effects of the inclination of a slope on the activity of each muscle, because training by running on a sloped track is commonly used for Thoroughbred racehorses. The effects of incline (from −6 to +6%) on the forelimbs and hind limbs during walking and trotting on a treadmill were evaluated by an integrated electromyogram (iEMG). The muscle activities in the forelimbs (5 horses) and hind limbs (4 horses) were measured separately. Two stainless steel wires were inserted into each of the brachiocephalicus (Bc), biceps brachii (BB), splenius (Sp), and pectoralis descendens (PD) in the forelimb experiment and into the longissimus dorsi (LD), vastus lateralis (VL), gluteus medius (GM), and biceps femoris (BF) in the hind limb experiment. The EMG recordings were taken at a sampling rate of 1,000 Hz. At a walk, the iEMG values for the forelimb were not significantly different under any of the inclinations. In the hind limb, the iEMG values for the GM and BF significantly decreased as the inclination decreased. At a trot, the iEMG values for the Bc in the forelimb significantly decreased as the inclination of the treadmill decreased. In the hind limb, the iEMG values for the LD, GM, and BF significantly decreased as the inclination decreased. Uphill exercise increased the iEMG values for the Bc, LD, GM, and BF, while downhill exercise resulted in little increase in the iEMG values. It was concluded that the effects of inclination on the muscle activities were larger for the uphill exercises, and for the hind limb muscles compared with the forelimb muscles. PMID:25558180

  20. The Effects of Inclination (Up and Down) of the Treadmill on the Electromyogram Activities of the Forelimb and Hind limb Muscles at a Walk and a Trot in Thoroughbred Horses.

    PubMed

    Takahashi, Toshiyuki; Matsui, Akira; Mukai, Kazutaka; Ohmura, Hajime; Hiraga, Atsushi; Aida, Hiroko

    2014-01-01

    It is important to know the effects of the inclination of a slope on the activity of each muscle, because training by running on a sloped track is commonly used for Thoroughbred racehorses. The effects of incline (from -6 to +6%) on the forelimbs and hind limbs during walking and trotting on a treadmill were evaluated by an integrated electromyogram (iEMG). The muscle activities in the forelimbs (5 horses) and hind limbs (4 horses) were measured separately. Two stainless steel wires were inserted into each of the brachiocephalicus (Bc), biceps brachii (BB), splenius (Sp), and pectoralis descendens (PD) in the forelimb experiment and into the longissimus dorsi (LD), vastus lateralis (VL), gluteus medius (GM), and biceps femoris (BF) in the hind limb experiment. The EMG recordings were taken at a sampling rate of 1,000 Hz. At a walk, the iEMG values for the forelimb were not significantly different under any of the inclinations. In the hind limb, the iEMG values for the GM and BF significantly decreased as the inclination decreased. At a trot, the iEMG values for the Bc in the forelimb significantly decreased as the inclination of the treadmill decreased. In the hind limb, the iEMG values for the LD, GM, and BF significantly decreased as the inclination decreased. Uphill exercise increased the iEMG values for the Bc, LD, GM, and BF, while downhill exercise resulted in little increase in the iEMG values. It was concluded that the effects of inclination on the muscle activities were larger for the uphill exercises, and for the hind limb muscles compared with the forelimb muscles.

  1. Surgical treatment of lower limb ischemia in diabetic patients – long-term results

    PubMed Central

    Inan, Bekir; Ugurlucan, Murat; Aydin, Cemalettin; Teker, Melike Elif

    2013-01-01

    Introduction Lower limb ischemia may cause nonhealing ulcers, infection, amputation and even mortality in diabetic patients. In this study, we review our data of ischemic lower limb revascularization procedures in diabetic patients and present the early, mid- and long-term results. Material and methods From March 2004 to September 2008, 83 patients with lower limb ischemia in Fontaine class III and IV underwent distal arterial bypass procedures. Saphenous vein grafts were used for below-knee arterial bypasses in all patients. In 16 (19%) patients femoropopliteal bypasses were performed with PTFE grafts. Short-term and long-term surgical results were evaluated. Results Ulcer recovery was determined in 36% of patients. Graft patency was 95% and 1 death (1%) occurred in short-term follow-up. In long-term follow-up the total effectiveness rate was 74%. Graft patency was 79% and 6 deaths (7%) occurred during the follow-up. Conclusions Lower limb ischemia is a serious event in patients with diabetes mellitus. The consequences may include increased mortality and morbidity in this particular patient population. However, distal arterial revascularizations are considerably effective procedures to avoid amputation, to eliminate symptoms, to promote ulcer recovery and to help the patient participate in social life with acceptable short, mid- and long-term follow-up results. PMID:24482653

  2. Prediction of Limb Salvage after Therapeutic Angiogenesis by Autologous Bone Marrow Cell Implantation in Patients with Critical Limb Ischemia

    PubMed Central

    Tara, Shuhei; Miyamoto, Masaaki; Takagi, Gen; Fukushima, Yoshimitsu; Kirinoki-ichikawa, Sonoko; Takano, Hitoshi; Takagi, Ikuyo; Mizuno, Hiroshi; Yasutake, Masahiro; Kumita, Shinichiro; Mizuno, Kyoichi

    2011-01-01

    Purpose: Despite advances in therapeutic angiogenesis by bone marrow cell implantation (BMCI), limb amputation remains a major unfavorable outcome in patients with critical limb ischemia (CLI). We sought to identify predictor(s) of limb salvage in CLI patients who received BMCI. Materials and Methods: Nineteen patients with CLI who treated by BMCI were divided into two groups; four patients with above-the-ankle amputation by 12 weeks after BMCI (amputation group) and the remaining 15 patients without (salvage group). We performed several blood-flow examinations before BMCI. Ankle-brachial index (ABI) was measured with the standard method. Transcutaneous oxygen tension (TcPO2) was measured at the dorsum of the foot, in the absence (baseline) and presence (maximum TcPO2) of oxygen inhalation. 99mtechnetium-tetrofosmin (99mTc-TF) perfusion index was determined at the foot and lower leg as the ratio of brain. Results: Maximum TcPO2 (p = 0.031) and 99mTc-TF perfusion index in the foot (p = 0.0068) was significantly higher in the salvage group than in the amputation group. Receiver operating characteristic (ROC) curve analysis identified maximum TcPO2 and 99mTc-TF perfusion index in the foot as having high predictive accuracy for limb salvage. Conclusion: Maximum TcPO2 and 99mTc-TF perfusion index in the foot are promising predictors of limb salvage after BMCI in CLI. PMID:23555423

  3. The significance of regional hemoglobin oxygen saturation values and limb-to-arm ratios of near-infrared spectroscopy to detect critical limb ischemia.

    PubMed

    Boezeman, Reinout Pe; Boersma, Doeke; Wille, Jan; Kelder, Johannes C; Visscher, Mareije I; Waanders, Frans Gj; Moll, Frans L; de Vries, Jean-Paul Pm

    2016-10-01

    This study examines the application of near-infrared spectroscopy to noninvasively detect critical limb ischemia using regional hemoglobin oxygen saturation in percentage values and regional hemoglobin oxygen saturation limb-to-arm ratios. The regional hemoglobin oxygen saturation values and regional hemoglobin oxygen saturation limb-to-arm ratios were calculated in 61 patients with critical limb ischemia (group A). Measurements were performed in rest at four fixed spots at the most affected lower limb and at a reference spot at both upper arms. Similar measurements were performed in the left lower limb of 30 age-matched control patients without peripheral arterial disease (group B). The regional hemoglobin oxygen saturation values and regional hemoglobin oxygen saturation limb-to-arm ratios were significantly different at all measured spots between the groups (all p < 0.001), except for the regional hemoglobin oxygen saturation limb-to-arm ratios of the distal vastus lateralis (p = 0.056). However, a broad overlap of individual regional hemoglobin oxygen saturation values and regional hemoglobin oxygen saturation limb-to-arm ratios was found in both groups, which resulted in poor discriminative predictive value of single measurements. Single measurements of regional hemoglobin oxygen saturation values and regional hemoglobin oxygen saturation limb-to-arm ratios at all measured spots have poor discriminative predictive value in detection of critical limb ischemia. Measurement of regional hemoglobin oxygen saturation values and regional hemoglobin oxygen saturation limb-to-arm ratios at any of the measurement spots has no added value in detecting lower limb ischemia in individuals compared with current diagnostic modalities.

  4. Connexions from large, ipsilateral hind limb muscle and skin afferents to the rostral main cuneate nucleus and to the nucleus X region in the cat.

    PubMed Central

    Johansson, H; Silfvenius, H

    1977-01-01

    1. Evidence is presented for an input from ipsilateral hind limb group I muscle afferents and low threshold cutaneous afferents, to cells in the rostral division of the main cuneate nucleus (rMCN) and in the region of the descending vestibular nucleus and the nucleus X of Brodal & Pompeiano (1957a), the (DV-X). 2. Thirteen group I-rMCN cells were recorded from. The functional properties of these cells were similar to those of nueleus Z (Landgren & Silfvenius, 1971; Johansson & Silfvenius, 1977a, b). The cells were monosynaptically linked to spinal dorsolateral fascicle (DLF) fibres. Nine cells projected to the contralateral thalamus, i.e. a second group I hind limb bulbothalamic tract is described. Ten cells were synaptically activated from the ipsilateral cerebellum from the anterior projection zone of the dorsal spinocerebellar tract (DSCT). Axon-collateral activation by DSCT fibres was established for two of these cells. They were both bulbothalamic relay cells. For the remaining eight cells, activated from the cerebellum, this was not proven. These cells could, however, either be linked to DSCT fibres or to short axon-collaterals of a cell body of unknown location. A projection from the rMCN to the cerebellum is described and agrees with recent anatomical findings. Two cells were not excited from the cerebellum. 3. Four rMCN cells were activated by cutaneous afferents with their secondary axons in the DLF. Suggestive evidence for a bulbothalamic cutaneous hind limb path via the rMCN is presented. Two cells were activated from the cerebellum, presumably via axon-collaterals of nonsegmental cells. 4. Eight group I-DV-X cells were recorded from. They were monosynaptically linked to spinal DLF fibres and resembled functionally the nucleus Z and rMCN cells when stimulated from the periphery. Two cells projected to the contralateral thalamus, and two others were synaptically excited. Seven cells were activated from the ipsilateral cerebellum. Two of them projected to

  5. Using multimodal imaging techniques to monitor limb ischemia: a rapid noninvasive method for assessing extremity wounds

    NASA Astrophysics Data System (ADS)

    Luthra, Rajiv; Caruso, Joseph D.; Radowsky, Jason S.; Rodriguez, Maricela; Forsberg, Jonathan; Elster, Eric A.; Crane, Nicole J.

    2013-03-01

    Over 70% of military casualties resulting from the current conflicts sustain major extremity injuries. Of these the majority are caused by blasts from improvised explosive devices. The resulting injuries include traumatic amputations, open fractures, crush injuries, and acute vascular disruption. Critical tissue ischemia—the point at which ischemic tissues lose the capacity to recover—is therefore a major concern, as lack of blood flow to tissues rapidly leads to tissue deoxygenation and necrosis. If left undetected or unaddressed, a potentially salvageable limb may require more extensive debridement or, more commonly, amputation. Predicting wound outcome during the initial management of blast wounds remains a significant challenge, as wounds continue to "evolve" during the debridement process and our ability to assess wound viability remains subjectively based. Better means of identifying critical ischemia are needed. We developed a swine limb ischemia model in which two imaging modalities were combined to produce an objective and quantitative assessment of wound perfusion and tissue viability. By using 3 Charge-Coupled Device (3CCD) and Infrared (IR) cameras, both surface tissue oxygenation as well as overall limb perfusion could be depicted. We observed a change in mean 3CCD and IR values at peak ischemia and during reperfusion correlate well with clinically observed indicators for limb function and vitality. After correcting for baseline mean R-B values, the 3CCD values correlate with surface tissue oxygenation and the IR values with changes in perfusion. This study aims to not only increase fundamental understanding of the processes involved with limb ischemia and reperfusion, but also to develop tools to monitor overall limb perfusion and tissue oxygenation in a clinical setting. A rapid and objective diagnostic for extent of ischemic damage and overall limb viability could provide surgeons with a more accurate indication of tissue viability. This may

  6. Comparative Anatomy of the Hind Limb Vessels of the Bearded Capuchins (Sapajus libidinosus) with Apes, Baboons, and Cebus capucinus: With Comments on the Vessels' Role in Bipedalism

    PubMed Central

    Aversi-Ferreira, Roqueline A. G. M. F.; de Abreu, Tainá; Pfrimer, Gabriel A.; Silva, Sylla F.; Ziermann, Janine M.; Carneiro-e-Silva, Frederico O.; Tomaz, Carlos; Tavares, Maria Clotilde H.; Maior, Rafael S.; Aversi-Ferreira, Tales A.

    2013-01-01

    Capuchin monkeys are known to exhibit sporadic bipedalism while performing specific tasks, such as cracking nuts. The bipedal posture and locomotion cause an increase in the metabolic cost and therefore increased blood supply to lower limbs is necessary. Here, we present a detailed anatomical description of the capuchin arteries and veins of the pelvic limb of Sapajus libidinosus in comparison with other primates. The arterial pattern of the bearded capuchin hind limb is more similar to other quadrupedal Cebus species. Similarities were also found to the pattern observed in the quadruped Papio, which is probably due to a comparable pelvis and the presence of the tail. Sapajus' traits show fewer similarities when compared to great apes and modern humans. Moreover, the bearded capuchin showed unique patterns for the femoral and the short saphenous veins. Although this species switches easily from quadrupedal to bipedal postures, our results indicate that the bearded capuchin has no specific or differential features that support extended bipedal posture and locomotion. Thus, the explanation for the behavioral differences found among capuchin genera probably includes other aspects of their physiology. PMID:24396829

  7. Impact of angiogenic therapy in the treatment of critical lower limb ischemia in an animal model.

    PubMed

    Reis, Paulo Eduardo Ocke; de Carvalho, Leonardo Pinto; Yasumura, Eduardo; da Silva, Flavia Helena; Garcia, Bianca Cristina; Beutel, Abram; Sacramento, Chester Bittencourt; Baptista-Silva, José Carlos Costa; de Campos, Ruy Ribeiro; Takiya, Christina Maeda; Borojevic, Radovan; Han, Sang Won

    2014-04-01

    Angiogenic therapies for critical limb ischemia were tested in a mouse model. The mice were anesthetized and their femoral arteries were ligated. The animals were treated with bone marrow mononuclear cells (BMMCs) alone, BMMCs combined with plasmid vector encoding granulocyte macrophage colony-stimulating factor (GM-CSF), received no treatment, or no intervention (controls). The degree of ischemia was monitored for 4 weeks using a visual scale. Muscle atrophy and strength were assessed at 4 weeks postoperatively; the mice were then killed. In treated animals, total necrosis of the limb was not found, the weight of the gastrocnemius and quadriceps muscles was significantly higher, functional ability and tissue regeneration were significantly increased, and muscle impairment and adipocyte presence were significantly reduced compared with untreated animals. At inducing angiogenesis, the BMMCs alone was more effective than BMMCs combined with plasmid vector encoding GM-CSF. Treated animals showed increased angiogenesis compared with ischemic untreated ones.

  8. The analysis of limbs acute ischemia during seasons on the territory of South Serbia.

    PubMed

    Damnjanović, Zoran; Jovanović, Milan; Janković, Irena; Cvetanović, Vladan; Smiljković, Igor; Janković, Dimitrije

    2013-02-01

    The aim of this study was to examine the seasons variations in incidence of limbs acute ischemia (LAI) as well as the connection between seasons with location of LAI, old age and gender. During the three year period between January 2009 and December 2011, at the Clinic for Vascular Surgery, Clinical Center of Nis, Serbia, 167 patients were hospitalized diagnosed with limbs acute ischemia. There was no statistically significant difference in patients distribution with LAI compared with seasons (p=0.726) and months of the year (p=0.0741). There was no statistically significant difference in patients age (p=0.066), sex (p=0.923) and LAI localization (p=0.219 ) in different seasons. The absence of seasonal and monthly patterns for the AIE creation as well as its localization is followed by the absence of a connection between the age and the sex..

  9. Development of a twenty-one-component finite element distal hind limb model: stress and strain in bovine digit structures as a result of loading on different floorings.

    PubMed

    Hinterhofer, C; Haider, H; Apprich, V; Ferguson, J C; Collins, S N; Stanek, C

    2009-03-01

    Finite element modeling is a unique way of introducing technical and material research into medical science. A bovine distal hind limb was scanned using computed tomography for geometric image capture and the data were subsequently divided (segmented) into 4 tissue types: bone, bone marrow, soft tissue, and the horn capsule. Material data from previous studies were integrated into the model. Flexor tendons were assembled as longitudinal structures starting at their cross-sectional areas at the height of the metatarsophalangeal joint, proceeding in the plantaro-distal direction and meeting the distal phalanx at the tuberculum flexorium. Three different flooring situations (full support floor, bearing weight in the abaxial half of the lateral claw and in the dorsal halves of both claws, respectively) were created to evaluate the effects of loading. Full support resulted in von Mises stress levels between 3.5 and 1.5 MPa for the osseous structures and some regions of the segmented soft tissue; stress patterns in the bulb and sole of the claw capsule (1.5 MPa) and in the floor (0.5 MPa) were similar to pressure plate data in vivo and in vitro, with corresponding strain values of 2.4%. Reduced support resulted in higher stresses (up to approximately 8 MPa) in bones, claw capsules, and tendons; high strains ( approximately 11%) were found in the soft tissue, depending on how the floor was constructed. Although the models may still be anatomically improved, stress and strain calculations are possible with results comparable to related research, and the model shows interaction between the 2 digits. This possibly will help with further understanding of the biomechanical function of this 2-digit structure. With respect to clinical interpretation, reduced support to the bovine hind limb increases focal stress peaks in the different tissues, which may indicate a location of potential injury.

  10. New aspects of delirium in elderly patients with critical limb ischemia

    PubMed Central

    van Eijsden, Willem A; Raats, Jelle W; Mulder, Paul GH; van der Laan, Lijckle

    2015-01-01

    Objective The primary objective was to identify possible risk factors for delirium in patients with critical limb ischemia undergoing surgery. The secondary objective was to study the effect of delirium on complications, the length of hospital stay, health care costs, and mortality. Methods All patients 65 years or older with critical limb ischemia undergoing surgery from February 2013 to July 2014 at Amphia Hospital, were included and followed up until December 31, 2014. Delirium was scored using the Delirium Observation Screening Scale (DOSS). Perioperative risk factors (age, comorbidity, factors of frailty, operation type, hemoglobulin, and transfusion) were collected and analyzed using logistic regression. Secondary outcomes were the number of complications, total hospital stay, extra health care costs per delirium, and mortality within 3 months and 6 months of surgery. Results We included 92 patients with critical limb ischemia undergoing surgery. Twenty-nine (32%) patients developed a delirium during admission, of whom 17 (59%) developed delirium preoperatively. After multivariable analysis, only diabetes mellitus (odds ratio [OR] =6.23; 95% confidence interval [CI]: 1.11–52.2; P=0.035) and Short Nutritional Assessment Questionnaire for Residential Care (SNAQ-RC) ≥3 (OR =5.55; 95% CI: 1.07–42.0; P=0.039) was significantly associated with the onset of delirium. Delirium was associated with longer hospital stay (P=0.001), increased health care costs, and higher mortality after 6 months (P<0.001). Conclusion Delirium is a common adverse event in patients with critical limb ischemia undergoing surgery with devastating outcome in the long term. Most patients developed delirium preoperatively, which indicates the need for early recognition and preventive strategies in the preoperative period. This study identified undernourishment and diabetes mellitus as independent risk factors for delirium. PMID:26451094

  11. The pros and cons of endovascular and open surgical treatments for patients with acute limb ischemia.

    PubMed

    Branco, B C; Montero-Baker, M F; Mills, J L

    2015-06-01

    The present review addresses the pros and cons of the current, wide variety of therapeutic options available for the treatment of acute limb ischemia (ALI). Despite five prospective randomized controlled trials comparing catheter directed thrombolysis and open surgical revascularization, no single treatment strategy can yet be considered optimal for patients with ALI. This report includes 20 years of published data to evaluate the efficacy and safety profile of thrombolytic agents and adjunctive endovascular techniques when compared to open surgical revascularization.

  12. Proteomic analysis of fibroblastema formation in regenerating hind limbs of Xenopus laevis froglets and comparison to axolotl

    PubMed Central

    2014-01-01

    Background To gain insight into what differences might restrict the capacity for limb regeneration in Xenopus froglets, we used High Performance Liquid Chromatography (HPLC)/double mass spectrometry to characterize protein expression during fibroblastema formation in the amputated froglet hindlimb, and compared the results to those obtained previously for blastema formation in the axolotl limb. Results Comparison of the Xenopus fibroblastema and axolotl blastema revealed several similarities and significant differences in proteomic profiles. The most significant similarity was the strong parallel down regulation of muscle proteins and enzymes involved in carbohydrate metabolism. Regenerating Xenopus limbs differed significantly from axolotl regenerating limbs in several ways: deficiency in the inositol phosphate/diacylglycerol signaling pathway, down regulation of Wnt signaling, up regulation of extracellular matrix (ECM) proteins and proteins involved in chondrocyte differentiation, lack of expression of a key cell cycle protein, ecotropic viral integration site 5 (EVI5), that blocks mitosis in the axolotl, and the expression of several patterning proteins not seen in the axolotl that may dorsalize the fibroblastema. Conclusions We have characterized global protein expression during fibroblastema formation after amputation of the Xenopus froglet hindlimb and identified several differences that lead to signaling deficiency, failure to retard mitosis, premature chondrocyte differentiation, and failure of dorsoventral axial asymmetry. These differences point to possible interventions to improve blastema formation and pattern formation in the froglet limb. PMID:25063185

  13. Effect of prolonged ischaemic time on muscular atrophy and regenerating nerve fibres in transplantation of the rat hind limb.

    PubMed

    Tsuji, Naoko; Yamashita, Shuji; Sugawara, Yasushi; Kobayashi, Eiji

    2012-09-01

    Our aim was to test the influence of cold ischaemia on replanted limbs, focusing on muscular atrophy and neurological recovery. Inbred wild-type and green fluorescent protein (GFP) transgenic (Tg) Lewis rats aged 8-10 weeks were used. The amputated limbs were transplanted at several cold ischaemic times (0, 1, 8, 12, 24, 48, and 72 hours). An arterial ischaemic model and a denervation model were used as controls. To study nerve regeneration, a GFP limb was transplanted on to the syngenic wild Lewis rat. These animals were evaluated histologically, electrophysiologically, and immunohistochemically. The longer the ischaemic time, the more evident was atrophy of the muscles. Electrophysiological investigation showed that the latency at 3 weeks was longer in the transplantation models than in the normal controls, particularly in the longer ischaemia group. Larger numbers of migrating Schwann cells were seen in the group with no delay than in the group that had been preserved for 12 hours. Ischaemia after amputation of a limb causes muscle cells to necrose and atrophy, and these changes worsen in proportion to the ischaemic preservation time. A delay in nerve regeneration and incomplete paralysis caused by malregeneration also affect muscular atrophy.

  14. Caffeine Mitigates Lung Inflammation Induced by Ischemia-Reperfusion of Lower Limbs in Rats

    PubMed Central

    Chou, Wei-Chi; Kao, Ming-Chang; Yue, Chung-Tai; Tsai, Pei-Shan; Huang, Chun-Jen

    2015-01-01

    Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR) of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group), sham-operation (Sham), or sham plus caffeine (n = 12 in each group). To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection) was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P < 0.001 and P = 0.008, resp.). Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2) and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (all P < 0.05). These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs. PMID:26648663

  15. Caffeine Mitigates Lung Inflammation Induced by Ischemia-Reperfusion of Lower Limbs in Rats.

    PubMed

    Chou, Wei-Chi; Kao, Ming-Chang; Yue, Chung-Tai; Tsai, Pei-Shan; Huang, Chun-Jen

    2015-01-01

    Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR) of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group), sham-operation (Sham), or sham plus caffeine (n = 12 in each group). To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection) was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P < 0.001 and P = 0.008, resp.). Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2) and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (all P < 0.05). These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs.

  16. Update and validation of the Society for Vascular Surgery wound, ischemia, and foot infection threatened limb classification system.

    PubMed

    Mills, Joseph L

    2014-03-01

    The diagnosis of critical limb ischemia, first defined in 1982, was intended to delineate a patient cohort with a threatened limb and at risk for amputation due to severe peripheral arterial disease. The influence of diabetes and its associated neuropathy on the pathogenesis-threatened limb was an excluded comorbidity, despite its known contribution to amputation risk. The Fontaine and Rutherford classifications of limb ischemia severity have also been used to predict amputation risk and the likelihood of tissue healing. The dramatic increase in the prevalence of diabetes mellitus and the expanding techniques of arterial revascularization has prompted modification of peripheral arterial disease classification schemes to improve outcomes analysis for patients with threatened limbs. The diabetic patient with foot ulceration and infection is at risk for limb loss, with abnormal arterial perfusion as only one determinant of outcome. The wound extent and severity of infection also impact the likelihood of limb loss. To better predict amputation risk, the Society for Vascular Surgery Lower Extremity Guidelines Committee developed a classification of the threatened lower extremity that reflects these important clinical considerations. Risk stratification is based on three major factors that impact amputation risk and clinical management: wound, ischemia, and foot infection. This classification scheme is relevant to the patient with critical limb ischemia because many are also diabetic. Implementation of the wound, ischemia, and foot infection classification system in critical limb ischemia patients is recommended and should assist the clinician in more meaningful analysis of outcomes for various forms of wound and arterial revascularizations procedures required in this challenging, patient population.

  17. Always Contact a Vascular Interventional Specialist Before Amputating a Patient with Critical Limb Ischemia

    SciTech Connect

    Met, Rosemarie; Koelemay, Mark J. W.; Bipat, Shandra; Legemate, Dink A.; Lienden, Krijn P. van; Reekers, Jim A.

    2010-06-15

    Patients with severe critical limb ischemia (CLI) due to long tibial artery occlusions are often poor candidates for surgical revascularization and frequently end up with a lower limb amputation. Subintimal angioplasty (SA) offers a minimally invasive alternative for limb salvage in this severely compromised patient population. The objective of this study was to evaluate the results of SA in patients with CLI caused by long tibial occlusions who have no surgical options for revascularization and are facing amputation. We retrospectively reviewed all consecutive patients with CLI due to long tibial occlusions who were scheduled for amputation because they had no surgical options for revascularization and who were treated by SA. A total of 26 procedures in 25 patients (14 males; mean age, 70 {+-} 15 [SD] years) were evaluated. Technical success rate was 88% (23/26). There were four complications, which were treated conservatively. Finally, in 10 of 26 limbs, no amputation was needed. A major amputation was needed in 10 limbs (7 below-knee amputations and 3 above-knee amputations). Half of the major amputations took place within 3 months after the procedure. Cumulative freedom of major amputation after 12 months was 59% (SE = 11%). In six limbs, amputation was limited to a minor amputation. Seven patients (28%) died during follow-up. In conclusion, SA of the tibial arteries seem to be a valuable treatment option to prevent major amputation in patients with CLI who are facing amputation due to lack of surgical options.

  18. Data set incongruence and correlated character evolution: An example of functional convergence in the hind-limbs of stifftail diving ducks

    USGS Publications Warehouse

    McCracken, K.G.; Harshman, J.; Mcclellan, D.A.; Afton, A.D.

    1999-01-01

    The unwitting inclusion of convergent characters in phylogenetic estimates poses a serious problem for efforts to recover phylogeny. Convergence is not inscrutable, however, particularly when one group of characters tracks phylogeny and another set tracks adaptive history. In such cases, convergent characters may be correlated with one or a few functional anatomical units and readily identifiable by using comparative methods. Stifftail ducks (Oxyurinae) offer one such opportunity to study correlated character evolution and function in the context of phylogenetic reconstruction. Morphological analyses place stifftail ducks as part of a large clade of diving ducks that includes the sea ducks (Mergini), Hymenolaimus, Merganetta, and Tachyeres, and possibly the pochards (Aythyini). Molecular analyses, on the other hand, place stifftails far from other diving ducks and suggest, moreover, that stifftails are polyphyletic. Mitochondrial cytochrome b gene sequences of eight stifftail species traditionally supposed to form a clade were compared with each other and with sequences from 50 other anseriform and galliform species. Stifftail ducks are not the sister group of sea ducks but lie outside the typical ducks (Anatinae). Of the four traditional stifftail genera, monophyly of Oxyura and its sister group relationship with Nomonyx are strongly supported. Heteronetta probably is the sister group of that clade, but support is weak. Biziura is not a true stifftail. Within Oxyura, Old World species (O. australis, O. leucocephala, O. mnccoa) appear to form a clade, with New World species (O. jamaicensis, O. vittata) branching basally. Incongruence between molecules and morphology is interpreted to be the result of adaptive specialization and functional convergence in the hind limbs of Biziura and true stifftails. When morphological characters are divided into classes, only hind-limb characters are significantly in conflict with the molecular tree. Likewise, null models of

  19. Data set incongruence and correlated character evolution: an example of functional convergence in the hind-limbs of stifftail diving ducks.

    PubMed

    McCracken, K G; Harshman, J; McClellan, D A; Afton, A D

    1999-12-01

    The unwitting inclusion of convergent characters in phylogenetic estimates poses a serious problem for efforts to recover phylogeny. Convergence is not inscrutable, however, particularly when one group of characters tracks phylogeny and another set tracks adaptive history. In such cases, convergent characters may be correlated with one or a few functional anatomical units and readily identifiable by using comparative methods. Stifftail ducks (Oxyurinae) offer one such opportunity to study correlated character evolution and function in the context of phylogenetic reconstruction. Morphological analyses place stifftail ducks as part of a large clade of diving ducks that includes the sea ducks (Mergini), Hymenolaimus, Merganetta, and Tachyeres, and possibly the pochards (Aythyini). Molecular analyses, on the other hand, place stifftails far from other diving ducks and suggest, moreover, that stifftails are polyphyletic. Mitochondrial cytochrome b gene sequences of eight stifftail species traditionally supposed to form a clade were compared with each other and with sequences from 50 other anseriform and galliform species. Stifftail ducks are not the sister group of sea ducks but lie outside the typical ducks (Anatinae). Of the four traditional stifftail genera, monophyly of Oxyura and its sister group relationship with Nomonyx are strongly supported. Heteronetta probably is the sister group of that clade, but support is weak. Biziura is not a true stifftail. Within Oxyura, Old World species (O. australis, O. leucocephala, O. maccoa) appear to form a clade, with New World species (O. jamaicensis, O. vittata) branching basally. Incongruence between molecules and morphology is interpreted to be the result of adaptive specialization and functional convergence in the hind limbs of Biziura and true stifftails. When morphological characters are divided into classes, only hind-limb characters are significantly in conflict with the molecular tree. Likewise, null models of

  20. Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia

    PubMed Central

    2012-01-01

    The therapeutic potential of mesenchymal stem cell (MSC) transplantation for the treatment of ischemic conditions such as coronary artery disease, peripheral arterial disease, and stroke has been explored in animal models and early-phase clinical trials. A substantial database documents the safety profile of MSC administration to humans in a large number of disease states. The mechanism of the therapeutic effect of MSC transplantation in ischemic disease has been postulated to be due to paracrine, immunomodulatory, and differentiation effects. This review provides an overview of the potential role of MSC-based therapy for critical limb ischemia (CLI), the comparison of MSC cellular therapy with angiogenesis gene therapy in CLI, and the proposed mechanism of action of MSC therapy. Preclinical efficacy data in animal models of hindlimb ischemia, current early-phase human trial data, and considerations for future MSC-based therapy in CLI will also be discussed. PMID:22846185

  1. Contribution of hind limb flexor muscle afferents to the timing of phase transitions in the cat step cycle.

    PubMed

    Hiebert, G W; Whelan, P J; Prochazka, A; Pearson, K G

    1996-03-01

    1. In this investigation, we tested the hypothesis that muscle spindle afferents signaling the length of hind-leg flexor muscles are involved in terminating extensor activity and initiating flexion during walking. The hip flexor muscle iliopsoas (IP) and the ankle flexors tibialis anterior (TA) and extensor digitorum longus (EDL) were stretched or vibrated at various phases of the step cycle in spontaneously walking decerebrate cats. Changes in electromyogram amplitude, duration, and timing were then examined. The effects of electrically stimulating group I and II afferents in the nerves to TA and EDL also were examined. 2. Stretch of the individual flexor muscles (IP, TA, or EDL) during the stance phase reduced the duration of extensor activity and promoted the onset of flexor burst activity. The contralateral step cycle also was affected by the stretch, the duration of flexor activity being shortened and extensor activity occurring earlier. Therefore, stretch of the flexor muscles during the stance phase reset the locomotor rhythm to flexion ipsilaterally and extension contralaterally. 3. Results of electrically stimulating the afferents from the TA and EDL muscles suggested that different groups of afferents were responsible for the resetting of the step cycle. Stimulation of the TA nerve reset the locomotor step cycle when the stimulus intensity was in the group II range (2-5 xT). By contrast, stimulation of the EDL nerve generated strong resetting of the step cycle in the range of 1.2-1.4 xT, where primarily the group Ia afferents from the muscle spindles would be activated. 4. Vibration of IP or EDL during stance reduced the duration of the extensor activity by similar amounts to that produced by muscle stretch or by electrical stimulation of EDL at group Ia strengths. This suggests that the group Ia afferents from IP and EDL are capable of resetting the locomotor pattern generator. Vibration of TA did not affect the locomotor rhythm. 5. Stretch of IP or

  2. Molecular Imaging of the Paracrine Proangiogenic Effects of Progenitor Cell Therapy in Limb Ischemia

    PubMed Central

    Ryu, Jae Choon; Davidson, Brian P.; Xie, Aris; Qi, Yue; Zha, Daogang; Belcik, J. Todd; Caplan, Evan S.; Woda, Juliana M.; Hedrick, Catherine C.; Hanna, Richard N.; Lehman, Nicholas; Zhao, Yan; Ting, Anthony; Lindner, Jonathan R.

    2013-01-01

    Background Stem cells are thought to enhance vascular remodeling in ischemic tissue in part through paracrine effects. Using molecular imaging, we tested the hypothesis that treatment of limb ischemia with multipotential adult progenitor cells (MAPC) promotes recovery of blood flow through the recruitment of pro-angiogenic monocytes. Methods and Results Hindlimb ischemia was produced in mice by iliac artery ligation and MAPC were administered intramuscularly on day 1. Optical imaging of luciferase-transfected MAPC indicated that cells survived for 1 week. Contrast-enhanced ultrasound on day 3, 7 and 21 showed a more complete recovery of blood flow and greater expansion of microvascular blood volume in MAPC-treated mice than in controls. Fluorescent microangiography demonstrated more complete distribution of flow to microvascular units in MAPC-treated mice. On ultrasound molecular imaging, expression of endothelial P-selectin and intravascular recruitment of CX3CR-1-positive monocytes was significantly higher in MAPC-treated than control groups at day 3 and 7 after arterial ligation. Muscle immunohistology showed a >10-fold greater infiltration of monocytes in MAPC-treated than control-treated ischemic limbs at all time points. Intravital microscopy of ischemic or TNF-α-treated cremaster muscle demonstrated that MAPC migrate to peri-microvascular locations and potentiate selectin-dependent leukocyte rolling. In vitro migration of human CD14+ monocytes was 10-fold greater in response to MAPC-conditioned than basal media. Conclusions In limb ischemia, MAPC stimulate the recruitment of pro-angiogenic monocytes through endothelial activation and enhanced chemotaxis. These responses are sustained beyond MAPC lifespan suggesting that paracrine effects promote flow recovery by rebalancing the immune response toward a more regenerative phenotype. PMID:23307829

  3. Treatment with Sildenafil and Donepezil Improves Angiogenesis in Experimentally Induced Critical Limb Ischemia

    PubMed Central

    Constantinescu, Ioana M.; Bolfa, Pompei; Mironiuc, Aurel I.

    2017-01-01

    Objectives. In this study, we aimed to demonstrate the role of sildenafil (an antagonist of phosphodiesterase type 5 (PDE-5)) and donepezil (a specific and reversible inhibitor of acetylcholinesterase (Ach)) in increasing ischemia-induced angiogenesis. Method. Critical limb ischemia was induced by ligation of the common femoral artery followed by ligation of the common iliac artery. The operated animals were divided into 3 groups: receiving sildenafil, receiving donepezil, and surgery alone; the contralateral lower limb was used as a negative control. The results were controlled based on clinical score and Doppler ultrasound. Gastrocnemius muscle samples were taken from all animals, both from the ischemic and nonischemic limb and were used for histopathological and immunohistochemical examination for the evaluation of the number of nuclei/field, endothelial cells (CD31), dividing cells (Ki-67), and vascular endothelial growth factor (VEGFR-3). Results. An increasing tendency of the number of nuclei/field with time was observed both in the case of sildenafil and donepezil treatment. The formation of new capillaries (the angiogenesis process) was more strongly influenced by donepezil treatment compared to sildenafil or no treatment. This treatment significantly influenced the capillary/fiber ratio, which was increased compared to untreated ligated animals. Sildenafil treatment led to a gradual increase in the number of dividing cells, which was significantly compared to the negative control group and compared to the ligation control group. The same effect (increase in the number of Ki-67 positive cells) was more obvious in the case of donepezil treatment. Conclusion. Donepezil treatment has a better effect in ligation-induced ischemia compared to sildenafil, promoting angiogenesis in the first place, and also arteriogenesis. PMID:28243607

  4. Acute Limb Ischemia and Coronary Artery Disease in a Case of Kimura’s Disease

    PubMed Central

    Heo, Woon; Jun, Hee Jae; Kang, Do Kyun; Min, Ho-Ki; Hwang, Youn-Ho; Kim, Ji Yong; Nam, Kyung Han

    2017-01-01

    Kimura disease (KD) is an immune-mediated chronic inflammatory disease of unknown etiology. KD has many complications associated with hypereosinophilia, including various forms of allergic reactions and eosinophilic lung disease. Additionally, hypereosinophilia is associated with hypercoagulability, which may lead to thromboembolic events. A 36-year-old man with KD presented with acute limb ischemia and coronary artery occlusion. He underwent thrombectomy, partial endarterectomy of both popliteal arteries, and coronary artery stent insertion. KD is a systemic disease that affects many organs and presents with thromboembolism and vasculitis. In a patient with KD, physicians should evaluate the vascular system, including the coronary arteries. PMID:28382271

  5. Subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) and rertograde access for critical limb ischemia.

    PubMed

    Hendricks, Nicholas J; Sabri, Saher S

    2014-09-01

    Retrograde access techniques involve the addition of a retrograde access into the distal target vessel to aid in recanalization of chronic total occlusions. Many patients with critical limb ischemia are also poor surgical candidates because of comorbidities or lack of suitable landing zone for bypass procedures. This approach may be helpful in the setting of chronic occlusions that cannot be crossed via conventional antegrade true-lumen approaches. Subintimal arterial flossing with antegrade-retrograde intervention technique can be used when the occlusion was crossed in the subintimal plane and antegrade re-entry techniques failed. It may also be useful for flush superficial femoral artery occlusions or those lesions that extend into the trifurcation vessels. Proficiency in these techniques allows limb salvage in patients who lack surgical options and would otherwise undergo amputation.

  6. Involvement of spinal α2 -adrenoceptors in prolonged modulation of hind limb withdrawal reflexes following acute noxious stimulation in the anaesthetized rabbit.

    PubMed

    Harris, John

    2016-03-01

    The role of spinal α2 -adrenoceptors in mediating long-lasting modulation of hind limb withdrawal reflexes following acute noxious chemical stimulation of distant heterotopic and local homotopic locations has been investigated in pentobarbitone-anaesthetized rabbits. Reflexes evoked in the ankle extensor muscle medial gastrocnemius (MG) by electrical stimulation of the ipsilateral heel, and reflexes elicited in the ankle flexor tibialis anterior and the knee flexor semitendinosus by stimulation at the base of the ipsilateral toes, could be inhibited for over 1 h after mustard oil (20%) was applied to either the snout or into the contralateral MG. The heel-MG response was also inhibited after applying mustard oil across the plantar metatarsophalangeal joints of the ipsilateral foot, whereas this homotopic stimulus facilitated both flexor responses. Mustard oil also caused a significant pressor effect when applied to any of the three test sites. The selective α2 -adrenoceptor antagonist, RX 821002 (100-300 μg, intrathecally), had no effect on reflexes per se, but did cause a decrease in mean arterial blood pressure. In the presence of the α2 -blocker, inhibitory and facilitatory effects of mustard oil on reflexes were completely abolished. These data imply that long-lasting inhibition of spinal reflexes following acute noxious stimulation of distant locations involves activation of supraspinal noradrenergic pathways, the effects of which are dependent on an intact α2 -adrenoceptor system at the spinal level. These pathways and receptors also appear to be involved in facilitation (sensitization) as well as inhibition of reflexes following a noxious stimulus applied to the same limb.

  7. Combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibody therapy prolongs allograft survival in rat hind-limb transplants.

    PubMed

    Ozer, K; Siemionow, M

    2001-10-01

    Immunosuppressive effects of monoclonal antibodies against adhesion molecules were validated in solid organ transplants. There have been only a few reports on the effect of these antibodies on limb transplantation. In this study, the authors investigated the effects of anti-ICAM-1 and anti-LFA-1 therapy in the rat hind-limb-cremaster transplantation model. Twenty transplantations were performed across a major histocompatibility barrier between Lewis Brown Norway (LBN, RT-1(l+n)) and Lewis (LEW, RT-1(l)) rats in four experimental groups of five animals each. Group 1 animals received only vehicle solution; Groups 2 and 3 received monoclonal antibodies against ICAM-1 and LFA-1, respectively; Group 4 received a combination dose. Treatments were continued for 7 days. Clinical signs of rejection were noted daily, and correlated with in vivo microcirculatory measurements. The activation of adhering leukocytes was significantly lower in rats treated with anti-ICAM-1, anti-LFA-1, and combination than in controls (p < 0.05). Transmigrating leukocytes were also reduced in antibody-treated groups, when compared to the control group (p < 0.05). The mean number of rolling lymphocytes was significantly reduced only in the combination group (p < 0.05). Endothelial edema index, a measure of endothelial swelling, was lowest in the combination group (p < 0.05). The first clinical signs of rejection were noted between the 5(th) and 9(th) days in the control group, on the 9(th) day in the anti-ICAM-1 or anti-LFA-1 groups, and on the 13(th) day with combination therapy. Monoclonal antibodies against LFA-1 or ICAM-1 alone inhibit the activation of leukocytes at the microcirculatory level but do not prolong graft survival. However, the combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies significantly prolonged allograft survival in this composite tissue transplantation model.

  8. Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat critical limb ischemia

    PubMed Central

    Beegle, Julie R; Magner, Nataly Lessa; Kalomoiris, Stefanos; Harding, Aja; Zhou, Ping; Nacey, Catherine; White, Jeannine Logan; Pepper, Karen; Gruenloh, William; Annett, Geralyn; Nolta, Jan A; Fierro, Fernando A

    2016-01-01

    Numerous clinical trials are utilizing mesenchymal stem cells (MSC) to treat critical limb ischemia, primarily for their ability to secrete signals that promote revascularization. These cells have demonstrated clinical safety, but their efficacy has been limited, possibly because these paracrine signals are secreted at subtherapeutic levels. In these studies the combination of cell and gene therapy was evaluated by engineering MSC with a lentivirus to overexpress vascular endothelial growth factor (VEGF). To achieve clinical compliance, the number of viral insertions was limited to 1–2 copies/cell and a constitutive promoter with demonstrated clinical safety was used. MSC/VEGF showed statistically significant increases in blood flow restoration as compared with sham controls, and more consistent improvements as compared with nontransduced MSC. Safety of MSC/VEGF was assessed in terms of genomic stability, rule-out tumorigenicity, and absence of edema or hemangiomas in vivo. In terms of retention, injected MSC/VEGF showed a steady decline over time, with a very small fraction of MSC/VEGF remaining for up to 4.5 months. Additional safety studies completed include absence of replication competent lentivirus, sterility tests, and absence of VSV-G viral envelope coding plasmid. These preclinical studies are directed toward a planned phase 1 clinical trial to treat critical limb ischemia. PMID:27610394

  9. Clinical staging of acute limb ischemia as the basis for choice of revascularization method: when and how to intervene.

    PubMed

    Rutherford, Robert B

    2009-03-01

    In acute lower limb ischemia, there are basically three management options: (1) clot removal by catheter-directed thrombolysis with or without percutaneous mechanical thrombectomy, (2) surgical thromboembolectomy followed by correction of underlying arterial lesions, and (3) anticoagulation with continued observation. Arterial embolic occlusion presents more abruptly and with more severe ischemia than arterial thrombosis, which occurs in narrowed arterial segments that have generally developed some degree of collateral circulation. The appropriate choice of treatment for acute limb ischemia depends to a great extent on the severity of the ischemia. Level of ischemia is readily determined by examining for sensory loss or motor deficit and interrogating the distal arteries and veins for audible flow signals with a handheld Doppler velocity detector. After clot removal, appropriate management of the responsible underlying lesion depends on its characteristics, best determined by vascular imaging. Staging the severity of ischemia according to clinical classification levels in the current reporting standards for lower extremity ischemia continues to serve as the basis for logical management decisions. This approach is outlined in algorithmic form and alternative pathways are discussed in this article.

  10. AUGMENTATION OF LIMB PERFUSION AND REVERSAL OF TISSUE ISCHEMIA PRODUCED BY ULTRASOUND-MEDIATED MICROBUBBLE CAVITATION

    PubMed Central

    Belcik, J. Todd; Mott, Brian H.; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J.; Ammi, Azzdine; Linden, Joel M.; Lindner, Jonathan R.

    2015-01-01

    Background Ultrasound can increase tissue blood flow in part through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation, and sought to characterize the biologic mediators. Methods and Results Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in non-ischemic mice after unilateral 10 min exposure to intermittent ultrasound alone (mechanical index [MI] 0.6 or 1.3) or ultrasound with lipid microbubbles (2×108 I.V.). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (p<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3-fold and 10-fold higher than control for MI 0.6 and 1.3, respectively; p<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase (eNOS) attenuated flow augmentation produced by ultrasound and microbubbles by 70% (p<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide (NO) production and muscle phospho-eNOS increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40–50% reduction in flow), ultrasound (MI 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control non-ischemic limb. Conclusions Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of eNOS. PMID:25834183

  11. Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia.

    PubMed

    Procházka, Václav; Jurčíková, Jana; Laššák, Ondrej; Vítková, Kateřina; Pavliska, Lubomír; Porubová, Ludmila; Buszman, Piotr P; Krauze, Agata; Fernandez, Carlos; Jalůvka, František; Špačková, Iveta; Lochman, Ivo; Jana, Dvořáčková; Merfeld-Clauss, Stephanie; March, Keith L; Traktuev, Dmitry O; Johnstone, Brian H

    2016-01-01

    Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent

  12. Use of the directional atherectomy for the treatment of femoro-popliteal lesions in patients with critical lower limb ischemia

    PubMed Central

    Bracale, Umberto Marcello; Vitale, Gaetano; Bajardi, Guido; Narese, Donatella; Dinoto, Ettore; Giribono, Anna Maria; Ferrara, Doriana; del Guercio, Luca; Midiri, Massimo; Pecoraro, Felice

    2016-01-01

    Femoro-popliteal PTA for the treatment of critical limb ischemia is frequently associated with unsatisfactory procedural success rates while directional atherectomy (DCA) has improved success rate since claudicant patients undergoing percutaneous treatment of femoro-popliteal obstructive disease. The aim of this prospective study is to evaluate the safety, efficacy and procedural success of DCA, at one year, in the percutaneous treatment of femoro-popliteal obstructive disease in patients with critical limb ischemia. Methods From March 2012 to March 2013 18 consecutive patients with critical limb ischemia were treated with DCA (Turbohawk/Covidien-ev3 Endovascular Inc., North Plymouth, Minnesota, USA) for the treatment of femoro-popliteal obstructive disease. Patients were evaluated at 12 months. Results Technical and procedural success was achieved in every patient. No in-hospital major adverse cardiovascular events occurred. Primary endpoint: freedom from any amputation was obtained in all patients. Secondary endpoints: clinical (Rutherford class improvement) and hemodynamic success (Ankle-brachial index improvement) was achieved in all patients. Conclusion The use of DCA for the treatment of femoro-popliteal obstructive disease is a safe and effective therapeutic strategy for patients with critical limb ischemia. The data included in our study should be considered hypothesis-generating in order to design of a randomized trial comparison with conventional PTA. PMID:27896226

  13. Dietary glutamine supplementation enhances endothelial progenitor cell mobilization in streptozotocin-induced diabetic mice subjected to limb ischemia.

    PubMed

    Su, Shiau-Tsz; Yeh, Chiu-Li; Hou, Yu-Chen; Pai, Man-Hui; Yeh, Sung-Ling

    2017-02-01

    Diabetes is a metabolic disorder with increased risk of vascular diseases. Tissue ischemia may occur with diabetic vascular complications. Bone marrow-derived endothelial progenitor cells (EPCs) constitute a reparative response to ischemic injury. This study investigated the effects of oral glutamine (GLN) supplementation on circulating EPC mobilization and expression of tissue EPC-releasing markers in diabetic mice subjected to limb ischemia. Diabetes was induced by a daily intraperitoneal injection of streptozotocin for 5 days. Diabetic mice were divided into 2 nonischemic groups and 6 ischemic groups. One of the nonischemic and 3 ischemic groups were fed the control diet, while the remaining 4 groups received diets with identical components except that part of the casein was replaced by GLN. The respective diets were fed to the mice for 3 weeks, and then the nonischemic mice were sacrificed. Unilateral hindlimb ischemia was created in the ischemic groups, and mice were sacrificed at 1, 7 or 21 days after ischemia. Their blood and ischemic muscle tissues were collected for further analyses. Results showed that plasma matrix metallopeptidase (MMP)-9 and the circulating EPC percentage increased after limb ischemia in a diabetic condition. Compared to groups without GLN, GLN supplementation up-regulated plasma stromal cell-derived factor (SDF)-1 and muscle MMP-9, SDF-1, hypoxia-inducible factor-1 and vascular endothelial growth factor gene expression. The CD31-immunoreactive intensities were also higher in the ischemic limb. These findings suggest that GLN supplementation enhanced circulating EPC mobilization that may promote endothelium repair at ischemic tissue in diabetic mice subjected to limb ischemia.

  14. Long-term outcomes following infrapopliteal angioplasty for critical limb ischemia

    PubMed Central

    Lo, Ruby C.; Darling, Jeremy; Bensley, Rodney P.; Dahlberg, Suzanne E.; Hamdan, Allen D.; Wyers, Mark; Schermerhorn, Marc L.

    2012-01-01

    Objectives Infrapopliteal angioplasty (PTA) is routinely used to treat critical limb ischemia (CLI) despite limited data on long-term outcomes. Methods We reviewed all patients undergoing infrapopliteal PTA for CLI from 2004–2012 stratified by TASC class. Outcomes included restenosis, primary patency, reintervention (w/ PTA or bypass), amputation, procedural complications, wound healing, and survival. Results Infrapopliteal PTA (stenting 14%, multilevel intervention 50%) was performed in 459 limbs of 413 patients (59% male) with technical success of 93% and perioperative complications in 11%. TASC class was 16% A, 22% B, 27% C, and 34% D. Multilevel interventions were performed in 50% of limbs and were evenly distributed among all TASC classes. All technical failures were TASC D lesions. Mean follow-up was 15 months. 5-year survival was 49%. One- and 5-year primary patency was 57% & 38% and limb salvage was 84% & 81%. Restenosis was associated with TASC C (HR 2.2, 95% CI 1.2–3.9, P=.010) and TASC D (HR 2.4, 95% CI 1.3–4.4, P=.004) lesions. Amputation rates were higher in patients who were not candidates for bypass (HR 4.4, 95% CI 2.6–7.5, P<.001) and with TASC D lesions (HR 3.8, 95% CI 1.1–12.5, P=.03). Unsuitability for bypass was also predictive of repeat PTA (HR 1.8, 95% CI 1.0–3.4, P=.047). Postoperative clopidogrel use was associated with lower rates of any revascularization (HR .46, 95% CI .25–.83, P=.011). Conclusions Infrapopliteal PTA is effective primary therapy for TASC A, B, and C lesions. Surgical bypass should be offered to patients with TASC D disease who are suitable candidates. Multilevel intervention does not adversely affect outcome. PMID:23375610

  15. [The use of genetic angiogenesis inductors in surgical treatment of chronic lower limb ischemia].

    PubMed

    Gavrilenko, A V; Voronov, D A; Bochkov, N P

    2013-01-01

    The efficacy and safety of gene-engineering recombinant constructions with endothelial growth factor gene and angiogenin for the treatment of the chronic lower limb ischemia were studied. 134 patients were included in prospective controlled study. The main group, who received both traditional treatment and genetic therapy, consisted of 74 patients. The rest 60 patients were included into the control group. Of 74 patients from the main group, genetic therapy was used together with conservative means in 39 patients and with reconstructive vascular operations in 35 patients. The gene-engineering angiogenesis stimulation therapy proved to be effective and safe. The combination of angiogenesis genetic stimulation with reconstructive vascular surgery demonstrated significantly better results, then monotherapy.

  16. Defining risks and predicting adverse events after lower extremity bypass for critical limb ischemia

    PubMed Central

    Siracuse, Jeffrey J; Huang, Zhen S; Gill, Heather L; Parrack, Inkyong; Schneider, Darren B; Connolly, Peter H; Meltzer, Andrew J

    2014-01-01

    Successful treatment of patients with critical limb ischemia (CLI), hinges on the adequacy of revascularization. However, CLI is associated with a severe burden of systemic atherosclerosis, and patients often suffer from multiple cardiovascular comorbidities. Therefore, CLI patients in general represent a cohort at increased risk for procedural complications and adverse events. Although endovascular therapy represents a minimally invasive alternative to open surgical bypass, the durability of surgical reconstruction is superior, and it remains the “gold standard” approach to revascularization in CLI. Therefore, selection of the optimal treatment modality for individual patients requires careful consideration of the procedural risks and likelihood of adverse events associated with surgery. Individualized decision-making with regard to revascularization strategy requires a comprehensive understanding of the likelihood of adverse outcomes after major surgery. Here we review the risks of surgical bypass in patients with CLI, with particular emphasis on the identification of preoperative variables that predict poor outcome. PMID:25018636

  17. Augmentation of arterial blood velocity with electrostimulation in patients with critical limb ischemia unsuitable for revascularization.

    PubMed

    Yilmaz, Seyhan; Mermi, Esra U; Zobaci, Ethem; Aksoy, Eray; Yastı, Çınar

    2017-04-01

    Aim This pilot study aimed to reveal whether combination of electrostimulation with iloprost treatment achieves better results compared to iloprost alone in patients with critical limb ischemia. Material and methods Patients were randomized into Group 1 ( n = 11, mean age: 65.3 ± 4.2 years, received iloprost infusion protocol alone) or Group 2 ( n = 11, mean age: 62.9 ± 6.7, received iloprost infusion plus standardized protocol of peroneal nerve electrostimulation). Electrostimulation was delivered with 1 Hz frequency, 27 mA current, and 200 ms pulse width. Peak blood flow velocities in the anterior and posterior tibialis arteries were measured with duplex ultrasound. Results There was a slight insignificant increase in blood velocity in anterior tibialis artery in Group 1 (from 17.6 ± 13.0 to 18.6 ± 13.1, p = 0.57), whereas the increase in Group 2 was marked (from 23.8 ± 18.3 to 32.2 ± 19.7, p = 0.01). Blood velocity in posterior tibialis artery also increased in both groups, but it was not of statistical significance. No significant difference was found between two groups in regard to final pulse oximetry oxygen saturation levels. Conclusion Electrostimulation of the peroneal nerve caused a substantial increase in anterior tibialis artery blood velocity when used as an adjunct to medical therapy in patients with critical limb ischemia.

  18. Endovascular recanalization of infrapopliteal occlusions in patients with critical limb ischemia

    PubMed Central

    Singh, Gagan D.; Armstrong, Ehrin J.; Yeo, Khung-Keong; Singh, Satinder; Westin, Gregory G.; Pevec, William C.; Dawson, David L.; Laird, John R.

    2014-01-01

    Background Endovascular therapies are increasingly used for treatment of critical limb ischemia (CLI). Infrapopliteal (IP) occlusions are common in CLI, and successful limb salvage may require restoration of arterial flow in the distribution of a chronically occluded vessel. We sought to describe the procedural characteristics and outcomes of patients with IP occlusions who underwent endovascular intervention for treatment of CLI. Methods All patients with IP interventions for treatment of CLI from 2006 to 2012 were included. Angiographic and procedural data were compared between patients who underwent intervention for IP occlusions vs IP stenosis. Restenosis was determined by Doppler ultrasound imaging. Limb salvage was the primary end point of the study. Additional end points included primary patency, primary assisted patency, secondary patency, occlusion crossing success, procedural success, and amputation-free survival. Results A total of 187 patients with CLI underwent interventions for 356 IP lesions, and 77 patients (41%) had interventions for an IP occlusion. Patients with an intervention for IP occlusion were more likely to have zero to one vessel runoff (83% vs 56%; P < .001) compared with interventions for stenosis. Compared with IP stenoses, IP occlusions were longer (118 ± 86 vs 73 ± 67 mm; P < .001) and had a smaller vessel diameter (2.5 ± 0.8 vs 2.7 ± 0.5 mm; P =.02). Wire crossing was achieved in 83% of IP occlusions, and the overall procedural success for IP occlusions was 79%. The overall 1-year limb salvage rate was 84%. Limb salvage was highest in the stenosis group, slightly lower in the successful occlusion group, and lowest in the failed occlusion group (92% vs 75% vs 58%, respectively; P = .02). Unsuccessfully treated IP occlusions were associated with a significantly higher likelihood of major amputation (hazard ratio, 5.79; 95% confidence interval, 1.89–17.7) and major amputation or death (hazard ratio, 2.69; 95% confidence interval

  19. Functional Imaging of the Foot with Perfusion Angiography in Critical Limb Ischemia

    SciTech Connect

    Reekers, Jim A.; Koelemay, Mark J. W.; Marquering, Henk A. Bavel, Ed T. van

    2016-02-15

    PurposeTo report on the first clinical experience with perfusion angiography (PA) of the foot in patients with chronic critical limb ischemia.Materials and MethodsPA is a post-processing software algorithm and no extra digital subtraction angiography (DSA) has to be performed for this analysis. The data used to test the feasibility of PA were obtained from a consecutive group of 89 patients with CLI who were treated with standard below the knee angioplasty and 12 separate patients who were not suitable for endovascular revascularization.ResultsMotion artifacts in the dataset of the DSA made post-procedural analysis impossible in 10 % intervention. In the majority of patients (59/68) PA showed an increase in volume flow in the foot after successful angioplasty of the crural vessels. However, in 9/68 patients no increase was seen after successful angioplasty. With the use of a local administered competitive α-adrenergic receptor antagonist, it is also possible to test and quantify the capillary resistance index which is a parameter for the remaining functionality of the microcirculation in CLI patients.ConclusionPA might be used as a new endpoint for lower limb revascularization and can also be used to test the functionality the microcirculation to identify sub-types of patients with CLI. Clinical evaluation and standardization of PA is mandatory before introduction in daily practice.

  20. Chronic lower limb ischemia and advanced renal failure. Do we possess sufficient therapeutic knowledge?

    PubMed

    Gacka, M; Adamiec, R

    2013-08-01

    Chronic lower limb ischemia diminishes the quality of life and is associated with a higher risk of limb amputation and cardiovascular mortality. Coexisting chronic renal disease can modulate the response to pharmacotherapy and revascularization, and thus influence prognosis. This paper reviews current literary evidence regarding therapeutic problems observed in patients with obliterative atherosclerosis and renal failure. We reviewed articles from peer-reviewed medical journals which were published between 2000 and 2011. The poorer clinical response in the discussed patients is not only connected with the direct failure of surgical and endovascular procedures, but first of all with the high mortality of the patients. There is still a lack of sufficient evidence on the effectiveness of currently used anti-atherosclerotic agents in patients with end-stage renal failure. A certain priority is the search for an effective therapeutic strategy that would reduce mortality associated with cardiovascular conditions in this particular group of patients. Identifying patients who can benefit most from costly endovascular procedures is another vital issue.

  1. Role of the femorofemoral crossover graft in acute lower limb ischemia due to acute type B aortic dissection.

    PubMed

    Corfield, Lorraine; McCormack, David J; Bell, Rachel; Taylor, Peter; Reidy, John

    2014-04-01

    Acute limb ischemia due to type B aortic dissection is rare and continues to be a management challenge. A case series is presented here with the aim of assessing the outcomes of treatment with a femorofemoral crossover graft with or without thoracic stent graft insertion. This is a combined retrospective and prospective review of nine cases of acute lower limb ischemia secondary to acute type B aortic dissection. The presenting features, radiological findings, treatment and outcomes were reviewed. Five patients had a femorofemoral crossover graft (FFXO) alone, two an FFXO with a thoracic stent graft and the eighth a thoracic and iliac stent. The other case was initially treated conservatively but subsequently required an FFXO. The mean follow-up was 16 (3-51) months. A further two thoracic stents were placed during the follow-up period. Thus five out of nine patients (56%) required aortic stenting. This series suggests that an FFXO is a reliable treatment for acute limb ischemia due to type B aortic dissection. However, these patients are often complex with ischemia in other vascular beds and are at risk of subsequent aneurysmal dilation.

  2. Pharmacokinetics of Acetaminophen in Hind Limbs Unloaded Mice: A Model System Simulating the Effects of Low Gravity on Astronauts in Space

    NASA Technical Reports Server (NTRS)

    Peterson, Amanda; Risin, Semyon A.; Ramesh, Govindarajan T.; Dasgupta, Amitava; Risin, Diana

    2008-01-01

    The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in Space. Low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration in astronauts. Acquiring of such knowledge has inherent difficulties due to limited opportunities for experimenting in Space. One of the approaches is to use model systems that simulate some of the Space conditions on Earth. In this study we used hind limbs unloaded mice (HLU) to investigate the possible changes in PK of acetaminophen, a widely used analgesic with high probability of use by astronauts. The HLU is recognized as an appropriate model for simulating the effects of low gravity on hemodynamic parameters. Mice were tail suspended (n = 24) for 24-96 hours prior to introduction of acetaminophen (150 - 300 mg/kg). The drug (in aqueous solution containing 10% ethyl alcohol by volume) was given orally by a gavage procedure and after the administration of acetaminophen mice were additionally suspended for 30 min, 1 and 2 hours. Control mice (n = 24) received the same dose of acetaminophen and were kept freely all the time. Blood specimens were obtained either from retroorbital venous sinuses or from heart. Acetaminophen concentration was measured in plasma by the fluorescent polarization immunoassay and the AxSYM analyzer (Abbott Laboratories). In control mice peak acetaminophen concentration was achieved at 30 min. By 1 hour the concentration decreased to less than 50% of the peak level and at 2 hours the drug was almost undetectable in the serum. HLU for 24 hours significantly altered the acetaminophen pharmacokinetic: at 30 min the acetaminophen concentrations were significantly (both statistically and medically significant) lower than in control mice. The concentrations also reduced less

  3. Successful carbon dioxide angiography guided endovascular thrombectomy of the superficial femoral artery in a young patient with critical limb ischemia.

    PubMed

    Giusca, Sorin; Eisele, Tom; Raupp, Dorothea; Eisenbach, Christoph; Korosoglou, Grigorios

    2017-03-01

    Currently, the treatment of thromboembolic ischemia of the lower extremities includes percutaneous rotational thrombectomy and aspiration devices. However, the standard approach for endovascular treatment requires the administration of iodine contrast agents, which is problematic in patients with pre-existing renal disease and diabetes. Herein, we describe a case of a CO2 angiography guided endovascular thrombectomy of the superficial femoral artery (SFA) in a young patient with critical limb ischemia. Mechanical thrombectomy using the Rotarex system, catheter aided aspiration and subsequent stent placement in the SFA was entirely guided using CO2 angiography.

  4. Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia

    PubMed Central

    Li, Yaqian; Liu, Wei; Liu, Fei; Zeng, Yang; Zuo, Simin; Feng, Siyu; Qi, Chunxiao; Wang, Bingjie; Yan, Xiaojun; Khademhosseini, Ali; Bai, Jing; Du, Yanan

    2014-01-01

    The promise of cell therapy for repair and restoration of damaged tissues or organs relies on administration of large dose of cells whose healing benefits are still limited and sometimes irreproducible due to uncontrollable cell loss and death at lesion sites. Using a large amount of therapeutic cells increases the costs for cell processing and the risks of side effects. Optimal cell delivery strategies are therefore in urgent need to enhance the specificity, efficacy, and reproducibility of cell therapy leading to minimized cell dosage and side effects. Here, we addressed this unmet need by developing injectable 3D microscale cellular niches (microniches) based on biodegradable gelatin microcryogels (GMs). The microniches are constituted by in vitro priming human adipose-derived mesenchymal stem cells (hMSCs) seeded within GMs resulting in tissue-like ensembles with enriched extracellular matrices and enhanced cell–cell interactions. The primed 3D microniches facilitated cell protection from mechanical insults during injection and in vivo cell retention, survival, and ultimate therapeutic functions in treatment of critical limb ischemia (CLI) in mouse models compared with free cell-based therapy. In particular, 3D microniche-based therapy with 105 hMSCs realized better ischemic limb salvage than treatment with 106 free-injected hMSCs, the minimum dosage with therapeutic effects for treating CLI in literature. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy for treating CLI with the lowest cell dosage in mouse models. This study offers a widely applicable cell delivery platform technology to boost the healing power of cell regenerative therapy. PMID:25197069

  5. Effects of electrical stimulation therapy on the blood flow in chronic critical limb ischemia patients following regenerative therapy

    PubMed Central

    Yamabata, Shiho; Shiraishi, Hirokazu; Munechika, Mai; Fukushima, Hideki; Fukuoka, Yoshiyuki; Hojo, Tatsuya; Shirayama, Takeshi; Horii, Motoyuki; Matoba, Satoaki; Kubo, Toshikazu

    2016-01-01

    Objectives: We investigated the effects of electrical stimulation therapy on cutaneous and muscle blood flow in critical limb ischemia patients following regenerative therapy. Methods: Three groups were studied: 10 healthy young subjects, 10 elderly subjects, and 7 critical limb ischemia patients after regenerative therapy. After 5 min rest, electrical stimulation was applied at 5 Hz on the tibialis anterior muscle for 10 min. We estimated the relative changes in oxyhemoglobin and total hemoglobin compared to the basal values at rest (Δ[HbO2], Δ[Hbtot]), which reflected the blood flow in the skin and muscle layer, and we simultaneously measured the tissue O2 saturation (StO2) throughout the electrical stimulation and recovery phase by near-infrared spectroscopy. Results: The Δ[HbO2] and Δ[Hbtot] values of the muscle layer in critical limb ischemia patients increased gradually and remained significantly higher at the 5-min and 10-min recovery periods after the electrical stimulation without reducing the StO2, but there is no significant change in the other two groups. Skin blood flow was not influenced by electrical stimulation in three groups. Conclusion: This improvement of the peripheral circulation by electrical stimulation would be beneficial as the adjunctive therapy after regenerative cell therapy. PMID:27504185

  6. Perfusion Angiography of the Foot in Patients with Critical Limb Ischemia: Description of the Technique

    SciTech Connect

    Jens, Sjoerd Marquering, Henk A.; Koelemay, Mark J. W.; Reekers, Jim A.

    2015-02-15

    ObjectiveTo study the feasibility of 2D perfusion imaging in critical limb ischemia (CLI).Methods/ResultsPerfusion angiography is a new technology which was tested in 18 patients with CLI of the foot. A standardized protocol was used with a catheter placed at the mid-part of the popliteal artery, and a total of 9 cc of non-ionic iodinated contrast material was injected at a rate of 3 cc/sec. The technology is based on early cardiology research where iodinated contrast agents were used for imaging of cardiac perfusion. During the first pass of the contrast, there is a significant diffusion of the contrast agents into the interstitial space, particularly for non-ionic and low-molecular-weight compounds.DiscussionThe original angiography data can be used to make a time–density curve, which represents the actual perfusion of the foot in time. Angiographic perfusion imaging is a post-processing modality for which no extra contrast or radiation is needed. With this technique, it is possible to get more information about the perfusion status and microcirculation of the foot. This is a step toward functional imaging in CLI patients.

  7. Use of the AngioSculpt scoring balloon for infrapopliteal lesions in patients with critical limb ischemia: 1-year outcome.

    PubMed

    Bosiers, Marc; Deloose, Koen; Cagiannos, Catherine; Verbist, Jürgen; Peeters, Patrick

    2009-01-01

    The AngioSculpt Scoring Balloon Catheter (AngioScore, Inc., Fremont, CA) is composed of a semicompliant balloon encircled by three nitinol spiral struts providing targeted lesion scoring on balloon inflation. Between April 2005 and April 2006, procedural and follow-up data on 31 patients (mean age 76 years; 54.8% males) endovascularly treated for severe infrapopliteal disease were collected. The AngioSculpt catheter was used to treat 36 complex, tibioperoneal, atherosclerotic lesions. All patients had symptomatic critical limb ischemia (Rutherford 4-5) and single-vessel runoff to the ankle. Complication-free survival at 1 month was the safety end point, whereas primary patency and limb salvage were the efficacy end points evaluated at 1 year. The AngioSculpt balloon was successfully inflated in all 36 target lesions. Eleven patients (35.5%) required additional stenting for minor dissections or suboptimal stenosis reduction. The 1-month complication-free survival was 96.8%. One-year survival, primary patency, and limb salvage rates were 83.9 +/- 6.6%, 61.0 +/- 9.3%, and 86.3 +/- 6.4%, respectively. The 1-year data show the AngioSculpt Scoring Balloon Catheter to be an effective and safe treatment for infrapopliteal, atherosclerotic lesions in patients with critical limb ischemia. However, more patients, a longer follow-up, and randomized studies comparing it with conventional balloon angioplasty and stenting in the infrapopliteal region are required.

  8. Perioperative iloprost and endothelial progenitor cells in uremic patients with severe limb ischemia undergoing peripheral revascularization.

    PubMed

    Coppolino, Giuseppe; Buemi, Antoine; Bolignano, Davide; Lacquaniti, Antonio; La Spada, Michele; Stilo, Francesco; De Caridi, Giovanni; Benedetto, Francesco; Loddo, Saverio; Buemi, Michele; Spinelli, Francesco

    2009-11-01

    The incidence of severe limb ischemia (SLI) is high among haemodialysis (HD) patients. Limb rescue rate after surgical revascularization is relatively poor compared with patients with normal renal function. Prostanoids are an interesting category as adjuvants to revascularization. New vessel growth develops not exclusively by proliferation of endothelial cells in vascular extremities but also by cells mobilized from the bone marrow (HSC), transformed into endothelial progenitor cells (EPC) contributing to both re-endothelialization and neovascularization. Basal number of HSC and EPC is significantly reduced in HD patients and correlated with a subsequent defective neovascularization. The aim of this study was to evaluate the effects of perioperative treatment with iloprost in uremic patients with acute ischemia of lower limbs, undergoing surgical revascularization, on endothelial progenitor cells, hypothesizing a possible biological mechanism induced by the prostanoids. A search was also made for vascular remodeling processes through the analysis of the concentrations of soluble adhesion molecules (i-CAM, v-CAM, e-selectin), biochemical markers of endothelial activation. Thirty HD patients with SLI undergoing peripheral revascularization were enrolled (15 were treated with iloprost and 15 with a placebo). Iloprost was administered as an intra-arterial bolus of 3000 ng over 1 to 3 min immediately after revascularization and in the same affected artery. Serum samples were taken before revascularization (T0), at 6 (T6) and 24 h (T24) after infusion to measure sICAM-1, sE-selectin, and sVCAM-1, and for quantification of HSC and EPC. Progenitors were identified by specific surface markers CD34+, CD133+ and VEGFR2+. Count was conducted using PROCOUNT performed in a TRUCOUNT tube and with a FACSort flow cytometer. Before revascularization, all patients showed a decreased number of HSC and EPC. After 6 h, HSC augmented significantly compared with T0 in both groups. The

  9. Outcomes of Infrainguinal Revascularizations with Endovascular First Strategy in Critical Limb Ischemia

    SciTech Connect

    Jens, Sjoerd; Conijn, Anne P. Frans, Franceline A.; Nieuwenhuis, Marieke B. B. Met, Rosemarie; Koelemay, Mark J. W. Legemate, Dink A.; Bipat, Shandra Reekers, Jim A.

    2015-06-15

    PurposeThis study was designed to study the outcome of infrainguinal revascularization in patients with critical limb ischemia (CLI) in an institution with a preference towards endovascular intervention first in patients with poor condition, unfavourable anatomy for surgery, no venous material for bypass, and old age.MethodsA prospective, observational cohort study was conducted between May 2007 and May 2010 in patients presenting with CLI. At baseline, the optimal treatment was selected, i.e., endovascular or surgical treatment. In case of uncertainty about the preferred treatment, a multidisciplinary team (MDT) was consulted. Primary endpoints were quality of life and functional status 6 and 12 months after initial intervention, assessed by the VascuQol and AMC Linear Disability Score questionnaires, respectively.ResultsIn total, 113 patients were included; 86 had an endovascular intervention and 27 had surgery. During follow-up, 41 % underwent an additional ipsilateral revascularisation procedure. For the total population, and endovascular and surgery subgroups, the VascuQol sum scores improved after 6 and 12 months (p < 0.01 for all outcomes) compared with baseline. The functional status improved (p = 0.043) after 12 months compared with baseline for the total population. Functional status of the surgery subgroup improved significantly after 6 (p = 0.031) and 12 (p = 0.044) months, but not that of the endovascular subgroup.ConclusionsOverall, the strategy of performing endovascular treatment first in patients with poor condition, unfavourable anatomy for surgery, no venous material for bypass, and old age has comparable or even slightly better results compared with the BASIL trial and other cohort studies. All vascular groups should discuss whether their treatment strategy should be directed at treating CLI patients preferably endovascular first and consider implementing an MDT to optimize patient outcomes.

  10. The ILAILL Study: Iloprost as Adjuvant to Surgery for Acute Ischemia of Lower Limbs

    PubMed Central

    de Donato, Gaetano; Gussoni, Gualberto; de Donato, Gianmarco; Andreozzi, Giuseppe Maria; Bonizzoni, Erminio; Mazzone, Antonino; Odero, Attilio; Paroni, Giovanni; Setacci, Carlo; Settembrini, Piergiorgio; Veglia, Fabrizio; Martini, Romeo; Setacci, Francesco; Palombo, Domenico

    2006-01-01

    Summary Background Data: High rate of complications has been reported following revascularization for acute limb ischemia (ALI). No adjuvant pharmacologic treatment, apart from anticoagulation and standard perioperative care, has been shown clinically effective. Objective: Aim of this study was to evaluate the effects of the prostacyclin analog iloprost as adjuvant to surgery for ALI. Methods: A total of 300 patients were randomly assigned to receive perioperative iloprost (intra-arterial, intraoperative bolus of 3000 ng, plus intravenous infusion of 0.5–2.0 ng/kg/min for 6 hours/day for 4–7 days following surgery), or placebo. The primary endpoint was the combined incidence of death and amputation at 3-month follow-up. Secondary endpoints were the incidence of each single major complication, total event rate, symptomatology, and tolerability. Results: The combined incidence of death and amputation was 19.9% in the placebo and 14.1% in the iloprost group (relative risk, 1.56; 95% confidence interval, 0.89–2.75, P = 0.12, Cox regression analysis). A statistically significant lower mortality (4.7%) was reported in patients receiving iloprost, compared with controls (10.6%; relative risk, 2.61; 95% confidence interval, 1.07–6.37, P = 0.03). The overall incidence of fatal plus major cardiovascular events was 33.1% and 22.8% in placebo and iloprost groups, respectively (relative risk, 1.61; 95% confidence interval, 1.04–2.49, P = 0.03). No serious adverse reactions occurred after iloprost administration, nor differences in the incidence of bleeding or hypotension between treatment groups. Conclusions: Although at lower levels than previously reported, our results confirm the severity of ALI. Iloprost as adjuvant to surgery significantly reduced mortality and overall major event rate. Further data are needed to support this finding, and to face a still open medical issue. PMID:16858180

  11. Balloon angioplasty in tibioperoneal interventions for patients with critical limb ischemia.

    PubMed

    Mustapha, J A; Diaz-Sandoval, Larry J

    2014-09-01

    Tibial arterial disease represents the final frontier in the battle against critical limb ischemia (CLI). Isolated infrapopliteal (IP) disease is mainly seen in the elderly (>80 years old), diabetic, and dialysis-dependent patients with CLI. With the development and evolution of catheter-based technology, endovascular therapy (mainly balloon angioplasty) has become the method of choice for revascularization in these patients. The most common challenges are the severely calcified lesion recalcitrant to dilation (as calcium is heterogeneously distributed in the arterial wall) and the long tibial chronic total occlusions. Percutaneous transluminal angioplasty achieves a technically successful result (<30% residual stenosis) in most cases, but it is limited by high restenosis rates. Although several devices have been used in the IP arena (including orbital and directional atherectomy, laser atherectomy, "contact" atherectomy [CROSSER, Bard], and re-entry devices), percutaneous transluminal angioplasty with plain old balloons has been the subject of most studies with several modified iterations, that is, cryoplasty, cutting balloons, focal force balloons, nitinol-"cage"-constrained balloons, tapered balloons, and most recently drug-coated balloons. In this article, we share our current approach to endovascular IP endovascular interventions. We cover the spectrum from pathophysiology, clinical indications, equipment choices, and procedural steps used in our laboratory when treating patients with CLI (which is synonymous with complex anatomy). Regarding what represents the "gold standard" for the treatment of IP disease, a definite answer is currently not available, as multiple studies looking at new generation drug-coated balloons used alone or in combination with different forms of atherectomy are currently under way. We anxiously wait for these results and in the meantime continue to design newer approaches.

  12. Early results from an angiosome-directed open surgical technique for venous arterialization in patients with critical lower limb ischemia

    PubMed Central

    Houlind, Kim; Christensen, Johnny; Hallenberg, Christian; Jepsen, Jørn M.

    2013-01-01

    Background Patients with critical lower limb ischemia without patent pedal arteries cannot be treated by the conventional arterial reconstruction. Venous arterialization has been suggested to improve limb salvage in this subgroup of patients but has not gained wide acceptance. We report our early experience after implementing deep and superficial venous arterialization of the lower limb. Materials and methods Ten patients with critical ischemia and without crural or pedal arteries available for conventional bypass surgery or angioplasty were treated with distal venous arterialization. Inflow was from the most distal unobstructed segment. Run-off was the dorsal pedal venous arch (n=5), the dorsal pedal venous arch and a concomitant vein of the posterior tibial artery (n=3), or the dorsal pedal venous arch and a concomitant vein of the common plantar artery (n=2) depending on the location of the ischemic lesion. Venous valves were destroyed using antegrade valvulotomes, guide wires, knob needles, or retrograde valvulotomes via an extra incision. Results Seven of the operated limbs were amputated after 23 (1–256) days (median [range]). The main reasons for amputation were lack of healing of either the original wound, of incisional wounds on the foot, or persisting pain at rest. In three cases, the bypass was open at the time of amputation. Two patients experienced complete wound healing after 231 and 342 days, respectively. By the end of follow-up, the last patient was ambulating with slow wound healing but without pain 309 days after surgery. Conclusion Venous arterialization may be used as a treatment of otherwise unsalveable limbs. The success rate is, however, limited. Technical optimization of the technique is warranted. PMID:24358432

  13. The Use of Below-Knee Percutaneous Transluminal Angioplasty in Arterial Occlusive Disease Causing Chronic Critical Limb Ischemia

    SciTech Connect

    Loefberg, Ann-Marie; Loerelius, Lars-Erik; Karacagil, Sadettin; Westman, Bo; Almgren, Bo; Berqgvist, David

    1996-09-15

    Purpose: To determine the efficacy, safety and long-term results of crural artery percutaneous transluminal angioplasty (PTA) in limbs with chronic critical limb ischemia (CLI). Methods: Patients undergoing crural artery PTA due to CLI were followed at regular clinic visits with ankle brachial pressure index (ABPI) measurements. PTA of the crural arteries was attempted either alone (n= 39) or in combination with PTA of the superficial and/or popliteal artery (n= 55) in 86 limbs (82 patients and 94 procedures) presenting with CLI. The ages of patients ranged from 37 to 94 years (mean 72 years). The indications for PTA were rest pain in 10 and ulcer/gangrene in 84 limbs.Results: A technically successful PTA with at least one crural level was achieved in 88% of cases (n= 83). Cumulative primary clinical success rates at 6, 12, 24, and 36 months were 55%, 51%, 36%, and 36%, respectively. Cumulative secondary clinical success and limb salvage rates at 36 months were 44% and 72%, respectively. Conclusion: PTA of the crural arteries might be considered the primary choice of treatment in patients with CLI and distal lesions with localized stenosis or segmental short occlusions.

  14. Ischemia

    NASA Astrophysics Data System (ADS)

    Byeon, Suk Ho; Kim, Min; Kwon, Oh Woong

    "Ischemia" implies a tissue damage derived from perfusion insufficiency, not just an inadequate blood supply. Mild thickening and increased reflectivity of inner retina and prominent inner part of synaptic portion of outer plexiform layer are "acute retinal ischemic changes" visible on OCT. Over time, retina becomes thinner, especially in the inner portion. Choroidal perfusion supplies the outer portion of retina; thus, choroidal ischemia causes predominant change in the corresponding tissue.

  15. Superiority of Transcutaneous Oxygen Tension Measurements in Predicting Limb Salvage After Below-the-Knee Angioplasty: A Prospective Trial in Diabetic Patients With Critical Limb Ischemia

    SciTech Connect

    Redlich, Ulf; Xiong, Yan Y.; Pech, Maciej; Tautenhahn, Joerg; Halloul, Zuhir; Lobmann, Ralf; Adolf, Daniela; Ricke, Jens; Dudeck, Oliver

    2011-04-15

    Purpose: To assess postprocedural angiograms, the ankle-brachial index (ABI), and transcutaneous oxygen tension (TcPO{sub 2}) to predict outcome after infrageniculate angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI) scheduled for amputation. Materials and Methods: PTA was performed in 28 diabetic patients with CLI confined to infrapopliteal vessels. We recorded patency of crural vessels, including the vascular supply of the foot as well as the ABI and TcPO{sub 2} of the foot. Results: Technical success rate was 92.9% (n = 26), and limb-salvage rate at 12 months was 60.7% (n = 17). The number of patent straight vessels above and below the level of the malleoli increased significantly in patients avoiding amputation. Amputation was unnecessary in 88.2% (n = 15) patients when patency of at least one tibial artery was achieved. In 72.7% (n = 8) of patients, patency of the peroneal artery alone was not sufficient for limb salvage. ABI was of no predictive value for limb salvage. TcPO{sub 2} values increased significantly only in patients not requiring amputation (P = 0.015). In patients with only one tibial artery supplying the foot or only a patent peroneal artery in postprocedural angiograms, TcPO{sub 2} was capable of reliably predicting the outcome. Conclusion: Below-the-knee PTA as an isolated part of therapy was effective to prevent major amputation in more than a half of diabetic patients with CLI. TcPO{sub 2} was a valid predictor for limb salvage, even when angiographic outcome criteria failed.

  16. Two-year outcome after Xpert stent implantation for treating below the knee lesions in critical limb ischemia.

    PubMed

    Bosiers, Marc; Lioupis, Christos; Deloose, Koen; Verbist, Jürgen; Peeters, Patrick

    2009-01-01

    We investigated the efficacy of Xpert (Abbott Vascular, Abbott Park, IL) nitinol stents for the treatment of infrapopliteal lesions in patients with Critical Limb Ischemia (CLI). Between May 2005 and November 2007, 94 CLI patients (70 male, mean age 73.5 years) received 134 Xpert stents in 102 limbs. Seventy-nine patients (71.2%) were scored as Rutherford Category 4, 31 patients (27.9%) as Category 5 and 1 patient (0.9%) as Category 6. Primary endpoint of this study was defined as 2-year duplex derived primary patency. Secondary endpoints were 2-year limb salvage rate and the absence of reintervention after the index procedure. Kaplan Meier analysis reported 2-year primary patency and limb salvage rates of 54.4% and 90.8%, respectively. Stratification by lesion location did not reveal any significant differences in 2-year primary patency rates in proximal and distal below the knee lesions. Our results suggest that treatment with nitinol Xpert stents can be considered effective for treating CLI patients, with satisfying patency outcome.

  17. Successful Endovascular Repair of an Iatrogenic Perforation of the Superficial Femoral Artery Using Self-Expanding Nitinol Supera Stents in a Patient with Acute Thromboembolic Limb Ischemia.

    PubMed

    Eisele, Tom; Muenz, Benedikt M; Korosoglou, Grigorios

    2016-01-01

    The treatment of acute thromboembolic limb ischemia includes well-established surgical thrombectomy procedures and, in recent times, also percutaneous rotational thrombectomy using Straub Rotarex® system. This modality not only enables efficient treatment of such thrombotic occlusion but also in rare cases may imply the risk of perforation of the occluded artery. Herein, we report the case of a perforation of the superficial femoral artery (SFA) in an elderly female patient with thromboembolic limb ischemia. The perforation was successfully treated by implantation of self-expanding nitinol Supera stents and without the need for implantation of a stent graft.

  18. Successful Endovascular Repair of an Iatrogenic Perforation of the Superficial Femoral Artery Using Self-Expanding Nitinol Supera Stents in a Patient with Acute Thromboembolic Limb Ischemia

    PubMed Central

    Eisele, Tom; Muenz, Benedikt M.

    2016-01-01

    The treatment of acute thromboembolic limb ischemia includes well-established surgical thrombectomy procedures and, in recent times, also percutaneous rotational thrombectomy using Straub Rotarex® system. This modality not only enables efficient treatment of such thrombotic occlusion but also in rare cases may imply the risk of perforation of the occluded artery. Herein, we report the case of a perforation of the superficial femoral artery (SFA) in an elderly female patient with thromboembolic limb ischemia. The perforation was successfully treated by implantation of self-expanding nitinol Supera stents and without the need for implantation of a stent graft. PMID:27213074

  19. Preliminary study of laser doppler perfusion signal by wavelet transform in patients with critical limb ischemia before and after revascularization.

    PubMed

    Ticcinelli, Valentina; Martini, Romeo; Bagno, Andrea

    2014-01-01

    The haemodynamics of skin microcirculation can be quantitatively evaluated by Laser Doppler Fluxmetry (LDF). LDF signal in human skin shows periodic oscillations. Spectral analysis by wavelet transform displays six characteristic frequency intervals (FI) from 0.005 to 2 Hz, related to distinct vascular structures activities: heart (0.6-2 Hz), sympathetic respiratory (0.145-0.6 Hz), myogenic (0.052-0.145 Hz), local sympathetic nerve (0.021-0.052 Hz) and endothelial cells NO dependent (0.0095-0.021 Hz) and NO independent (0.005-0.0095 Hz). The most advanced stage of peripheral arterial obstructive disease is the critical limb ischemia (CLI), which causes the reduction of blood perfusion threatening limb viability. Besides macrocirculatory alterations, many studies have shown microvascular misdistribution of skin blood flow as the main factor that leads patients to CLI. Revascularization can save limb and patient's life, too. In the present study, LDF signals have been recorded on the skin of the foot dorsum in 15 patients suffering from CLI. LDF signals have been analyzed before and after limb revascularization by means of the wavelet analysis. Significant changes in frequency distribution before and after limb revascularization have been detected: the median normalized values of spectral power increases for 49.8% (p = 0.0341) in the frequency range 0.050328-0.053707 Hz, whereas spectral power decreases for 77.1% (p = 0.0179) in the frequency range 0.018988-0.029284 Hz. We can conclude that changes in the frequency intervals occur after revascularization, shifting from a prevailing endothelial activity toward a prevailing sympathetic activity.

  20. Role of contrast-enhanced ultrasound arterial mapping in surgical planning for patients with critical limb ischemia.

    PubMed

    Mestre, Xavier Martí; Coll, Ramon Vila; Villegas, Antoni Romera; Rico, Carlos Martínez

    2015-06-01

    The goal of the study described here was to evaluate the role of contrast-enhanced ultrasound (CEUS) arterial mapping in surgical planning in cases of critical limb ischemia. From March 2007 to December 2012, 565 consecutive patients with critical limb ischemia of the lower limbs were treated and initially examined with only ultrasound (US) arterial mapping. For 479 of the 565 patients, basic US examination results were deemed sufficient for surgical planning (group A). That is, US examination provided sufficient information to decide a surgical plan to treat those patients. In the remaining 86 patients, basic US examination was insufficient for revascularization planning, and CEUS examination was performed (group B). In 5 cases, CEUS results were also insufficient for surgical planning, as a suitable outflow vessel was not visualized. In these cases, a pre-operative arteriogram was performed. To assess the usefulness of CEUS, we compared results of examinations with and without contrast administration, surgical findings and angiographic findings when available. Data were collected prospectively. Examinations were compared by establishing the degree of agreement between results of paired examinations and degree of agreement between CEUS results and surgical findings. Clinical, hemodynamic (ankle-brachial index) and duplex follow-up was performed at 1 and 3 mo to evaluate cumulative patency of the procedures in each group. Within group B, degree of agreement between basic US and CEUS was 46.5%. CEUS resulted in a change in the surgical plan in 46 of 86 patients. Among all 565 patients, degree of agreement between surgical decision based on basic ultrasound arterial mapping and final decision based on surgical findings was 87.1%, and improved to 95.2% with CEUS (p = 0.00001, κ index = 0.823). Degree of agreement between the ultrasound-based decision and surgical findings was 97.5% in group A (κ index = 0.818) and 94.2% in group B (κ = 0.848). There was no

  1. Acute Stroke and Limb Ischemia Secondary to Catastrophic Massive Intracardiac Thrombus in a 40-Year-Old Patient With Dilated Cardiomyopathy

    PubMed Central

    Jeon, Gi Jung; Song, Bong Gun; Park, Yong Hwan; Kang, Gu Hyun; Chun, Woo Jung; Oh, Ju Hyeon

    2012-01-01

    Dilated cardiomyopathy has been associated with left ventricular (LV) thrombosis which leads to substantial morbidity and mortality as a site for systemic emboli. We report an interesting case of a stroke and acute limb ischemia secondary to a large mobile pedunculated LV thrombus in 40-year-old patient with dilated cardiomyopathy.

  2. Mid-Term Outcomes of Endovascular Treatment for TASC-II D Femoropopliteal Occlusive Disease with Critical Limb Ischemia

    SciTech Connect

    Torres-Blanco, Álvaro Edo-Fleta, Gemma; Gómez-Palonés, Francisco; Molina-Nácher, Vicente; Ortiz-Monzón, Eduardo

    2016-03-15

    PurposeThe purpose of the study was to assess the safety and midterm effectiveness of endovascular treatment in Trans-Atlantic Inter-Society Consensus II (TASC-II) D femoropopliteal occlusions in patients with critical limb ischemia (CLI).MethodsPatients with CLI who underwent endovascular treatment for TASC-D de novo femoropopliteal occlusive disease between September 2008 and December 2013 were selected. Data included anatomic features, pre- and postprocedure ankle-brachial index, duplex ultrasound, and periprocedural complications. Sustained clinical improvement, limb salvage rate, freedom from target lesion revascularization (TLR), and freedom from target extremity revascularization (TER) were assessed by Kaplan–Meier estimation and predictors of restenosis/occlusion with Cox analysis.ResultsThirty-two patients underwent treatment of 35 TASC-D occlusions. Mean age was 76 ± 9. Mean lesion length was 23 ± 5 cm. Twenty-eight limbs (80 %) presented tissue loss. Seventeen limbs underwent treatment by stent, 13 by stent-graft, and 5 by angioplasty. Mean follow-up was 29 ± 20 months. Seven patients required major amputation and six patients died during follow-up. Eighteen endovascular and three surgical TLR procedures were performed due to restenosis or occlusion. Estimated freedom from TLR and TER rates at 2 years were 41 and 76 %, whereas estimated primary and secondary patency rates were 41 and 79 %, respectively.ConclusionsEndovascular treatment for TASC II D lesions is safe and offers satisfying outcomes. This patient subset would benefit from a minimally invasive approach. Follow-up is advisable due to a high rate of restenosis. Further follow-up is necessary to know the long-term efficacy of these procedures.

  3. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI).

    PubMed

    Mills, Joseph L; Conte, Michael S; Armstrong, David G; Pomposelli, Frank B; Schanzer, Andres; Sidawy, Anton N; Andros, George

    2014-01-01

    Critical limb ischemia, first defined in 1982, was intended to delineate a subgroup of patients with a threatened lower extremity primarily because of chronic ischemia. It was the intent of the original authors that patients with diabetes be excluded or analyzed separately. The Fontaine and Rutherford Systems have been used to classify risk of amputation and likelihood of benefit from revascularization by subcategorizing patients into two groups: ischemic rest pain and tissue loss. Due to demographic shifts over the last 40 years, especially a dramatic rise in the incidence of diabetes mellitus and rapidly expanding techniques of revascularization, it has become increasingly difficult to perform meaningful outcomes analysis for patients with threatened limbs using these existing classification systems. Particularly in patients with diabetes, limb threat is part of a broad disease spectrum. Perfusion is only one determinant of outcome; wound extent and the presence and severity of infection also greatly impact the threat to a limb. Therefore, the Society for Vascular Surgery Lower Extremity Guidelines Committee undertook the task of creating a new classification of the threatened lower extremity that reflects these important considerations. We term this new framework, the Society for Vascular Surgery Lower Extremity Threatened Limb Classification System. Risk stratification is based on three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). The implementation of this classification system is intended to permit more meaningful analysis of outcomes for various forms of therapy in this challenging, but heterogeneous population.

  4. LOX-1 plays an important role in ischemia-induced angiogenesis of limbs.

    PubMed

    Shiraki, Takeru; Aoyama, Takuma; Yokoyama, Chiharu; Hayakawa, Yuka; Tanaka, Toshiki; Nishigaki, Kazuhiko; Sawamura, Tatsuya; Minatoguchi, Shinya

    2014-01-01

    LOX-1, lectin-like oxidized low-density lipoprotein (LDL) receptor-1, is a single transmembrane receptor mainly expressed on endothelial cells. LOX-1 mediates the uptake of oxidized LDL, an early step in atherosclerosis; however, little is known about whether LOX-1 is involved in angiogenesis during tissue ischemia. Therefore, we examined the role of LOX-1 in ischemia-induced angiogenesis in the hindlimbs of LOX-1 knockout (KO) mice. Angiogenesis was evaluated in a surgically induced hindlimb ischemia model using laser Doppler blood flowmetry (LDBF) and histological capillary density (CD) and arteriole density (AD). After right hindlimb ischemia, the ischemic/nonischemic hindlimb blood flow ratio was persistently lower in LOX-1 KO mice than in wild-type (WT) mice. CD and AD were significantly smaller in LOX-1 KO mice than in WT mice on postoperative day 14. Immunohistochemical analysis revealed that the number of macrophages infiltrating ischemic tissues was significantly smaller in LOX-1 KO mice than in WT mice. The number of infiltrated macrophages expressing VEGF was also significantly smaller in LOX-1 KO mice than in WT mice. Western blot analysis and ROS production assay revealed that LOX- KO mice show significant decrease in Nox2 expression, ROS production and HIF-1α expression, the phosphorylation of p38 MAPK and NF-κB p65 subunit as well as expression of redox-sensitive vascular cell adhesion molecule-1 (VCAM-1) and LOX-1 itself in ischemic muscles, which is supposed to be required for macrophage infiltration expressing angiogenic factor VEGF. Reduction of VEGF expression successively suppressed the phosphorylation of Akt and eNOS, which accelerated angiogenesis, in the ischemic leg of LOX-1 KO mice. Our findings indicate that LOX-1 plays an important role in ischemia-induced angiogenesis by 1) Nox2-ROS-NF-κB activation, 2) upregulated expression of adhesion molecules: VCAM-1 and LOX-1 and 3) promoting macrophage infiltration, which expresses angiogenic

  5. The protective effect of cilostazol on isolated rabbit femoral arteries under conditions of ischemia and reperfusion: the role of the nitric oxide pathway

    PubMed Central

    Santos, Mariana R.G.A.; Celotto, Andréa C; Capellini, Verena K; Evora, Paulo R B; Piccinato, Carlos E; Joviliano, Edwaldo E

    2012-01-01

    OBJECTIVES: The clinical significance of ischemia/reperfusion of the lower extremities demands further investigation to enable the development of more effective therapeutic alternatives. This study investigated the changes in the vascular reactivity of the rabbit femoral artery and nitric oxide metabolites under partial ischemia/reperfusion conditions following cilostazol administration. METHODS: Ischemia was induced using infrarenal aortic clamping. The animals were randomly divided into seven groups: Control 90 minutes, Ischemia/Reperfusion 90/60 minutes, Control 120 minutes, Ischemia/Reperfusion 120/90 minutes, Cilostazol, Cilostazol before Ischemia/Reperfusion 120/90 minutes, and Ischemia 120 minutes/Cilostazol/Reperfusion 90 minutes. Dose-response curves for sodium nitroprusside, acetylcholine, and the calcium ionophore A23187 were obtained in isolated femoral arteries. The levels of nitrites and nitrates in the plasma and skeletal muscle were determined using chemiluminescence. RESULTS: Acetylcholine- and A23187-induced relaxation was reduced in the Ischemia/Reperfusion 120/90 group, and treatment with cilostazol partially prevented this ischemia/reperfusion-induced endothelium impairment. Only cilostazol treatment increased plasma levels of nitrites and nitrates. An elevation in the levels of nitrites and nitrates was observed in muscle tissues in the Ischemia/Reperfusion 120/90, Cilostazol/Ischemia/Reperfusion, and Ischemia/Cilostazol/Reperfusion groups. CONCLUSION: Hind limb ischemia/reperfusion yielded an impaired endothelium-dependent relaxation of the femoral artery. Furthermore, cilostazol administration prior to ischemia exerted a protective effect on endothelium-dependent vascular reactivity under ischemia/reperfusion conditions. PMID:22358243

  6. Long-Term Outcomes of Diabetic Patients With Critical Limb Ischemia Followed in a Tertiary Referral Diabetic Foot Clinic

    PubMed Central

    Uccioli, Luigi; Gandini, Roberto; Giurato, Laura; Fabiano, Sebastiano; Pampana, Enrico; Spallone, Vincenza; Vainieri, Erika; Simonetti, Giovanni

    2010-01-01

    OBJECTIVE We describe the long-term outcomes of 510 diabetic patients with critical limb ischemia (CLI) and an active foot ulcer or gangrene, seen at the University Hospital of Rome Tor Vergata, a tertiary care clinic. RESEARCH DESIGN AND METHODS These patients were seen between November 2002 and November 2007 (mean follow-up 20 ± 13 months [range 1–66 months]). The Texas Wound Classification was used to grade these wounds that were either class C (ischemia) and D (ischemia+infection) and grade 2–3 (deep–very deep). This comprehensive treatment protocol includes rapid and extensive initial debridement, aggressive use of peripheral percutaneous angioplasty, empirical intravenous antibiotic therapy, and strict follow-up. RESULTS The protocol was totally applied (with percutaneous angioplasty [PA+]) in 456 (89.4%) patients and partially (without percutaneous angioplasty [PA−]) in 54 (10.6%) patients. Outcomes for the whole group and PA+ and PA− patients are, respectively: healing, n = 310 (60.8%), n = 284 (62.3%), and n = 26 (48.1%); major amputation, n = 80 (15.7%), n = 67 (14.7%), and n = 13 (24.1%); death, n = 83 (16.25%), n = 68 (14.9%), and n = 15 (27.8%); and nonhealing, n = 37 (7.25%), n = 37 (8.1%), and n = 0 (0%) (χ2 <0.0009). Predicting variables at multivariate analysis were the following: for healing, ulcer dimension, infection, and ischemic heart disease; and for major amputation, ulcer dimension, number of minor amputations, and age. Additional predicting variables for PA+ patients were the following: for healing, transcutaneous oxygen tension [ΔTcPo2]; and for major amputation, basal TcPo2, basal A1C, ΔTcPo2, and percutaneous angioplasty technical failure. CONCLUSIONS Early diagnosis of CLI, aggressive treatment of infection, and extensive use of percutaneous angioplasty in ischemic affected ulcers offers improved outcome for many previously at-risk limbs. Ulcer size >5 cm2 indicates a reduced chance of healing and increased risk of major

  7. Liposome-encapsulated hemoglobin improves energy metabolism in skeletal muscle ischemia and reperfusion in the rat.

    PubMed

    Kurita, Daisuke; Kawaguchi, Akira T; Aso, Kensuke; Yamano, Mariko; Minamitani, Haruyuki; Haida, Munetaka

    2012-02-01

    The effect of liposome-encapsulated hemoglobin (LEH) was tested in a rodent model of limb ischemia and reperfusion--causing local reperfusion injury and a cascade of systemic responses. Intracellular pH (pHi) and phosphocreatine (PCr)/inorganic phosphate (Pi) ratio were serially monitored using ³¹P-nuclear magnetic resonance spectroscopy with a 2-cm solenoid coil on a rodent hind limb. After baseline measurements, the right hind limb underwent ischemia for 70 min, followed 10 min later by intravenous administration of LEH (10 mL/kg, n = 6), homologous red blood cells (RBCs, n = 6), saline (n = 6), or no treatment (n = 6). Reperfusion was then observed for an additional 60 min. While pHi decreased precipitously after the onset of ischemia and even following reperfusion, LEH-treated rats had significantly milder intracellular acidosis compared with all other groups during ischemia, and after reperfusion as well throughout the observation with the saline-treated rats. In contrast, the PCr/Pi ratio decreased regardless of treatment after ischemia until reperfusion, when the ratio returned toward normal or the energy status improved only in the LEH-treated rats, while the ratio remained depressed in the control animals receiving RBC, saline, or no treatment. Morphological studies 7 days later revealed a tendency toward suppressed mononuclear cell infiltration with preservation of muscular mass and structure in the LEH-treated rats. LEH treatment after early limb ischemia appeared to improve intracellular energy metabolism and eventually preserve skeletal muscle in a rodent model of limb ischemia and reperfusion.

  8. Pretreatment with Fish Oil-Based Lipid Emulsion Modulates Muscle Leukocyte Chemotaxis in Murine Model of Sublethal Lower Limb Ischemia

    PubMed Central

    Shih, Yao-Ming; Shih, Juey-Ming; Yeh, Chiu-Li; Li, Cheng-Che

    2017-01-01

    This study investigated the effects of a fish oil- (FO-) based lipid emulsion on muscle leukocyte chemotaxis and inflammatory responses in a murine model of limb ischemia-reperfusion (IR) injury. Mice were assigned randomly to 1 sham (sham) group, 2 ischemic groups, and 2 IR groups. The sham group did not undergo the ischemic procedure. The mice assigned to the ischemic or IR groups were pretreated intraperitoneally with either saline or FO-based lipid emulsion for 3 consecutive days. The IR procedure was induced by applying a 4.5 oz orthodontic rubber band to the left thigh above the greater trochanter for 120 min and then cutting the band to allow reperfusion. The ischemic groups were sacrificed immediately while the IR groups were sacrificed 24 h after reperfusion. Blood, IR-injured gastrocnemius, and lung tissues were collected for analysis. The results showed that FO pretreatment suppressed the local and systemic expression of several IR-induced proinflammatory mediators. Also, the FO-pretreated group had lower blood Ly6ChiCCR2hi monocyte percentage and muscle M1/M2 ratio than the saline group at 24 h after reperfusion. These findings suggest that FO pretreatment may have a protective role in limb IR injury by modulating the expression of proinflammatory mediators and regulating the polarization of macrophage. PMID:28182087

  9. High-Mobility Group Box-1 Protein Promotes Angiogenesis After Peripheral Ischemia in Diabetic Mice Through a VEGF-Dependent Mechanism

    PubMed Central

    Biscetti, Federico; Straface, Giuseppe; De Cristofaro, Raimondo; Lancellotti, Stefano; Rizzo, Paola; Arena, Vincenzo; Stigliano, Egidio; Pecorini, Giovanni; Egashira, Kensuke; De Angelis, Giulia; Ghirlanda, Giovanni; Flex, Andrea

    2010-01-01

    OBJECTIVE High-mobility group box-1 (HMGB1) protein is a nuclear DNA-binding protein released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. Diabetic human and mouse tissues contain lower levels of HMGB1 than their normoglycemic counterparts. Deficient angiogenesis after ischemia contributes to worse outcomes of peripheral arterial disease in patients with diabetes. To test the hypothesis that HMGB1 enhances ischemia-induced angiogenesis in diabetes, we administered HMGB1 protein in a mouse hind limb ischemia model using diabetic mice. RESEARCH DESIGN AND METHODS After the induction of diabetes by streptozotocin, we studied ischemia-induced neovascularization in the ischemic hind limb of normoglycemic, diabetic, and HMGB1-treated diabetic mice. RESULTS We found that the perfusion recovery was significantly attenuated in diabetic mice compared with normoglycemic control mice. Interestingly, HMGB1 protein expression was lower in the ischemic tissue of diabetic mice than in normoglycemic mice. Furthermore, we observed that HMGB1 administration restored the blood flow recovery and capillary density in the ischemic muscle of diabetic mice, that this process was associated with the increased expression of vascular endothelial growth factor (VEGF), and that HMGB1-induced angiogenesis was significantly reduced by inhibiting VEGF activity. CONCLUSIONS The results of this study show that endogenous HMGB1 is crucial for ischemia-induced angiogenesis in diabetic mice and that HMGB1 protein administration enhances collateral blood flow in the ischemic hind limbs of diabetic mice through a VEGF-dependent mechanism. PMID:20200317

  10. [The use of vascular prothesis Gore Viabahn in the managment of the lower limbs ischemia].

    PubMed

    Pupka, Artur; Szyber, Przemysław Piotr; Skóra, Jan; Pawłowski, Stanisław

    2011-01-01

    The chronic lower limbs ischaemia is caused mainly by arteriosclerosis. After insufficient conservative treatment only the surgical intervention can salvage the limb. The revascularisation surgery can be performed by open surgery with implantation of the prosthetic bypass or by endovascular angioplasty with stent. This second method seems to be the best alternative for the patients with several concomitant systemic diseases. Nevertheless it is limited by presence of the long-distance arteriosclerotic lesions. The resolve of that problem is use of new generation of long endovascular covered stents. They can be succesfuly used in aorto-femoral and femoro-popliteal segment. Their efficiacy is simmilar to traditional prosthetic grafts.

  11. Alternative Techniques for Treatment of Complex Below-the Knee Arterial Occlusions in Diabetic Patients With Critical Limb Ischemia

    SciTech Connect

    Gandini, Roberto; Uccioli, Luigi; Spinelli, Alessio; Del Giudice, Costantino Ros, Valerio Da; Volpi, Tommaso; Meloni, Marco; Simonetti, Giovanni

    2013-02-15

    The purpose of this study was to describe alternative endovascular (EV) techniques and assess their feasibility and efficacy in minimizing failure rates in limb salvage for the treatment of complex below-the knee (BTK) occlusions that could not be crossed with a conventional antegrade access. Between December 2007 and November 2010, 1,035 patients (557 male) underwent EV treatment for critical limb ischemia in our institution. In 124 (12% [83 male], mean age 68.2 {+-} 0.5 years) patients, transfemoral antegrade revascularization attempt failed, and an alternative approach was used. Follow-up was performed at 1 and 6 months. Results were compared with 56 patients treated between November 2002 and November 2007, in whom conventional technique was unsuccessful and unconventional techniques were not adopted. Technical success was achieved in 119 (96%) patients. The limb-salvage rates were 96.8% and 83% at 1- and 6-month follow-up, respectively. Sixteen (12.9%) and 33 (26.6%) patients underwent reintervention at 1- and 6-month follow-up, respectively. Transcutaneous oxygen tension increased at 1 month (44.7 {+-} 1.1 vs. 15.7 {+-} 0.8 mmHg; p < 0.001) and remained stable at follow-up. Twenty (16.1%) patients required major amputation. Thirteen (10.4%) patients died during follow-up. In our previous experience, percutaneous transluminal angioplasty failure, amputation, and death rates were 10.9, 39.2, and 23.2%, respectively. Alternative techniques allowed a significant decrease of major amputation and death rates (p = 0.0001 and p = 0.02, respectively). The use of alternative techniques seems feasible in case of a failed antegrade BTK revascularization attempt and could minimize failure rates in the treatment of complex occlusions while providing satisfying clinical success rates at 6 months.

  12. Results of distal revascularization in elderly patients for critical ischemia of the lower limbs.

    PubMed

    Illuminati, G; Calio, F G; Bertagni, A; Piermattei, A; Vietri, F; Martinelli, V

    1999-04-01

    Thirty eight patients over 75 years of age were operated upon of 40 distal arterial revascularizations for critical ischaemia of the lower limbs. Arterial reconstruction was proposed to ambulatory, self sufficient patients, with a patent artery of the leg or the foot in continuity with pedal arch, at arteriography. The revascularized artery was the peroneal in 14 cases, the anterior tibial in 11, the posterior tibial in 9, the dorsalis pedis in 5, and the external plantar artery in 1 case. Postoperative mortality was 2.6%. No postoperative arterial occlusion occurred and no postoperative amputation needed to be performed. The mean follow-up of 37 patients surviving operation was 21 months (ext. 2-52 months). At 36 months interval, patients' survival was 43%, primary patency rate was 57%, and limb salvage rate was 76%, at life-table analysis. Distal revascularization enables a good number of elderly patients in critical ischaemia of the lower limb, to enjoy an active, independent life, with a viable limb.

  13. [The results in chronic ischemia of the lower limbs. The Granada-90 Geriatric Angiology Study (2)].

    PubMed

    Peñafiel Marfil, R; García Rospide, V; Moreno Padilla, F; González Ríos, F J; Ros Die, E

    1992-01-01

    Results of a study about the chronic ischaemia of the lower limbs and its correlation with age, sex and previous diagnosis, are presented. Also, a comparison between previous diagnosis and results following the methodology exposed, was made. Study group included 433 older patients, randomizadely selected and permanent residents of some geriatric centers of the Oriental Andalucy.

  14. Cilostazol improves the response to ischemia in diabetic mice by a mechanism dependent on PPARγ.

    PubMed

    Biscetti, Federico; Pecorini, Giovanni; Arena, Vincenzo; Stigliano, Egidio; Angelini, Flavia; Ghirlanda, Giovanni; Ferraccioli, Gianfranco; Flex, Andrea

    2013-12-05

    Cilostazol is effective for the treatment of peripheral ischemia. This compound has several beneficial effects on platelet aggregation, serum lipids and endothelial cells, and we recently found that it enhances collateral blood flow in the ischemic hind limbs of mice. Peroxisome proliferator-activated receptor (PPAR)γ, a receptor for thiazolidinediones, plays a role in angiogenesis. The aim of this work was to investigate the underlying molecular mechanisms and effects of cilostazol in a model of peripheral ischemia in diabetic mice. We induced diabetes in mice by streptozotocin (STZ) administration and studied ischemia-induced angiogenesis in the ischemic hind limbs of cilostazol-treated and untreated control mice. We found that perfusion recovery was significantly improved in treated compared with control diabetic mice. Interestingly, we found that the expression of PPARγ is reduced in ischemic tissues of diabetic mice. Furthermore, we discovered that local inhibition of the activity of this nuclear receptor decreased the angiogenic response to cilostazol treatment. Finally, we noted that this phenomenon is dependent on VEGF and modulated by PPARγ. Cilostazol administration enhances collateral blood flow in the ischemic hind limbs of STZ-induced diabetic mice through a PPARγ-dependent mechanism.

  15. Endovascular recanalization techniques for popliteal arterial occlusive injury with limb-threatening ischemia secondary to trauma.

    PubMed

    Mine, Takahiko; Murata, Satoru; Yasui, Daisuke; Tajima, Hiroyuki; Kawamata, Hiroshi; Yokota, Hiroyuki; Kumita, Shin-Ichiro

    2014-01-01

    To date, no ideal endovascular strategy has been established for traumatic arterial occlusion. Here, we report the outcomes of a combination of endovascular recanalization techniques applied in two patients with high risk of leg amputation. A 33-year-old man with popliteal artery occlusion due to blunt trauma was treated by balloon angioplasty with long inflation time and aspiration thrombectomy. A 74-year-old woman with popliteal artery occlusion after total knee replacement was treated by aspiration thrombectomy and stent placement. In both cases, we achieved satisfactory recanalization, and peripheral ischemia was absent even 1 year later.

  16. Why critical limb ischemia criteria are not applicable to diabetic foot and what the consequences are.

    PubMed

    Jörneskog, G

    2012-01-01

    Neuropathy, peripheral arterial occlusive disease and microvascular disturbances are important factors contributing to foot problems in diabetic patients. In the diabetic foot with ischemia, the alterations in skin microvascular function are pronounced including severely reduced capillary circulation and abolished hyperaemic responses. These microvascular disturbances, which are superimposed on the already existing structural diabetic microangiopathy, are compatible with a state of "chronic capillary ischemia" and an increased shunting of blood through arteriovenous channels. This maldistribution of blood in skin microcirculation is not detected by measurement of peripheral blood pressure (systolic ankle blood pressure, systolic toe blood pressure). As indicated in several studies toe blood pressure is a poor predictor of local tissue perfusion, tissue survival and healing of chronic foot ulcers. Consequently, the disturbances in peripheral tissue perfusion of the diabetic foot may be underestimated leading to delayed vascular interventions and/or medical treatment. Thus, measurements of peripheral blood pressure, e.g. toe blood pressure, should be combined with investigations of local tissue perfusion in order to get an adequate estimation of peripheral tissue perfusion in diabetic patients. For this purpose local skin microcirculation can be investigated by transcutaneous oxygen tension of the forefoot. Also, due to these reasons, the threshold for revascularization should be lower in diabetic patients with foot ulcer.

  17. Autologous Bone Marrow Mononuclear Cell Therapy is Safe and Promotes Amputation Free Survival in Patients with Critical Limb Ischemia

    PubMed Central

    Murphy, Michael P.; Lawson, Jeffrey H.; Rapp, Brian M.; Dalsing, Michael C.; Klein, Janet; Wilson, Michael G.; Hutchins, Gary D.; March, Keith L.

    2011-01-01

    Objective The purpose of this phase I open label non-randomized trial was to assess the safety and efficacy of autologous bone marrow mononuclear cell (ABMNC) therapy in promoting amputation free survival (AFS) in patients with critical limb ischemia (CLI). Methods Between September 2005 and March 2009 twenty-nine patients (30 limbs), with a median age of 66 (range 23–84) (14 male,15 female) with CLI were enrolled . Twentyone limbs presented with rest pain (RP), six with RP and ulceration, and three with ulcer only. All patients were not candidates for surgical bypass due to absence of a patent artery below the knee and/or endovascular approaches to improving perfusion was not possible as determined by an independent vascular surgeon. Patients were treated with an average dose of 1.7 ± 0.7 × 109 ABMNC injected intramuscularly in the index limb distal to the anterior tibial tuberosity. The primary safety endpoint was accumulation of serious adverse events and the primary efficacy endpoint was AFS at one year. Secondary endpoints at 12 weeks post-treatment were changes in first toe pressure (FTP), toe-brachial index (TBI), ankle-brachial index (ABI), and transcutaneous oxygen measurements (TcPO2). Perfusion of the index limb was measured with PET-CT with intra-arterial infusion of H2O15. Rest pain (RP), using a 10-cm visual analog scale, quality of life using the VascuQuol questionnaire, and ulcer healing were assessed at each follow-up interval. Subpopulations of endothelial progenitor cells were quantified prior to ABMNC administration using immunocytochemistry and fluorescent activated cell sorting. Results There were two serious adverse events however there no procedure related deaths. Amputation-free survival at one-year was 86.3%. There was a significant increase in FTP (10.2+ 6.2 mmHg, P=.02) and TBI (0.10± 0.05, P=.02) and a trend in improvement in ABI (0.08±0.04, P=.73). Perfusion Index by PET-CT H2O15 increased by 19.3 ± 3.1 and RP decreased

  18. Intraarterial Infusion Therapy via a Subcutaneous Port for Limb-Threatening Ischemia: A Pilot Study

    SciTech Connect

    Strecker, Ernst-Peter K.; Ostheim-Dzerowycz, Wladimir; Boos, Irene B.L.

    1998-03-15

    Purpose: To present the initial results of a new percutaneously implantable catheter port system (PIPS) used for long-term intraarterial infusion therapy in patients with severe ischemic limb disease. Methods: Ten patients with deep, extended ischemic ulcerations (all 10) and osteomyelitis (6/10) of the foot received intraarterial infusions of prostaglandine E{sub 1} and antibiotics, if indicated, via a new port catheter system with the port placed subcutaneously above the groin after percutaneous introduction and the catheter tip placed into the superficial or deep femoral artery. Results: Port implantation and repeated port access were uncomplicated. During the follow-up period (mean 11 months, range 1 week-50 months), port migration, leakage, or infection was not observed. Three catheters thrombosed and were opened by fibrinolysis with recombinant tissue plasminogen activator instilled via the port. Treatment success was achieved in 8 patients: relief from rest pain (8 patients), reduction of ulcer size (4/8), and complete healing (4/8). Limb savage rate was 80%. In 2 patients amputation could not be avoided. Conclusion: Selective long-term arterial infusion therapy presents a valuable therapeutic regimen for limb salvage. With the new catheter port system, repeated local intraarterial infusion is safe and simple.

  19. Pedal-plantar loop technique for a challenging below-the-knee chronic total occlusion: a novel approach to percutaneous revascularization in critical lower limb ischemia.

    PubMed

    Fusaro, Massimiliano; Dalla Paola, Luca; Biondi-Zoccai, Giuseppe

    2007-02-01

    Arterial revascularization by means of percutaneous transluminal angioplasty (PTA) is a mainstay in the management of patients with peripheral artery disease and critical limb ischemia (CLI). However, when employing standard approaches, percutaneous transluminal angioplasty (PTA) of below-the-knee arteries may fail in up to 20% of cases. In the present article, we report on a novel interventional strategy, the pedal-plantar loop technique, which we successfully employed in a patient with critical lower limb ischemia. This technique may sensibly increase success rates of PTA in very challenging total occlusions of below-the-knee arteries (e.g., those lacking a proximal occlusion stump). Technical points pertinent to this case are clearly illustrated, including the need to accurately choose guidewires and balloons of appropriate length, and the extensive use of the subintimal angioplasty technique.

  20. Characterization of the Cellular Output of a Point-of-Care Device and the Implications for Addressing Critical Limb Ischemia.

    PubMed

    Woodell-May, Jennifer E; Tan, Matthew L; King, William J; Swift, Matthew J; Welch, Zachary R; Murphy, Michael P; McKale, James M

    2015-01-01

    Critical limb ischemia (CLI) is a terminal disease with high morbidity and healthcare costs due to limb loss. There are no effective medical therapies for patients with CLI to prevent amputation. Cell-based therapies are currently being investigated to address this unmet clinical need and have shown promising preliminary results. The purpose of this study was to characterize the output of a point-of-care cell separator (MarrowStim P.A.D. Kit), currently under investigation for the treatment of CLI, and compare its output with Ficoll-based separation. The outputs of the MarrowStim P.A.D. Kit and Ficoll separation were characterized using an automated hematology analyzer, colony-forming unit (CFU) assays, and tubulogenesis assays. Hematology analysis indicated that the MarrowStim P.A.D. Kit concentrated the total nucleated cells, mononuclear cells, and granulocytes compared with baseline bone marrow aspirate. Cells collected were positive for VEGFR-2, CD3, CD14, CD34, CD45, CD56, CD105, CD117, CD133, and Stro-1 antigen. CFU assays demonstrated that the MarrowStim P.A.D. Kit output a significantly greater number of mesenchymal stem cells and hematopoietic stem cells compared with cells output by Ficoll separation. There was no significant difference in the number of endothelial progenitor cells output by the two separation techniques. Isolated cells from both techniques formed interconnected nodes and microtubules in a three-dimensional cell culture assay. This information, along with data currently being collected in large-scale clinical trials, will help instruct how different cellular fractions may affect the outcomes for CLI patients.

  1. Limb-Threatening Ischemia in a Young Man with Cathinone "Bath Salt" Intoxication: A Case Report.

    PubMed

    Saleh, Asem; Tittley, Jacques; Anand, Sonia

    2016-10-01

    "Bath salts" are synthetic designer drugs that have stimulant properties and are a growing medical concern. The chemical compounds in the mixtures have an affinity for receptors in the brain resulting in a stimulant effect similar to that seen with methamphetamines and cocaine. Although illegal in Canada, these drugs are widely available online with over 20 synthetic drugs marketed as "bath salts" and used increasingly among recreational drug users. Much of the medical literature regarding these drugs comes from emergency medicine case reports, which outline the acute, severe medical, and psychiatric effects of "bath salt" toxicity. In this report, we outline severe vascular limb compromise, which occurred in a 24-year-old man who took large doses of bath salts obtained online from China. We detail our experience to re-establish perfusion to the limbs, and the morbidities encountered due to the ischemic insult our patient experienced. The duration and clinical presentation of "bath salt" toxicity are frequently complicated by lack of toxicology screens for the agents on board, and lack of any pharmacokinetic evidence surrounding these synthetic compounds. Although "bath salts" are now illegal in Canada, these drugs are widely available online and have become an increasing public health concern that involves significant morbidity and mortality to users. Creating a base of knowledge and front-line experience are the only current tool in combating the diverse detrimental aftermath of these synthetic agents' abuse.

  2. Phase Ib Safety, Two-Dose Study of MultiGeneAngio in Patients with Chronic Critical Limb Ischemia.

    PubMed

    Flugelman, Moshe Y; Halak, Moshe; Yoffe, Boris; Schneiderman, Jacob; Rubinstein, Chen; Bloom, Allan-Isaac; Weinmann, Eran; Goldin, Ilya; Ginzburg, Victor; Mayzler, Olga; Hoffman, Aaron; Koren, Belly; Gershtein, Diana; Inbar, Michal; Hutoran, Marina; Tsaba, Adili

    2017-03-01

    Critical limb ischemia (CLI) is the most severe presentation of peripheral arterial disease. We developed cell-based therapy entailing intra-arterial injection of autologous venous endothelial cells (ECs) modified to express angiopoietin 1, combined with autologous venous smooth muscle cells (SMCs) modified to express vascular endothelial growth factor. This combination promoted arteriogenesis in animal models and was safe in patients with limiting claudication. In an open-label, phase Ib study, we assessed the safety and efficacy of this therapy in CLI patients who failed or were unsuitable for surgery or intravascular intervention. Of 23 patients enrolled, 18 with rest pain or non-healing ulcers (Rutherford categories 4 and 5) were treated according to protocol, and 5 with significant tissue loss (Rutherford 6) were treated under compassionate treatment. Patients were assigned randomly to receive 1 × 10(7) or 5 × 10(7) (EC-to-SMC ratio, 1:1) of the cell combination. One-year amputation-free survival rate was 72% (13/18) for Rutherford 4 and 5 patients; all 5 patients with Rutherford 6 underwent amputation. Of the 12 with unhealing ulcers at dosing, 6 had complete healing and 2 others had >66% reduction in ulcer size. Outcomes did not differ between the dose groups. No severe adverse events were observed related to the therapy.

  3. FDA perspective on objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia.

    PubMed

    Kumar, Allison; Brooks, Steven S; Cavanaugh, Kenneth; Zuckerman, Bram

    2009-12-01

    The article by Conte et al.(1) on behalf of the Society for Vascular Surgery (SVS) in this issue of the Journal of Vascular Surgery provides guidelines for improving the consistency and interpretability of clinical trials intended to evaluate treatment options for patients with critical limb ischemia (CLI). This article identifies a number of key challenges with conducting and comparing CLI trials, including the wide spectrum of clinical presentations that CLI encompasses, the use of disparate eligibility criteria and endpoint measurements, and logistical and economic considerations that can limit study initiation and completion. The authors propose definitions for a number of performance goals derived from historical surgical literature as a means of reducing the negative impact of these factors. The current editorial reviews aspects of this proposal from the perspective of the authors in terms of their understanding of the statutory obligations of the U.S. Food and Drug Administration (FDA) to regulate the marketing of cardiovascular devices based on valid scientific evidence.

  4. Sulodexide as Adjunctive Therapy in Diabetic Foot Patients With Critical Limb Ischemia Treated With Percutaneous Transluminal Angioplasty.

    PubMed

    Piaggesi, Alberto; Abbruzzese, Lorenza; Mattaliano, Chiara; Bargellini, Irene; Cicorelli, Antonello; Iacopi, Elisabetta; Lunardi, Alessandro; Coppelli, Alberto; Goretti, Chiara; Cioni, Roberto

    2014-06-01

    We evaluated the safety and efficacy of sulodexide, a biocompound of glycosamin-glicans, as adjunct medical therapy to percutaneous transluminal angioplasty (PTA) in diabetes mellitus (DM) patients with critical limb ischemia (CLI). We studied 27 consecutive DM patients with CLI successfully subjected to PTA who, on top of standard antiplatelet therapy, received sulodexide 25 mg bid, and were followed-up for 24 weeks, monitoring adverse events, transcutaneous oxygen tension (TcPO2), ankle-brachial pressure index, pain, and ulcer dimension. At the end of follow-up, ulcer healing, amputation rates, and cardiovascular risk profile of patients were evaluated. Patients were compared with a historical superimposable control group that was treated for the same indications in the same way as the study group, except for sulodexide inception. No differences in ulcer healing and amputation rates were found at the end of follow-up between the groups. In the study group, TcPO2 was significantly (P < .05) higher at the end of follow-up, and pain intensity was reduced more rapidly. Plasma fibrinogen and plasma creatinine concentration were significantly (P < .05) reduced in study group at the end of follow-up. No differences in adverse events were observed between the groups during follow-up. Our data suggest that sulodexide administration after PTA, on top of antiplatelet therapy, may improve the outcome of PTA in DM patients with CLI by improving microcirculatory function.

  5. Effect of thymoquinone, a constituent of Nigella sativa L., on ischemia-reperfusion in rat skeletal muscle.

    PubMed

    Hosseinzadeh, Hossein; Taiari, Samaneh; Nassiri-Asl, Marjan

    2012-05-01

    Thymoquinone have been shown to decrease ischemia-reperfusion injury (IRI) in some tissues such as gastric mucosa and brain. In this study, the effect of thymoquinone was evaluated on an animal model of IRI in the rat hind limb. Hind limb ischemia was induced by clamping the common femoral artery and vein. After 2 h ischemia, the clamp on the femoral vessels was taken off and the animal underwent 1 h reperfusion. Muscle injuries were evaluated by recording the electromyographic (EMG) potentials and performing some biochemical analysis including thiobarbituric acid reactive substances (TBARS), total sulfhydryl (SH) groups, and antioxidant capacity of muscle using ferric reducing ability of plasma (FRAP) assay. Ischemia was induced using free-flap surgery in skeletal muscle. Thymoquinone (20, 40 and 80 mg/kg) and normal saline (10 ml/kg) were administered intraperitoneally 1 h prior to reperfusion. The average peak-to-peak amplitude during ischemic reperfusion was significantly increased in thymoquinone groups in comparison with the control group. Following thymoquinone administration, the total SH contents and antioxidant capacity were elevated in muscle flap. The malondialdehyde (MDA) level was declined significantly in test groups. It is concluded that thymoquinone have some protective effects against the muscle tissue injury caused by lower limb ischemia-reperfusion.

  6. Clinical Outcome Following Infra-Inguinal Percutaneous Transluminal Angioplasy for Critical Limb Ischemia

    SciTech Connect

    Matsagas, Miltiadis I.; Rivera, Marco A.; Tran, Tan; Mitchell, Adam; Robless, Peter; Davies, Alun H.; Geroulakos, George

    2003-06-15

    Objective: The aim of this study was to assess the efficacy and durability of infra-inguinal PTA in patients with CLI, in terms of clinical outcome. Design:Retrospective study of 50 consecutive patients with CLI that were exclusively treated by infra-inguinal PTA. Methods: The indications for intervention were rest pain in seven (14%) patients,non-healing ulcers in 27 (54%), and gangrenous lesions in 16 (32%).Thirty-three (66%) of these patients presented with a single arterial lesion, and the remaining 17 (34%) with multilevel arterial lesions.Kaplan-Meier analysis was used to assess survival, patency,limb-salvage rates, and amputation-free survival. Results: A total of 67 endovascular procedures were performed and 59 (88.1%) of them were considered to be technically successful. The median follow-up period was 12 months (interquartilerange: 17 months). The 30-day mortality was 4%, while the cumulative survival rates at 12, 24, and 36 months were 73%, 67%, and 59%,respectively. The cumulative primary patency rates at 12 and 24 months were 63% and 52%, respectively, and remained unchanged thereafter.The estimated secondary patency rate was 72% at 36 months. There was only one below-knee amputation in the patients that were treated exclusively with infra-inguinal PTA. The cumulative amputation-free survival at the same period was estimated at 60%. Conclusions: Infra-inguinal PTA had a good early and late outcome in this series of patients with a limited life expectancy.These results are comparable to historical results of surgical revascularization in the treatment of CLI. There is need for a randomized study to determine the primary optimal interventional approach for patients with CLI.

  7. Improving the therapeutic efficacy of mesenchymal stromal cells to restore perfusion in critical limb ischemia through pulsed focused ultrasound

    PubMed Central

    Tebebi, Pamela A.; Kim, Saejeong J.; Williams, Rashida A.; Milo, Blerta; Frenkel, Victor; Burks, Scott R.; Frank, Joseph A.

    2017-01-01

    Mesenchymal stem cells (MSC) are promising therapeutics for critical limb ischemia (CLI). Mechanotransduction from pulsed focused ultrasound (pFUS) upregulates local chemoattractants to enhance homing of intravenously (IV)-infused MSC and improve outcomes. This study investigated whether pFUS exposures to skeletal muscle would improve local homing of iv-infused MSCs and their therapeutic efficacy compared to iv-infused MSCs alone. CLI was induced by external iliac arterial cauterization in 10–12-month-old mice. pFUS/MSC treatments were delayed 14 days, when surgical inflammation subsided. Mice were treated with iv-saline, pFUS alone, IV-MSC, or pFUS and IV-MSC. Proteomic analyses revealed pFUS upregulated local chemoattractants and increased MSC tropism to CLI muscle. By 7 weeks post-treatment, pFUS + MSC significantly increased perfusion and CD31 expression, while reducing fibrosis compared to saline. pFUS or MSC alone reduced fibrosis, but did not increase perfusion or CD31. Furthermore, MSCs homing to pFUS-treated CLI muscle expressed more vascular endothelial growth factor (VEGF) and interleukin-10 (IL-10) than MSCs homing to non-pFUS-treated muscle. pFUS + MSC improved perfusion and vascular density in this clinically-relevant CLI model. The molecular effects of pFUS increased both MSC homing and MSC production of VEGF and IL-10, suggesting microenvironmental changes from pFUS also increased potency of MSCs in situ to further enhance their efficacy. PMID:28169278

  8. Improving the therapeutic efficacy of mesenchymal stromal cells to restore perfusion in critical limb ischemia through pulsed focused ultrasound.

    PubMed

    Tebebi, Pamela A; Kim, Saejeong J; Williams, Rashida A; Milo, Blerta; Frenkel, Victor; Burks, Scott R; Frank, Joseph A

    2017-02-07

    Mesenchymal stem cells (MSC) are promising therapeutics for critical limb ischemia (CLI). Mechanotransduction from pulsed focused ultrasound (pFUS) upregulates local chemoattractants to enhance homing of intravenously (IV)-infused MSC and improve outcomes. This study investigated whether pFUS exposures to skeletal muscle would improve local homing of iv-infused MSCs and their therapeutic efficacy compared to iv-infused MSCs alone. CLI was induced by external iliac arterial cauterization in 10-12-month-old mice. pFUS/MSC treatments were delayed 14 days, when surgical inflammation subsided. Mice were treated with iv-saline, pFUS alone, IV-MSC, or pFUS and IV-MSC. Proteomic analyses revealed pFUS upregulated local chemoattractants and increased MSC tropism to CLI muscle. By 7 weeks post-treatment, pFUS + MSC significantly increased perfusion and CD31 expression, while reducing fibrosis compared to saline. pFUS or MSC alone reduced fibrosis, but did not increase perfusion or CD31. Furthermore, MSCs homing to pFUS-treated CLI muscle expressed more vascular endothelial growth factor (VEGF) and interleukin-10 (IL-10) than MSCs homing to non-pFUS-treated muscle. pFUS + MSC improved perfusion and vascular density in this clinically-relevant CLI model. The molecular effects of pFUS increased both MSC homing and MSC production of VEGF and IL-10, suggesting microenvironmental changes from pFUS also increased potency of MSCs in situ to further enhance their efficacy.

  9. Three-Dimensional Rotational Angiography of the Foot in Critical Limb Ischemia: A New Dimension in Revascularization Strategy

    SciTech Connect

    Jens, Sjoerd; Lucatelli, Pierleone; Koelemay, Mark J. W.; Marquering, Henk A. Reekers, Jim A.

    2013-06-15

    Purpose. To evaluate the additional value of three-dimensional rotational angiography (3DRA) of the foot compared with digital subtraction angiography (DSA) in patients with critical limb ischemia (CLI). Technique. For 3DRA, the C-arm was placed in the propeller position with the foot in an isocentric position. The patient's unaffected foot was positioned in a footrest outside the field of view. For correct timing of 3DRA, the delay from contrast injection in the popliteal artery at the level of knee joint to complete pedal arterial enhancement was assessed using DSA. With this delay, 3DRA was started after injection of 15 ml contrast. Imaging of the 3DRA could directly be reconstructed and visualized.Materials and MethodsPatients undergoing 3DRA of the foot were prospectively registered. DSA and 3DRA images were scored separately for arterial patency and presence of collaterals. Treatment strategies were proposed based on DSA with and without the availability of 3DRA. Results. Eleven patients underwent 3DRA of the foot. One 3DRA was not included because the acquisition was focused on the heel instead of the entire foot. Diagnostic quality of 3DRA was good in all ten patients. 3DRA compared with DSA showed additional patent arteries in six patients, patent plantar arch in three patients, and collaterals between the pedal arteries in five patients. Additional information from 3DRA resulted in a change of treatment strategy in six patients. Conclusion, 3DRA of the foot contains valuable additional real-time information to better guide peripheral vascular interventions in patients with CLI and nonhealing tissue lesions.

  10. Infrapopliteal calcification patterns in critical limb ischemia: diagnostic, pathologic and therapeutic implications in the search for the endovascular holy grail.

    PubMed

    Mustapha, Jihad A; Diaz-Sandoval, Larry J; Saab, Fadi

    2017-02-27

    Critical limb ischemia (CLI) represents the terminal stage of peripheral arterial disease (PAD) and is characterized by multilevel and multivessel disease. Amongst patients with infrainguinal disease, approximately one third have predominantly isolated infrapopliteal disease and the remaining two thirds, a combination of femoropopliteal and infrapopliteal disease. Isolated infrapopliteal disease is mainly seen in the elderly, diabetic, or dialysis-dependent patients. These patients have higher risk of amputation and shorter amputation-free survival. Infrapopliteal disease presents with either complex high-grade calcified tandem lesions in multiple vessels or with long chronic total occlusion (CTO) segments with plaques characterized by higher calcium and lower fibro-fatty content than the inflow vessels, as arterial calcium deposition increases as we progress distally in the arterial tree. Vascular calcification occurs in both intima and media. Intimal calcification leads to development of calcified atheroma and occlusive lesions. Medial calcification leads to stiffening and decrease in arterial wall elasticity and compliance leading to atherosclerosis, reduced perfusion, and PAD, increasing cardiovascular mortality among patients with end-stage renal disease. This article attempts to review the implications of the diverse pathologic patterns of calcium distribution in infrapopliteal vessels of CLI patients, on the diagnostic modalities, technological developments, and the evolution of therapeutic approaches to improve outcomes among these patients. A critical analysis of the currently available data is provided, pointing to the surprising omission on the role of calcium on outcomes, and future directions are discussed. Is infrapopliteal calcium a roadblock or the avenue towards new paths? Necessity remains the mother of invention.

  11. AMS INSIGHT--absorbable metal stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis.

    PubMed

    Bosiers, Marc; Peeters, Patrick; D'Archambeau, Olivier; Hendriks, Jeroen; Pilger, Ernst; Düber, Christoph; Zeller, Thomas; Gussmann, Andreas; Lohle, Paul N M; Minar, Erich; Scheinert, Dierk; Hausegger, Klaus; Schulte, Karl-Ludwig; Verbist, Jürgen; Deloose, Koen; Lammer, J

    2009-05-01

    Endoluminal treatment of infrapopliteal artery lesions is a matter of controversy. Bioabsorbable stents are discussed as a means to combine mechanical prevention of vessel recoil with the advantages of long-term perspectives. The possibility of not having a permanent metallic implant could permit the occurrence of positive remodeling with lumen enlargement to compensate for the development of new lesions. The present study was designed to investigate the safety of absorbable metal stents (AMSs) in the infrapopliteal arteries based on 1- and 6-month clinical follow-up and efficacy based on 6-month angiographic patency. One hundred seventeen patients with 149 lesions with chronic limb ischemia (CLI) were randomized to implantation of an AMS (60 patients, 74 lesions) or stand-alone percutaneous transluminal angioplasty (PTA; 57 patients, 75 lesions). Seven PTA-group patients "crossed over" to AMS stenting. The study population consisted of patients with symptomatic CLI (Rutherford categories 4 and 5) and de novo stenotic (>50%) or occlusive atherosclerotic disease of the infrapopliteal arteries who presented with a reference diameter of between 3.0 and 3.5 mm and a lesion length of <15 mm. The primary safety endpoint was defined as absence of major amputation and/or death within 30 days after index intervention and the primary efficacy endpoint was the 6-month angiographic patency rate as confirmed by core-lab quantitative vessel analysis. The 30-day complication rate was 5.3% (3/57) and 5.0% (3/60) in patients randomized for PTA alone and PTA followed by AMS implantation, respectively. On an intention-to-treat basis, the 6-month angiographic patency rate for lesions treated with AMS (31.8%) was significantly lower (p = 0.013) than the rate for those treated with PTA (58.0%). Although the present study indicates that the AMS technology can be safely applied, it did not demonstrate efficacy in long-term patency over standard PTA in the infrapopliteal vessels.

  12. Combined autologous bone marrow mononuclear cell and gene therapy as the last resort for patients with critical limb ischemia

    PubMed Central

    Skóra, Jan; Pupka, Artur; Janczak, Dariusz; Barć, Piotr; Dawiskiba, Tomasz; Korta, Krzysztof; Baczyńska, Dagmara; Garcarek, Jerzy

    2014-01-01

    Introduction Our study was designed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell (MNC) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia (CLI). Material and methods Thirty-two patients with CLI persisting for 12–48 months (average time 27.5 months) were randomized into 2 groups, each group consisting of 16 patients. In the first group, administration of autologous bone marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed. The patients from the second group were treated pharmacologically with pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was performed before and finally 3 months after treatment. The pain was evaluated using the Visual Analog Scale (VAS) before and after 3 months. Results Ankle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 (p < 0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1. In this group angiography showed the development of collateral vessels. Ischemic ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not improve in any patient; moreover the complete healing of skin ulcers was not found in any of the patients of this group. Amputation was performed in 4 (25.0%) patients in group 1, and in 8 patients (50%) from group 2. Conclusions These data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe, and a more feasible and effective method of treatment than the conventional therapy. However, both therapies are limited by the degree of microcirculation damage. PMID:25995748

  13. Rationale and Design of Randomized Clinical Trial for the Assessment of Macitentan Efficiency as Coadjuvant Treatment to Open and Endovascular Revascularization in Critical Limb Ischemia

    PubMed Central

    Michel, Ignacio; De Haro, Joaquin; Bleda, Silvia; Laime, Ilsem V.; Uyaguari, Jhenifer; Acin, Francisco

    2016-01-01

    INTRODUCTION Critical limb ischemia (CLI) is defined by ischemic rest pain, tissue loss, or both, secondary to arterial insufficiency, and its prevalence is increasing mainly as a result of the worldwide high prevalence of diabetes. Currently, there are no available conclusive data on the efficacy of any coadjuvant therapy after revascularization procedure benefiting amputation and patency rates. Macitentan is an orally active dual endothelin (ET) receptor antagonist that may contribute to reduce the amputation rate and improve revascularization patency in CLI. METHODS/DESIGN REVASC is a proposed pilot, open-label, controlled, randomized, single-center clinical double-blind trial to be conducted in Spain on a study population of European patients with CLI, which will compare the clinical outcomes and cost-effectiveness of macitentan coadjuvant treatment after limb revascularization with the standard antiplatelet treatment strategy for severe limb ischemia. Patients are randomized 1:1 to receive macitentan or placebo for 12 weeks. The primary clinical end point will be amputation-free survival rate at 12 months, defined as the time to major (above the ankle) amputation for the index (trial) limb or death from any cause, whichever comes first. Secondary outcomes include overall survival, quality of life, in-hospital mortality and morbidity, repeat interventions, healing of tissue loss, and hemodynamic changes following revascularization. Sample size is estimated as 120 patients. The economic analysis will consist of two components: a “within-study” analysis, which will be based on study end points; and a “model-based” analysis, which will extrapolate and compare costs and effects likely to accrue beyond the study follow-up period. DISCUSSION The REVASC trial is designed to be pragmatic and represents current practice of the real-world population management after limb revascularization for CLI due to atherosclerosis. Current evidence does not support any

  14. An experimental model of ischemia in rabbit hindlimb.

    PubMed Central

    Hong, J. H.; Bahk, Y. W.; Suh, J. S.; Kwak, B. K.; Shim, H. J.; Kim, J. S.; Kim, H. S.; Moon, Y. H.; Kim, S. J.; Chung, J. W.; Park, J. H.

    2001-01-01

    This study was performed to establish an experimental model of ischemia for the investigation of new treatment modality of limb-threatening ischemia. We produced ischemia in the hindlimbs of 8 New Zealand white rabbits. Under general anesthesia, the left femoral artery was exposed, freed, and excised from distal external iliac artery to proximal popliteal and saphenous arteries. And then both hindlimbs were serially examined to assess the ischemia according to the time table until postoperative 6 weeks. We assessed clinical observation, blood pressure, radioisotopic perfusion scan, and angiography. Clinical ischemic changes of the operated feet were observed in 63%. The blood pressure of left calves was measurable on postoperative day 3 (p<0.05, vs preoperative day 2) and then gradually increased to reach a plateau in postoperative week 6. Radioisotopic arterial perfusion showed similar profiles as in blood pressure. Angiography of ischemic hindlimbs demonstrated a few collateral vessels arising from the internal iliac artery with the reconstitution of the posterior tibial artery in postoperative week 2. In postoperative week 6, collaterals remained the same in number. However, these became dilated and tortuous and showed reconstitution in distal hindleg. In conclusion, this is a reproducible, measurable, and economical animal model of hind limb ischemia. PMID:11641535

  15. Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression.

    PubMed

    Wang, T; Zhou, Y T; Chen, X N; Zhu, A X

    2014-09-01

    Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T0), 1 h (T1), 3 h (T3), 6 h (T6), 12 h (T12), and 24 h (T24). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T0-T24), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.

  16. Platelet-derived miR-92a downregulates cysteine protease inhibitor cystatin C in type II diabetic lower limb ischemia

    PubMed Central

    ZHANG, YUNFENG; GUAN, QIANG; JIN, XING

    2015-01-01

    The aim of the present study was to investigate the effect of microRNA (miR)-92a on cystatin C expression in patients with type II diabetes and lower limb ischemia. A total of 199 patients diagnosed with type II diabetes were included in the study and divided into three experimental groups: Simple type II diabetes mellitus (T2DM; n=60) group; type II diabetes with light to moderate occlusion (LLI-LM; n=70) group; and the type II diabetes with severe occlusion (LLI-S; n=69) group according to the patient ankle-brachial index score. In addition, 60 healthy individuals were examined as a control population. The expression levels of various biochemical indices were detected, including cystatin C in the peripheral blood. The expression levels of miR-92a and cystatin C mRNA were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the correlation between miR-92a, cystatin C and the pathological development of type II diabetic lower limb ischemia was analyzed. The protein expression levels of cystatin C were detected using western blot analysis. Bioinformatic analysis indicated that miR-92a was able to downregulate cystatin C expression, and this result was supported by endothelial cell transfection. In the transfection assay, an miR-92a mimic downregulated cystatin C expression, while an miR-92a inhibitor upregulated cystatin C expression. The results of the RT-qPCR indicated that the expression levels of miR-92a in the LLI-S group were reduced compared with those in the T2DM and LLI-LM groups, and significantly lower compared with those in the negative control group. Platelet-derived miR-92a appeared to downregulate cystatin C expression in patients with type II diabetes and lower limb ischemia. Therefore, the combined detection of miR-92a and cystatin C may be useful as a method for clinically screening patients with type II diabetes for lower limb ischemia. PMID:26136970

  17. Simvastatin inhibits inflammation in ischemia-reperfusion injury.

    PubMed

    Zhao, Yilin; Feng, Qingzhao; Huang, Zhengjie; Li, Wenpeng; Chen, Baisheng; Jiang, Long; Wu, Binglin; Ding, Weiji; Xu, Gang; Pan, Heng; Wei, Wei; Luo, Weiyuan; Luo, Qi

    2014-10-01

    Ischemia/reperfusion (I/R) is associated with leukocyte accumulation and tissue injury. The aim of this research was to investigate the protective effect of simvastatin on hind limb I/R inflammation and tissue damage. Mice were subjected to hind limb ischemic insult for 2 h and were simultaneously administered an intraperitoneal injection of simvastatin (5 mg/kg); this was followed by 36 h of reperfusion. Myeloperoxidase (MPO) levels in the muscles of the hind limb were determined. CXC chemokines and pro-inflammatory cytokines, such as macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and P-selectin, were assessed using enzyme-linked immunosorbent assay (ELISA). Leukocyte rolling and adhesion in vitro was assessed to indicate leukocyte recruitment at the site of inflammation. Quantitative measurement of skeletal muscle tissue injury was performed. The fluorescent dye level in tissue and serum was used to determine hind limb vascular leakage and tissue edema after I/R. Systemic and differentiated leukocytes were also counted. Simvastatin significantly reduced MIP-2, KC, TNF-α, MPO, IL-6, and P-selectin levels compared to the sham group and I/R plus pretreatment with phosphate-buffered saline (PBS) group (P<0.05). Compared to the sham group and I/R plus PBS group, the I/R plus simvastatin group had attenuated inflammation, vascular leakage, and muscular damage (P<0.05). Simvastatin also significantly inhibited leukocyte rolling and adhesion compared to PBS (P<0.05). Our results suggest that simvastatin may be an effective protectant against tissue injury associated with I/R.

  18. The BEST-CLI trial: a multidisciplinary effort to assess whether surgical or endovascular therapy is better for patients with critical limb ischemia.

    PubMed

    Menard, Matthew T; Farber, Alik

    2014-03-01

    Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease and is associated with a risk of limb loss. This vascular condition is currently treated with limb revascularization by surgery or endovascular intervention performed by a variety of specialists. Because both open vascular bypass and the less invasive endovascular therapy can be performed in selected patients with CLI, there exists significant disagreement as to which therapy should be performed first and which is more successful. The paucity of comparative effectiveness data to guide treatment of CLI has prompted a multidisciplinary effort to organize the Best Endovascular Versus Best Surgical Therapy in Patients With CLI (BEST-CLI) trial. The BEST-CLI trial is a pragmatic, multicenter, open-label, randomized trial that compares best endovascular therapy with best open surgical treatment in patients eligible for both treatments. BEST-CLI aims to provide urgently needed clinical guidance for CLI management by using a pragmatic design comparing the effectiveness of established techniques while allowing for the introduction of newer therapies as they become available; a novel primary endpoint that includes limb amputation rates, repeat intervention, and mortality; a multidisciplinary structure that fosters cooperation among interventional cardiologists, interventional radiologists, vascular surgeons, and vascular medicine specialists; and novel techniques to evaluate the cost-effectiveness and quality-of-life outcomes of the two treatment strategies being tested.

  19. Increased Pre-operative Pulse Pressure Predicts Procedural Complications and Mortality in Patients Undergoing Tibial Interventions for Critical Limb Ischemia

    PubMed Central

    Darling, Jeremy D.; Lee, Vanessa; Schermerhorn, Marc L.; Guzman, Raul J.

    2015-01-01

    Introduction Pulse pressure is a non-invasive measure of arterial stiffness. Elevated pulse pressure is associated with an increased risk of cardiovascular events and death. The effects of pulse pressure on outcomes after endovascular interventions for critical limb ischemia (CLI), however, are unknown. We thus evaluated whether increased pre-operative pulse pressure was associated with adverse outcomes and mortality in patients undergoing endovascular tibial artery intervention. Methods All patients undergoing endovascular tibial intervention for CLI at a single institution from 2004 to 2014 were included in this study. Pre-operative pulse pressure was derived from measurements obtained in the holding area prior to the procedure. Patients were divided into 2 groups based on pulse pressure, < 80 or ≥ 80. Patient demographics and co-morbidities were documented, and outcomes including procedural complications, repeat intervention, amputation, and mortality were recorded. Multivariable logistic regression was utilized to account for patient demographics and comorbidities. Results Of 371 patients, 186 patients had a pre-operative pulse pressure <80 and 185 had a pre-operative pulse pressure ≥80. No significant differences in patient demographics or comorbidities were identified; however there was a trend toward older age in patients with elevated pulse pressure (70 vs. 72, P = 0.07). On univariate analysis, procedural complications (21% vs. 13%, P = 0.02), reinterventions (26% vs. 17%, P < 0.01), and restenosis (32% vs. 23%, P = 0.03) were more common among patients with pulse pressure ≥ 80. Procedural complications remained significant on multivariate analysis (OR 1.8, 95% CI 1.0-3.1, P = 0.04). There was no difference in 30-day mortality; however increased mortality was seen at 5 years of follow-up (OR: 1.6, 95% CI: 1.0-2.5, P = 0.04) following multivariable analysis. Conclusions Increased pre-operative pulse pressure is associated with procedural complications

  20. CXCR4 Overexpression in Human Adipose Tissue-Derived Stem Cells Improves Homing and Engraftment in an Animal Limb Ischemia Model.

    PubMed

    Kim, MiJung; Kim, Dong-Ik; Kim, Eun Key; Kim, Chan-Wha

    2017-02-16

    We investigated the effects of transplantation of CXCR4-overexpressing adipose tissue-derived stem cells (ADSCs) into a mouse diabetic hindlimb ischemia model on homing and engraftment as early as 48 h after transplant. CXCR4-overexpressing ADSCs were intramuscularly or intravenously injected into diabetic mice with hindlimb ischemia. After 48 h, muscle tissues in the femur and tibia were collected, and the CXCR4 expression pattern was analyzed by immunofluorescence staining. The homing and engraftment of transplanted CXCR4-overexpressing ADSCs into the ischemic area were significantly increased, and intravenous (systemic) injection resulted in the more effective delivery of stem cells to the target site 48 h posttransplantation. Furthermore, CXCR4-overexpressing ADSCs more efficiently contributed to long-term engraftment and muscle tissue regeneration than normal ADSCs in a limb ischemia model. In addition, the homing and engraftment of ADSCs were correlated with the CXCR4 transfection efficiency. These results demonstrated that enhanced CXCR4 signaling could significantly improve the early homing and engraftment of ADSCs into ischemic areas as well as the long-term engraftment and ultimate muscle tissue regeneration.

  1. A study of the relationships of changes in pain and gait after tourniquet-induced ischemia-reperfusion in rats

    PubMed Central

    Aihara, Kazuki; Ono, Takeya; Umei, Namiko; Tsumiyama, Wakako; Tasaka, Atsushi; Ishikura, Hideki; Sato, Yuta; Matsumoto, Tomohiro; Oki, Sadaaki

    2017-01-01

    [Purpose] The purpose of this study was to determine the relationships of changes in pain and gait after ischemia reperfusion was induced by tourniquet in rats. [Subjects and Methods] The subjects were six ten-week-old male Wistar rats. Ischemia was induced in the left lower limbs of the experimental rats at a pressure of 300 mmHg for 90 minutes. Pain behavior evaluations were measured using the von Frey test in all the rats’ hind limbs. A consistently increasing plantar stimulus was applied until the rats exhibited an escape behavior. For the evaluation of gait, a two-dimensional motion analysis system was used to measure the distance from the calcaneus to the floor (DCF) and toe extension angle (TEA) during gait. The evaluations were performed in the normal state, 3 hours after ischemia-reperfusion, and daily until 7 days after ischemia-reperfusion. [Results] Compared with the normal state, the means of the pain threshold showed a significant decrease until 4 days after ischemia. In addition, both TEA and DCF continued to show a significant decrease at 7 days after ischemia as compared with the normal state. [Conclusion] This study revealed that hyperalgesia occurs after ischemia-reperfusion, and recovery of hyperalgesia occurred earlier than gait dysfunction recovery. PMID:28210050

  2. Safety and Effectiveness of Bone Marrow Cell Concentrate in the Treatment of Chronic Critical Limb Ischemia Utilizing a Rapid Point-of-Care System

    PubMed Central

    Gupta, Saniya; Sethi, Dalip; Powell, Richard J.; Harris, Kenneth Lee; Jungla, Nungshi; Arambam, Priyadarshini; Kaul, Upendra; Seth, Ashok; Bukhari, Suhail

    2017-01-01

    Critical limb ischemia (CLI) is the end stage of lower extremity peripheral vascular disease (PVD) in which severe obstruction of blood flow results in ischemic rest pain, ulcers and/or gangrene, and a significant risk of limb loss. This open-label, single-arm feasibility study evaluated the safety and therapeutic effectiveness of autologous bone marrow cell (aBMC) concentrate in revascularization of CLI patients utilizing a rapid point-of-care device. Seventeen (17) no-option CLI patients with ischemic rest pain were enrolled in the study. Single dose of aBMC, prepared utilizing an intraoperative point-of-care device, the Res-Q™ 60 BMC system, was injected intramuscularly into the afflicted limb and patients were followed up at regular intervals for 12 months. A statistically significant improvement in Ankle Brachial Index (ABI), Transcutaneous Oxygen Pressure (TcPO2), mean rest pain and intermittent claudication pain scores, wound/ ulcer healing, and 6-minute walking distance was observed following aBMC treatment. Major amputation-free survival (mAFS) rate and amputation-free rates (AFR) at 12 months were 70.6% and 82.3%, respectively. In conclusion, aBMC injections were well tolerated with improved tissue perfusion, confirming the safety, feasibility, and preliminary effectiveness of aBMC treatment in CLI patients. PMID:28194186

  3. Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.

    PubMed

    Acín, Francisco; Varela, César; López de Maturana, Ignacio; de Haro, Joaquín; Bleda, Silvia; Rodriguez-Padilla, Javier

    2014-01-01

    Our aim was to describe our experience with infrapopliteal endovascular procedures performed in diabetic patients with ischemic ulcers and critical ischemia (CLI). A retrospective study of 101 procedures was performed. Our cohort was divided into groups according to the number of tibial vessels attempted and the number of patent tibial vessels achieved to the foot. An angiosome anatomical classification of ulcers were used to describe the local perfusion obtained after revascularization. Ischemic ulcer healing and limb salvage rates were measured. Ischemic ulcer healing at 12 months and limb salvage at 24 months was similar between a single revascularization and multiple revascularization attempts. The group in whom none patent tibial vessel to the foot was obtained presented lower healing and limb salvage rates. No differences were observed between obtaining a single patent tibial vessel versus more than one tibial vessel. Indirect revascularization of the ulcer through arterial-arterial connections provided similar results than those obtained after direct revascularization via its specific angiosome tibial artery. Our results suggest that, in CLI diabetic patients with ischemic ulcers that undergo infrapopliteal endovascular procedures, better results are expected if at least one patent vessel is obtained and flow is restored to the local ischemic area of the foot.

  4. Safety and Effectiveness of Bone Marrow Cell Concentrate in the Treatment of Chronic Critical Limb Ischemia Utilizing a Rapid Point-of-Care System.

    PubMed

    Ponemone, Venkatesh; Gupta, Saniya; Sethi, Dalip; Suthar, Manish; Sharma, Monika; Powell, Richard J; Harris, Kenneth Lee; Jungla, Nungshi; Arambam, Priyadarshini; Kaul, Upendra; Seth, Ashok; Bukhari, Suhail

    2017-01-01

    Critical limb ischemia (CLI) is the end stage of lower extremity peripheral vascular disease (PVD) in which severe obstruction of blood flow results in ischemic rest pain, ulcers and/or gangrene, and a significant risk of limb loss. This open-label, single-arm feasibility study evaluated the safety and therapeutic effectiveness of autologous bone marrow cell (aBMC) concentrate in revascularization of CLI patients utilizing a rapid point-of-care device. Seventeen (17) no-option CLI patients with ischemic rest pain were enrolled in the study. Single dose of aBMC, prepared utilizing an intraoperative point-of-care device, the Res-Q™ 60 BMC system, was injected intramuscularly into the afflicted limb and patients were followed up at regular intervals for 12 months. A statistically significant improvement in Ankle Brachial Index (ABI), Transcutaneous Oxygen Pressure (TcPO2), mean rest pain and intermittent claudication pain scores, wound/ ulcer healing, and 6-minute walking distance was observed following aBMC treatment. Major amputation-free survival (mAFS) rate and amputation-free rates (AFR) at 12 months were 70.6% and 82.3%, respectively. In conclusion, aBMC injections were well tolerated with improved tissue perfusion, confirming the safety, feasibility, and preliminary effectiveness of aBMC treatment in CLI patients.

  5. Suppression of Sproutys Has a Therapeutic Effect for a Mouse Model of Ischemia by Enhancing Angiogenesis

    PubMed Central

    Taniguchi, Koji; Sasaki, Ken-ichiro; Watari, Kousuke; Yasukawa, Hideo; Imaizumi, Tsutomu; Ayada, Toranoshin; Okamoto, Fuyuki; Ishizaki, Takuma; Kato, Reiko; Kohno, Ri-ichiro; Kimura, Hiroshi; Sato, Yasufumi; Ono, Mayumi; Yonemitsu, Yoshikazu; Yoshimura, Akihiko

    2009-01-01

    Sprouty proteins (Sproutys) inhibit receptor tyrosine kinase signaling and control various aspects of branching morphogenesis. In this study, we examined the physiological function of Sproutys in angiogenesis, using gene targeting and short-hairpin RNA (shRNA) knockdown strategies. Sprouty2 and Sprouty4 double knockout (KO) (DKO) mice were embryonic-lethal around E12.5 due to cardiovascular defects. The number of peripheral blood vessels, but not that of lymphatic vessels, was increased in Sprouty4 KO mice compared with wild-type (WT) mice. Sprouty4 KO mice were more resistant to hind limb ischemia and soft tissue ischemia than WT mice were, because Sprouty4 deficiency causes accelerated neovascularization. Moreover, suppression of Sprouty2 and Sprouty4 expression in vivo by shRNA targeting accelerated angiogenesis and has a therapeutic effect in a mouse model of hind limb ischemia. These data suggest that Sproutys are physiologically important negative regulators of angiogenesis in vivo and novel therapeutic targets for treating peripheral ischemic diseases. PMID:19424491

  6. Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia.

    PubMed

    Zaccagnini, Germana; Palmisano, Anna; Canu, Tamara; Maimone, Biagina; Lo Russo, Francesco M; Ambrogi, Federico; Gaetano, Carlo; De Cobelli, Francesco; Del Maschio, Alessandro; Esposito, Antonio; Martelli, Fabio

    2015-01-01

    Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

  7. Effects of dexmedetomidine on renal tissue after lower limb ischemia reperfusion injury in streptozotocin induced diabetic rats

    PubMed Central

    Erbatur, Meral Erdal; Sezen, Şaban Cem; Bayraktar, Aslıhan Cavunt; Arslan, Mustafa; Kavutçu, Mustafa; Aydın, Muhammed Enes

    2017-01-01

    ABSTRACT Aim: The aim of this study was to investigate whether dexmedetomidine – administered before ischemia – has protective effects against lower extremity ischemia reperfusion injury that induced by clamping and subsequent declamping of infra-renal abdominal aorta in streptozotocin-induced diabetic rats. Material and Methods: After obtaining ethical committee approval, four study groups each containing six rats were created (Control (Group C), diabetes-control (Group DM-C), diabetes I/R (Group DM-I/R), and diabetes-I/R-dexmedetomidine (Group DM-I/R-D). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DM-C. In Group DM-I/R, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DM-I/R-D, 100 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia period. At the end of reperfusion, period biochemical and histopathological evaluation of renal tissue specimen were performed. Results: Thiobarbituric acid reactive substance (TBARS), Superoxide dismutase (SOD), Nitric oxide synthase (NOS), Catalase (CAT) and Glutathion S transferase (GST) levels were found significantly higher in Group DM-I/R when compared with Group C and Group DM-C. In the dexmedetomidine-treated group, TBARS, NOS, CAT, and GST levels were significantly lower than those measured in the Group D-I/R. In histopathological evaluation, glomerular vacuolization (GV), tubular dilatation (TD), vascular vacuolization and hypertrophy (VVH), tubular cell degeneration and necrosis (TCDN), tubular hyaline cylinder (THC), leucocyte infiltration (LI), and tubular cell spillage (TCS) in Group DM-I/R were significantly increased when compared with the control group

  8. Beneficial effect of pentoxifylline into the testis of rats in an experimental model of unilateral hindlimb ischemia/reperfusion injury

    PubMed Central

    Takhtfooladi, Mohammad Ashrafzadeh; Moayer, Fariborz; Takhtfooladi, Hamed Ashrafzadeh

    2015-01-01

    ABSTRACT Objective The objective of the present study was to investigate the role of pentoxifylline (PTX) on remote testicular injury caused by unilateral hind limb ischemia/reperfusion of rats. Materials and Methods Twenty healthy male Wistar rats were allocated randomly into two groups: ischemia/reperfusion (IR group) and ischemia/reperfusion + pentoxifylline (IR+PTX group). Ischemia was induced by placement of a rubber tourniquet at the greater trochanter for 2h. Rats in IR+PTX group received PTX (40 mg/kg IP) before the reperfusion period. At 24h after reperfusion, testes were removed and levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and myeloperoxidase (MPO) activity were determined in testicular tissues. Three rats of each group were used for wet/ dry weight ratio measurement. Testicular tissues were also examined histopathologically under light microscopy. Results Activities of SOD and CAT in testicular tissues were decreased by ischemia/ reperfusion (P<0.05). Significantly increased MDA levels in testicular tissues were decreased by PTX treatment (P<0.05). MPO activity in testicular tissues in the IR group was significantly higher than in the IR+PTX group (P<0.05). The wet/dry weight ratio of testicular tissues in the IR group was significantly higher than in the IR+PTX group (P<0.05). Histopathologically, there was a statistically significant difference between two groups (P<0.05). Conclusions According to histological and biochemical findings, we conclude that PTX has preventive effects in the testicular injury induced by hind limb ischemia/reperfusion. PMID:26200554

  9. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) and the (hoped for) dawn of evidence-based treatment for advanced limb ischemia.

    PubMed

    Conte, Michael S

    2010-05-01

    The Bypass versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial is the only randomized controlled trial (RCT) to date comparing open surgical bypass with endovascular therapy for severe limb ischemia (SLI). In their initial 2005 publication, the BASIL investigators reported that the main clinical outcomes (overall survival and amputation-free survival) were no different at 2 years after randomization to angioplasty-first or bypass-first revascularization strategies. However, beyond 2 years there appeared to be a benefit for open bypass surgery, providing impetus for an extension study. The final analysis of the long-term outcomes from BASIL is now presented in a set of articles that are reviewed in this commentary. The benefit of initial randomization to open surgery for patients surviving > or =2 years (70% of the BASIL cohort) was confirmed. When outcomes were analyzed by treatment received, patients who had received prosthetic bypass grafts (25% of the surgical arm) fared much more poorly than those treated with a vein bypass. Patients who underwent surgical bypass after an initial failed angioplasty also fared significantly worse than those who were treated initially with bypass surgery. Health-related quality of life measures and costs were not significantly different overall. There are many controversies surrounding the BASIL trial and its interpretation, which are reviewed herein. These include the choice of study population, end points examined, and the nature of procedures performed. The BASIL trial confirms the primacy of open surgical bypass with vein for most patients with SLI and raises questions about the sequelae of failed endovascular interventions. Further multicenter trials are needed to address the large gap in evidence for treatment selection in this patient population.

  10. Treatment of Mouse Limb Ischemia with an Integrative Hypoxia-Responsive Vector Expressing the Vascular Endothelial Growth Factor Gene

    PubMed Central

    Yasumura, Eduardo Gallatti; Stilhano, Roberta Sessa; Samoto, Vívian Yochiko; Matsumoto, Priscila Keiko; de Carvalho, Leonardo Pinto; Valero Lapchik, Valderez Bastos; Han, Sang Won

    2012-01-01

    Constitutive vascular endothelial growth factor (VEGF) gene expression systems have been extensively used to treat peripheral arterial diseases, but most of the results have not been satisfactory. In this study, we designed a plasmid vector with a hypoxia-responsive element sequence incorporated into it with the phiC31 integrative system (pVHAVI) to allow long-term VEGF gene expression and to be activated under hypoxia. Repeated activations of VEGF gene expression under hypoxia were confirmed in HEK293 and C2C12 cells transfected with pVHAVI. In limb ischemic mice, the local administration of pVHAVI promoted gastrocnemius mass and force recovery and ameliorated limb necrosis much better than the group treated with hypoxia-insensitive vector, even this last group had produced more VEGF in muscle. Histological analyses carried out after four weeks of gene therapy showed increased capillary density and matured vessels, and reduced number of necrotic cells and fibrosis in pVHAVI treated group. By our study, we demonstrate that the presence of high concentration of VEGF in ischemic tissue is not beneficial or is less beneficial than maintaining a lower but sufficient and long-term concentration of VEGF locally. PMID:22470498

  11. Cool excimer laser-assisted angioplasty (CELA) and tibial balloon angioplasty (TBA) in management of infragenicular arterial occlusion in critical lower limb ischemia (CLI).

    PubMed

    Sultan, Sherif; Tawfick, Wael; Hynes, Niamh

    2013-04-01

    We aim to compare cool excimer laser-assisted angioplasty (CELA) versus tibial balloon angioplasty (TBA) in patients with critical limb ischemia (CLI) with tibial artery occlusive disease. The primary end point is sustained clinical improvement (SCI) and amputation-free survival (AFS). The secondary end points are binary restenosis, target extremity revascularization (TER), and cost-effectiveness. From June 2005 to October 2010, 1506 patients were referred with peripheral vascular disease and 572 with CLI. A total of 80 patients underwent 89 endovascular revascularizations (EVRs) for tibial occlusions, 47 using TBA and 42 using CELA. All patients were Rutherford category 4 to 6. Three-year SCI was enhanced with CELA (81%) compared to TBA (63.8%; P = .013). Three-year AFS significantly improved with CELA (95.2%) versus TBA (89.4%; P = .0165). Three-year freedom from TER was significantly improved with CELA (92.9%) versus 78.7% TBA (P = .026). Three-year freedom from MACE was comparable in both the groups (P = .455). Patients with CELA had significantly improved quality time without symptoms of disease or toxicity of treatment (Q-TWiST) at 3 years (10.5 months; P = .048) with incremental cost of €2073.19 per quality-adjusted life year gained. Tibial EVR provides exceptional outcome in CLI. The CELA has superior SCI, AFS, and freedom from TER, with improved Q-TWiST and cost-effectiveness.

  12. Female gender and oral anticoagulants are associated with wound complications in lower extremity vein bypass: An analysis of 1404 operations for critical limb ischemia

    PubMed Central

    Nguyen, Louis L.; Brahmanandam, Soma; Bandyk, Dennis F.; Belkin, Michael; Clowes, Alexander W.; Moneta, Gregory L.; Conte, Michael S.

    2010-01-01

    Background Infrainguinal bypass (IB) surgery is an effective means of improving arterial circulation to the lower extremity for patients with critical limb ischemia (CLI). However, wound complications (WC) of the surgical incision following IB can impart significant morbidity. Methods A retrospective analysis of WC from the 1404 patients enrolled in a multicenter clinical trial of vein bypass grafting for CLI was performed. Univariate and multivariable regression models were used to determine WC predictors and associated outcomes, including graft patency, limb salvage, quality of life (QoL), resource utilization (RU), and mortality. Results A total of 543 (39%) patients developed a reported WC within 30 days of surgery, with infections (284, 52%) and hematoma/hemorrhage (121, 22%) being the most common type. Postoperative anticoagulation (odds ratio [OR], 1.554; 95% confidence interval [CI] 1.202 to 2.009; P = .0008) and female gender (OR, 1.376; 95% CI, 1.076 to 1.757; P = .0108) were independent factors associated with WC. Primary, primary-assisted, and secondary graft patency rates were not influenced by the presence of WC; though, patients with WC were at increased risk for limb loss (hazard ratio [HR], 1.511; 95% CI 1.096 to 2.079; P = .0116) and higher mortality (HR, 1.449; 95% CI 1.098 to 1.912; P = .0089). WC was not significantly associated with lower QoL at 3 months (4.67 vs 4.79, P = .1947) and 12 months (5.02 vs 5.13, P = .2806). However, the subset of patients with serious WC (SWC) demonstrated significantly lower QoL at 3 months compared with patients without WC, (4.43 vs 4.79, respectively, P = .0166), though this difference was not seen at 12 months (4.94 vs 5.13, P = .2411). Patients with WC had higher RU than patients who did not have WC. Mean index length of hospital stay (LOS) was 2.3 days longer, mean cumulative 1-year LOS was 8.1 days longer, and mean number of hospitalizations was 0.5 occurrences greater for patients with WC compared with

  13. A prospective feasibility study of duplex ultrasound arterial mapping, digital-subtraction angiography, and magnetic resonance angiography in management of critical lower limb ischemia by endovascular revascularization.

    PubMed

    Lowery, A J; Hynes, N; Manning, B J; Mahendran, M; Tawfik, S; Sultan, S

    2007-07-01

    Duplex ultrasound arterial mapping (DUAM) allows precise evaluation of peripheral vascular disease (PVD). However, magnetic resonance angiography (MRA) and digital-subtraction angiography (DSA) are the diagnostic tools used most frequently prior to intervention. Our aim was to compare clinical pragmatism, hemodynamic outcomes, and cost-effectiveness when using DUAM alone compared to DSA or MRA as preoperative assessment tools for endovascular revascularization (EvR) in critical lower limb ischemia (CLI). From 2002 through 2005, 465 patients were referred with PVD. Of these, 199 had CLI and 137 required EvR. Preoperative diagnostic evaluation included DUAM (n = 41), DSA (n = 50), or MRA (n = 46). EvR was aortoiliac in 27% of cases and infrainguinal in 73%. Patients were assessed at day 1, 6 weeks, 3 months, and 6 months. Composite end points were relief of rest pain, ulcer/gangrene healing, and increase in perfusion pressure, as measured by ankle-brachial index (ABI) and digital pressures. Patency by DUAM, limb salvage, morbidity, mortality, length of stay, and cost-effectiveness were compared between groups using nonparametric t-test, analysis of variance, and Kaplan-Meier analysis. The three groups were comparable in terms of age, sex, comorbidity, and Society for Vascular Surgery/International Society of Cardiovascular Surgery clinical classification. Six-month mean improvement in ABI in the DUAM group was comparable to that in the DSA group (P = 0.25) and significantly better than that in the MRA group (P < 0.05). Six-month patency rates for the DUAM group were comparable to those in the DSA group (P = 0.68, relative risk [RR] = 0.74, 95% confidence interval [CI] 0.18-2.99) and superior to that in the MRA group (P = 0.022, RR = 0.255, 95% CI 0.09-0.71). Length of hospital stay was lower in the DUAM group compared with the DSA group (P < 0.0001) and the MRA group (P = 0.0003). The cost of DUAM is lower than that of both DSA and MRA. DUAM accurately identified the

  14. Endovascular treatment of acute limb ischemia and proximal deep vein thrombosis using rotational thrombectomy: A review of published literature.

    PubMed

    Lichtenberg, Michael; Stahlhoff, Friedrich-Wilhelm; Boese, Dirk

    2013-01-01

    Acute and subacute ischemia of the lower extremity is still a common reason for amputation. The treatment of this condition includes the well known procedure of local thrombolysis, surgical thrombectomy and, in recent times, percutaneous mechanical thrombectomy procedures such as rotational thrombectomy. However, in randomized studies Fogarty's procedure of surgical thrombectomy was associated with a high rate of perioperative complications and, in part, low technical success rates. On the other hand, local thrombolysis is associated with hemorrhage as well as high costs because of measures requiring substantial resources, such as intensive care monitoring or repeat angiographies. In several studies, the endovascular therapy options of Straub Rotarex® and Aspirex® systems, both products of technical advancements in the field, were shown to be successful in terms of amputation-free survival. Their use was also associated with low complication rates. The majority of studies were focused on arterial blood flow in the femur. However, in the meantime several registers and studies have shown that the systems can also be effectively used to treat proximal deep vein thrombosis. In the present report we review the current study-based value of rotational thrombectomy in the venous and arterial system.

  15. The Use of the 'Preclosure' Technique for Antegrade Aspiration Thrombectomy with Large Catheters in Acute Limb Ischemia

    SciTech Connect

    Funke, C. Pfiffner, R.; Husmann, M.; Pfammatter, T.

    2013-04-15

    This study was designed to assess retrospectively short- and mid-term outcomes of the use of a suture-mediated closure device to close the antegrade access in patients undergoing percutaneous aspiration thrombectomy with large catheters for acute leg ischemia. Between November 2005 and February 2010, a suture-mediated active closure system (ProGlide{sup Registered-Sign} 6F, Abbott) was placed before arterial sheath (mean 9 F, range 6-12 F) introduction in 101 patients (74 men, 73 %, mean age 70.1 {+-} 12.6 years standard deviation). Data regarding mortality, complications, and factors contributing to vascular complications at the access site was collected for 6 month after the intervention to detect device-related problems. As a coincidence, 77 patients had follow-up visits for a duplex ultrasound. There were a total of 19 vascular complications (19 %) at the puncture site, all of which were of hemorrhagic nature and none of which consisted of vessel occlusion. Two major outcome complications (2 %) occurred. A retroperitoneal hematoma and a serious inguinal bleeding required additive treatment and did not result in permanent sequelae. Nine cases involved death of which eight were not attributable to the closure and one remained unclear. Successful closure was achieved in 95 patients (94 %); additional manual compression was sufficient in the majority of the remaining patients. Numerous factors contributing to vascular complications were encountered. With acceptable short- and mid-term outcomes, the 'preclose' technique can be a reliable option for the closure of a large antegrade femoral access even for patients at a high risk of vascular complications, such as those undergoing aspiration thrombectomy.

  16. Paroxetine alleviates rat limb post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia.

    PubMed

    Tang, Jun; Dong, Jing; Yang, Li; Gao, Lingqi; Zheng, Jijian

    2015-01-01

    Long-lasting neuroplastic changes induced by transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors enhances and prolongs inflammatory hyperalgesia. Here, we investigated the effects of paroxetine (a selective serotonin reuptake inhibitor and GRK2 inhibitor) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). After ischemia-reperfusion (I/R) injury, the ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli and the expression levels of GRK2 protein and mRNA in the ipsilateral SCGs all decreased significantly; the ipsilateral cold allodynia scores increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly at day 2-day 9 after I/R injury, but still higher than those in ipsilateral SCGs. After paroxetine administration, the ipsilateral 50% PWTs at day 2, 7, 14, and 21 were significantly higher than those in control group; The GRK2 protein and mRNA levels in ipsilateral SCGs were also significantly up-regulated after day1; The ipsilateral cold allodynia scores were significantly reduced after day7. No significant differences were found in the contralateral 50% PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly at day1-day7 after paroxetine administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and paroxetine might alleviate this allodynia through GRK2 protein upregulation in SCGs.

  17. Paroxetine alleviates rat limb post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia

    PubMed Central

    Tang, Jun; Dong, Jing; Yang, Li; Gao, Lingqi; Zheng, Jijian

    2015-01-01

    Long-lasting neuroplastic changes induced by transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors enhances and prolongs inflammatory hyperalgesia. Here, we investigated the effects of paroxetine (a selective serotonin reuptake inhibitor and GRK2 inhibitor) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). After ischemia-reperfusion (I/R) injury, the ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli and the expression levels of GRK2 protein and mRNA in the ipsilateral SCGs all decreased significantly; the ipsilateral cold allodynia scores increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly at day 2-day 9 after I/R injury, but still higher than those in ipsilateral SCGs. After paroxetine administration, the ipsilateral 50% PWTs at day 2, 7, 14, and 21 were significantly higher than those in control group; The GRK2 protein and mRNA levels in ipsilateral SCGs were also significantly up-regulated after day1; The ipsilateral cold allodynia scores were significantly reduced after day7. No significant differences were found in the contralateral 50% PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly at day1-day7 after paroxetine administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and paroxetine might alleviate this allodynia through GRK2 protein upregulation in SCGs. PMID:25932137

  18. Role of Hydrogen Sulfide in Ischemia-Reperfusion Injury

    PubMed Central

    Wu, Dongdong; Wang, Jun; Li, Hui; Xue, Mengzhou; Ji, Ailing; Li, Yanzhang

    2015-01-01

    Ischemia-reperfusion (I/R) injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved situation in clinical practice, especially in the field of solid organ transplantation. Hydrogen sulfide (H2S) is the third gaseous signaling molecule and plays a broad range of physiological and pathophysiological roles in mammals. H2S could protect against I/R injury in many organs and tissues, such as heart, liver, kidney, brain, intestine, stomach, hind-limb, lung, and retina. The goal of this review is to highlight recent findings regarding the role of H2S in I/R injury. In this review, we present the production and metabolism of H2S and further discuss the effect and mechanism of H2S in I/R injury. PMID:26064416

  19. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia

    PubMed Central

    2013-01-01

    Background Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. Methods Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. Results Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. Conclusion BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. Trial registration NIH website (http

  20. Role of serum levels of angiogenic cytokines in assessment of angiogenesis after stem cell therapy of diabetic patients with critical limb ischemia.

    PubMed

    Dubsky, Michal; Jirkovska, Alexandra; Bem, Robert; Fejfarova, Vladimira; Varga, Martin; Kolesar, Libor; Pagacova, Libuse; Sykova, Eva; Jude, Edward B

    2014-01-01

    The release of proangiogenic cytokines into the circulation after stem cell (SC) therapy and compensatory increase of angiogenesis inhibitors may reflect local vasculogenesis but also can increase the risk of side effects. The aim of our study was to evaluate serum levels of angiogenic cytokines with regard to the assessment of local and systemic vasculogenesis in diabetic patients with no-option critical limb ischemia (NO-CLI). Twenty-five diabetic patients with NO-CLI treated with SCs isolated from bone marrow or stimulated peripheral blood were included in the study. Serum levels of proangiogenic cytokines (VEGF, bFGF, Ang-1, PDGF-AA, and PDGF-BB) and an antiangiogenic cytokine (endostatin) were assessed 6 months after cell treatment, compared to baseline values, and correlated with the number of injected CD34(+) cells. The clinical effect of SC therapy (assessed by changes in TcPO2) and potential systemic vasculogenesis (assessed by eye fundus examination) were evaluated after 6 months. Serum levels of angiogenic inhibitor endostatin increased significantly after 1 and 3 months (p = 0.0003), but no significant increase in serum levels of proangiogenic cytokines was observed. A significant correlation between number of injected CD34(+) cells and serum levels of endostatin was observed (r = 0.41, p < 0.05); however, proangiogenic cytokines did not correlate with CD34(+) cells. No correlation between increase in TcPO2 after treatment and serum levels of any of the angiogenic cytokines were seen, and no signs of systemic vasculogenesis in the retina were observed after 6 months. Despite the significant increase in the levels of the angiogenic inhibitor endostatin following SC treatment, there was no risk of systemic vasculogenesis after SC therapy as documented by serum levels of proangiogenic cytokines or changes in the retina.

  1. Hydrogen Sulfide Levels and Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI)

    PubMed Central

    Islam, Kazi N; Polhemus, David J; Donnarumma, Erminia; Brewster, Luke P; Lefer, David J

    2015-01-01

    Background Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are endogenous enzymatic sources of hydrogen sulfide (H2S). Functions of H2S are mediated by several targets including ion channels and signaling proteins. Nuclear factor-erythroid 2-related factor 2 is responsible for the expression of antioxidant response element–regulated genes and is known to be upregulated by H2S. We examined the levels of H2S, H2S-producing enzymes, and nuclear factor-erythroid 2-related factor 2 activation status in skeletal muscle obtained from critical limb ischemia (CLI) patients. Methods and Results Gastrocnemius tissues were attained postamputation from human CLI and healthy control patients. We found mRNA and protein levels of cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase were significantly decreased in skeletal muscle of CLI patients as compared to control. H2S and sulfane sulfur levels were significantly decreased in skeletal muscle of CLI patients. We also observed significant reductions in nuclear factor-erythroid 2-related factor 2 activation as well as antioxidant proteins, such as Cu, Zn-superoxide dismutase, catalase, and glutathione peroxidase in skeletal muscle of CLI patients. Biomarkers of oxidative stress, such as malondialdehyde and protein carbonyl formation, were significantly increased in skeletal muscle of CLI patients as compared to healthy controls. Conclusions The data demonstrate that H2S bioavailability and nuclear factor-erythroid 2-related factor 2 activation are both attenuated in CLI tissues concomitant with significantly increased oxidative stress. Reductions in the activity of H2S-producing enzymes may contribute to the pathogenesis of CLI. PMID:25977470

  2. Study of the stability of packaging and storage conditions of human mesenchymal stem cell for intra-arterial clinical application in patient with critical limb ischemia.

    PubMed

    Gálvez-Martín, Patricia; Hmadcha, Abdelkrim; Soria, Bernat; Calpena-Campmany, Ana C; Clares-Naveros, Beatriz

    2014-04-01

    Critical limb ischemia (CLI) is associated with significant morbidity and mortality. In this study, we developed and characterized an intra-arterial cell suspension containing human mesenchymal stem cells (hMSCs) for the treatment of CLI. Equally, the stability of cells was studied in order to evaluate the optimal conditions of storage that guarantee the viability from cell processing to the administration phase. Effects of various factors, including excipients, storage temperature and time were evaluated to analyze the survival of hMSCs in the finished medicinal product. The viability of hMSCs in different packaging media was studied for 60 h at 4 °C. The best medium to maintain hMSCs viability was then selected to test storage conditions (4, 8, 25 and 37 °C; 60 h). The results showed that at 4 °C the viability was maintained above 80% for 48 h, at 8 °C decreased slightly, whereas at room temperature and 37 °C decreased drastically. Its biocompatibility was assessed by cell morphology and cell viability assays. During stability study, the stored cells did not show any change in their phenotypic or genotypic characteristics and physicochemical properties remained constant, the ability to differentiate into adipocytes and osteocytes and sterility requirements were also unaltered. Finally, our paper proposes a packing media composed of albumin 20%, glucose 5% and Ringer's lactate at a concentration of 1×10(6) cells/mL, which must be stored at 4 °C as the most suitable to maintain cell viability (>80%) and without altering their characteristics for more than 48 h.

  3. Muscle Derived Stem Cells Stimulate Muscle Myofiber Repair and Counteract Fat Infiltration in a Diabetic Mouse Model of Critical Limb Ischemia

    PubMed Central

    Tsao, J; Kovanecz, I; Awadalla, N; Gelfand, R; Sinha-Hikim, I; White, RA; Gonzalez-Cadavid, NF

    2017-01-01

    Background Critical Limb Ischemia (CLI) affects patients with Type 2 Diabetes (T2D) and obesity, with high risk of amputation and post-surgical mortality, and no effective medical treatment. Stem cell therapy, mainly with bone marrow mesenchymal, adipose derived, endothelial, hematopoietic, and umbilical cord stem cells, is promising in CLI mouse and rat models and is in clinical trials. Their general focus is on angiogenic repair, with no reports on the alleviation of necrosis, lipofibrosis, and myofiber regeneration in the ischemic muscle, or the use of Muscle Derived Stem Cells (MDSC) alone or in combination with pharmacological adjuvants, in the context of CLI in T2D. Methods Using a T2D mouse model of CLI induced by severe unilateral femoral artery ligation, we tested: a) the repair efficacy of MDSC implanted into the ischemic muscle and the effects of concurrent intraperitoneal administration of a nitric oxide generator, molsidomine; and b) whether MDSC may partially counteract their own repair effects by stimulating the expression of myostatin, the main lipofibrotic agent in the muscle and inhibitor of muscle mass. Results MDSC: a) reduced mortality, and b) in the ischemic muscle, increased stem cell number and myofiber central nuclei, reduced fat infiltration, myofibroblast number, and myofiber apoptosis, and increased smooth muscle and endothelial cells, as well as neurotrophic factors. The content of myosin heavy chain 2 (MHC-2) myofibers was not restored and collagen was increased, in association with myostatin overexpression. Supplementation of MDSC with molsidomine failed to stimulate the beneficial effects of MDSC, except for some reduction in myostatin overexpression. Molsidomine given alone was rather ineffective, except for inhibiting apoptosis and myostatin overexpression. Conclusions MDSC improved CLI muscle repair, but molsidomine did not stimulate this process. The combination of MDSC with anti-myostatin approaches should be explored to restore

  4. Bilateral Administration of Autologous CD133+ Cells in Ambulatory Patients with Refractory Critical Limb Ischemia: Lessons Learned from a Pilot Randomized, Double blind, Placebo-controlled Trial

    PubMed Central

    Raval, Amish N.; Schmuck, Eric; Tefera, Girma; Leitzke, Cathlyn; Ark, Cassondra Vander; Hei, Derek; Centanni, John M.; de Silva, Ranil; Koch, Jill; Chappell, Richard; Hematti, Peiman

    2014-01-01

    Introduction CD133+ cells confer angiogenic potential and may be beneficial for the treatment of critical limb ischemia (CLI). However, patient selection, blinding methods and endpoints for clinical trials is challenging. We hypothesized that bilateral intramuscular administration of cytokine mobilized CD133+ cells in ambulatory patients with refractory CLI would be feasible and safe. Methods In this double-blind, randomized, sham-controlled trial, subjects received subcutaneous injections of granulocyte colony stimulating factor (10 mcg/kg/d) for 5 days, followed by leukapheresis, and intramuscular administration of 50-400 million sorted CD133+ cells delivered into both legs. Control subjects received normal saline injections, sham leukapheresis and intramuscular injection of placebo buffered solution. Subjects were followed for 1 year. An aliquot of CD133+ cells was collected from each subject to test for genes associated with cell senescence. Results 70 subjects were screened, of whom 10 were eligible. Subject enrollment was suspended due to a high rate of mobilization failure in subjects randomized to treatment. Of 10 subjects enrolled (7 randomized to treatment, 3 randomized to control), there were no differences in serious adverse events at 12 months and blinding was preserved. There were non-significant trends toward improved amputation free survival, 6 minute walk distance, walking impairment questionnaire and quality of life in subjects randomized to treatment. Successful CD133+ mobilizers expressed fewer senescence associated genes compared to poor mobilizers. Conclusion Bilateral administration of autologous CD133+ cell in ambulatory CLI subjects was safe and blinding was preserved. However, poor mobilization efficiency combined with high CD133+ senescence suggests futility in this approach. PMID:25239491

  5. Hinds Community College MSEIP program

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Student Assistant Antoinette Davis (left) of Utica; Carmella Forsythe, 13, of Clinton; Terri Henderson, 14, of Clinton; Tyra Greer, 12, of Port Gibson; and Kala Battle, 14, of Edwards, answer curriculum questions about NASA's Return to Flight mission exhibit at StenniSphere, the visitor center at NASA's Stennis Space Center (SSC) near Bay St. Louis, Miss. The girls were on a field trip to StenniSphere with fellow participants in Hinds Community College's MSEIP (Minority Science Engineering Improvement Program) summer program. MSEIP encourages students to pursue and prepare for careers in science, technology, engineering and math.

  6. Prospective multicenter study of quality of life before and after lower extremity vein bypass in 1404 patients with critical limb ischemia

    PubMed Central

    Nguyen, Louis L.; Moneta, Gregory L.; Conte, Michael S.; Bandyk, Dennis F.; Clowes, Alexander W.; Seely, B. Lynn

    2010-01-01

    Background Patients with critical limb ischemia (CLI) have multiple comorbidities and limited life spans. The ability of infrainguinal vein bypass to improve quality of life (QoL) in patients with CLI has therefore been questioned. Prospective preoperative and postoperative QoL data for patients undergoing lower extremity vein bypass for CLI are presented. Methods A validated, disease-specific QoL questionnaire (VascuQoL) with activity, symptom, pain, emotional, and social domains and responses scored 1 (lowest QoL) to 7 (best QoL) was administered before surgery and at 3 and 12 months after lower extremity vein bypass for CLI. Changes in QoL at 3 and 12 months after lower extremity vein bypass and multiple predetermined variables potentially influencing QoL after lower extremity vein bypass were analyzed to determine the effect of lower extremity vein bypass on QoL in CLI patients. Results A total of 1404 patients had lower extremity vein bypass for CLI at 83 centers in the United States and Canada as part of the PREVENT III clinical trial. Surveys were completed in 1296 patients at baseline, 862 patients at 3 months, and 732 patients at 12 months. The global QoL score (mean ± SD) was 2.8 ± 1.1 at baseline and was 4.7 ± 1.4 and 5.1 ± 1.4 at 3 and 12 months, respectively. Mean changes from baseline at 3 and 12 months were statistically significant (P < .0001). Improved QoL scores extended across all domains. Diabetes and the development of graft-related events were associated with decreased improvement in QoL scores, though the mean relative change from baseline remained positive. Conclusions Patients with CLI have a low QoL at baseline that is improved at 3 and 12 months after lower extremity vein bypass. QoL improvements are lower in diabetic patients and those who develop graft-related events. Successful revascularization can be expected to improve QoL in patients with CLI, with benefits that are sustained to at least 1 year. PMID:17098529

  7. Digital image analysis of striated skeletal muscle tissue injury during reperfusion after induced ischemia

    NASA Astrophysics Data System (ADS)

    Rosero Salazar, Doris Haydee; Salazar Monsalve, Liliana

    2015-01-01

    Conditions such as surgical procedures or vascular diseases produce arterial ischemia and reperfusion injuries, which generate changes in peripheral tissues and organs, for instance, in striated skeletal muscle. To determine such changes, we conducted an experimental method in which 42 male Wistar rat were selected, to be undergone to tourniquet application on the right forelimb and left hind limb, to induce ischemia during one and three hours, followed by reperfusion periods starting at one hour and it was prolonged up to 32 days. Extensor carpi radialis longus and soleus respectively, were obtained to be processed for histochemical and morphometric analysis. By means of image processing and detection of regions of interest, variations of areas occupied by muscle fibers and intramuscular extracellular matrix (IM-ECM) throughout reperfusion were observed. In extensor carpi radialis longus, results shown reduction in the area occupied by muscle fibers; this change is significant between one hour and three hours ischemia followed by 16 hours, 48 hours and 32 days reperfusión (p˂0.005). To compare only periods of reperfusión that continued to three hours ischemia, were found significant differences, as well. For area occupied by IM-ECM, were identified increments in extensor carpi radialis longus by three hours ischemia and eight to 16 days reperfusion; in soleus, was observed difference by one hour ischemia with 42 hours reperfusion, and three hours ischemia followed by four days reperfusion (p˂0.005). Skeletal muscle develops adaptive changes in longer reperfusion, to deal with induced injury. Descriptions beyond 32 days reperfusion, can determine recovering normal pattern.

  8. Increased SCE levels in Mediterranean Italian buffaloes affected by limb malformation (transversal hemimelia).

    PubMed

    Peretti, V; Ciotola, F; Albarella, S; Restucci, B; Meomartino, L; Ferretti, L; Barbieri, V; Iannuzzi, L

    2008-01-01

    In recent years some buffalo farms in Campania have reported the birth of calves with limb malformation, especially with transversal hemimelia. We investigated 20 Mediterranean Italian buffaloes (8 males and 12 females) from one day to six months of age, of which 10 were affected by transversal hemimelia (group 1) and 10 were healthy controls (group 2). The following clinical and radiological patterns were observed in the malformed animals: hind limbs amputated, the right amputated off the second tarsus bones and the left amputated off the proximal epiphysis metatarsus, and the right thoracic limb hypoplasic (1 female); left hind limb amputated off the proximal epiphysis metatarsus (2 females and 1 male); left hind limb amputated off the third tarsus bones (1 female); left hind limb amputated off the tibia (1 female and 1 male); left hind limb amputated off the distal epiphysis metatarsus (1 female); left hind limb amputated off the first phalanx (1 male); right hind limb amputated off the proximal epiphysis metatarsus (1 male). In their malformed limbs all the animals presented more or less developed outlines of claws. The mean rate of SCE/cell in animals with transversal hemimelia was 8.80 +/- 3.19, that of the controls 6.61 +/- 2.73. The difference was statistically significant (P < 0.001).

  9. Protective Effects of HDL Against Ischemia/Reperfusion Injury.

    PubMed

    Gomaraschi, Monica; Calabresi, Laura; Franceschini, Guido

    2016-01-01

    Several lines of evidence suggest that, besides being a strong independent predictor of the occurrence of primary coronary events, a low plasma high density lipoprotein (HDL) cholesterol level is also associated with short- and long-term unfavorable prognosis in patients, who have recovered from a myocardial infarction, suggesting a direct detrimental effect of low HDL on post-ischemic myocardial function. Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that HDL are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been also confirmed in other tissues and organs, as brain and hind limb. HDL were shown to act on coronary endothelial cells, by limiting the increase of endothelium permeability and promoting vasodilation and neoangiogenesis, on white blood cells, by reducing their infiltration into the ischemic tissue and the release of pro-inflammatory and matrix-degrading molecules, and on cardiomyocytes, by preventing the activation of the apoptotic cascade. Synthetic HDL retains the cardioprotective activity of plasma-derived HDL and may become a useful adjunctive therapy to improve clinical outcomes in patients with acute coronary syndromes or undergoing coronary procedures.

  10. Severe Lower Limb Ischemia by Massive Arterial Thrombosis Revealing an Acute Myeloid Leukemia Needing for Leg Amputation: Clinical and Emotional Aspects Related to the Communication with the Patient and His Family

    PubMed Central

    Taormina, Calogero; Mosa, Clara; Di Marco, Floriana; Valentino, Fabrizio; Trizzino, Angela; Guadagna, Paola; Talarico, Francesco

    2016-01-01

    Large vessel thrombosis is a very rare clinical presentation of acute leukemia, generally associated with coagulopathy, usually characteristic of acute promyelocytic leukemia. A 13- year-old boy with a previously undiagnosed acute myeloid leukemia was referred to our hospital with acute ischemia of the right lower limb due to occlusion of the right external iliac artery, treated with emergency double surgical thromboembolectomy and chemotherapy. The thrombotic complication resulted in leg amputation. Now the boy is well in complete remission, with a good social integration and quality of life, 30 months after completing treatment. The report highlights the crucial role of early diagnosis and subsequent chemotherapy in avoiding amputation. We particularly focused critical and emotional aspects related to the communication about the leg amputation with the patient and his family. PMID:28058104

  11. Cellular basis of differential limb growth in postnatal gray short-tailed opossums (Monodelphis domestica).

    PubMed

    Beiriger, Anastasia; Sears, Karen E

    2014-06-01

    While growth has been studied extensively in invertebrates, the mechanisms by which it is controlled in vertebrates, particularly in mammals, remain poorly understood. In this study, we investigate the cellular basis of differential limb growth in postnatal Monodelphis domestica, the gray short-tailed opossum, to gain insights into the mechanisms regulating mammalian growth. Opossums are an ideal model for the study of growth because they are born with relatively large, well-developed forelimbs and small hind limbs that must "catch up" to the forelimb before the animal reaches adulthood. Postnatal Days 1-17 were identified as a key period of growth for the hind limbs, during which they undergo accelerated development and nearly quadruple in length. Histology performed on fore- and hind limbs from this period indicates a higher rate of cellular differentiation in the long bones of the hind limbs. Immunohistochemical assays indicate that cellular proliferation is also occurring at a significantly greater rate in the long bones of the hind limb at 6 days after birth. Taken together, these results suggest that a faster rate of cellular proliferation and differentiation in the long bones of the hind limb relative to those of the forelimb generates a period of accelerated growth through which the adult limb phenotype of M. domestica is achieved. Assays for gene expression suggest that the molecular basis of this differential growth differs from that previously identified for differential pre-natal growth in opossum fore- and hind limbs.

  12. Hypoxia inducible factor stabilization improves defective ischemia-induced angiogenesis in a rodent model of chronic kidney disease.

    PubMed

    Schellinger, Isabel N; Cordasic, Nada; Panesar, Julian; Buchholz, Björn; Jacobi, Johannes; Hartner, Andrea; Klanke, Bernd; Jakubiczka-Smorag, Joanna; Burzlaff, Nicolai; Heinze, Eva; Warnecke, Christina; Raaz, Uwe; Willam, Carsten; Tsao, Philip S; Eckardt, Kai-Uwe; Amann, Kerstin; Hilgers, Karl F

    2017-03-01

    Chronic kidney disease (CKD) is associated with increased risk and worse prognosis of cardiovascular disease, including peripheral artery disease. An impaired angiogenic response to ischemia may contribute to poor outcomes of peripheral artery disease in patients with CKD. Hypoxia inducible factors (HIF) are master regulators of angiogenesis and therefore represent a promising target for therapeutic intervention. To test this we induced hind-limb ischemia in rats with CKD caused by 5/6 nephrectomy and administered two different treatments known to stabilize HIF protein in vivo: carbon monoxide and a pharmacological inhibitor of prolyl hydroxylation 2-(1-chloro-4- hydroxyisoquinoline-3-carboxamido) acetate (ICA). Expression levels of pro-angiogenic HIF target genes (Vegf, Vegf-r1, Vegf-r2, Ho-1) were measured by qRT-PCR. Capillary density was measured by CD31 immunofluorescence staining and HIF expression was evaluated by immunohistochemistry. Capillary density in ischemic skeletal muscle was significantly lower in CKD animals compared to sham controls. Rats with CKD showed significantly lower expression of HIF and all measured pro-angiogenic HIF target genes, including VEGF. Both HIF stabilizing treatments rescued HIF target gene expression in animals with CKD and led to significantly higher ischemia-induced capillary sprouting compared to untreated controls. ICA was effective regardless of whether it was administered before or after induction of ischemia and led to a HIF expression in skeletal muscle. Thus, impaired ischemia-induced angiogenesis in rats with CKD can be improved by HIF stabilization, even if started after onset of ischemia.

  13. Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial cell growth factor receptor signaling

    PubMed Central

    Yoshida, Sumiko; Aihara, Ken-ichi; Ikeda, Yasumasa; Sumitomo-Ueda, Yuka; Uemoto, Ryoko; Ishikawa, Kazue; Ise, Takayuki; Yagi, Shusuke; Iwase, Takashi; Mouri, Yasuhiro; Sakari, Matomo; Matsumoto, Takahiro; Takeyama, Ken-ichi; Akaike, Masashi; Matsumoto, Mitsuru; Sata, Masataka; Walsh, Kenneth; Kato, Shigeaki; Matsumoto, Toshio

    2014-01-01

    Background Hypoandrogenemia is associated with an increased risk of ischemic diseases. Since actions of androgens are exerted through androgen receptor (AR) activation, we studied hind limb ischemia in AR knockout (KO) mice to elucidate the role of AR in response to ischemia. Methods and Results Both male and female ARKO mice exhibited impaired blood flow recovery, more cellular apoptosis and a higher incidence of autoamputation after ischemia. In ex vivo and in vivo angiogenesis studies, AR-deficient vascular endothelial cells showed reduced angiogenic capability. In ischemic limbs of ARKO mice, reductions in the phosphorylation of the Akt protein kinase and endothelial nitric oxide synthase (eNOS) were observed despite a robust increase in hypoxia-inducible factor 1α and vascular endothelial cell growth factor (VEGF) gene expression. In in vitro studies, siRNA-mediated ablation of AR in vascular endothelial cells blunted VEGF-stimulated phosphorylation of Akt and eNOS. Immunoprecipitation experiments documented an association between AR and kinase insert domain protein receptor (KDR) that promoted the recruitment of downstream signaling components. Conclusion These results document a physiological role of AR in gender-independent angiogenic potency and provide evidence for a novel cross-talk between androgen/AR signaling and VEGF/KDR signaling pathways. PMID:23723256

  14. Endovascular Techniques in Limb Salvage: Stents

    PubMed Central

    El-Sayed, Hosam F.

    2013-01-01

    In patients with critical limb ischemia, the first-line approach for limb salvage has shifted over the past decade from bypass surgery to endovascular intervention. Stenting for the treatment of lower-extremity arterial occlusive disease is an important tool and continues to evolve, with new stent designs and technologies that have been developed to provide superior patency rates and limb salvage. In this article, we discuss the role of peripheral stenting in the treatment of patients with critical limb ischemia, including a review of the relevant current literature and the future directions of such interventions. PMID:23805339

  15. Use of the Trellis{sup TM} Peripheral Infusion System for Enhancement of rt-PA Thrombolysis in Acute Lower Limb Ischemia

    SciTech Connect

    Tsetis, Dimitrios K. Katsamouris, Asterios N.; Androulakakis, Zacharias; Chamalakis, Konstantinos; Kostas, Theodoros; Chlapoutakis, Konstantinos; Gourtsoyiannis, Nicholas C.

    2003-11-15

    The Trellis{sup TM} Peripheral Infusion System is an over-the-wire 0.035'' guidewire compatible device, designed to isolate a region of the peripheral vasculature to allow for lytic drug infusion and dispersion. We used it successfully through a percutaneous approach in two cases of acute thrombosis of a native lower limb artery. The total amount of rt-PA used was 12 and 9 mg, respectively and was delivered through bolus injections obviating the need for a supplementary continuous infusion of the agent. The time for dissolution of thrombus was 45 and 35 minutes, respectively. No complications were observed.

  16. 4. EAST ELEVATION OF HINDS PLANT. NOTE BUTTRESSING AS ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. EAST ELEVATION OF HINDS PLANT. NOTE BUTTRESSING AS ON EAGLE MOUNTAIN FOR SEISMIC REINFORCEMENT. - Hinds Pump Plant, East of Joshua Tree National Monument, 5 miles north of Route 10, Hayfield, Riverside County, CA

  17. Remote Limb Ischemic Postconditioning Protects Against Neonatal Hypoxic–Ischemic Brain Injury in Rat Pups by the Opioid Receptor/Akt Pathway

    PubMed Central

    Zhou, Yilin; Fathali, Nancy; Lekic, Tim; Ostrowski, Robert P.; Chen, Chunhua; Martin, Robert D.; Tang, Jiping; Zhang, John H.

    2013-01-01

    Background and Purpose Remote ischemic postconditoning, a phenomenon in which brief ischemic stimuli of 1 organ protect another organ against an ischemic insult, has been demonstrated to protect the myocardium and adult brain in animal models. However, mediators of the protection and underlying mechanisms remain to be elucidated. In the present study, we tested the hypothesis that remote limb ischemic postconditioning applied immediately after hypoxia provides neuroprotection in a rat model of neonatal hypoxia–ischemia (HI) by mechanisms involving activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway. Methods HI was induced in postnatal Day 10 rat pups by unilateral carotid ligation and 2 hours of hypoxia. Limb ischemic postconditioning was induced by 4 conditioning cycles of 10 minutes of ischemia and reperfusion on both hind limbs immediately after HI. The opioid antagonist naloxone, phosphatidylinositol-3-kinase inhibitor wortmannin, or opioid agonist morphine was administered to determine underlying mechanisms. Infarct volume, brain atrophy, and neurological outcomes after HI were evaluated. Expression of phosphorylated Akt, Bax, and phosphorylated ERK1/2 was determined by Western blotting. Results Limb ischemic postconditioning significantly reduced infarct volume at 48 hours and improved functional outcomes at 4 weeks after HI. Naloxone and wortmannin abrogated the postconditioning-mediated infarct-limiting effect. Morphine given immediately after hypoxia also decreased infarct volume. Furthermore, limb ischemic postconditioning recovered Akt activity and decreased Bax expression, whereas no differences in phosphorylated ERK1/2expression were observed. Conclusions Limb ischemic postconditioning protects against neonatal HI brain injury in rats by activating the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway. PMID:21183744

  18. 8. MAIN INLET FROM FILTER GALLERY AND CANAL INTO HINDS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. MAIN INLET FROM FILTER GALLERY AND CANAL INTO HINDS PLANT. VIEW LOOKING DUE WEST OF HINDS COMPLEX IN BACKGROUND OF SAND FILTERS. - Hinds Pump Plant, East of Joshua Tree National Monument, 5 miles north of Route 10, Hayfield, Riverside County, CA

  19. Hind, John R (1823-1895)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    English astronomer, discovered in 1852 a small nebula in Taurus which, in 1861, was found by HEINRICH D'ARREST to have disappeared. By the end of the year, D'Arrest and OTTO WILHELM STRUVE had recovered it. Hind's variable nebula, as it came to be called, demonstrated that at least some nebulae were small, as nothing larger than a light year in dimension can disappear in a year. The nebula is a ...

  20. Limb ischemia, an alarm signal to a thromboembolic cascade - renal infarction and nephrectomy followed by surgical suppression of the left atrial appendage.

    PubMed

    Caraşca, Cosmin; Borda, Angela; Incze, Alexandru; Caraşca, Emilian; Frigy, Attila; Suciu, HoraŢiu

    2016-01-01

    We present the case of a 55-year-old male with mild hypertension and brief episodes of paroxysmal self-limiting atrial fibrillation (AF) since 2010. Despite a small cardioembolic risk score, CHA2DS2-Vasc=1 (Congestive heart failure, Hypertension, Age=75, Diabetes melitus, prior Stroke), the patient is effectively anticoagulated using acenocumarol. In December 2014, he showed signs of plantar transitory ischemia, for which he did not address the doctor. In early January 2015, he urgently presented at the hospital with left renal pain, caused by a renal infarction, diagnosed by computed tomography (CT) angiography. Left nephrectomy was performed with pathological confirmation. He was discharged with effective anticoagulation treatment. Within the next two weeks, he suffered a transitory ischemic event and a stroke, associated with right sided hemiparesis. On admission, AF was found and converted to sinus rhythm with effective anticoagulation - international normalized ratio (INR) of 2.12. Transthoracic echocardiography detected no pathological findings. Transesophageal echocardiography showed an expended left atrial appendage (LAA) with a slow blood flow (0.2 m÷s) and spontaneous echocontrast. Considering these clinical circumstances, surgical LAA suppression was decided on as a last therapeutic resort. Postoperative evolution was favorable; the patient is still free of ischemic events, one year post-intervention. Some morphological and hemodynamic characteristics of LAA may add additional thromboembolic risk factors, not included in scores. Removing them by surgical LAA suppression may decrease the risk of cardioembolic events. Intraoperative presence of thrombus makes it an indisputable proof.

  1. Suppression of morphogenesis in embryonic mouse limbs exposed in vitro to excess gravity

    NASA Technical Reports Server (NTRS)

    Duke, Jackie C.

    1983-01-01

    The effect of excess gravity on in vitro mammalian limb chondrogenesis is studied. Limb buds from mice of various gestational stages were exposed to excess gravity (2.6G) using a culture centrifuge. Both forelimbs and hind limbs were cultured, and the development of various limb elements was scored after four to six days. The 2.6G force significantly depressed the development of limb elements when applied during the teratogen-sensitive period of chondrogenesis.

  2. Administration of Adult Human Bone Marrow-Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells in Critical Limb Ischemia Due to Buerger's Disease: Phase II Study Report Suggests Clinical Efficacy.

    PubMed

    Gupta, Pawan K; Krishna, Murali; Chullikana, Anoop; Desai, Sanjay; Murugesan, Rajkumar; Dutta, Santanu; Sarkar, Uday; Raju, Radhakrishnan; Dhar, Anita; Parakh, Rajiv; Jeyaseelan, Lakshmanan; Viswanathan, Pachaiyappan; Vellotare, Prasanth Kulapurathu; Seetharam, Raviraja N; Thej, Charan; Rengasamy, Mathiyazhagan; Balasubramanian, Sudha; Majumdar, Anish S

    2017-03-01

    Critical limb ischemia (CLI) due to Buerger's disease is a major unmet medical need with a high incidence of morbidity. This phase II, prospective, nonrandomized, open-label, multicentric, dose-ranging study was conducted to assess the efficacy and safety of i.m. injection of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (BMMSC) in CLI due to Buerger's disease. Patients were allocated to three groups: 1 and 2 million cells/kg body weight (36 patients each) and standard of care (SOC) (18 patients). BMMSCs were administered as 40-60 injections in the calf muscle and locally, around the ulcer. Most patients were young (age range, 38-42 years) and ex-smokers, and all patients had at least one ulcer. Both the primary endpoints-reduction in rest pain (0.3 units per month [SE, 0.13]) and healing of ulcers (11% decrease in size per month [SE, 0.05])-were significantly better in the group receiving 2 million cells/kg body weight than in the SOC arm. Improvement in secondary endpoints, such as ankle brachial pressure index (0.03 [SE, 0.01] unit increase per month) and total walking distance (1.03 [SE, 0.02] times higher per month), were also significant in the group receiving 2 million cells/kg as compared with the SOC arm. Adverse events reported were remotely related or unrelated to BMMSCs. In conclusion, i.m. administration of BMMSC at a dose of 2 million cells/kg showed clinical benefit and may be the best regimen in patients with CLI due to Buerger's disease. However, further randomized controlled trials are required to confirm the most appropriate dose. Stem Cells Translational Medicine 2017;6:689-699.

  3. Rabbit rectus femoris muscle for ischemia-reperfusion studies: an improved model.

    PubMed

    Hoballah, J J; Mohan, C R; Schipper, P H; Chalmers, R T; Corry, D C; Corson, J D

    1996-11-01

    The rabbit rectus femoris muscle was evaluated as a potential model for skeletal muscle reperfusion injury studies. Six white New Zealand rabbits were used. On one randomly selected hind limb, ischemia was induced by direct clamping of the rectus femoris muscle's vascular pedicle. On the other side, blood flow was interrupted by clamping the femoral artery above and below the origin of the vascular pedicle that supplies the rectus femoris muscle. The duration of normothermic ischemia was 4 hr and was followed by 24 hr of normothermic reperfusion. The interruption and restoration of blood flow was monitored using a laser flow meter. The rectus femoris muscles were weighed on a suspension spring balance prior to ischemia and at the end of reperfusion to estimate edema. The extent of muscle necrosis was determined using planimetry following staining with nitroblue tetrazolium. The muscle necrosis obtained by direct clamping of the vascular pedicle (66.9 +/- 14.3%) was significantly greater than that obtained by indirect clamping (18.6 +/- 11.4%) (P < 0.03 by t test). Unlike the indirect clamping technique, direct clamping achieved a good magnitude of muscle necrosis, thus allowing that specific model to be used in skeletal muscle reperfusion injury studies. The muscle weight gain observed in the direct clamping muscle group was 19.8 +/- 9.0% and was significantly greater than that observed in the opposite group being 6.3 +/- 6.5% (P < 0.05 by t test). The rabbit rectus femoris muscle is a suitable model for evaluating skeletal muscle reperfusion injury provided that direct clamping of the vascular pedicle is utilized.

  4. Myocardial Ischemia

    MedlinePlus

    ... typically on the left side of the body (angina pectoris). Other signs and symptoms — which might be experienced ... ed. Philadelphia, Pa.: Saunders Elsevier; 2014. Podrid PJ. Angina pectoris: Chest pain caused by myocardial ischemia. www.uptodate. ...

  5. How do the substrate reaction forces acting on a gecko's limbs respond to inclines?

    NASA Astrophysics Data System (ADS)

    Wang, Zhouyi; Dai, Zhendong; Li, Wei; Ji, Aihong; Wang, Wenbao

    2015-02-01

    Locomotion is an essential character of animals, and excellent moving ability results from the delicate sensing of the substrate reaction forces (SRF) acting on body and modulating the behavior to adapt the motion requirement. The inclined substrates present in habitats pose a number of functional challenges to locomotion. In order to effectively overcome these challenges, climbing geckos execute complex and accurate movements that involve both the front and hind limbs. Few studies have examined gecko's SRF on steeper inclines of greater than 90°. To reveal how the SRFs acting on the front and hind limbs respond to angle incline changes, we obtained detailed measurements of the three-dimensional SRFs acting on the individual limbs of the tokay gecko while it climbed on an inclined angle of 0-180°. The fore-aft forces acting on the front and hind limbs show opposite trends on inverted inclines of greater than 120°, indicating propulsion mechanism changes in response to inclines. When the incline angles change, the forces exerted in the normal and fore-aft directions by gecko's front and hind limbs are reassigned to take full advantage of limbs' different roles in overcoming resistance and in propelling locomotion. This also ensures that weight acts in the angle range between the forces generated by the front and hind limbs. The change in the distribution of SRF with a change in the incline angle is directly linked to the favorable trade-off between locomotive maneuverability and stability.

  6. 5. HINDS PUMPING FLOOR FROM WEST END TOP OF UNIT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. HINDS PUMPING FLOOR FROM WEST END TOP OF UNIT #9 (LENS STOPPED DOWN ALL THE WAY FOR DEPTH OF FIELD ENHANCEMENT). - Hinds Pump Plant, East of Joshua Tree National Monument, 5 miles north of Route 10, Hayfield, Riverside County, CA

  7. Contemporary Treatment for Critical Ischemia: The Evidence for Interventional Radiology or Surgery

    PubMed Central

    Hussey, Keith; Chandramohan, Sivanathan

    2014-01-01

    This article is a review of the evidence regarding the management of patients with critical limb ischemia. The aim of the study is to discuss the definition, incidence, and clinical importance of critical limb ischemia, as well as the aims of treatment in terms of quality of life and limb salvage. Endovascular and surgical treatments should not be viewed as competing therapies. In fact, these are complementary techniques each with strengths and weaknesses. The authors will propose a strategy based on the available evidence for deciding the optimal approach to management of patients with critical limb ischemia. PMID:25435654

  8. Artificial Limbs

    MedlinePlus

    ... you are missing an arm or leg, an artificial limb can sometimes replace it. The device, which is ... activities such as walking, eating, or dressing. Some artificial limbs let you function nearly as well as before.

  9. Ergotism unresponsive to multiple therapeutic modalities, including sodium nitroprusside, resulting in limb loss.

    PubMed

    Musikatavorn, Khrongwong; Suteparuk, Suchai

    2008-02-01

    Unlike epidemics in past centuries, patients suffering from peripheral vascular ischemia related to ergotism now rarely lose a limb because of vasodilator therapies. We report a patient with ischemia from ergotamine tartrate who failed to recover with medical therapy, resulting in limb amputation.

  10. Embolization of Onyx Causing Acute Limb Ischemia.

    PubMed

    Lind, Benjamin B; Briggs, Charles S; Golan, John; Gupta, NavYash

    2017-01-01

    We present the case of a patient with a refractory type II endoleak treated with translumbar Onyx with passage of the Onyx material into the endograft and subsequent embolization to the infrainguinal vasculature. This report represents a new complication of Onyx embolization that, to our knowledge, has not previously been described in the literature.

  11. Plgf-/-eNos-/- mice show defective angiogenesis associated with increased oxidative stress in response to tissue ischemia.

    PubMed

    Gigante, Bruna; Morlino, Giulia; Gentile, Maria Teresa; Persico, Maria Graziella; De Falco, Sandro

    2006-05-01

    Neo-angiogenesis is a complex phenomenon modulated by the concerted action of several molecular factors. We have generated a congenic line of knockout mice carrying null mutations of both placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS), two genes that play a pivotal role in the regulation of pathological angiogenesis. In the present study, we describe the phenotype of this new experimental animal model after surgically induced hind-limb ischemia. Plgf-/-, eNos-/-, Plgf-/- eNos-/-, and wild-type C57BL/6J mice were studied. Plgf-/- eNos-/- mice showed the most severe phenotype: self-amputation, and death occurred in up to 47% of the animals studied; in ischemic legs, capillary density was severely reduced; macrophage infiltration and oxidative stress increased as compared to the other groups of animals. These changes were associated with an up-regulation of both inducible NOS (iNOS) expression and vascular endothelial growth factor (VEGF) protein levels in ischemic limbs, and to an increased extent of protein nitration. Our results demonstrate that the deletion of these two genes, Plgf, which acts in synergism with VEGF, and eNos, a downstream mediator of VEGF, determines a significant change in the vascular response to an ischemic stimulus and that oxidative stress within the ischemic tissue represents a crucial factor to maintain tissue homeostasis.

  12. Cross-limb vascular shunting for major limb replantation.

    PubMed

    Lee, Yao-Chou; Lee, Jing-Wei

    2009-02-01

    In the management of traumatic major limb amputation, rapid re-establishment of circulation to the amputated part is imperative so as to prevent complications related to reperfusion injury, especially for those already suffering from prolonged ischemia. A temporary, extra-anatomic cross limb shunting with infusion lines can be used to perfuse the amputated part almost instantaneously. This allows the surgeon to carry out skeletal fixation and other reparative works in an unhurried manner. The cannulation site is targeted at intact vessels far away from the injury zone, obviating the need to explore and handle traumatized vessels at the mangled stump ends, thus greatly simplifying and expediting the revascularization process. Such a method had been successfully applied in 2 young people suffering traumatic arm amputation and thigh amputation, respectively. We suggested that such a procedure could be a useful adjunct in the field of major limb replantation.

  13. Diannexin protects against renal ischemia reperfusion injury and targets phosphatidylserines in ischemic tissue.

    PubMed

    Wever, Kimberley E; Wagener, Frank A D T G; Frielink, Cathelijne; Boerman, Otto C; Scheffer, Gert J; Allison, Anthony; Masereeuw, Rosalinde; Rongen, Gerard A

    2011-01-01

    Renal ischemia/reperfusion injury (IRI) frequently complicates shock, renal transplantation and cardiac and aortic surgery, and has prognostic significance. The translocation of phosphatidylserines to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed phosphatidylserines by the annexin A5 (ANXA5) homodimer Diannexin protects against renal IRI. Protective effects of Diannexin on the kidney were studied in a mouse model of mild renal IRI. Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution and targeting. When comparing its biodistribution and elimination to ANXA5, Diannexin was found to have a distinct distribution pattern and longer blood half-life. Diannexin targeted specifically to the ischemic muscle and its affinity exceeded that of ANXA5. Targeting of both proteins was inhibited by pre-treatment with unlabeled ANXA5, suggesting that Diannexin targets specifically to ischemic tissues via phosphatidylserine-binding. This study emphasizes the importance of phosphatidylserine translocation in the pathophysiology of IRI. We show for the first time that Diannexin protects against renal IRI, making it a promising therapeutic tool to prevent IRI in a clinical setting. Our results indicate that Diannexin is a potential new imaging agent for the study of phosphatidylserine-exposing organs in vivo.

  14. Local delivery of VEGF and SDF enhances endothelial progenitor cell recruitment and resultant recovery from ischemia.

    PubMed

    Anderson, Erin M; Kwee, Brian J; Lewin, Sarah A; Raimondo, Theresa; Mehta, Manav; Mooney, David J

    2015-04-01

    Biomaterials may improve outcomes of endothelial progenitor-based therapies for the treatment of ischemic cardiovascular disease, due to their ability to direct cell behavior. We hypothesized that local, sustained delivery of exogenous vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF) from alginate hydrogels could increase recruitment of systemically infused endothelial progenitors to ischemic tissue, and subsequent neovascularization. VEGF and SDF were found to enhance in vitro adhesion and migration of outgrowth endothelial cells (OECs) and circulating angiogenic cells (CACs), two populations of endothelial progenitors, by twofold to sixfold, and nearly doubled recruitment to both ischemic and nonischemic muscle tissue in vivo. Local delivery of VEGF and SDF to ischemic hind-limbs in combination with systemic CAC delivery significantly improved functional perfusion recovery over OEC delivery, or either treatment alone. Compared with OECs, CACs were more responsive to VEGF and SDF treatment, promoted in vitro endothelial sprout formation in a paracrine manner more potently, and demonstrated greater influence on infiltrating inflammatory cells in vivo. These studies demonstrate that accumulation of infused endothelial progenitors can be enriched using biomaterial-based delivery of VEGF and SDF, and emphasize the therapeutic benefit of using CACs for the treatment of ischemia.

  15. H2O2-responsive molecularly engineered polymer nanoparticles as ischemia/reperfusion-targeted nanotherapeutic agents

    NASA Astrophysics Data System (ADS)

    Lee, Dongwon; Bae, Soochan; Hong, Donghyun; Lim, Hyungsuk; Yoon, Joo Heung; Hwang, On; Park, Seunggyu; Ke, Qingen; Khang, Gilson; Kang, Peter M.

    2013-07-01

    The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the overproduction of reactive oxygen species (ROS). Hydrogen peroxide (H2O2), the most abundant form of ROS produced during I/R, causes inflammation, apoptosis and subsequent tissue damages. Here, we report H2O2-responsive antioxidant nanoparticles formulated from copolyoxalate containing vanillyl alcohol (VA) (PVAX) as a novel I/R-targeted nanotherapeutic agent. PVAX was designed to incorporate VA and H2O2-responsive peroxalate ester linkages covalently in its backbone. PVAX nanoparticles therefore degrade and release VA, which is able to reduce the generation of ROS, and exert anti-inflammatory and anti-apoptotic activity. In hind-limb I/R and liver I/R models in mice, PVAX nanoparticles specifically reacted with overproduced H2O2 and exerted highly potent anti-inflammatory and anti-apoptotic activities that reduced cellular damages. Therefore, PVAX nanoparticles have tremendous potential as nanotherapeutic agents for I/R injury and H2O2-associated diseases.

  16. Differences in the timing of prechondrogenic limb development in mammals: the marsupial-placental dichotomy resolved.

    PubMed

    Sears, Karen E

    2009-08-01

    In contrast to placentals, marsupials are born with forelimbs that are greatly developmentally advanced relative to their hind limbs. Despite significant interest, we still do not know why this is the case, or how this difference is achieved developmentally. Studies of prechondrogenic and chondrogenic limbs have supported the traditional hypothesis that marsupial forelimb development is accelerated in response to the functional requirements of the newborn's crawl to the teat. However, limb ossification studies have concluded that, rather than the forelimb being accelerated, hind limb development is delayed. By increasing the taxonomic coverage and number of prechondrogenic events relative to previous studies, and combining traditional phylogenetic analyses of event sequences with novel analyses of relative developmental rates, this study demonstrates that the timing of limb development in marsupials is more complex than commonly thought. The marsupial phenotype was derived through two independent evolutionary changes in developmental rate: (1) an acceleration of the forelimb's first appearance and (2) a delay of hind limb development from the bud stage onward. Surprisingly, this study also provides some support for an evolutionary acceleration of the marsupial hind limb's first appearance. Further study is needed on the developmental and genetic mechanisms driving these major evolutionary transitions.

  17. Short Hairpin RNA Silencing of PHD-2 Improves Neovascularization and Functional Outcomes in Diabetic Wounds and Ischemic Limbs

    PubMed Central

    Paik, Kevin J.; Maan, Zeshaan N.; Zielins, Elizabeth R.; Duscher, Dominik; Whittam, Alexander J.; Morrison, Shane D.; Brett, Elizabeth A.; Ransom, Ryan C.; Hu, Michael S.; Wu, Joseph C.; Gurtner, Geoffrey C.; Longaker, Michael T.; Wan, Derrick C.

    2016-01-01

    The transcription factor hypoxia-inducible factor 1-alpha (HIF-1α) is responsible for the downstream expression of over 60 genes that regulate cell survival and metabolism in hypoxic conditions as well as those that enhance angiogenesis to alleviate hypoxia. However, under normoxic conditions, HIF-1α is hydroxylated by prolyl hydroxylase 2, and subsequently degraded, with a biological half-life of less than five minutes. Here we investigated the therapeutic potential of inhibiting HIF-1α degradation through short hairpin RNA silencing of PHD-2 in the setting of diabetic wounds and limb ischemia. Treatment of diabetic mouse fibroblasts with shPHD-2 in vitro resulted in decreased levels of PHD-2 transcript demonstrated by qRT-PCR, higher levels of HIF-1α as measured by western blot, and higher expression of the downstream angiogenic genes SDF-1 and VEGFα, as measured by qRT-PCR. In vivo, shPHD-2 accelerated healing of full thickness excisional wounds in diabetic mice compared to shScr control, (14.33 ± 0.45 days vs. 19 ± 0.33 days) and was associated with an increased vascular density. Delivery of shPHD-2 also resulted in improved perfusion of ischemic hind limbs compared to shScr, prevention of distal digit tip necrosis, and increased survival of muscle tissue. Knockdown of PHD-2 through shRNA treatment has the potential to stimulate angiogenesis through overexpression of HIF-1α and upregulation of pro-angiogenic genes downstream of HIF-1α, and may represent a viable, non-viral approach to gene therapy for ischemia related applications. PMID:26967994

  18. Limb Loss

    MedlinePlus

    ... limb. Learning how to use it takes time. Physical therapy can help you adapt. Recovery from the loss of a limb can be hard. Sadness, anger, and frustration are common. If you are having a tough time, talk to your doctor. Treatment with medicine or counseling can help.

  19. HD 38451 - J. R. Hind's star that changed colour

    NASA Astrophysics Data System (ADS)

    Warner, Brian; Sneden, Christopher

    1988-09-01

    In 1851, John Russell Hind announced that a star previously observed by him to be very red had become bluish white in color. It is shown that this star, HD 38451, is a ninth magnitude shell star which presumably was ejecting a shell when Hind first observed it. From high dispersion coude spectra, low dispersion IUE spectra, and ground-based photometry, HD 38451 is found to be a normal A21V shell star. Its current values of E(B-V) of about 0.14 is probably caused by interstellar rather than circumstellar reddening. There remains a problem to reconcile the large amount of reddening present when Hind first observed the star with its evidently small diminution in visual brightness at that time.

  20. Boots on horses: limb protection or hyperflexion training aids in the showjumping horse.

    PubMed

    Murphy, Jack

    2008-01-01

    Showjumping riders regularly employ various schooling strategies to control the horse's jump stride kinematics (JSK). Strategies include plyometric training regimes with fences of different heights and widths set at specific distances. Gymnastic grids teach the horse to jump cleanly. Rapping, once used almost routinely, is no longer in vogue. However, the use of performance enhancing (PE) boots on the distal hind limbs to alter equine JSK has become popular. There are two broad categories of PE boots: weighted and pressure. Some riders use so-called weighted boots on the horses' hind limbs during training and in competition to improve the jump stride. The application of so-called pressure boots may be little more than an adaptation of this technique. It appears that the PE boots induce hyperflexion of the hind limbs and incline the horse to jump fences cleanly. In the absence of scientific appraisal, it is unclear if such boots are acceptable and innovative training aids within equitation.

  1. Critical evaluation of endovascular surgery for limb salvage.

    PubMed

    Lucas, Layla C; Mills, Joseph L

    2011-01-01

    Rest pain, tissue loss, and gangrene are manifestations of critical limb ischemia caused by peripheral arterial disease and define a patient subgroup at highest risk for major limb amputation. Patients with nonhealing lower extremity wounds should be screened for the risk factors for peripheral arterial disease and offered noninvasive vascular testing. The diagnosis of critical limb ischemia mandates prompt institution of medical and surgical management to achieve the best chance of limb salvage. Surgical intervention has evolved from primary amputation to open bypass to the present era of endovascular therapy. The goals of surgical bypass and endovascular therapy are to improve perfusion sufficiently to permit healing. Despite poorer patency rates and the more frequent need for reintervention, endovascular therapy has been shown in multiple retrospective studies to achieve limb salvage similar to open bypass. Only one large, prospective, randomized controlled trial exists comparing open bypass with endovascular therapy: The Bypass versus Angioplasty in Severe Limb Ischemia of the Leg (BASIL) trial. Close clinical surveillance and serial monitoring of limb perfusion by means of noninvasive arterial studies are needed to determine the need for further vascular intervention. Limb salvage patients suffer from multiple comorbidities and benefit from a multidisciplinary, team approach to care.

  2. Conditional effect of selenium on the mammalian hind gut microbiota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Selenium (Se) status is linked to cancer risk in humans and other mammals. Because Se is used by certain microbial species which contain selenoproteins, and because hind gut microfloral composition is linked to cancer development, we proposed that supranutritional Se could reduce tumorigenisis by af...

  3. What the Primary Care Provider Needs to Know for Limb Salvage

    PubMed Central

    Street, Tiffany K.

    2012-01-01

    Primary care providers are often the first providers to evaluate a patient for peripheral arterial disease (PAD). Understanding the various presentations of PAD symptoms can prevent the disease from progressing to critical limb ischemia and eventual limb loss. This article provided the primary care provider with information needed to prevent limb loss and promote limb salvage, including risk factor management, clinical presentation, physical exam findings, and treatment options. PMID:23342193

  4. The spatial organization of central sensitization of hind limb flexor reflexes in the decerebrated, spinalized rabbit.

    PubMed

    Clarke, R W; Harris, J

    2001-01-01

    This study was designed to investigate the relationship between the location of a noxious stimulus and the magnitude and duration of the plastic effects induced by that stimulus in withdrawal reflexes acting about the knee and the ankle, in rabbits. Reflexes were evoked in the nerves to the anterior tibial and semitendinosus flexor muscles by electrical stimulation at the toes. Repetitive, high intensity electrical stimulation of nerve trunks (sural, medial gastrocnemius, superficial peroneal, tibial, 100 pulses, 20 V, 1 ms at 0.5 Hz) was generally found to be a poor method for inducing central sensitization in these flexor reflexes. 'Natural' noxious stimulation induced more reliable enhancement of both reflexes. Mechanical (clamp) or chemical (mustard oil) stimulation of the heel induced prolonged (median duration >30 min) increases in reflexes to both muscles. Mechanical (clamp and superficial pinch) or chemical (mustard oil) stimulation of the toes, and injection of bradykinin into the gastrocnemius muscles or into the soft tissues of the sole of the foot, also led to enhancement of both reflexes, with the median duration of potentiation between 7 and 30 min. The effects obtained from deep tissue stimulation were generally weaker than those obtained after stimulation of superficial structures. These data show that there were no major differences in the effects obtained from the heel vs the toes, or between the two reflexes. It appears that the spatial organization of the spinal mechanisms underlying central sensitization of flexor withdrawal reflexes is rather more crudely drawn than that pertaining to the reflexes themselves. Furthermore, the data indicate that in the present preparation, afferents from deep tissues are no more effective in generating central sensitization than those from superficial structures.

  5. Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats

    NASA Astrophysics Data System (ADS)

    Zhao, Fan; Li, Dijie; Arfat, Yasir; Chen, Zhihao; Liu, Zonglin; Lin, Yu; Ding, Chong; Sun, Yulong; Hu, Lifang; Shang, Peng; Qian, Airong

    2014-12-01

    Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones. After HLU for 4 weeks, the rats were then subjected to reloading for 1 week, 2 weeks and 3 weeks, and then the BMD of the femur, tibia and lumbar spine in rats were assessed by dual energy X-ray absorptiometry (DXA) every week. The mechanical properties of the femur were determined by three-point bending test. Dry bone and bone ash of femur were obtained through Oven-Drying method and were weighed respectively. Serum alkaline phosphatase (ALP) and serum calcium were examined through ELISA and Atomic Absorption Spectrometry. The results showed that 4 weeks of HLU significantly decreased body weight of rats and reloading for 1 week, 2 weeks or 3 weeks did not recover the weight loss induced by HLU. However, after 2 weeks of reloading, BMD of femur and tibia of HLU rats partly recovered (+10.4%, +2.3%). After 3 weeks of reloading, the reduction of BMD, energy absorption, bone mass and mechanical properties of bone induced by HLU recovered to some extent. The changes in serum ALP and serum calcium induced by HLU were also recovered after reloading. Our results indicate that a short period of reloading could not completely recover bone after a period of unloading, thus some interventions such as mechanical vibration or pharmaceuticals are necessary to help bone recovery.

  6. Effect of Endotoxin on Oxygen Consumption By a Flow-Controlled Canine Hind-Limb Preparation

    DTIC Science & Technology

    1980-10-01

    a reduction in the cardiac metabolic units of the periphery, (3) the red bloodq output and a widening of the central arteriovenous cell or...explained readily by the reduction in takeoff of the profunda femoris artery; the internal + SNum ber Volume 88 Effect of endotoxin on oxygen

  7. Morphological changes in neurons of the hind limb reflex arc during long term immobilization

    NASA Technical Reports Server (NTRS)

    Tkachenko, Z. Y.

    1980-01-01

    Twelve adult rabbits were immobilized for 9 to 31 days, followed by histological study of the nerve processes of lumbar vertebra 7 and sacral vertebra 1, the sciatic nerve and the motor endings of the thigh muscles. In the spinal ganglia, dystrophic changes of increasing severity with immobilization time were found, including pericellular edema, vacuolized neuroplasm, pycnotic changes, cytolysis and destruction. Chromatophilic matter decreased and was partly bleached, and amitotic division occurred. A portion of the sciatic nerve fibers were argentophilic, and some fragmentary decomposition occurred. Considerable dystrophic changes occurred in the motor nerve endings.

  8. Capillary-to-fiber ratio of hind limb muscles in the male Syrian golden hamster.

    PubMed

    Swisher, Anne K; Alway, Stephen E; Yeater, Rachel

    2004-04-01

    The hamster has been the accepted model of emphysema since the 1970s, demonstrating disease-related effects on respiratory skeletal muscle. However, there is scant information available about the model's ability to replicate the peripheral skeletal muscle changes seen in human disease, such as alterations in capillarity. The present study described the capillary-to-fiber ratio (C/F) of normal hamster plantaris, gastrocnemius, and soleus muscles in eight animals. C/F was 1.72 +/- 0.38 for plantaris, 1.95 +/- 0.40 for gastrocnemius, and 2.22 +/- 0.43 for soleus. C/F of soleus was significantly greater (P < 0.01) than plantaris. The C/F of hamster hindlimb muscles varies from those seen in rat species, and having baseline data on hamsters makes it possible to determine the effects of emphysema on C/F in this model.

  9. Cellular proliferation in the skin of X-rayed newt limbs (with a note on x-ray-induced limb regression)

    SciTech Connect

    Wertz, R.L.

    1982-07-01

    Left hind limbs, including the pelvis, of adult newts (Notophthalmus viridescens) were locally irradiated with a dose of x-rays that inhibited regeneration (2,000 R). This x-ray dose and other doses (700-2,000 R) capable of inhibiting limb regeneration also cause limb regression prior to amputation. Before limb regression occurred, there was a latent period of 3 to 6 weeks. Limb regression was characterized by necrotic wasting and resorption of distal elements. The degree of loss was variable and dependent upon dosage. After this further degenerative changes were not noted. Proliferation of epidermal cells was examined 4 days after irradiation prior to limb regression or after x-ray-induced degeneration of the limbs had ended. Proliferative activity in x-rayed limbs was also compared at various stages of contralateral control limb regeneration. Limbs examined after x-ray-induced limb regression had ended showed levels of (/sup 3/H)-thymidine incorporation into DNA comparable to normal epidermis. In contrast, limbs examined 4 days after irradiation had lower levels of DNA synthesis (P much less than 0.01). Amputation of limbs in both groups caused an increase in DNA synthesis (P much less than 0.01). Histological examination showed that cellular proliferation was associated primarily with the epidermis. These results indicate that epidermal cell proliferation was not resistant to x-rays. However, levels of normal cell division were observed after amputation of after cessation of x-ray-induced limb regression.

  10. A possible function of the preference for hind nipples in prairie voles (Microtus ochrogaster).

    PubMed

    McGuire, B

    2001-12-01

    Prairie vole pups (Microtus ochrogaster) in laboratory cages prefer hind nipples. In this research, the author observed 8 litters of prairie voles in a seminatural environment to confirm the preference for hind nipples and to determine if young on hind nipples were groomed more frequently or dislodged less frequently than were young on other nipples. Prairie vole pups in seminatural environments preferred hind nipples; this preference was illustrated by the progressive use of more anterior nipples only as litter size increased and by the reluctance of pups to voluntarily release their hold on hind nipples. Maternal grooming of young did not vary with suckling location. Prairie vole young on hind nipples, however, were dislodged less frequently than were young on other nipples. Less frequent dislodgment from hind nipples during maternal movements may play a role in the preference for hind nipples in prairie voles.

  11. Edge detection of red hind grouper vocalizations in the littorals

    NASA Astrophysics Data System (ADS)

    Matthews, Cameron A.; Beaujean, Pierre-Philippe

    2016-05-01

    Littoral regions typically present to passive sensors as a high noise acoustic environment, particularly with respect to port and harbor regions where tidal variation, often characterized as pink, mixes with reverberation from on-shore business and commercial shipping, often characterized as white. Some fish in these regions, in particular epiphenalius Guttatus or more commonly the red hind grouper, emit relatively narrowband tones in low frequencies to communicate with other fish in such regions. The impact of anthropogenic noise sources on the red Hind and other fish is a topical area of interest for wildlife fisheries, private sportsmen and military offices that is not considered here; the fact that fish species continue to populate and communicate in these regions in the presence of high noise content lends some study to the signal content and modeling of a potential biologically inspired receiver structure.

  12. Ubx Regulates Differential Enlargement and Diversification of Insect Hind Legs

    PubMed Central

    Mahfooz, Najmus; Turchyn, Nataliya; Mihajlovic, Michelle; Hrycaj, Steven; Popadić, Aleksandar

    2007-01-01

    Differential enlargement of hind (T3) legs represents one of the hallmarks of insect evolution. However, the actual mechanism(s) responsible are yet to be determined. To address this issue, we have now studied the molecular basis of T3 leg enlargement in Oncopeltus fasciatus (milkweed bug) and Acheta domesticus (house cricket). In Oncopeltus, the T3 tibia displays a moderate increase in size, whereas in Acheta, the T3 femur, tibia, and tarsus are all greatly enlarged. Here, we show that the hox gene Ultrabithorax (Ubx) is expressed in the enlarged segments of hind legs. Furthermore, we demonstrate that depletion of Ubx during embryogenesis has a primary effect in T3 legs and causes shortening of leg segments that are enlarged in a wild type. This result shows that Ubx is regulating the differential growth and enlargement of T3 legs in both Oncopeltus and Acheta. The emerging view suggests that Ubx was co-opted for a novel role in regulating leg growth and that the transcriptional modification of its expression may be a universal mechanism for the evolutionary diversification of insect hind legs. PMID:17848997

  13. Hind Right Approach Pancreaticoduodenectomy: From Skill to Indications

    PubMed Central

    Georgescu, Stefan; Ursulescu, Corina

    2014-01-01

    Background. Pancreaticoduodenectomy is the potentially curative treatment for malignant and several benign conditions of the pancreatic head and periampullary region. While performing pancreaticoduodenectomy, early neck division may be impossible or inadequate in case of hepatic artery anatomic variants, suspected involvement of the superior mesenteric vessels, intraductal papillary mucinous neoplasm, and pancreatic head bleeding pseudoaneurysm. Our work aims to highlight a particular hind right approach pancreaticoduodenectomy in selected indications and assess the preliminary results. Methods. We describe our early hind right approach to the retropancreatic vasculature during pancreaticoduodenectomy by mesopancreas dissection before any pancreatic or digestive transection. Results. We used this approach in 52 patients. Thirty-two had hepatic artery anatomic variant and 2 had bleeding pancreatic head pseudoaneurysm. The hepatic artery variant was preserved in all cases out of 2 in which arterial reconstruction was performed. In nine patients with intraductal papillary mucinous neoplasms the pancreaticoduodenectomy was extended to the body in 6 and totalized in 3 patients. Seven patients with adenocarcinoma involving the portomesenteric axis required venous resection and reconstruction. Conclusions. Early hind right approach is advocated in selected cases of pancreaticoduodenectomy to improve locoregional vascular control and determine, safely and early, whether there is mesopancreas involvement. PMID:25221601

  14. Use of Tourniquets and their Effects on Limb Function in the Modern Combat Environment

    DTIC Science & Technology

    2010-03-01

    hemorrhage. Perhaps genetics may affect tolerance to tourniquet ischemia -reperfusion, which is also widely variable. Also, environmental factors, such as...hemorrhage control possibly shortening ischemia time, one factor in decreasing tourniquet risk. Successful placement of a pressure dressing was common...jury medical history or peripheral vascular status of the casualty may be unknown. The ischemia -reperfusion effects on the injured limb caused by

  15. Stenting in Acute Lower Limb Arterial Occlusions

    SciTech Connect

    Raja, Jowad; Munneke, Graham; Morgan, Robert; Belli, Anna-Maria

    2008-07-15

    Management of critical limb ischemia of acute onset includes surgical embolectomy, bypass grafting, aspiration thrombectomy, thrombolysis, and mechanical thrombectomy followed by treatment of the underlying cause. We present our experience with the use of stents to treat acute embolic/thrombotic occlusions in one iliac and three femoropopliteal arteries. Although this is a small case series, excellent immediate and midterm results suggest that stenting of acute occlusions of the iliac, superficial femoral, and popliteal arteries is a safe and effective treatment option.

  16. Critical Hand Ischemia After Radial Access for Coronary Angiography – Case Report

    PubMed Central

    Bojakowski, Krzysztof; Zawadzki, Michał; Mruk, Bartosz; Andziak, Piotr; Walecki, Jerzy

    2017-01-01

    Summary Background Radial artery is now the most frequent access for coronary angiography and intervention. Despite the common opinion that it is safer than femoral access, it has the potential for serious complications. One of them is upper limb ischemia caused by radial artery thrombosis. Case Report We are presenting a case of critical hand ischemia after coronary angiography performed through radial access despite existing risk factors, which may be considered as relative contraindications. Conclusions In the presented case, decision was made to use radial access despite several risk factors of upper limb ischemia – diabetes, end-stage renal failure, hyperparathyroidism, or even symptoms of left upper limb ischemia. Furthermore, for diagnostic coronary angiography 5F instead of 4F introducer was used. PMID:28144386

  17. 5-AZA-2'-DEOXYCYTIDINE INDUCED CYTOTOXICITY AND LONG BONE REDUCTION DEFECTS IN THE MURINE LIMB

    EPA Science Inventory

    The antineoplastic drug 5-aza-2'-deoxycytidine (dAZA) is a DNA hypomethylating agent that can be used to induce hind limb phocomelia in the offspring of CD-1 Swiss Webster mice. Previously, our laboratory investigated the possibility that dAZA induced alterations in gene express...

  18. Improved decoding of limb-state feedback from natural sensors.

    PubMed

    Wagenaar, J B; Ventura, V; Weber, D J

    2009-01-01

    Limb state feedback is of great importance for achieving stable and adaptive control of FES neuroprostheses. A natural way to determine limb state is to measure and decode the activity of primary afferent neurons in the limb. The feasibility of doing so has been demonstrated by [1] and [2]. Despite positive results, some drawbacks in these works are associated with the application of reverse regression techniques for decoding the afferent neuronal signals. Decoding methods that are based on direct regression are now favored over reverse regression for decoding neural responses in higher regions in the central nervous system [3]. In this paper, we apply a direct regression approach to decode the movement of the hind limb of a cat from a population of primary afferent neurons. We show that this approach is more principled, more efficient, and more generalizable than reverse regression.

  19. Stereotaxic Device for Optical Imaging of Mice Hind Feet

    PubMed Central

    Cole, Richard; Hoffman, Timothy; Smith, Jason; Herron, Bruce

    2013-01-01

    Imaging of in vivo model systems, especially mouse models, has revolutionized our understanding of normal and pathological developments. However, mice present several challenges for imaging. They are living and therefore breathing organisms with a fast heart rate (>500 beat/min), which necessitates the need for restraints and positioning controls that do not compromise their normal physiology. We present here a device that immobilizes the rear legs of a mouse while retaining the ability to position both the hind feet and legs for reproducible imaging deep below the skin's surface. The device is highly adjustable to accommodate mice, 5 weeks of age and older. The function of this device is demonstrated by imaging the vasculature ∼250 μm beneath the skin in the hind leg. Whereas the overall dimensions are for a motorized stage (Märzhäuser Wetzlar GmbH, Wetzlar, Germany), minor modifications would allow it to be customized for use with most commercially available stages that accept an insert. PMID:23997660

  20. Propulsive forces of mudskipper fins and salamander limbs during terrestrial locomotion: implications for the invasion of land.

    PubMed

    Kawano, Sandy M; Blob, Richard W

    2013-08-01

    The invasion of land was a pivotal event in vertebrate evolution that was associated with major appendicular modifications. Although fossils indicate that the evolution of fundamentally limb-like appendages likely occurred in aquatic environments, the functional consequences of using early digited limbs, rather than fins, for terrestrial propulsion have had little empirical investigation. Paleontological and experimental analyses both have led to the proposal of an early origin of "hind limb-driven" locomotion among tetrapods or their ancestors. However, the retention of a pectoral appendage that had already developed terrestrial adaptations has been proposed for some taxa, and few data are available from extant functional models that can provide a foundation for evaluating the relative contributions of pectoral and pelvic appendages to terrestrial support among early stem tetrapods. To examine these aspects of vertebrate locomotor evolution during the invasion of land, we measured three-dimensional ground reaction forces (GRFs) produced by isolated pectoral fins of mudskipper fishes (Periophthalmus barbarus) during terrestrial crutching, and compared these to isolated walking footfalls by the forelimbs and hind limbs of tiger salamanders (Ambystoma tigrinum), a species with subequally-sized limbs that facilitate comparisons to early tetrapods. Pectoral appendages of salamanders and mudskippers exhibited numerous differences in GRFs. Compared with salamander forelimbs, isolated fins of mudskippers bear lower vertical magnitudes of GRFs (as a proportion of body weight), and had GRFs that were oriented more medially. Comparing the salamanders' forelimbs and hind limbs, although the peak net GRF occurs later in stance for the forelimb, both limbs experience nearly identical mediolateral and vertical components of GRF, suggesting comparable contributions to support. Thus, forelimbs could also have played a significant locomotor role among basal tetrapods that had limbs

  1. TIE2-expressing monocytes/macrophages regulate revascularization of the ischemic limb

    PubMed Central

    Patel, Ashish S; Smith, Alberto; Nucera, Silvia; Biziato, Daniela; Saha, Prakash; Attia, Rizwan Q; Humphries, Julia; Mattock, Katherine; Grover, Steven P; Lyons, Oliver T; Guidotti, Luca G; Siow, Richard; Ivetic, Aleksandar; Egginton, Stuart; Waltham, Matthew; Naldini, Luigi; De Palma, Michele; Modarai, Bijan

    2013-01-01

    A third of patients with critical limb ischemia (CLI) will eventually require limb amputation. Therapeutic neovascularization using unselected mononuclear cells to salvage ischemic limbs has produced modest results. The TIE2-expressing monocytes/macrophages (TEMs) are a myeloid cell subset known to be highly angiogenic in tumours. This study aimed to examine the kinetics of TEMs in patients with CLI and whether these cells promote neovascularization of the ischemic limb. Here we show that there are 10-fold more circulating TEMs in CLI patients, and removal of ischemia reduces their numbers to normal levels. TEM numbers in ischemic muscle are two-fold greater than normoxic muscle from the same patient. TEMs from patients with CLI display greater proangiogenic activity than TIE2-negative monocytes in vitro. Using a mouse model of hindlimb ischemia, lentiviral-based Tie2 knockdown in TEMs impaired recovery from ischemia, whereas delivery of mouse macrophages overexpressing TIE2, or human TEMs isolated from CLI patients, rescued limb ischemia. These data suggest that enhancing TEM recruitment to the ischemic muscle may have the potential to improve limb neovascularization in CLI patients. PMID:23653322

  2. Effects of Ibuprofen and High-Voltage Electric Stimulation on Acute Edema Formation After Blunt Trauma to Limbs of Rats

    PubMed Central

    Dolan, Michael G; Graves, Paul; Nakazawa, Chika; Delano, Teresa; Hutson, Alan; Mendel, Frank C

    2005-01-01

    Context: Ibuprofen is widely used to manage pain and inflammation after orthopaedic trauma, but its effect on acute swelling has not been investigated. Cathodal high-voltage pulsed current (CHVPC) at 120 pulses per second and 90% of visible motor threshold is known to curb edema formation after blunt trauma to the hind limbs of rats. Objective: To examine the effects of ibuprofen, continuous CHVPC, and simultaneous ibuprofen and CHVPC on acute edema formation after blunt trauma to the hind limbs of rats. Design: Randomized, parallel-group, repeated-measures design. Setting: Laboratory animal facility. Participants: A total of 21 3-month-old Zucker Lean rats (mass = 288 ± 55 g) were studied. Intervention(s): We assessed the effects of ibuprofen, continuous CHVPC, and simultaneous ibuprofen and CHVPC on acute edema formation after blunt trauma to the hind limbs of rats. Main Outcome Measure(s): Limb volumes were measured immediately before and after trauma and every 30 minutes over the 4 hours of the experiment. Results: Volumes of treated limbs of all 3 experimental groups were smaller (P < .05) than those of untreated limbs, but no treatment was more effective than another. Conclusions: Ibuprofen, CHVPC, and simultaneous ibuprofen and CHVPC effectively curbed edema after blunt injury by roughly 50% relative to untreated but similarly injured control limbs of rats. PMID:15970957

  3. Spinal cord ischemia secondary to hypovolemic shock.

    PubMed

    Oh, Jacob Yl; Kapoor, Siddhant; Koh, Roy Km; Yang, Eugene Wr; Hee, Hwan-Tak

    2014-12-01

    A 44-year-old male presented with symptoms of spinal cord compression secondary to metastatic prostate cancer. An urgent decompression at the cervical-thoracic region was performed, and there were no complications intraoperatively. Three hours postoperatively, the patient developed acute bilateral lower-limb paralysis (motor grade 0). Clinically, he was in class 3 hypovolemic shock. An urgent magnetic resonance imaging (MRI) was performed, showing no epidural hematoma. He was managed aggressively with medical therapy to improve his spinal cord perfusion. The patient improved significantly, and after one week, he was able to regain most of his motor functions. Although not commonly reported, spinal cord ischemia post-surgery should be recognized early, especially in the presence of hypovolemic shock. MRI should be performed to exclude other potential causes of compression. Spinal cord ischemia needs to be managed aggressively with medical treatment to improve spinal cord perfusion. The prognosis depends on the severity of deficits, and is usually favorable.

  4. A comparison of the moment arms of pelvic limb muscles in horses bred for acceleration (Quarter Horse) and endurance (Arab).

    PubMed

    Crook, T C; Cruickshank, S E; McGowan, C M; Stubbs, N; Wilson, A M; Hodson-Tole, E; Payne, R C

    2010-07-01

    Selective breeding for performance has resulted in distinct breeds of horse, such as the Quarter Horse (bred for acceleration) and the Arab (bred for endurance). Rapid acceleration, seen during Quarter Horse racing, requires fast powerful muscular contraction and the generation of large joint torques, particularly by the hind limb muscles. This study compared hind limb moment arm lengths in the Quarter Horse and Arab. We hypothesized that Quarter Horse hind limb extensor muscles would have longer moment arms when compared to the Arab, conferring a greater potential for torque generation at the hip, stifle and tarsus during limb extension. Six Quarter Horse and six Arab hind limbs were dissected to determine muscle moment arm lengths for the following muscles: gluteus medius, biceps femoris, semitendinosus, vastus lateralis, gastrocnemius (medialis and lateralis) and tibialis cranialis. The moment arms of biceps femoris (acting at the hip) and gastrocnemius lateralis (acting at the stifle) were significantly longer in the Quarter Horse, although the length of the remaining muscle moment arms were similar in both breeds of horse. All the Quarter Horse muscles were capable of generating greater muscle moments owing to their greater physiological cross-sectional area (PCSA) and therefore greater isometric force potential, which suggests that PCSA is a better determinant of muscle torque than moment arm length in these two breeds of horse. With the exception of gastrocnemius and tibialis cranialis, the observed muscle fascicle length to moment arm ratio (MFL : MA ratio) was greater for the Arab horse muscles. It appears that the Arab muscles have the potential to operate at slower velocities of contraction and hence generate greater force outputs when compared to the Quarter Horse muscles working over a similar range of joint motion; this would indicate that Arab hind limb muscles are optimized to function at maximum economy rather than maximum power output.

  5. Threatened limb from stingray injury.

    PubMed

    Shiraev, Timothy P; Marucci, Damian; McMullin, Gabrielle

    2016-01-01

    We present the case of a 43-year-old female who suffered a stingray injury to her left ankle. The sting caused occlusion of the dorsalis pedis artery, causing dry gangrene of the medial forefoot. A below knee amputation was recommended but she was transferred for a second opinion. A Prostaglandin E1 infusion was commenced, resulting in alleviation of pain and improvement in perfusion. Amputation of great and second toes was performed, with the head of the first metatarsal preserved and covered via a cross-over skin flap raised from the contralateral leg. Achilles tendon lengthening was then performed to return the foot to a functional position. This case serves to highlight the utility of prostaglandin infusion, and the requirement for a multidisciplinary approach to critical limb ischemia in order to avoid major amputation.

  6. Population characteristics of a recovering US Virgin Islands red hind spawning aggregation following protection

    PubMed Central

    Nemeth, Richard S.

    2006-01-01

    Many species of groupers form spawning aggregations, dramatic events where 100s to 1000s of individuals gather annually at specific locations for reproduction. Spawning aggregations are often targeted by local fishermen, making them extremely vulnerable to over fishing. The Red Hind Bank Marine Conservation District located in St. Thomas, United States Virgin Islands, was closed seasonally in 1990 and closed permanently in 1999 to protect an important red hind Epinephelus guttatus spawning site. This study provides some of the first information on the population response of a spawning aggregation located within a marine protected area. Tag-and-release fishing and fish transects were used to evaluate population characteristics and habitat utilization patterns of a red hind spawning aggregation between 1999 and 2004. Compared with studies conducted before the permanent closure, the average size of red hind increased mostly during the seasonal closure period (10 cm over 12 yr), but the maximum total length of male red hind increased by nearly 7 cm following permanent closure. Average density and biomass of spawning red hind increased by over 60% following permanent closure whereas maximum spawning density more than doubled. Information from tag returns indicated that red hind departed the protected area following spawning and migrated 6 to 33 km to a ca. 500 km2 area. Protection of the spawning aggregation site may have also contributed to an overall increase in the size of red hind caught in the commercial fishery, thus increasing the value of the grouper fishery for local fishermen. PMID:16612415

  7. Optimizing the use of Limb Tourniquets in Tactical Combat Casualty Care: TCCC Guidelines Change 14-02

    DTIC Science & Technology

    2014-02-01

    Sebesta JA, Blackbourne LH, Herbert GS, Kauvar DS, Baer DG, Walters TJ, Mullenix PS, Holcomb JB, 31 st Combat Support Hospital Research Group...K, Dixon P, Cowart J, Spencer J, Rasmussen TE. Hemorrhagic shock worsens neuromuscular recovery in a porcine model of hind limb vascular injury and

  8. Methods for Acute and Subacute Murine Hindlimb Ischemia

    PubMed Central

    Padgett, Michael E.; McCord, Timothy J.; McClung, Joseph M.; Kontos, Christopher D.

    2016-01-01

    Peripheral artery disease (PAD) is a leading cause of cardiovascular morbidity and mortality in developed countries, and animal models that reliably reproduce the human disease are necessary to develop new therapies for this disease. The mouse hindlimb ischemia model has been widely used for this purpose, but the standard practice of inducing acute limb ischemia by ligation of the femoral artery can result in substantial tissue necrosis, compromising investigators' ability to study the vascular and skeletal muscle tissue responses to ischemia. An alternative approach to femoral artery ligation is the induction of gradual femoral artery occlusion through the use of ameroid constrictors. When placed around the femoral artery in the same or different locations as the sites of femoral artery ligation, these devices occlude the artery over 1-3 days, resulting in more gradual, subacute ischemia. This results in less substantial skeletal muscle tissue necrosis, which may more closely mimic the responses seen in human PAD. Because genetic background influences outcomes in both the acute and subacute ischemia models, consideration of the mouse strain being studied is important in choosing the best model. This paper describes the proper procedure and anatomical placement of ligatures or ameroid constrictors on the mouse femoral artery to induce subacute or acute hindlimb ischemia in the mouse. PMID:27403963

  9. Effects of transient ischemia on nutrient flow and arteriovenous shunting in canine hindlimb.

    PubMed Central

    Kennedy, T J; Miller, S H; Nellis, S H; Buck, D; Flaim, S F; Graham, W P; Davis, T S

    1981-01-01

    A canine model was developed to simulate use of a pneumatic tourniquet in the clinical setting in order to study the acute and delayed effects of transient ischemia on limb and tissue blood flow, using radioactive microspheres and electromagnetic flow probes. Experimental femoral artery flow rose markedly after tourniquet ischemia, and remained significantly elevated for 24 hours (p less than 0.01). Blood flow to the rectus femoris and anterior tibial muscles rose significantly (p less than 0.05) immediately after tourniquet ischemia, and the latter remained significantly elevated at 24 hours (p less than 0.05). Blood flow to the skin of the experimental limbs was elevated significantly (p less than 0.05), immediately ater tourniquet ischemia, and at no other time. Blood flow to the nerves did not increase to its maximum until 15 minutes after tourniquet deflation, and by 24 hours was normal. Tibial and femoral marrow blood flow remained significantly lower in the experimental limb throughout the 24-hour period. Ater tourniquet ischemia (300 mmhg; 2 hours), greatly increased femoral artery flow was related to reactive hyperemia in skin, muscle, and nerve. Twenty-four hours after tourniquet deflation, there was a significant increase in femoral artery and anterior tibial muscle blood flow, and significant arteriovenous shunting from the experimental limb. These data suggest that the hemodynamic response to a transient ischemic injury is more prolonged and of greater magnitude than previously believed. PMID:7212787

  10. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury.

    PubMed

    Yin, Fei; Guo, Li; Meng, Chun-yang; Liu, Ya-juan; Lu, Ri-feng; Li, Peng; Zhou, Yu-bo

    2014-05-02

    It is unknown whether transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can repair spinal cord ischemia-reperfusion injury (SCII) in a rat model through an anti-apoptotic effect. Adult rats were divided into untreated or sham-operated controls, untreated models of SCII (uSCII) and BM-MSC-transplanted models of SCII (tSCII; labeled with CM-Dill transplanted at 1 h and 24 h after reperfusion). According to evaluation of hind-limb motor function, the motor functions of tSCII rats were significantly better than those of uSCII rats by the seventh day. H&E and TUNEL staining showed that the spinal cords of uSCII rats contained damaged neural cells with nuclear pyknosis and congestion of blood vessels, with a high percentage of apoptotic neural cells, while the spinal cords of tSCII rats were nearly normal with significantly fewer apoptotic neural cells. Immunohistochemistry and double immunofluorescence staining revealed that in tSCII rats CASP3 and neurofilament-H (NF-H) levels were 14.57% and 174% those of uSCII rats, respectively, and in tSCII rats the ratio of BAX to BCL2 was reduced by nearly 50%. The differentiation of transplanted CM-Dil-labeled BM-MSCs into neurons and astrocytes was observed in the spinal cords of the tSCII rats under laser scanning confocal microscopy. These results showed that transplantation of BM-MSCs improved functional recovery after SCII via anti-apoptosis.

  11. Electroacupuncture preconditioning and postconditioning inhibit apoptosis and neuroinflammation induced by spinal cord ischemia reperfusion injury through enhancing autophagy in rats.

    PubMed

    Fang, Bo; Qin, Meiman; Li, Yun; Li, Xiaoqian; Tan, Wenfei; Zhang, Ying; Ma, Hong

    2017-03-06

    Electroacupuncture (EA) has beneficial effects on spinal cord ischemia reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. This study aimed to investigate the role of autophagy in the protection of EA preconditioning and postconditioning against spinal cord I/R injury. For this, spinal cord I/R injury was induced by 14min occlusion of the aortic arch, and rats were treated with EA for 20min before or after the surgery. The expression of autophagy components, light chain 3 and Beclin 1, was assessed by Western blot. The hind-limb motor function was assessed using the Basso-Beattie-Bresnahan (BBB) criteria, and motor neurons in the ventral gray matter were counted by histological examination. The apoptosis of neurocyte was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and matrix metalloproteinase-9 (MMP-9) was also measured using Western blot or enzyme-linked immunosorbent assay (ELISA). Either EA preconditioning or postconditioning enhanced autophagy, and minimized the neuromotor dysfunction and histopathological deficits after spinal cord I/R injury. In addition, EA suppressed I/R-induced apoptosis and increased in the expression of TNF-α, IL-1β, and MMP-9. In contrast, the autophagic inhibitor (3-methyladenine, 3-MA) inhibited the neuroprotective effects of EA. Moreover, 3-MA increased the apoptosis and the expression of TNF-α, IL-1β, and MMP-9. In summary, these findings suggested that EA preconditioning and postconditioning could alleviate spinal cord I/R injury, which was partly mediated by autophagy upregulation-induced inhibition of apoptosis and neuroinflammation.

  12. Lymph pump mechanics in the rabbit hind leg.

    PubMed

    Ikomi, F; Schmid-Schönbein, G W

    1996-07-01

    The mechanisms that govern fluid uptake by the initial lymphatics and adjustment of lymph flow rates remain to a large degree uncertain. The aim of this study was to examine how passive tissue movement contributes to lymph flow rates. Lymph fluid was collected via a cannula inserted into one of the popliteal prenodal lymphatics in the rabbit hind leg. Lymph flow rates were measured during periodic whole leg rotation and controlled oscillatory massage of the dorsal skin of the foot. Without whole leg rotation, lymph flow remained at low values (< 0.01 ml/h). Introduction of whole leg passive rotation caused a frequency-dependent increase in lymph flow rates, which were increased linearly with the log of frequency between 0.03 and 1.0 Hz. Local skin massage in the region of the initial lymphatics also led to a similar increase of lymph flow rates dependent on frequency as well as amplitude of skin displacement. Lymph flow rates during local skin massage reached a comparable order of magnitude regardless of whether the animal was alive or the heart had been arrested, suggesting that local lymph flow rates can be adjusted by periodic tissue motion independently of capillary fluid filtration pressures. The results indicate that periodic expansion and compression of initial lymphatics provide a mechanism for lymph pumping.

  13. Cholesterol metabolism: the main pathway acting downstream of cytochrome P450 oxidoreductase in skeletal development of the limb.

    PubMed

    Schmidt, Katy; Hughes, Catherine; Chudek, J A; Goodyear, Simon R; Aspden, Richard M; Talbot, Richard; Gundersen, Thomas E; Blomhoff, Rune; Henderson, Colin; Wolf, C Roland; Tickle, Cheryll

    2009-05-01

    Cytochrome P450 oxidoreductase (POR) is the obligate electron donor for all microsomal cytochrome P450 enzymes, which catalyze the metabolism of a wide spectrum of xenobiotic and endobiotic compounds. Point mutations in POR have been found recently in patients with Antley-Bixler-like syndrome, which includes limb skeletal defects. In order to study P450 function during limb and skeletal development, we deleted POR specifically in mouse limb bud mesenchyme. Forelimbs and hind limbs in conditional knockout (CKO) mice were short with thin skeletal elements and fused joints. POR deletion occurred earlier in forelimbs than in hind limbs, leading additionally to soft tissue syndactyly and loss of wrist elements and phalanges due to changes in growth, cell death, and skeletal segmentation. Transcriptional analysis of E12.5 mouse forelimb buds demonstrated the expression of P450s involved in retinoic acid, cholesterol, and arachidonic acid metabolism. Biochemical analysis of CKO limbs confirmed retinoic acid excess. In CKO limbs, expression of genes throughout the whole cholesterol biosynthetic pathway was upregulated, and cholesterol deficiency can explain most aspects of the phenotype. Thus, cellular POR-dependent cholesterol synthesis is essential during limb and skeletal development. Modulation of P450 activity could contribute to susceptibility of the embryo and developing organs to teratogenesis.

  14. Skeletal limb abnormalities

    MedlinePlus

    ... medlineplus.gov/ency/article/003170.htm Skeletal limb abnormalities To use the sharing features on this page, please enable JavaScript. Skeletal limb abnormalities refers to a variety of bone structure problems ...

  15. Bypass surgery for lower extremity limb salvage: vein bypass.

    PubMed

    El-Sayed, Hosam F

    2012-01-01

    Bypass surgery for limb salvage in cases of chronic limb ischemia is a well-established treatment modality. Use of an autogenous vein provides the best conduit for infrainguinal arterial bypass procedures, particularly for bypass to the infrapopliteal arteries. In this article, we discuss infrainguinal vein bypass surgery including indications, perioperative care, and long-term follow up. We also discuss the outcomes of the procedure with regard to patient survival and limb salvage. The autogenous vein continues to be the best available conduit with the highest patency rate and the best treatment option. Compared to all other revascularization options for infrainguinal disease, the vein bypass has the best limb salvage and long-term survival in patients appropriately selected for the procedure.

  16. Limb-threatening ischemia secondary to a congenital acromioclavicular remnant.

    PubMed

    Enlow, Jonathan M; McGregor, Walter E

    2009-07-01

    Upper extremity vascular compromise from thoracic outlet syndrome is rare and is usually the result of a "cervical rib," anterior scalene muscle abnormality, or clavicular trauma. We report a case of acute axillary artery thrombosis secondary to a congenital acromioclavicular remnant in a 40-year-old woman.

  17. Major ozonated autohemotherapy in chronic limb ischemia with ulcerations.

    PubMed

    de Monte, Amato; van der Zee, Hoyte; Bocci, Velio

    2005-04-01

    This paper reports the beneficial effects of ozone autohemotherapy (OHT) in 2 patients afflicted with painful, intractable leg ulcers. One patient had diabetes mellitus type II (DM), the other had vasculitis. Both patients had seen multiple specialists, including a dermatologist, an internist, and a vascular surgeon, but their clinical course continued to worsen. When the pain became intolerable, the patients came to our pain clinic. Chemical lumbar sympathectomy as well as epidural blockade with bupivacaine and morphine were moderately effective in reducing their pain but had no effect on the ulcers. Only after OHT treatments were performed for several months was satisfactory healing observed.

  18. Permanent antibiotic impregnated intramedullary nail in diabetic limb salvage: a case report and literature review.

    PubMed

    Woods, Jason B; Lowery, Nicholas J; Burns, Patrick R

    2012-01-01

    Managing complications after attempted hind foot and ankle arthrodesis with intramedullary nail fixation is a challenge. This situation becomes more problematic in the patient with diabetes mellitus and multiple comorbidities. Infection and subsequent osteomyelitis can be a devastating, limb threatening complication associated with these procedures. The surgeon must manage both the infectious process and the skeletal instability concurrently. This article provides a literature review and detailed management strategies for a modified technique of employing antibiotic impregnated polymethylmethacrylate-coated intramedullary nailing.

  19. A comparative study of trabecular bone mass distribution in cursorial and non-cursorial limb joints.

    PubMed

    Chirchir, Habiba

    2015-05-01

    Skeletal design among cursorial animals is a compromise between a stable body that can withstand locomotor stress and a light design that is energetically inexpensive to grow, maintain, and move. Cursors have been hypothesized to reduce distal musculoskeletal mass to maintain a balance between safety and energetic cost due to an exponential increase in energetic demand observed during the oscillation of the distal limb. Additionally, experimental research shows that the cortical bone in distal limbs experiences higher strains and remodeling rates, apparently maintaining lower mass at the expense of a smaller safety factor. This study tests the hypothesis that the trabecular bone mass in the distal limb epiphyses of cursors is relatively lower than that in the proximal limb epiphyses to minimize the energetic cost of moving the limb. This study utilized peripheral quantitative computed tomography scanning to measure the trabecular mass in the lower and upper limb epiphyses of hominids, cercopithecines, and felids that are considered cursorial and non-cursorial. One-way ANOVA with Tukey post hoc corrections was used to test for significant differences in trabecular mass across limb epiphyses. The results indicate that overall, both cursors and non-cursors exhibit varied trabecular mass in limb epiphyses and, in certain instances, conform to a proximal-distal decrease in mass irrespective of cursoriality. Specifically, hominid and cercopithecine hind limb epiphyses exhibit a proximal-distal decrease in mass irrespective of cursorial adaptations. These results suggest that cursorial mammals employ other energy saving mechanisms to minimize energy costs during running.

  20. Regeneration of limb joints in the axolotl (Ambystoma mexicanum).

    PubMed

    Lee, Jangwoo; Gardiner, David M

    2012-01-01

    In spite of numerous investigations of regenerating salamander limbs, little attention has been paid to the details of how joints are reformed. An understanding of the process and mechanisms of joint regeneration in this model system for tetrapod limb regeneration would provide insights into developing novel therapies for inducing joint regeneration in humans. To this end, we have used the axolotl (Mexican Salamander) model of limb regeneration to describe the morphology and the expression patterns of marker genes during joint regeneration in response to limb amputation. These data are consistent with the hypothesis that the mechanisms of joint formation whether it be development or regeneration are conserved. We also have determined that defects in the epiphyseal region of both forelimbs and hind limbs in the axolotl are regenerated only when the defect is small. As is the case with defects in the diaphysis, there is a critical size above which the endogenous regenerative response is not sufficient to regenerate the joint. This non-regenerative response in an animal that has the ability to regenerate perfectly provides the opportunity to screen for the signaling pathways to induce regeneration of articular cartilage and joints.

  1. Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

    PubMed Central

    Nguyen, Gerard K.; Monahan, John F. W.; Davis, Gabrielle B.; Lee, Yong Suk; Ragina, Neli P.; Wang, Charles; Zhou, Zhao Y.; Hong, Young Kwon; Spivak, Ryan M.; Wong, Alex K.

    2013-01-01

    The field of reconstructive microsurgery is experiencing tremendous growth, as evidenced by recent advances in face and hand transplantation, lower limb salvage after trauma, and breast reconstruction. Common to all of these procedures is the creation of a nutrient vascular supply by microsurgical anastomosis between a single artery and vein. Complications related to occluded arterial inflow and obstructed venous outflow are not uncommon, and can result in irreversible tissue injury, necrosis, and flap loss. At times, these complications are challenging to clinically determine. Since early intervention with return to the operating room to re-establish arterial inflow or venous outflow is key to flap salvage, the accurate diagnosis of early stage complications is essential. To date, there are no biochemical markers or serum assays that can predict these complications. In this study, we utilized a rat model of flap ischemia in order to identify the transcriptional signatures of venous congestion and arterial ischemia. We found that the critical ischemia time for the superficial inferior epigastric fasciocutaneus flap was four hours and therefore performed detailed analyses at this time point. Histolgical analysis confirmed significant differences between arterial and venous ischemia. The transcriptome of ischemic, congested, and control flap tissues was deciphered by performing Affymetrix microarray analysis and verified by qRT-PCR. Principal component analysis revealed that arterial ischemia and venous congestion were characterized by distinct transcriptomes. Arterial ischemia and venous congestion was characterized by 408 and 1536>2-fold differentially expressed genes, respectively. qRT-PCR was used to identify five candidate genes Prol1, Muc1, Fcnb, Il1b, and Vcsa1 to serve as biomarkers for flap failure in both arterial ischemia and venous congestion. Our data suggests that Prol1 and Vcsa1 may be specific indicators of venous congestion and allow clinicians to

  2. [Cerebral ischemia and histamine].

    PubMed

    Adachi, Naoto

    2002-10-01

    Cerebral ischemia induces excess release of glutamate and an increase in the intracellular Ca2+ concentration, which provoke catastrophic enzymatic processes leading to irreversible neuronal injury. Histamine plays the role of neurotransmitter in the central nervous system, and histaminergic fibers are widely distributed in the brain. In cerebral ischemia, release of histamine from nerve endings has been shown to be enhanced by facilitation of its activity. An inhibition of the histaminergic activity in ischemia aggravates the histologic outcome. In contrast, intracerebroventricular administration of histamine improves the aggravation, whereas blockade of histamine H2 receptors aggravates ischemic injury. Furthermore, H2 blockade enhances ischemic release of glutamate and dopamine. These findings suggest that central histamine provides beneficial effects against ischemic neuronal damage by suppressing release of excitatory neurotransmitters. However, histaminergic H2 action facilitates the permeability of the blood-brain barrier and shows deleterious effects on cerebral edema.

  3. Accuracy and precision of equine gait event detection during walking with limb and trunk mounted inertial sensors.

    PubMed

    Olsen, Emil; Andersen, Pia Haubro; Pfau, Thilo

    2012-01-01

    The increased variations of temporal gait events when pathology is present are good candidate features for objective diagnostic tests. We hypothesised that the gait events hoof-on/off and stance can be detected accurately and precisely using features from trunk and distal limb-mounted Inertial Measurement Units (IMUs). Four IMUs were mounted on the distal limb and five IMUs were attached to the skin over the dorsal spinous processes at the withers, fourth lumbar vertebrae and sacrum as well as left and right tuber coxae. IMU data were synchronised to a force plate array and a motion capture system. Accuracy (bias) and precision (SD of bias) was calculated to compare force plate and IMU timings for gait events. Data were collected from seven horses. One hundred and twenty three (123) front limb steps were analysed; hoof-on was detected with a bias (SD) of -7 (23) ms, hoof-off with 0.7 (37) ms and front limb stance with -0.02 (37) ms. A total of 119 hind limb steps were analysed; hoof-on was found with a bias (SD) of -4 (25) ms, hoof-off with 6 (21) ms and hind limb stance with 0.2 (28) ms. IMUs mounted on the distal limbs and sacrum can detect gait events accurately and precisely.

  4. Artificial insemination following observational versus electronic methods of estrus detection in red deer hinds (Cervus elephus).

    PubMed

    Bowers, S D; Brown, C G; Strauch, T A; Gandy, B S; Neuendorff, D A; Randel, R D; Willard, S T

    2004-08-01

    The objectives were to determine the efficacy of the HeatWatch (HW) electronic estrus detection system for monitoring behavioral estrus (including duration and intensity) in red deer hinds and to evaluate pregnancy rate to AI after detected estrus. Red deer hinds (Cervus elephus; n = 50) were allocated into two treatment groups: AI following synchronization (CIDR/PMSG) and observed estrus (induced estrus group: IE; n = 25) or AI following the detection of natural estrus (NE; n = 25) without hormonal treatment. Hinds were fitted with two HeatWatch (HW) electronic estrus detection transmitters, one above the tail (bottom) and one between the tuber coxae of the pelvic girdle (top), and visual observations for mounting activity began with the aid of young sterile red deer stags (18 months old) fitted with marking harnesses. Hinds in both groups were inseminated (10-12h after observed estrus) with frozen-thawed red deer semen using a transvaginal/cervical AI approach. Following a 26-day period of AI, hinds were placed with a mature fertile stag for an additional 30-day natural breeding period. Pregnancy diagnosis was performed 57 and 86 days after the start of AI. While the hinds were housed with the young stags, 82% were detected in estrus by visual appraisal of stag crayon marks, but only 32% of these were detected by HW. In contrast, in the hinds housed with the mature stag, 93% detected in estrus by crayon marks were also detected by HW. The top HW transmitter consistently recorded more mounts (P < 0.05) than the bottom transmitter. The pregnancy rate was numerically better in IE versus NE hinds (42% versus 29%, P > 0.10). In summary, there were no differences (P > 0.10) in the intensity (number) or duration of mounts (detected by HW) during estrus in IE versus NE hinds, and HW was most effective in detecting estrus in the presence of a heavier, mature stag versus a younger stag. When used in combination with transvaginal AI, an overall first-service pregnancy rate

  5. Passive Exercise of the Hind Limbs after Complete Thoracic Transection of the Spinal Cord Promotes Cortical Reorganization

    PubMed Central

    Knudsen, Eric B.; Shumsky, Jed; Moxon, Karen A.

    2013-01-01

    Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes – such as increased cardiovascular fitness, improved circulation and neuroendocrine changes – that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity – specifically ADCY1 and BDNF – increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain. PMID:23349859

  6. Correlative Imaging of the Murine Hind Limb Vasculature and Muscle Tissue by MicroCT and Light Microscopy

    PubMed Central

    Schaad, Laura; Hlushchuk, Ruslan; Barré, Sébastien; Gianni-Barrera, Roberto; Haberthür, David; Banfi, Andrea; Djonov, Valentin

    2017-01-01

    A detailed vascular visualization and adequate quantification is essential for the proper assessment of novel angiomodulating strategies. Here, we introduce an ex vivo micro-computed tomography (microCT)-based imaging approach for the 3D visualization of the entire vasculature down to the capillary level and rapid estimation of the vascular volume and vessel size distribution. After perfusion with μAngiofil®, a novel polymerizing contrast agent, low- and high-resolution scans (voxel side length: 2.58–0.66 μm) of the entire vasculature were acquired. Based on the microCT data, sites of interest were defined and samples further processed for correlative morphology. The solidified, autofluorescent μAngiofil® remained in the vasculature and allowed co-registering of the histological sections with the corresponding microCT-stack. The perfusion efficiency of μAngiofil® was validated based on lectin-stained histological sections: 98 ± 0.5% of the blood vessels were μAngiofil®-positive, whereas 93 ± 2.6% were lectin-positive. By applying this approach we analyzed the angiogenesis induced by the cell-based delivery of a controlled VEGF dose. Vascular density increased by 426% mainly through the augmentation of medium-sized vessels (20–40 μm). The introduced correlative and quantitative imaging approach is highly reproducible and allows a detailed 3D characterization of the vasculature and muscle tissue. Combined with histology, a broad range of complementary structural information can be obtained. PMID:28169309

  7. Ontogenetic changes in limb bone structural proportions in mountain gorillas (Gorilla beringei beringei).

    PubMed

    Ruff, Christopher B; Burgess, M Loring; Bromage, Timothy G; Mudakikwa, Antoine; McFarlin, Shannon C

    2013-12-01

    Behavioral studies indicate that adult mountain gorillas (Gorilla beringei) are the most terrestrial of all nonhuman hominoids, but that infant mountain gorillas are much more arboreal. Here we examine ontogenetic changes in diaphyseal strength and length of the femur, tibia, humerus, radius, and ulna in 30 Virunga mountain gorillas, including 18 immature specimens and 12 adults. Comparisons are also made with 14 adult western lowland gorillas (Gorilla gorilla gorilla), which are known to be more arboreal than adult mountain gorillas. Infant mountain gorillas have significantly stronger forelimbs relative to hind limbs than older juveniles and adults, but are nonsignificantly different from western lowland gorilla adults. The change in inter-limb strength proportions is abrupt at about two years of age, corresponding to the documented transition to committed terrestrial quadrupedalism in mountain gorillas. The one exception is the ulna, which shows a gradual increase in strength relative to the radius and other long bones during development, possibly corresponding to the gradual adoption of stereotypical fully pronated knuckle-walking in older juvenile gorillas. Inter-limb bone length proportions show a contrasting developmental pattern, with hind limb/forelimb length declining rapidly from birth to five months of age, and then showing no consistent change through adulthood. The very early change in length proportions, prior to significant independent locomotion, may be related to the need for relatively long forelimbs for climbing in a large-bodied hominoid. Virunga mountain gorilla older juveniles and adults have equal or longer forelimb relative to hind limb bones than western lowland adults. These findings indicate that both ontogenetically and among closely related species of Gorilla, long bone strength proportions better reflect actual locomotor behavior than bone length proportions.

  8. [The relation between gene of lipoprotein-lipase and carrier protein of cholesterol ethers and life duration in patients with chronic cerebral ischemia].

    PubMed

    Kostomarov, I V; Vodolagina, N N; Malygina, N A; Mitina, Z S

    2008-01-01

    Comparative analysis of frequency distribution of genotypes and alleles of HindIII-polymorphism of gene LPL and TaqIB-polymorphism of gene CETP in 267 patients of various ages with chronic cerebral ischemia (CCI) was performed. Relation between age and polymorphous variants of genes LPL and CETP was noticed. It was shown that genotype of H+H+ HindIII-polymorphism of and genotype B1B1 TaqIB-polymorphism of gene CETP were found more frequently in more young patients with chronic cerebral ischemia (CCI). Since there is an association of these genotypes with atherogenic dislipidemias, they apparently can be considered as risk factors of CCI development. On the contrary, genotype of gene LPL and B2 allele of gene CETP in patients elder 90 years (long-livers) are found significantly more frequently than in younger patients, that makes possible to consider they as markers of favorable course of disease and patients' long life.

  9. The hydraulic mechanism of the unfolding of hind wings in Dorcus titanus platymelus (order: Coleoptera).

    PubMed

    Sun, Jiyu; Ling, Mingze; Wu, Wei; Bhushan, Bharat; Tong, Jin

    2014-04-09

    In most beetles, the hind wings are thin and fragile; when at rest, they are held over the back of the beetle. When the hind wing unfolds, it provides the necessary aerodynamic forces for flight. In this paper, we investigate the hydraulic mechanism of the unfolding process of the hind wings in Dorcus titanus platymelus (Oder: Coleoptera). The wing unfolding process of Dorcus titanus platymelus was examined using high speed camera sequences (400 frames/s), and the hydraulic pressure in the veins was measured with a biological pressure sensor and dynamic signal acquisition and analysis (DSA) during the expansion process. We found that the total time for the release of hydraulic pressure during wing folding is longer than the time required for unfolding. The pressure is proportional to the length of the wings and the body mass of the beetle. A retinal camera was used to investigate the fluid direction. We found that the peak pressures correspond to two main cross-folding joint expansions in the hind wing. These observations strongly suggest that blood pressure facilitates the extension of hind wings during unfolding.

  10. The hydraulic mechanism in the hind wing veins of Cybister japonicus Sharp (order: Coleoptera).

    PubMed

    Sun, Jiyu; Wu, Wei; Ling, Mingze; Bhushan, Bharat; Tong, Jin

    2016-01-01

    The diving beetles (Dytiscidae, Coleoptera) are families of water beetles. When they see light, they fly to the light source directly from the water. Their hind wings are thin and fragile under the protection of their elytra (forewings). When the beetle is at rest the hind wings are folded over the abdomen of the beetle and when in flight they unfold to provide the necessary aerodynamic forces. In this paper, the unfolding process of the hind wing of Cybister japonicus Sharp (order: Coleoptera) was investigated. The motion characteristics of the blood in the veins of the structure system show that the veins have microfluidic control over the hydraulic mechanism of the unfolding process. A model is established, and the hind wing extending process is simulated. The blood flow and pressure changes are discussed. The driving mechanism for hydraulic control of the folding and unfolding actions of beetle hind wings is put forward. This can assist the design of new deployable micro air vehicles and bioinspired deployable systems.

  11. The hydraulic mechanism in the hind wing veins of Cybister japonicus Sharp (order: Coleoptera)

    PubMed Central

    Wu, Wei; Ling, Mingze; Tong, Jin

    2016-01-01

    Summary The diving beetles (Dytiscidae, Coleoptera) are families of water beetles. When they see light, they fly to the light source directly from the water. Their hind wings are thin and fragile under the protection of their elytra (forewings). When the beetle is at rest the hind wings are folded over the abdomen of the beetle and when in flight they unfold to provide the necessary aerodynamic forces. In this paper, the unfolding process of the hind wing of Cybister japonicus Sharp (order: Coleoptera) was investigated. The motion characteristics of the blood in the veins of the structure system show that the veins have microfluidic control over the hydraulic mechanism of the unfolding process. A model is established, and the hind wing extending process is simulated. The blood flow and pressure changes are discussed. The driving mechanism for hydraulic control of the folding and unfolding actions of beetle hind wings is put forward. This can assist the design of new deployable micro air vehicles and bioinspired deployable systems. PMID:27547607

  12. Analysis of the HindIII-catalyzed reaction by time-resolved crystallography

    SciTech Connect

    Kawamura, Takashi; Kobayashi, Tomoki; Watanabe, Nobuhisa

    2015-02-01

    A time-resolved study using the freeze-trap method elucidates the mechanism of the DNA-cleaving reaction of HindIII. In order to investigate the mechanism of the reaction catalyzed by HindIII, structures of HindIII–DNA complexes with varying durations of soaking time in cryoprotectant buffer containing manganese ions were determined by the freeze-trap method. In the crystal structures of the complexes obtained after soaking for a longer duration, two manganese ions, indicated by relatively higher electron density, are clearly observed at the two metal ion-binding sites in the active site of HindIII. The increase in the electron density of the two metal-ion peaks followed distinct pathways with increasing soaking times, suggesting variation in the binding rate constant for the two metal sites. DNA cleavage is observed when the second manganese ion appears, suggesting that HindIII uses the two-metal-ion mechanism, or alternatively that its reactivity is enhanced by the binding of the second metal ion. In addition, conformational change in a loop near the active site accompanies the catalytic reaction.

  13. Role of simvastatin and/or antioxidant vitamins in therapeutic angiogenesis in experimental diabetic hindlimb ischemia: effects on capillary density, angiogenesis markers, and oxidative stress.

    PubMed

    El-Azab, Mona F; Hazem, Reem M; Moustafa, Yasser M

    2012-09-05

    Therapeutic angiogenesis has emerged as an attractive approach for the management of peripheral arterial disease in diabetic patients. Oxidative stress generated and aggravated by prolonged hyperglycemia may interfere with and destroy the newly formed blood vessels. Angiogenic effect of simvastatin has been reported; however, its exact mechanism is yet to be evaluated. In addition, the exact role of antioxidant vitamins in diabetic peripheral arterial disease is still controversial. The present study was undertaken to investigate the therapeutic potential of simvastatin and antioxidant vitamins (E and C) and their combined effects on angiogenesis in diabetic hind-limb ischemia. Streptozotocin diabetic rats were treated for 6 weeks with simvastatin either alone or in combination with vitamin E or vitamin C. Parameters of angiogenesis, nitric oxide, heme oxygenase-1 (HO-1), and oxidative stress markers were evaluated. CD31 immunostaining revealed an increased capillary density in ischemic gastrocnemious tissue of diabetic rats treated with either simvastatin or its combination with vitamin C. This effect was accompanied by up-regulated plasma levels of HO-1, nitric oxide, vascular endothelial growth factor (VEGF) and its intra-muscular receptor type-2 (Flk-1). Tissue reduced glutathione and antioxidant enzymes activities were normalized in groups treated with antioxidant vitamins or their combination with simvastatin with concomitant blunting of lipid peroxidation. Vitamins E and C, through their antioxidant effects, evidently enhanced the angiogenic effect of simvastatin in ischemic diabetic muscle. Hence, the use of antioxidant vitamins combined with statins to induce therapeutic angiogenesis is a promising strategy in the management of diabetes-associated peripheral arterial disease.

  14. Laser angioplasty of totally occluded arteries of the limb

    NASA Astrophysics Data System (ADS)

    Szopinski, Piotr; Hara, Marek; Noszczyk, Wojciech

    1996-03-01

    The authors summarize their experience in the use of Nd-YAG laser in chronic occlusion of lower limb arteries. Percutaneous transluminal laser angioplasty (PTLA) with laser-heated metal and sapphire tips were used as an adjuvant to conventional balloon angioplasty. In cases of reocclusions, endovascular stents were implanted. Laser recanalization was performed in 46 arteries (iliac, superficial femoral, and popliteal). Indications for the procedure were: limb salvage, claudication below 100 m, and temporal or rest pain. Initial clinical and hemodynamic improvement was observed in 37 (80%) patients. Four perforations occurred without clinical sequel. The one-year cumulative clinical patency was 27 (58%) of the 46 lesions. PTLA may be appropriate for high-risk patients, who are unsuitable for surgical reconstruction because of the concomitant diseases. The combination of laser recanalization and implantation of vascular stents may be a promising method in the management of limb ischemia.

  15. Successful Intraarterial Thrombolysis of an Ischemic Limb Four Days After Laparoscopic Cholecystectomy

    SciTech Connect

    Sandison, Andrew J. P.; Edmondson, Robert A.; Panayiotopoulos, Yiannis; Reidy, John F.; McColl, Ian; Taylor, Peter R.

    1998-03-15

    Intraarterial thrombolysis is usually contraindicated after abdominal surgery because of the risk of bleeding. However, it is a highly effective treatment for embolic acute limb ischemia, particularly for clearing the distal vessels. We report a case in which intraarterial thrombolysis was safely used 4 days after laparoscopic cholecystectomy in a patient with an acutely ischemic leg due to embolus.

  16. Inhibitory effects of prior low-dose x-irradiation on ischemia-reperfusion injury in mouse paw.

    PubMed

    Kataoka, Takahiro; Mizuguchi, Yuko; Yoshimoto, Masaaki; Taguchi, Takehito; Yamaoka, Kiyonori

    2007-11-01

    We have reported that low-dose, unlike high-dose, irradiation enhanced antioxidation function and reduced oxidative damage. On the other hand, ischemia-reperfusion injury is induced by reactive oxygen species. In this study, we examined the inhibitory effects of prior low-dose X-irradiation on ischemia-reperfusion injury in mouse paw. BALB/c mice were irradiated by sham or 0.5 Gy of X-ray. At 4 hrs after irradiation, the left hind leg was bound 10 times with a rubber ring for 0.5, 1, or 2 hrs and the paw thickness was measured. Results show that the paw swelling thickness by ischemia for 0.5 hr was lower than that for 2 hrs. At 1 hr after reperfusion from ischemia for 1 hr, superoxide dismutase activity in serum was increased in those mice which received 0.5 Gy irradiation and in the case of the ischemia for 0.5 or 1 hr, the paw swelling thicknesses were inhibited by 0.5 Gy irradiation. In addition, interstitial edema in those mice which received 0.5 Gy irradiation was less than that in the mice which underwent by sham irradiation. These findings suggest that the ischemia-reperfusion injury is inhibited by the enhancement of antioxidation function by 0.5 Gy irradiation.

  17. The evolving concept of physiological ischemia training vs. ischemia preconditioning.

    PubMed

    Ni, Jun; Lu, Hongjian; Lu, Xiao; Jiang, Minghui; Peng, Qingyun; Ren, Caili; Xiang, Jie; Mei, Chengyao; Li, Jianan

    2015-11-01

    Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning.

  18. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1988-03-15

    The basic goal of the Limestone Injection Multistage Burner (LIMB) demonstration is to extend LIMB technology development to a full-scale application on a representative wall-fired utility boiler. The successful retrofit of LIMB to an existing boiler is expected to demonstrate that (a) reductions of 50 percent or greater in SO{sub x} and NO{sub x} emissions can be achieved at a fraction of the cost of add-on FGD systems, (b) boiler reliability, operability, and steam production can be maintained at levels existing prior to LIMB retrofit, and (c) technical difficulties attributable to LIMB operation, such as additional slagging and fouling, changes in ash disposal requirements, and an increased particulate load, can be resolved in a cost-effective manner. The primary fuel to be used will be an Ohio bituminous coal having a nominal sulfur content of 3 percent or greater.

  19. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1988-09-15

    The basic goal of the Limestone Injection Multistage Burner (LIMB) demonstration is to extend LIMB technology development to a full-scale application on a representative wall-fired utility boiler. The successful retrofit of LIMB to an existing boiler is expected to demonstrate that (a) reductions of 50 percent or greater in SO and NO emissions can be achieved at a fraction of the cost of add-on FGD systems, (b) boiler reliability, operability, and steam production can be maintained at levels existing prior to LIMB retrofit, and (c) technical difficulties attributable to LIMB operation, such as additional slagging and fouling, changes in ash disposal requirements, and an increased particulate load, can be resolved in a cost-effective manner. The primary fuel to be used will be an Ohio bituminous coal having a nominal sulfur content of 3 percent or greater.

  20. Hox gene expression leads to differential hind leg development between honeybee castes.

    PubMed

    Bomtorin, Ana Durvalina; Barchuk, Angel Roberto; Moda, Livia Maria; Simoes, Zila Luz Paulino

    2012-01-01

    Beyond the physiological and behavioural, differences in appendage morphology between the workers and queens of Apis mellifera are pre-eminent. The hind legs of workers, which are highly specialized pollinators, deserve special attention. The hind tibia of worker has an expanded bristle-free region used for carrying pollen and propolis, the corbicula. In queens this structure is absent. Although the morphological differences are well characterized, the genetic inputs driving the development of this alternative morphology remain unknown. Leg phenotype determination takes place between the fourth and fifth larval instar and herein we show that the morphogenesis is completed at brown-eyed pupa. Using results from the hybridization of whole genome-based oligonucleotide arrays with RNA samples from hind leg imaginal discs of pre-pupal honeybees of both castes we present a list of 200 differentially expressed genes. Notably, there are castes preferentially expressed cuticular protein genes and members of the P450 family. We also provide results of qPCR analyses determining the developmental transcription profiles of eight selected genes, including abdominal-A, distal-less and ultrabithorax (Ubx), whose roles in leg development have been previously demonstrated in other insect models. Ubx expression in workers hind leg is approximately 25 times higher than in queens. Finally, immunohistochemistry assays show that Ubx localization during hind leg development resembles the bristles localization in the tibia/basitarsus of the adult legs in both castes. Our data strongly indicate that the development of the hind legs diphenism characteristic of this corbiculate species is driven by a set of caste-preferentially expressed genes, such as those encoding cuticular protein genes, P450 and Hox proteins, in response to the naturally different diets offered to honeybees during the larval period.

  1. Critical ischemia time in a model of spinal cord section. A study performed on dogs

    PubMed Central

    Garcia Martinez, David; Rosales Corral, Sergio A.; Flores Soto, Mario E.; Velarde Silva, Gustavo; Portilla de Buen, Eliseo

    2006-01-01

    Vascular changes after acute spinal cord trauma are important factors that predispose quadriplegia, in most cases irreversible. Repair of the spinal blood flow helps the spinal cord recovery. The average time to arrive and perform surgery is 3 h in most cases. It is important to determine the critical ischemia time in order to offer better functional prognosis. A spinal cord section and vascular clamping of the spinal anterior artery at C5–C6 model was used to determine critical ischemia time. The objective was to establish a critical ischemia time in a model of acute spinal cord section. Four groups of dogs were used, anterior approach and vascular clamp of spinal anterior artery with 1, 2, 3, and 4 h of ischemia and posterior hemisection of spinal cord at C5–C6 was performed. Clinical evaluation was made during 12 weeks and morphological evaluation at the end of this period. We obtained a maximal neurological coordination at 23 days average. Two cases showed sequels of right upper limb paresis at 1 and 3 ischemia hours. There was nerve conduction delay of 56% at 3 h of ischemia. Morphological examination showed 25% of damaged area. The VIII and IX Rexed’s laminae were the most affected. The critical ischemia time was 3 h. Dogs with 4 h did not exhibit any recovery. PMID:17024402

  2. Radiological Evaluation of Bowel Ischemia

    PubMed Central

    Dhatt, Harpreet S.; Behr, Spencer C; Miracle, Aaron; Wang, Zhen Jane; Yeh, Benjamin M.

    2015-01-01

    Intestinal ischemia, which refers to insufficient blood flow to the bowel, is a potentially catastrophic entity that may require emergent intervention or surgery in the acute setting. Although the clinical signs and symptoms of intestinal ischemia are nonspecific, CT findings can be highly suggestive in the correct clinical setting. In this chapter we review the CT diagnosis of arterial, venous, and non-occlusive intestinal ischemia. We discuss the vascular anatomy, pathophysiology of intestinal ischemia, CT techniques for optimal imaging, key and ancillary radiological findings, and differential diagnosis. In the setting of an acute abdomen, rapid evaluation is necessary to identify intraabdominal processes that require emergent surgical intervention (1). While a wide-range of intraabdominal diseases may be present from trauma to inflammation, one of the most feared disorders is mesenteric ischemia, also known as intestinal ischemia, which refers to insufficient blood flow to the bowel (2). Initial imaging evaluation for intestinal ischemia is typically obtained with CT. Close attention to technique and search for key radiologic features with relation to the CT technique is required. Accurate diagnosis depends on understanding the vascular anatomy, epidemiology, and pathophysiology of various forms of mesenteric ischemia and their corresponding radiological findings on MDCT. At imaging, not only is inspection of the bowel itself important, but evaluation of the mesenteric fat, vasculature, and surrounding peritoneal cavity also helps improves accuracy in the diagnosis of bowel ischemia. PMID:26526436

  3. Earth Limb Radiance Transformation.

    DTIC Science & Technology

    1981-03-02

    AD-A097 523 AEROSPACE CORP EL SEGUNDO CA CHEMISTRY AND PHYSICS LAB F/G 4/1 EARTH LIMB RADIANCE TRANSFORMATION (U) MAR AI S 4 YOUNG F0701-80 -C-0081... Earth Limb Radiance Trafisformation Prepared by S. J. YOUNG Chemistr and Physics Laboratory Laboratory Operations The Aerospace Corporation S.El...ITLEK (and Subtitle) TYPE OF REPORT & P53100 COVERED Earth Limb Radiance Transformation. ( Interim ./ / /TR-OJ081(697j7-g4)-l-- i7.Step hen J. Young

  4. Out on a Limb: Investigating the Anatomy of Tree Limbs

    ERIC Educational Resources Information Center

    Shaw, Edward L.

    2008-01-01

    The author presents several upper elementary science activities involving tree limbs that were collected after severe weather conditions. The activities involved 3rd-grade students arranging tree limb pieces in the correct order from the trunk to the tip of the limb, measuring the pieces, determining the age of a tree limb by its rings,…

  5. Phantom limb pain

    MedlinePlus

    ... Philadelphia, PA: Elsevier; 2015:chap 54. Nikolajsen L, Springer JS, Haroutiunian S. Phantom limb pain. In: Benzon HT, ... medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- ...

  6. Hyaluronan in limb morphogenesis.

    PubMed

    Li, Yingcui; Toole, Bryan P; Dealy, Caroline N; Kosher, Robert A

    2007-05-15

    Hyaluronan (HA) is a large glycosaminoglycan that is not only a structural component of extracellular matrices, but also interacts with cell surface receptors to promote cell proliferation, migration, and intracellular signaling. HA is a major component of the extracellular matrix of the distal subapical mesenchymal cells of the developing limb bud that are undergoing proliferation, directed migration, and patterning in response to the apical ectodermal ridge (AER), and has the functional potential to be involved in these processes. Here we show that the HA synthase Has2 is abundantly expressed by the distal subridge mesodermal cells of the chick limb bud and also by the AER itself. Has2 expression and HA production are downregulated in the proximal central core of the limb bud during the formation of the precartilage condensations of the skeletal elements, suggesting that downregulation of HA may be necessary for the close juxtaposition of cells and the resulting cell-cell interactions that trigger cartilage differentiation during condensation. Overexpression of Has2 in the mesoderm of the chick limb bud in vivo results in the formation of shortened and severely malformed limbs that lack one or more skeletal elements. Skeletal elements that do form in limbs overexpressing Has2 are reduced in length, exhibit abnormal morphology, and are positioned inappropriately. We also demonstrate that sustained HA production in micromass cultures of limb mesenchymal cells inhibits formation of precartilage condensations and subsequent chondrogenesis, indicating that downregulation of HA is indeed necessary for formation of the precartilage condensations that trigger cartilage differentiation. Taken together these results suggest involvement of HA in various aspects of limb morphogenesis.

  7. Production of prostaglandins in placentae and corpus luteum in pregnant hinds of red deer (Cervus elaphus).

    PubMed

    Korzekwa, A J; Szczepańska, A; Bogdaszewski, M; Nadolski, P; Malż, P; Giżejewski, Z

    2016-03-01

    Prostaglandins (PGs) are synthesized from arachidonic acid by prostaglandin synthase 2 (PTGS2) and specific terminal PG synthases such as PGES and PGFS. The role of PGs in the reproductive processes of domestic ruminants is well recognized, whereas in cervidae, it is almost unknown, although it is noteworthy because some species of this family are valued in meat production and trophies. The aim of this study was to determine an effective marker of pregnancy and investigate the production and secretion of PGs in placenta and CL tissue in pregnancy. In the preliminary experiment, the levels of progesterone and 17-β estradiol (RIA; N = 14 divided into seven pregnant and seven nonpregnant hinds) were measured in the peripheral blood. In the main experiment, a comparison of messenger RNA (real-time polymerase chain reaction) and protein expression (Western blotting) of PTGS2, PGES, and PGFS, the level of prostaglandin E2 (PGE2) and PGF2α in the placentae and CL in pregnant hinds (aged 3-4 years, ca. 100 days of pregnancy, N = 6). In pregnant hinds, the level of progesterone in the blood was higher than that in nonpregnant hinds (P < 0.05), whereas the level of E2 was similar in all animals (P > 0.05). The highest messenger RNA expression of PTGS2, PGES, and PGFS was observed in the placentae than in the CL (P < 0.05). The protein expression of PTGS2 and PGES was elevated in the placentae compared with the CL (P < 0.05). The PGE2 output was the highest in cotyledonary tissue (P < 0.05). Pregnancy development in hinds around 100 days is regulated by arachidonic acid metabolites, especially PGE2 produced by the placentae, which production increases in pregnancy. Further studies are required to unravel the mechanisms involved in the regulation of PG and biosynthetic enzymes in uteroplacental and ovarian tissues during pregnancy in red deer females.

  8. Ischemia causes muscle fatigue

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  9. Limb regeneration: a new development?

    PubMed

    Nacu, Eugen; Tanaka, Elly M

    2011-01-01

    Salamander limb regeneration is a classical model of tissue morphogenesis and patterning. Through recent advances in cell labeling and molecular analysis, a more precise, mechanistic understanding of this process has started to emerge. Long-standing questions include to what extent limb regeneration recapitulates the events observed in mammalian limb development and to what extent are adult- or salamander- specific aspects deployed. Historically, researchers studying limb development and limb regeneration have proposed different models of pattern formation. Here we discuss recent data on limb regeneration and limb development to argue that although patterning mechanisms are likely to be similar, cell plasticity and signaling from nerves play regeneration-specific roles.

  10. Oligodendrogenesis after cerebral ischemia

    PubMed Central

    Zhang, Ruilan; Chopp, Michael; Zhang, Zheng Gang

    2013-01-01

    Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs) that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain. PMID:24194700

  11. Shock, acute disseminated intravascular coagulation, and microvascular thrombosis: is 'shock liver' the unrecognized provocateur of ischemic limb necrosis?

    PubMed

    Warkentin, T E; Pai, M

    2016-02-01

    For unknown reasons, a small minority of critically ill patients with septic or cardiogenic shock, multiorgan failure, and disseminated intravascular coagulation develop symmetrical acral (distal extremity) limb loss due to microvascular thrombosis ('limb gangrene with pulses'). Case reports have described preceding 'shock liver' in some critically ill patients who developed such a picture of ischemic limb necrosis. This suggests that profoundly disturbed procoagulant-anticoagulant balance featuring uncontrolled generation of thrombin-resulting from failure of the protein C and antithrombin natural anticoagulant systems due to insufficient hepatic synthesis of these crucial proteins-could explain the microvascular thrombosis and associated limb loss. We hypothesize that shock liver is the key predisposing risk factor underlying ischemic limb necrosis in the majority of patients who develop this complication in the setting of acute disseminated intravascular coagulation complicating septic or cardiogenic shock. As shock liver precedes onset of limb ischemia by several days, therapeutic intervention may be possible.

  12. Limb development and evolution: a frog embryo with no apical ectodermal ridge (AER)

    PubMed Central

    RICHARDSON, MICHAEL K.; CARL, TIMOTHY F.; HANKEN, JAMES; ELINSON, RICHARD P.; COPE, CELIA; BAGLEY, PETER

    1998-01-01

    The treefrog Eleutherodactylus coqui is a direct developer — it has no tadpole stage. The limb buds develop earlier than in metamorphosing species (indirect developers, such as Xenopus laevis). Previous molecular studies suggest that at least some mechanisms of limb development in E. coqui are similar to those of other vertebrates and we wished to see how limb morphogenesis in this species compares with that in other vertebrates. We found that the hind limb buds are larger and more advanced than the forelimbs at all stages examined, thus differing from the typical amniote pattern. The limb buds were also small compared to those in the chick. Scanning and transmission electron microscopy showed that although the apical ectoderm is thickened, there was no apical ectodermal ridge (AER). In addition, the limb buds lacked the dorsoventral flattening seen in many amniotes. These findings could suggest a mechanical function for the AER in maintaining dorsoventral flattening, although not all data are consistent with this view. Removal of distal ectoderm from E. coqui hindlimb buds does not stop outgrowth, although it does produce anterior defects in the skeletal pattern. The defects are less severe when the excisions are performed earlier. These results contrast with the chick, in which AER excision leads to loss of distal structures. We suggest that an AER was present in the common ancestor of anurans and amniotes and has been lost in at least some direct developers including E. coqui. PMID:9688504

  13. Unsteady aerodynamics of flapping flight - A fluid-structure interaction study of fore-hind wing phase difference

    NASA Astrophysics Data System (ADS)

    Rasani, M. R.; Shamsudeen, A.; Sulaiman, M. N.

    2016-11-01

    Flights of dragonflies, various insects and birds have been a subject of active research that may offer insight towards enhanced aerodynamic performance at low Reynolds numbers. To that end, we mimick the flapping biomechanics of a dragonfly by two thin flat airfoils plunging in tandem with each other. In the present study, we aim to investigate the effect of difference in flapping phase between fore and hind wings towards their aerodynamic performances. We computationally simulate incompressible, viscous, laminar flow around two thin flat airfoils that are purely plunging, at a Strouhal number of 0.25 and Reynolds number of 6500, using a flow solver in an Arbitrary Lagrangian-Eulerian framework. Kinematics of both fore and hind wing flapping followed a similar sinusoidal function but with relative phase angle difference to each other, that were varied between -50° to +50° including two cases were phase difference is 0° (i.e. in-phase fore-hind wing flapping) and +90° (i.e. fore wing lags hind wing by 90°). Numerical results indicate that maximum lift and drag forces for each fore and hind wings occur at phase angle of -40° and that power efficiency of tandem wings are better at phase angles when hind wing leads the fore wing, with maximum power efficiency occurring at a fore-hind wing phase difference of +30°. The complex fore-hind wing vortex interaction indicate likely benefit on the hind wing as it interacts with the fore wing at different phase angles.

  14. Limb salvage surgery

    PubMed Central

    Kadam, Dinesh

    2013-01-01

    The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy. PMID:24501463

  15. [Limb edema and lymphoscintigraphy].

    PubMed

    Bourgeois, P; Munck, D; Belgrado, J P; Leduc, O; Leduc, A

    2003-02-01

    Lymphoscintigraphic investigations represent techniques of nuclear medicine very contributive for the management and treatment of the limb edemas, either primary or secundary. Their principle is presented and methodologies proposed in the literature are reviewed. Their diagnostic contributions are detailed. The sensitivities and specificities of several protocols of investigation are reported. Some limitations of these examinations are analyzed and discussed. Clinical indications for their use are proposed and their interest with regard to the various treatments that can be applied to these limb edemas is discussed.

  16. JKTLD: Limb darkening coefficients

    NASA Astrophysics Data System (ADS)

    Southworth, John

    2015-11-01

    JKTLD outputs theoretically-calculated limb darkening (LD) strengths for equations (LD laws) which predict the amount of LD as a function of the part of the star being observed. The coefficients of these laws are obtained by bilinear interpolation (in effective temperature and surface gravity) in published tables of coefficients calculated from stellar model atmospheres by several researchers. Many observations of stars require the strength of limb darkening (LD) to be estimated, which can be done using theoretical models of stellar atmospheres; JKTLD can help in these circumstances.

  17. Interaction between the fore- and hind-wings in hovering flight of modelled dragonfly

    NASA Astrophysics Data System (ADS)

    Kweon, Jihoon; Choi, Haecheon

    2009-11-01

    In the present study, we investigate the interaction between the fore- and hind-wings in hovering flight of modelled dragonfly using 3D numerical simulation. The three-dimensional wing shape is based on that of Aeschna juncea (Norberg 1972) and numerically realized using an immersed boundary method (Kim et al. 2001). The wing flapping motion is modelled using a sinusoidal function and the stroke plane angle is 60^o. We consider 12 different phase differences between the fore- and hind-wings (φ=0^o ˜ 330^o). The Reynolds number is 1,000 based on the maximum translational velocity and mean chord length. In counter stroke (φ=180^o), the wing-tip vortices from both wings are connected, generating an entangled wing-tip vortex (e-WTV). A strong downward motion induced by this vortex decreases the vertical force in the following stroke (Kweon & Choi 2008). In parallel stroke (φ=0^o), both wings meet e-WTV during the upstroke and thus the decrease of vertical force is small. At φ=270^o, although e-WTV is generated on a relatively narrow region, the hind-wing moves downward along with e-WTV, resulting in a significant reduction of vertical force on the hind-wing. Therefore, the sum of vertical forces on both wings is maximum with parallel stroke and minimum at φ=270^o. The power required has a similar trend to the vertical force and thus the efficiency does not show a large variation with the phase difference.

  18. Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion.

    PubMed

    Thews, O; Hummel, M; Kelleher, D K; Lecher, B; Vaupel, P

    2002-12-02

    Isolated limb perfusion allows the direct application of therapeutic agents to a tumour-bearing extremity. The present study investigated whether the dihydropyridine-type Ca(2+)-channel blocker nifedipine could improve blood flow and oxygenation status of experimental tumours during isolated limb perfusion. Perfusion was performed by cannulation of the femoral artery and vein in rats bearing DS-sarcoma on the hind foot dorsum. Perfusion rate was adjusted to maintain a perfusion pressure of 100-140 mmHg throughout the experiment. Following equilibration, nifedipine was continuously infused for 30 min (8.3 microg min(-1) kg(-1) BW). During constant-pressure isolated limb perfusion, nifedipine can significantly increase perfusion rate (+100%) and RBC flux (+60%) through experimental leg tumours. "Steal phenomena" in favour of the surrounding normal tissue and oedema formation were not observed. Despite the increased oxygen availability (+63%) seen upon application of this calcium channel blocker, nifedipine does not result in a substantial reduction of tumour hypoxia, most probably due to an increase in O(2) uptake with rising O(2) supply to the tumour-bearing hind limb. Nifedipine application during isolated limb perfusion can enhance tumour microcirculation and may therefore promote the delivery (pharmacokinetics) of anti-cancer drugs to the tumour and by this improve the efficacy of pressure-controlled isolated limb perfusion.

  19. HindSight: Encouraging Exploration through Direct Encoding of Personal Interaction History.

    PubMed

    Feng, Mi; Deng, Cheng; Peck, Evan M; Harrison, Lane

    2017-01-01

    Physical and digital objects often leave markers of our use. Website links turn purple after we visit them, for example, showing us information we have yet to explore. These "footprints" of interaction offer substantial benefits in information saturated environments - they enable us to easily revisit old information, systematically explore new information, and quickly resume tasks after interruption. While applying these design principles have been successful in HCI contexts, direct encodings of personal interaction history have received scarce attention in data visualization. One reason is that there is little guidance for integrating history into visualizations where many visual channels are already occupied by data. More importantly, there is not firm evidence that making users aware of their interaction history results in benefits with regards to exploration or insights. Following these observations, we propose HindSight - an umbrella term for the design space of representing interaction history directly in existing data visualizations. In this paper, we examine the value of HindSight principles by augmenting existing visualizations with visual indicators of user interaction history (e.g. How the Recession Shaped the Economy in 255 Charts, NYTimes). In controlled experiments of over 400 participants, we found that HindSight designs generally encouraged people to visit more data and recall different insights after interaction. The results of our experiments suggest that simple additions to visualizations can make users aware of their interaction history, and that these additions significantly impact users' exploration and insights.

  20. Cloning and genetic variability of a HindIII repetitive DNA in Acrossocheilus paradoxus (Cyprinidae).

    PubMed

    Wu, W L; Wang, J P; Tseng, M C; Chiang, T Y

    1999-08-01

    Thirty clones of a highly repetitive HindIII fragment of DNA from seven populations of Acrossocheilus paradoxus (Cyprinidae) were isolated and sequenced. The fragment represents a tandemly repeated sequence, with a monomeric unit of 270 bp, amounting to 0.08-0.10% of the fish genome. Higher units of this monomer appear as a ladder in Southern blots. The HindIII satellite DNA family is conserved in three genera of the Cyprinidae. Variation in nucleotide sequences of this repetitive fragment, which is A+T-rich, is distributed both within individuals and among populations. High overall nucleotide divergence (dij = 0.056 +/- 0.001) was detected among clones of the HindIII satellite DNAs of Acrossocheilus paradoxus. Based on the molecular clock hypothesis, the maximum evolutionary rate was estimated to be 5.3 x 10(-7) substitutions per site per year. Lineage sorting may have contributed to the genetic heterogeneity within individuals and populations. Cladistic analyses indicated a closer phylogeographic relationship between populations of the central and south regions in Taiwan.

  1. Artificial limb connection

    NASA Technical Reports Server (NTRS)

    Owens, L. J.

    1974-01-01

    Connection simplifies and eases donning and removing artificial limb; eliminates harnesses and clamps; and reduces skin pressures by allowing bone to carry all tensile and part of compressive loads between prosthesis and stump. Because connection is modular, it is easily modified to suit individual needs.

  2. Umbilical Cord-Derived Mesenchymal Stem Cells Relieve Hindlimb Ischemia through Enhancing Angiogenesis in Tree Shrews

    PubMed Central

    Yin, Cunping; Liang, Yuan; Zhang, Jian; Li, Zian; Pang, Rongqing

    2016-01-01

    Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis. PMID:27651800

  3. Umbilical Cord-Derived Mesenchymal Stem Cells Relieve Hindlimb Ischemia through Enhancing Angiogenesis in Tree Shrews.

    PubMed

    Yin, Cunping; Liang, Yuan; Zhang, Jian; Ruan, Guangping; Li, Zian; Pang, Rongqing; Pan, Xinghua

    2016-01-01

    Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis.

  4. Intestinal ischemia in neonates and children.

    PubMed

    Jeican, Ionuţ Isaia; Ichim, Gabriela; Gheban, Dan

    2016-01-01

    The article reviews the intestinal ischemia theme on newborn and children. The intestinal ischemia may be either acute - intestinal infarction (by vascular obstruction or by reduced mesenteric blood flow besides the occlusive mechanism), either chronic. In neonates, acute intestinal ischemia may be caused by aortic thrombosis, volvulus or hypoplastic left heart syndrome. In children, acute intestinal ischemia may be caused by fibromuscular dysplasia, volvulus, abdominal compartment syndrome, Burkitt lymphoma, dermatomyositis (by vascular obstruction) or familial dysautonomia, Addison's disease, situs inversus abdominus (intraoperative), burns, chemotherapy administration (by nonocclusive mesenteric ischemia). Chronic intestinal ischemia is a rare condition in pediatrics and can be seen in abdominal aortic coarctation or hypoplasia, idiopathic infantile arterial calcinosis.

  5. Proteomic analysis of blastema formation in regenerating axolotl limbs

    PubMed Central

    2009-01-01

    Background Following amputation, urodele salamander limbs reprogram somatic cells to form a blastema that self-organizes into the missing limb parts to restore the structure and function of the limb. To help understand the molecular basis of blastema formation, we used quantitative label-free liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)-based methods to analyze changes in the proteome that occurred 1, 4 and 7 days post amputation (dpa) through the mid-tibia/fibula of axolotl hind limbs. Results We identified 309 unique proteins with significant fold change relative to controls (0 dpa), representing 10 biological process categories: (1) signaling, (2) Ca2+ binding and translocation, (3) transcription, (4) translation, (5) cytoskeleton, (6) extracellular matrix (ECM), (7) metabolism, (8) cell protection, (9) degradation, and (10) cell cycle. In all, 43 proteins exhibited exceptionally high fold changes. Of these, the ecotropic viral integrative factor 5 (EVI5), a cell cycle-related oncoprotein that prevents cells from entering the mitotic phase of the cell cycle prematurely, was of special interest because its fold change was exceptionally high throughout blastema formation. Conclusion Our data were consistent with previous studies indicating the importance of inositol triphosphate and Ca2+ signaling in initiating the ECM and cytoskeletal remodeling characteristic of histolysis and cell dedifferentiation. In addition, the data suggested that blastema formation requires several mechanisms to avoid apoptosis, including reduced metabolism, differential regulation of proapoptotic and antiapoptotic proteins, and initiation of an unfolded protein response (UPR). Since there is virtually no mitosis during blastema formation, we propose that high levels of EVI5 function to arrest dedifferentiated cells somewhere in the G1/S/G2 phases of the cell cycle until they have accumulated under the wound epidermis and enter mitosis in response to neural and

  6. Interaction of the elytra and hind wing of a rhinoceros beetle (Trypoxylus dichotomus) during a take-off mode

    NASA Astrophysics Data System (ADS)

    Oh, Seungyoung; Oh, Sehyeong; Choi, Haecheon; Lee, Boogeon; Park, Hyungmin; Kim, Sun-Tae

    2015-11-01

    The elytra are a pair of hardened wings that cover the abdomen of a beetle to protect beetle's hind wings. During the take-off, these elytra open and flap in phase with the hind wings. We investigate the effect of the elytra flapping on beetle's aerodynamic performance. Numerical simulations are performed at Re=10,000 (based on the wingtip mean velocity and mean chord length of the hind wing) using an immersed boundary method. The simulations are focused on a take-off, and the wing kinematics used is directly obtained from the experimental observations using high speed cameras. The simulation result shows three-dimensional vortical structures generated by the hind wing of the beetle and their interaction with the elytra. The presence of elytra has a negative effect on the lift generation by the hind wings, but the lift force on the elytra themselves is negligible. Further discussions on the elytra - hind wing interaction will be provided during the presentation. Supported by UD130070ID.

  7. [Retinal ischemia and nitric oxide].

    PubMed

    Neroev, V V; Arkhipova, M M

    2003-01-01

    Retinal ischemia is the main chain in the pathogenesis of vascular diseases of the eye. It was established that nitric oxide (NO) plays the key role in the development of ischemia. Recent understanding of the NO role, as a universal regulator of the cellular and tissue metabolism, is presented. The authors' and published data were used to design a scheme of pathogenesis of retinal ischemia with regard for the NO role. NO can produce both positive and negative effects depending on a stage of the process, NO concentration and on a number of other factors if they are present. Initial stages of hypoxia/ischemia are accompanied by an activation of all forms of NO-synthases (NOS) caused by the influence of biologically active substances (cytokines, prostaglandins, serotonin, bradykinin, glycolisis suboxide products etc.). The activation of inducible NOS, which synthesize a bigger quantity of NO possessing a direct cytotoxic action and contributing to the production of highly toxic radical of peroxinitrit, is in the focus of attention. The damage of cellular structures due to free-radical processes leads to the development of endothelial, macrophage and thrombocyte malfunctions, which manifest itself through a reduced activity of endothelial NOS and through disruption of NO-dependent processes (vasospasm, an increased aggregation of platelets and a reduced fibrinolytic activity). A sharp reduction of NO synthesis substrate (L-arginine) is observed in patients with retinal ischemia. The aggravation of ischemia causes a decrease of NO synthesis due to an exhaustion of L-arginine and its intensified consumption in the course of free-radical processes. The use of NO-inhibitors and of NO-donors at different stages of retinal ischemia prevents the development of neovascularization and proliferation.

  8. Diversity of limb-bone safety factors for locomotion in terrestrial vertebrates: evolution and mixed chains.

    PubMed

    Blob, Richard W; Espinoza, Nora R; Butcher, Michael T; Lee, Andrew H; D'Amico, Angela R; Baig, Faraz; Sheffield, K Megan

    2014-12-01

    During locomotion over land, vertebrates' limb bones are exposed to loads. Like most biological structures, limb bones have a capacity to withstand greater loads than they usually experience, termed a safety factor (SF). How diverse are limb-bone SFs, and what factors correlate with such variation? We have examined these questions from two perspectives. First, we evaluated locomotor SF for the femur in diverse lineages, including salamanders, frogs, turtles, lizards, crocodilians, and marsupials (opossums). Comparisons with values for hind-limb elements in running birds and eutherian mammals indicate phylogenetic diversity in limb-bone SF. A high SF (∼7) is primitive for tetrapods, but low magnitudes of load and elevated strength of bones contribute to different degrees across lineages; moreover, birds and eutherians appear to have evolved lower SFs independently. Second, we tested the hypothesis that SFs would be similar across limb bones within a taxon by comparing data from the humerus and femur of alligators. Both in bending and in torsion, we found a higher SF for the humerus than for the femur. Such a "mixed chain" of different SFs across elements has been predicted if bones have differing variabilities in load, different costs to maintain, or high SF values in general. Although variability in load is similar for the humerus and femur, a high SF may be less costly for the humerus because it is smaller than the femur. The high SFs of alligators also might facilitate differences in SF among their limb bones. Beyond these specific findings, however, a more general implication of our results is that evaluations of the diversity of limb-bone SFs can provide important perspective to direct future research. In particular, more complete understanding of variation in SF could provide insight into factors that promoted the evolutionary radiation of terrestrial locomotor function in vertebrates.

  9. Regeneration inducers in limb regeneration.

    PubMed

    Satoh, Akira; Mitogawa, Kazumasa; Makanae, Aki

    2015-08-01

    Limb regeneration ability, which can be observed in amphibians, has been investigated as a representative phenomenon of organ regeneration. Recently, an alternative experimental system called the accessory limb model was developed to investigate early regulation of amphibian limb regeneration. The accessory limb model contributed to identification of limb regeneration inducers in urodele amphibians. Furthermore, the accessory limb model may be applied to other species to explore universality of regeneration mechanisms. This review aims to connect the insights recently gained to emboss universality of regeneration mechanisms among species. The defined molecules (BMP7 (or2) + FGF2 + FGF8) can transform skin wound healing to organ (limb) regeneration responses. The same molecules can initiate regeneration responses in some species.

  10. Radiographic features of the limbs of juvenile and subadult loggerhead sea turtles (Caretta caretta)

    PubMed Central

    Valente, Ana Luisa; Marco, Ignasi; Zamora, Maria Angeles; Parga, Maria Luz; Lavín, Santiago; Alegre, Ferran; Cuenca, Rafaela

    2007-01-01

    This study aimed to provide the normal radiographic anatomic appearance of the limbs of the loggerhead sea turtle, Caretta caretta. Dorsopalmar and dorsoplantar radiographs were taken of the forelimbs and hindlimbs of 15 juvenile and 15 subadult loggerhead sea turtles, 17 alive and 13 dead. For comparison, computed tomographic, gross anatomic, osteologic, and histologic studies were performed on the limbs of 5 of the sea turtles. Bones from the distal part of the fore and hind flippers were seen in detail with a mammographic film–screen combination. The pectoral and pelvic girdles, superimposed by the carapace, were better seen on standard radiographs with the use of rare-earth intensifying screens. Mammographic radiographs of the manus of 5 small juvenile turtles showed active growth zones. Visualization of bone contours in the distal part of the limbs was clearer than in mammals owing to the very few superimpositions. The presence of a substantial amount of cartilage in the epiphyses produced better visibility of limb ends. We conclude that use of a mammography film–screen combination is the best way to evaluate the bony and joint structures of the limbs of sea turtles. Radiography provides reliable images for clinical purposes. Considering the low cost and logistics of this technique, it is a practical ancillary test for marine animal rehabilitation centers to use. PMID:17955906

  11. Passive resting state and history of antagonist muscle activity shape active extensions in an insect limb

    PubMed Central

    Ache, Jan M.

    2012-01-01

    Limb movements can be driven by muscle contractions, external forces, or intrinsic passive forces. For lightweight limbs like those of insects or small vertebrates, passive forces can be large enough to overcome the effects of gravity and may even generate limb movements in the absence of active muscle contractions. Understanding the sources and actions of such forces is therefore important in understanding motor control. We describe passive properties of the femur-tibia joint of the locust hind leg. The resting angle is determined primarily by passive properties of the relatively large extensor tibiae muscle and is influenced by the history of activation of the fast extensor tibiae motor neuron. The resting angle is therefore better described as a history-dependent resting state. We selectively stimulated different flexor tibiae motor neurons to generate a range of isometric contractions of the flexor tibiae muscle and then stimulated the fast extensor tibiae motor neuron to elicit active tibial extensions. Residual forces in the flexor muscle have only a small effect on subsequent active extensions, but the effect is larger for distal than for proximal flexor motor neurons and varies with the strength of flexor activation. We conclude that passive properties of a lightweight limb make substantial and complex contributions to the resting state of the limb that must be taken into account in the patterning of neuronal control signals driving its active movements. Low variability in the effects of the passive forces may permit the nervous system to accurately predict their contributions to behavior. PMID:22357791

  12. [Recurrent intestinal ischemia due to factor VIII].

    PubMed

    Castellanos Monedero, Jesús Javier; Legaz Huidobro, María Luisa; Galindo Andugar, María Angeles; Rodríguez Pérez, Alvaro; Mantrana del Valle, José María

    2008-01-01

    Intestinal ischemia is difficult to diagnose and can be caused by several etiologic processes. We report the case of a female patient with recurrent bowel ischemia due to small vessel thrombosis, which is caused by factor VIII, a procoagulant factor.

  13. Remote limb ischemic conditioning enhances motor learning in healthy humans.

    PubMed

    Cherry-Allen, Kendra M; Gidday, Jeff M; Lee, Jin-Moo; Hershey, Tamara; Lang, Catherine E

    2015-06-01

    Brief bouts of sublethal ischemia have been shown to protect exposed tissue (ischemic conditioning) and tissues at remote sites (remote ischemic conditioning) against subsequent ischemic challenges. Given that the mechanisms of this protective phenomenon are multifactorial and epigenetic, we postulated that remote limb ischemic conditioning (RLIC) might enhance mechanisms responsible for neural plasticity, and thereby facilitate learning. Specifically, we hypothesized that conditioning of the nervous system with RLIC, achieved through brief repetitive limb ischemia prior to training, would facilitate the neurophysiological processes of learning, thus making training more effective and more long-lasting. Eighteen healthy adults participated in this study; nine were randomly allocated to RLIC and nine to sham conditioning. All subjects underwent seven consecutive weekday sessions and 2-wk and 4-wk follow-up sessions. We found that RLIC resulted in significantly greater motor learning and longer retention of motor performance gains in healthy adults. Changes in motor performance do not appear to be due to a generalized increase in muscle activation or muscle strength and were not associated with changes in serum brain-derived neurotrophic factor (BDNF) concentration. Of note, RLIC did not enhance cognitive learning on a hippocampus-dependent task. While future research is needed to establish optimal conditioning and training parameters, this inexpensive, clinically feasible paradigm might ultimately be implemented to enhance motor learning in individuals undergoing neuromuscular rehabilitation for brain injury and other pathological conditions.

  14. Remote limb ischemic conditioning enhances motor learning in healthy humans

    PubMed Central

    Cherry-Allen, Kendra M.; Gidday, Jeff M.; Lee, Jin-Moo; Hershey, Tamara

    2015-01-01

    Brief bouts of sublethal ischemia have been shown to protect exposed tissue (ischemic conditioning) and tissues at remote sites (remote ischemic conditioning) against subsequent ischemic challenges. Given that the mechanisms of this protective phenomenon are multifactorial and epigenetic, we postulated that remote limb ischemic conditioning (RLIC) might enhance mechanisms responsible for neural plasticity, and thereby facilitate learning. Specifically, we hypothesized that conditioning of the nervous system with RLIC, achieved through brief repetitive limb ischemia prior to training, would facilitate the neurophysiological processes of learning, thus making training more effective and more long-lasting. Eighteen healthy adults participated in this study; nine were randomly allocated to RLIC and nine to sham conditioning. All subjects underwent seven consecutive weekday sessions and 2-wk and 4-wk follow-up sessions. We found that RLIC resulted in significantly greater motor learning and longer retention of motor performance gains in healthy adults. Changes in motor performance do not appear to be due to a generalized increase in muscle activation or muscle strength and were not associated with changes in serum brain-derived neurotrophic factor (BDNF) concentration. Of note, RLIC did not enhance cognitive learning on a hippocampus-dependent task. While future research is needed to establish optimal conditioning and training parameters, this inexpensive, clinically feasible paradigm might ultimately be implemented to enhance motor learning in individuals undergoing neuromuscular rehabilitation for brain injury and other pathological conditions. PMID:25867743

  15. Spatial Distribution and Conservation of Speckled Hind and Warsaw Grouper in the Atlantic Ocean off the Southeastern U.S.

    PubMed Central

    Farmer, Nicholas A.; Karnauskas, Mandy

    2013-01-01

    There is broad interest in the development of efficient marine protected areas (MPAs) to reduce bycatch and end overfishing of speckled hind (Epinephelus drummondhayi) and warsaw grouper (Hyporthodus nigritus) in the Atlantic Ocean off the southeastern U.S. We assimilated decades of data from many fishery-dependent, fishery-independent, and anecdotal sources to describe the spatial distribution of these data limited stocks. A spatial classification model was developed to categorize depth-grids based on the distribution of speckled hind and warsaw grouper point observations and identified benthic habitats. Logistic regression analysis was used to develop a quantitative model to predict the spatial distribution of speckled hind and warsaw grouper as a function of depth, latitude, and habitat. Models, controlling for sampling gear effects, were selected based on AIC and 10-fold cross validation. The best-fitting model for warsaw grouper included latitude and depth to explain 10.8% of the variability in probability of detection, with a false prediction rate of 28–33%. The best-fitting model for speckled hind, per cross-validation, included latitude and depth to explain 36.8% of the variability in probability of detection, with a false prediction rate of 25–27%. The best-fitting speckled hind model, per AIC, also included habitat, but had false prediction rates up to 36%. Speckled hind and warsaw grouper habitats followed a shelf-edge hardbottom ridge from North Carolina to southeast Florida, with speckled hind more common to the north and warsaw grouper more common to the south. The proportion of habitat classifications and model-estimated stock contained within established and proposed MPAs was computed. Existing MPAs covered 10% of probable shelf-edge habitats for speckled hind and warsaw grouper, protecting 3–8% of speckled hind and 8% of warsaw grouper stocks. Proposed MPAs could add 24% more probable shelf-edge habitat, and protect an additional 14–29% of

  16. Spatial distribution and conservation of speckled hind and warsaw grouper in the Atlantic Ocean off the southeastern U.S.

    PubMed

    Farmer, Nicholas A; Karnauskas, Mandy

    2013-01-01

    There is broad interest in the development of efficient marine protected areas (MPAs) to reduce bycatch and end overfishing of speckled hind (Epinephelus drummondhayi) and warsaw grouper (Hyporthodus nigritus) in the Atlantic Ocean off the southeastern U.S. We assimilated decades of data from many fishery-dependent, fishery-independent, and anecdotal sources to describe the spatial distribution of these data limited stocks. A spatial classification model was developed to categorize depth-grids based on the distribution of speckled hind and warsaw grouper point observations and identified benthic habitats. Logistic regression analysis was used to develop a quantitative model to predict the spatial distribution of speckled hind and warsaw grouper as a function of depth, latitude, and habitat. Models, controlling for sampling gear effects, were selected based on AIC and 10-fold cross validation. The best-fitting model for warsaw grouper included latitude and depth to explain 10.8% of the variability in probability of detection, with a false prediction rate of 28-33%. The best-fitting model for speckled hind, per cross-validation, included latitude and depth to explain 36.8% of the variability in probability of detection, with a false prediction rate of 25-27%. The best-fitting speckled hind model, per AIC, also included habitat, but had false prediction rates up to 36%. Speckled hind and warsaw grouper habitats followed a shelf-edge hardbottom ridge from North Carolina to southeast Florida, with speckled hind more common to the north and warsaw grouper more common to the south. The proportion of habitat classifications and model-estimated stock contained within established and proposed MPAs was computed. Existing MPAs covered 10% of probable shelf-edge habitats for speckled hind and warsaw grouper, protecting 3-8% of speckled hind and 8% of warsaw grouper stocks. Proposed MPAs could add 24% more probable shelf-edge habitat, and protect an additional 14-29% of speckled

  17. Practical Use of Emergency Tourniquets to Stop Bleeding in Major Limb Trauma

    DTIC Science & Technology

    2008-02-01

    been associated with surgical shortening of injured limbs, based on the surgeon’s concern about pro- longed ischemia .14 Consequently, many tourniquet...without surgery. In the other nine patients (9 tour- niquets, 2%), all patients required surgery to treat deep soft tissue injuries without named...inappropriate use was corrected on the spot, and a fasciotomy was performed followed by a late below- knee amputation after a flap failure in the United

  18. Pediatric Traumatic Limb Amputation: The Principles of Management and Optimal Residual Limb Lengths

    PubMed Central

    Khan, Muhammad Adil Abbas; Javed, Ammar Asrar; Rao, Dominic Jordan; Corner, J Antony; Rosenfield, Peter

    2016-01-01

    Pediatric traumatic limb amputations are rare and their acute and long term management can be challenging in this subgroup of patients. The lengthy and costly hospital stays, and resulting physical and psychological implications leads to significant morbidity. We present a summary of treatment principles and the evidence base supporting the management options for this entity. The initial management focuses on resuscitating and stabilization of the patients, administration of appropriate and adequate analgesics, and broad spectrum antibiotics. The patient should ideally be managed by an orthopedic or a plastic surgeon and when an amputation is warranted, the surgical team should aim to conserve as much of the viable physis as possible aimed at allowing bone development in a growing child. A subsequent wound inspection should be performed to assess for signs of ischemia or non-viability of tissue. Depending on the child’s age, approximations of the ideal residual limb length can be calculated using our guidelines, allowing an ideal stump length at skeletal maturity for a well-fitting and appropriate prosthesis. Myodesis and myoplasties can be performed according to the nature of the amputation. Removable rigid dressings are safe and cost effective offering better protection of the stump. Complications such as necrosis and exostosis, on subsequent examination, warrant further revisions. Other complications such as neuromas can be prevented by proximal division of the nerves. Successful rehabilitation can be accomplished with a multidisciplinary approach, involving physiotherapist, play therapist and a child psychiatrist, in addition to the surgeon and primary care providers. PMID:27308235

  19. Anisotropy and non-homogeneity of an Allomyrina Dichotoma beetle hind wing membrane.

    PubMed

    Ha, N S; Jin, T L; Goo, N S; Park, H C

    2011-12-01

    Biomimetics is one of the most important paradigms as researchers seek to invent better engineering designs over human history. However, the observation of insect flight is a relatively recent work. Several researchers have tried to address the aerodynamic performance of flapping creatures and other natural properties of insects, although there are still many unsolved questions. In this study, we try to answer the questions related to the mechanical properties of a beetle's hind wing, which consists of a stiff vein structure and a flexible membrane. The membrane of a beetle's hind wing is small and flexible to the point that conventional methods cannot adequately quantify the material properties. The digital image correlation method, a non-contact displacement measurement method, is used along with a specially designed mini-tensile testing system. To reduce the end effects, we developed an experimental method that can deal with specimens with as high an aspect ratio as possible. Young's modulus varies over the area in the wing and ranges from 2.97 to 4.5 GPa in the chordwise direction and from 1.63 to 2.24 GPa in the spanwise direction. Furthermore, Poisson's ratio in the chordwise direction is 0.63-0.73 and approximately twice as large as that in the spanwise direction (0.33-0.39). From these results, we can conclude that the membrane of a beetle's hind wing is an anisotropic and non-homogeneous material. Our results will provide a better understanding of the flapping mechanism through the formulation of a fluid-structure interaction analysis or aero-elasticity analysis and meritorious data for biomaterial properties database as well as a creative design concept for a micro aerial flapper that mimics an insect.

  20. Anatomy of the hind legs and actions of their muscles during jumping in leafhopper insects.

    PubMed

    Burrows, Malcolm

    2007-10-01

    The rapid and simultaneous depression of the trochantera about the coxae of both hind legs of leafhoppers are the key joint movements powering a jump. The present study analyses the structure of these joints and the actions of the muscles that move them. The hind coxae are huge and are linked to each other at the midline by a protrusion from one coxa that inserts in a socket of the other and acts like a press-stud (popper) fastener. This asymmetry is not reflected in any left- or right-handed preference either within one species or between species. The movements of the joints in a jump are monitored by a number of possible proprioceptors that should be activated when a hind leg is fully levated in preparation for a jump: a hair row and two hair plates on the coxa, a hair plate on a trochanteral pivot with a coxa, and femoral spines at the femoro-tibial joint. The depressor and levator muscles that move the trochanter are of similar size and together occupy the greater part of the metathorax. Their lever arms are similar when the leg is fully levated, but the lever arm of the depressor increases with initial depression of the coxo-trochanteral joint while that of the levator declines. A jump is preceded by activity in the trochanteral depressor and levator muscles, which results in a forward movement of the coxa and metathorax with the trochanter fully levated. This period of co-contraction could result in storage of energy in skeletal structures in the thorax. Just before the rapid depression of the trochanter in the jump movement the frequency of depressor spikes increases while that in the levator declines, releasing any force stored by the preceding muscle contractions. These bursts of depressor spikes occur at the same time in the left and right muscles but none of the individual motor spikes appeared to be synchronous on the two sides.

  1. A new technique using roentgen stereophotogrammetry to measure changes in the spatial conformation of bovine hind claws in response to external loads.

    PubMed

    Ouweltjes, W; Gussekloo, S W S; Spoor, C W; van Leeuwen, J L

    2016-02-01

    Claw and locomotion problems are widespread in ungulates. Although it is presumed that mechanical overload is an important contributor to claw tissue damage and impaired locomotion, deformation and claw injury as a result of mechanical loading has been poorly quantified and, as a result, practical solutions to reduce such lesions have been established mostly through trial and error. In this study, an experimental technique was developed that allowed the measurement under controlled loading regimes of minute deformations in the lower limbs of dissected specimens from large ungulates. Roentgen stereophotogrammetric analysis (RSA) was applied to obtain 3D marker coordinates with an accuracy of up to 0.1 mm with optimal contrast and to determine changes in the spatial conformation. A force plate was used to record the applied forces in three dimensions. The results obtained for a test sample (cattle hind leg) under three loading conditions showed that small load-induced deformations and translations as well as small changes in centres of force application could be measured. Accuracy of the order of 0.2-0.3 mm was feasible under practical circumstances with suboptimal contrast. These quantifications of claw deformation during loading improve understanding of the spatial strain distribution as a result of external loading and the risks of tissue overload. The method promises to be useful in determining load-deformation relationships for a wide variety of specimens and circumstances.

  2. Limb salvage versus amputation. Preliminary results of the Mangled Extremity Severity Score.

    PubMed

    Helfet, D L; Howey, T; Sanders, R; Johansen, K

    1990-07-01

    Objective criteria can predict amputation after lower-extremity trauma. The authors examined the hypothesis that objective data, available early in the evaluation of patients with severe skeletal/soft-tissue injuries of the lower extremity with vascular compromise, might discriminate the salvageable from the unsalvageable limbs. The Mangled Extremity Severity Score (MESS) was developed by reviewing 25 trauma victims with 26 severe lower-extremity open fractures with vascular compromise. The four significant criteria (with increasing points for worsening prognosis) were skeletal/soft-tissue injury, limb ischemia, shock, and patient age. (There was a significant difference in the mean MESS scores; 4.88 in 17 limbs salvaged and 9.11 in nine limbs amputated; p less than 0.01). This scoring system was then prospectively evaluated in 26 lower-extremity open fractures with vascular injury over a 12-month period at two trauma centers. Again, there was a significant difference in the mean MESS scores; 4.00 for the 14 salvaged limbs and 8.83 for the 12 amputated limbs (p less than 0.01). In both the prospective and retrospective studies, a MESS score of greater than or equal to 7 had a 100% predictable value for amputation. This relatively simple, readily available scoring system of objective criteria was highly accurate in acutely discriminating between limbs that were salvageable and those that were unsalvageable and better managed by primary amputation.

  3. Temporary arterial shunts to maintain limb perfusion after arterial injury: an animal study

    NASA Technical Reports Server (NTRS)

    Dawson, D. L.; Putnam, A. T.; Light, J. T.; Ihnat, D. M.; Kissinger, D. P.; Rasmussen, T. E.; Bradley, D. V. Jr

    1999-01-01

    BACKGROUND: Temporary shunt placement can quickly restore perfusion after extremity arterial injury. This study examined the adequacy of limb blood flow with shunt use, non-heparin-bonded shunt patency over prolonged periods, and the safety of this technique. METHODS: Common iliac arteries were divided and 4.0-mm Silastic Sundt shunts placed in 16 anesthetized pigs. Eight (group I) had shunts placed immediately; eight others (group II) were shunted after an hour of limb ischemia and hemorrhagic shock. Physiologic parameters and femoral artery blood flow in both hindlimbs were continuously monitored. Limb lactic acid generation, oxygen utilization, and hematologic and metabolic effects were serially evaluated for 24 hours. RESULTS: Shunts remained patent in 13 of 16 pigs. Shunts thrombosed in two group I animals because of technical errors, but functioned well after thrombectomy and repositioning. Patency could not be maintained in one animal that died from shock. Flow in group I shunted limbs was 57 (+/-11 SD) % of control. For group II animals in shock, shunted limb flow initially averaged 46 +/- 15% of control, but 4 hours after shunt placement, the mean limb blood flow was the same as in group I. Increased oxygen extraction compensated for the lower flow. Lactic acid production was not increased in comparison to control limbs. CONCLUSION: Shunts provided adequate flow in this model of extremity trauma. Correctly placed shunts stayed patent for 24 hours, without anticoagulation, if shunt placement followed resuscitation.

  4. Claw and limb disorders in 12 Norwegian beef-cow herds

    PubMed Central

    Fjeldaas, Terje; Nafstad, Ola; Fredriksen, Bente; Ringdal, Grethe; Sogstad, Åse M

    2007-01-01

    Background The main aim of the study was to assess the prevalence of claw and limb disorders in Norwegian beef-cow herds. Methods Twenty-six herds with ≥15 cow-years were selected by computerized systematic assignment from the three most beef cattle-dense regions of Norway. The study population consisted of 12 herds with 28 heifers and 334 cows. The animals were trimmed and examined once by claw trimmers during the late winter and spring of 2003. The seven claw trimmers had been taught diagnosing and recording of claw lesions. Environment, feeding and management routines, age and breed, culling and carcass characteristics were also recorded. Results Lameness was recorded in 1.1% of the animals, and only in hind claws. Pericarpal swellings were recorded in one animal and peritarsal lesions in none. In total, claw and limb disorders including lameness were recorded in 29.6% of the animals, 4.1% with front and 28.2% with hind limb disorders, respectively. Most lesions were mild. Laminitis-related claw lesions were recorded in 18.0% of the animals and infectious lesions in 16.6%. The average claw length was 84 mm in front claws and 89 mm in hind claw. Both laminitis-related and infectious claw lesions were more prevalent with increasing age. Carcasses from animals with claw and limb disorders were on average 34 kg heavier than carcasses from animals without such disorders (p = 0.02). Our results also indicate association between some management factors and claw lesions. Conclusion The study shows that the prevalence of lameness was low in 12 Norwegian beef-cow herds compared to beef-cattle herds in other countries and also that there were less claw and limb disorders in these herds compared to foreign dairy-cattle herds. The prevalence of lameness and white-line fissures was approximately the same as in Norwegian dairy herds whereas less dermatitis, heel-horn erosions, haemorrhages of the sole and the white line and sole ulcers were recorded. PMID:17892582

  5. Animal models of cerebral ischemia

    NASA Astrophysics Data System (ADS)

    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  6. Saving the limb in diabetic patients with ischemic foot lesions complicated by acute infection.

    PubMed

    Clerici, Giacomo; Faglia, Ezio

    2014-12-01

    Ischemia and infection are the most important factors affecting the prognosis of foot ulcerations in diabetic patients. To improve the outcome of these patients, it is necessary to aggressively treat 2 important pathologies--namely, occlusive arterial disease affecting the tibial and femoral arteries and infection of the ischemic diabetic foot. Each of these 2 conditions may lead to major limb amputation, and the presence of both critical limb ischemia (CLI) and acute deep infection is a major risk factor for lower-extremity amputation. Thus, the management of diabetic foot ulcers requires specific therapeutic approaches that vary significantly depending on whether foot lesions are complicated by infection and/or ischemia. A multidisciplinary team approach is the key to successful treatment of a diabetic foot ulcer: ischemic diabetic foot ulcers complicated by acute deep infection pose serious treatment challenges because high levels of skill, organization, accuracy, and timing of intervention are required to maximize the chances of limb salvage: these complex issues are better managed by a multidisciplinary clinical group.

  7. Intramuscular Transplantation and Survival of Freshly Isolated Bone Marrow Cells following Skeletal Muscle Ischemia-reperfusion Injury

    DTIC Science & Technology

    2013-01-01

    used to deplete highly differentiated cells. This depletion enriches for stem and progenitor cells and has been applied to a variety of disease and...limb ischemia due to peripheral artery disease . Cell Transplant. 2009;18(3):371Y380. 8. Murphy MP, Lawson JH, Rapp BM, Dalsing MC, Klein J, Wilson MG...ischemia. J Vasc Surg. 2011;53(6):1565Y1574.e1. 9. Zhong W, Sumita Y, Ohba S, Kawasaki T, Nagai K, Ma G, Asahina I. In vivo comparison of the bone

  8. Distal limb perfusion: Achilles' heel in peripheral venoarterial extracorporeal membrane oxygenation.

    PubMed

    Mohite, Prashant N; Fatullayev, Javid; Maunz, Olaf; Kaul, Sundip; Sabashnikov, Anton; Weymann, Alexander; Saez, Diana G; Patil, Nikhil P; Zych, Bartlomiej; Popov, Aron F; DeRobertis, Fabio; Bahrami, Toufan; Amrani, Mohamed; Simon, Andre R

    2014-11-01

    Extracorporeal membrane oxygenation (ECMO) is a temporary mechanical circulatory assist method that offers circulatory as well as respiratory support efficiently via peripheral access; however, it is liable to complications. Limb ischemia is one of the notorious complications of ECMO but can be avoided utilizing a proper distal limb perfusion method. A retrospective study of patients undergoing peripheral venoarterial (VA) ECMO for various reasons between June 2010 and December 2012 was performed. All patients were evaluated by our multidisciplinary team for suitability as candidates for ECMO. A peripheral VA-ECMO circuit was implanted via groin: inflow cannula in the femoral vein, an outflow cannula and distal-perfusion cannula, or an introducer sheath in the femoral artery. During the study period, 83 patients underwent various types of ECMO; 45 received peripheral VA-ECMO. Distal limb perfusion was achieved with an introducer sheath (6-8 Fr) in 13 cases and with a distal-perfusion cannula (10-12 Fr) in 32 cases. Nine (20%) patients developed signs of ischemia; five (11.2%) were treated conservatively, while four (8.8%) required surgical intervention. One patient required a below-knee amputation. The incidences of limb ischemia and limb ischemia requiring surgical intervention were significantly higher for the introducer sheath compared with the cannula (30.6 vs. 15.6% and 15.4 vs. 6.25%, respectively). Moreover, the patients supported on ECMO with a distal-perfusion cannula spent a significantly longer time on ECMO compared with the ones in whom an introducer sheath was used (11.9 ± 9.1 vs. 7.7 ± 4.3 days). The mean cannula size was significantly greater than the mean introducer sheath size (11.1 ± 1.3 vs. 7.0 ± 1.1 Fr). Use of a distal-perfusion cannula is a most reliable method of limb perfusion in peripheral VA-ECMO. The cannula can ensure adequate and smooth perfusion of the limb owing to its large caliber, its less turbulent flow, the ability it

  9. Glutaminase Increases in Rat Dorsal Root Ganglion Neurons after Unilateral Adjuvant-Induced Hind Paw Inflammation

    PubMed Central

    Hoffman, E. Matthew; Zhang, Zijia; Schechter, Ruben; Miller, Kenneth E.

    2016-01-01

    Glutamate is a neurotransmitter used at both the peripheral and central terminals of nociceptive primary sensory neurons, yet little is known concerning regulation of glutamate metabolism during peripheral inflammation. Glutaminase (GLS) is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and is implicated in producing elevated levels of glutamate in central and peripheral terminals. A potential mechanism for increased levels of glutamate is an elevation in GLS expression. We assessed GLS expression after unilateral hind paw inflammation by measuring GLS immunoreactivity (ir) with quantitative image analysis of L4 dorsal root ganglion (DRG) neurons after one, two, four, and eight days of adjuvant-induced arthritis (AIA) compared to saline injected controls. No significant elevation in GLS-ir occurred in the DRG ipsilateral to the inflamed hind paw after one or two days of AIA. After four days AIA, GLS-ir was elevated significantly in all sizes of DRG neurons. After eight days AIA, GLS-ir remained elevated in small (<400 µm2), presumably nociceptive neurons. Western blot analysis of the L4 DRG at day four AIA confirmed the elevated GLS-ir. The present study indicates that GLS expression is increased in the chronic stage of inflammation and may be a target for chronic pain therapy. PMID:26771651

  10. The D1 family dopamine receptor, DopR, potentiates hind leg grooming behavior in Drosophila

    PubMed Central

    Pitmon, E.; Stephens, G.; Parkhurst, S. J.; Wolf, F. W.; Kehne, G.; Taylor, M.

    2016-01-01

    Drosophila groom away debris and pathogens from the body using their legs in a stereotyped sequence of innate motor behaviors. Here, we investigated one aspect of the grooming repertoire by characterizing the D1 family dopamine receptor, DopR. Removal of DopR results in decreased hind leg grooming, as substantiated by quantitation of dye remaining on mutant and RNAi animals vs. controls and direct scoring of behavioral events. These data are also supported by pharmacological results that D1 receptor agonists fail to potentiate grooming behaviors in headless DopR flies. DopR protein is broadly expressed in the neuropil of the thoracic ganglion and overlaps with TH‐positive dopaminergic neurons. Broad neuronal expression of dopamine receptor in mutant animals restored normal grooming behaviors. These data provide evidence for the role of DopR in potentiating hind leg grooming behaviors in the thoracic ganglion of adult Drosophila. This is a remarkable juxtaposition to the considerable role of D1 family dopamine receptors in rodent grooming, and future investigations of evolutionary relationships of circuitry may be warranted. PMID:26749475

  11. Nerve growth factor induced hyperalgesia in the rat hind paw is dependent on circulating neutrophils.

    PubMed

    Bennett, G; al-Rashed, S; Hoult, J R; Brain, S D

    1998-09-01

    The mechanisms by which nerve growth factor (NGF) induces thermal hyperalgesia and neutrophil accumulation have been investigated in the rat. Thermal nociceptive thresholds in rat hind paw were measured as the time taken for paw withdrawal from a heat source and neutrophil accumulation was measured in hind paw and dorsal skin samples using a myeloperoxidase assay. NGF (23-80 pmol intraplantar (i.pl.) injection) induced a significant (P < 0.05, n = 6-16) thermal hyperalgesia at 5 h after injection and significant neutrophil accumulation (P < 0.05, n = 6) was observed with NGF (40 pmol). In dorsal skin, where multiple samples can be assessed, intradermal (i.d.) NGF was 10-30 times less potent than interleukin-1beta in inducing neutrophil accumulation. The 5-lipoxygenase inhibitor ZM230487 (10 nmol co-injected with NGF) significantly attenuated neutrophil accumulation and hyperalgesia induced by NGF; unlike the histamine and 5-hydroxytryptamine antagonists (mepyramine and methysergide) which were without effect at the times measured. Furthermore, depletion of circulating neutrophils (using a rabbit anti-rat neutrophil antibody) abolished NGF induced hyperalgesia. These results indicate that neutrophils, which accumulate in response to a 5-lipoxygenase product, play a crucial role in NGF-induced hyperalgesia.

  12. Controversies in cardiovascular care: silent myocardial ischemia

    NASA Technical Reports Server (NTRS)

    Hollenberg, N. K.

    1987-01-01

    The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

  13. DYSREGULATED SELECTIN EXPRESSION AND MONOCYTE RECRUITMENT DURING ISCHEMIA-RELATED VASCULAR REMODELING IN DIABETES MELLITUS

    PubMed Central

    Carr, Chad L.; Qi, Yue; Davidson, Brian; Chadderdon, Scott; Jayaweera, Ananda R.; Belcik, J. Todd; Benner, Cameron; Xie, Aris; Lindner, Jonathan R.

    2011-01-01

    Objective Diabetes mellitus (DM) is associated with impaired ischemia-related vascular remodeling and also dysregulation of the inflammatory response. We sought to determine whether impaired selectin-mediated monocyte recruitment in ischemic tissues contributes to blunted ischemia-mediated angiogenesis in DM. Methods and Results Contrast-enhanced ultrasound (CEU) perfusion imaging and molecular imaging of endothelial P-selectin expression in the proximal hindlimb were performed at 1,3, and 21 days after arterial ligation in wild-type and db/db mice. Ligation reduced muscle blood flow to ≈0.05 ml/min/g in both strains. Significant recovery of flow occurred only in wild-type mice (60–65% of baseline flow). On molecular imaging in db/db mice, baseline P-selectin signal was 4-fold higher in db/db compared to wild-type mice (p<0.01) but increased minimally in at day one after ischemia whereas signal increased approximately 10-fold in wild-type mice (p<0.01). Immunohistology of the hindlimb demonstrated severely reduced monocyte recruitment in db/db mice compared to wild-type mice. Local treatment with monocyte chemotactic protein-1 (MCP-1) corrected the deficits in post-ischemic P-selectin expression and monocyte recruitment in db/d mice, and led to greater recovery in blood flow. Conclusions In DM, there is dysregulation of the selectin response to limb ischemia which leads to impaired monocyte recruitment, which may be mechanistically related to reduced vascular remodeling in limb ischemia. PMID:21885854

  14. Limb lengthening in achondroplasia

    PubMed Central

    Chilbule, Sanjay K; Dutt, Vivek; Madhuri, Vrisha

    2016-01-01

    Background: Stature lengthening in skeletal dysplasia is a contentious issue. Specific guidelines regarding the age and sequence of surgery, methods and extent of lengthening at each stage are not uniform around the world. Despite the need for multiple surgeries, with their attendant complications, parents demanding stature lengthening are not rare, due to the social bias and psychological effects experienced by these patients. This study describes the outcome and complications of extensive stature lengthening performed at our center. Materials and Methods: Eight achondroplasic and one hypochondroplasic patient underwent bilateral transverse lengthening for tibiae, humeri and femora. Tibia lengthening was carried out using a ring fixator and bifocal corticotomy, while a monolateral pediatric limb reconstruction system with unifocal corticotomy was used for the femur and humerus. Lengthening of each bone segment, height gain, healing index and complications were assessed. Subgroup analysis was carried out to assess the effect of age and bone segment on the healing index. Results: Nine patients aged five to 25 years (mean age 10.2 years) underwent limb lengthening procedures for 18 tibiae, 10 femora and 8 humeri. Four patients underwent bilateral lengthening of all three segments. The mean length gain for the tibia, femur and humerus was 15.4 cm (100.7%), 9.9 cm (52.8%) and 9.6 cm (77.9%), respectively. Healing index was 25.7, 25.6 and 20.6 days/cm, respectively, for the tibia, femur and humerus. An average of 33.3% height gain was attained. Lengthening of both tibia and femur added to projected height achieved as the 3rd percentile of standard height in three out of four patients. In all, 33 complications were encountered (0.9 complications per segment). Healing index was not affected by age or bone segment. Conclusion: Extensive limb lengthening (more than 50% over initial length) carries significant risk and should be undertaken only after due consideration. PMID

  15. Lipotyphla limb myology comparison.

    PubMed

    Neveu, Pauline; Gasc, Jean-Pierre

    2002-05-01

    Fore- and hindlimb muscles were dissected in four species of Lipotyphla: the western European hedgehog Erinaceus europaeus (Erinaceidae, Erinaceinae); the moonrat Echinosorex gymnura (Erinaceidae, Hylomyinae or Galericinae); the tailless tenrec Tenrec ecaudatus (Tenrecidae, Tenrecinae); and the common European white-toothed shrew Crocidura russula (Soricidae, Soricinae). This work completely reviews the limb musculature of these walking mammals. Twelve myological characters were evaluated in order to disclose phylogenetic relationships. The cladogram obtained supported previous ones based on cranial and dental characters. This study shows that myological characters are valuable in phylogenetic analyses.

  16. Sirt1 in cerebral ischemia

    PubMed Central

    Koronowski, Kevin B.; Perez-Pinzon, Miguel A.

    2015-01-01

    Cerebral ischemia is among the leading causes of death worldwide. It is characterized by a lack of blood flow to the brain that results in cell death and damage, ultimately causing motor, sensory, and cognitive impairments. Today, clinical treatment of cerebral ischemia, mostly stroke and cardiac arrest, is limited and new neuroprotective therapies are desperately needed. The Sirtuin family of oxidized nicotinamide adenine dinucleotide (NAD+)-dependent deacylases has been shown to govern several processes within the central nervous system as well as to possess neuroprotective properties in a variety of pathological conditions such as Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease, among others. Recently, Sirt1 in particular has been identified as a mediator of cerebral ischemia, with potential as a possible therapeutic target. To gather studies relevant to this topic, we used PubMed and previous reviews to locate, select, and resynthesize the lines of evidence presented here. In this review, we will first describe some functions of Sirt1 in the brain, mainly neurodevelopment, learning and memory, and metabolic regulation. Second, we will discuss the experimental evidence that has implicated Sirt1 as a key protein in the regulation of cerebral ischemia as well as a potential target for the induction of ischemic tolerance. PMID:26819971

  17. Ontogeny of joint mechanics in squirrel monkeys (Saimiri boliviensis): functional implications for mammalian limb growth and locomotor development

    PubMed Central

    Young, Jesse W.

    2009-01-01

    Summary Juvenile animals must often compete against adults for common resources, keep pace during group travel and evade common predators, despite reduced body size and an immature musculoskeletal system. Previous morphometric studies of a diverse array of mammals, including jack rabbits, cats and capuchin monkeys, have identified growth-related changes in anatomy, such as negative allometry of limb muscle mechanical advantage, which should theoretically permit young mammals to overcome such ontogenetic limits on performance. However, it is important to evaluate the potential impact of such `compensatory' growth trajectories within the context of developmental changes in locomotor behavior. I used standard kinematic and kinetic techniques to investigate the ontogenetic scaling of joint postures, substrate reaction forces, joint load arm lengths and external joint moments in an ontogenetic sample of squirrel monkeys (Saimiri boliviensis). Results indicated that young squirrel monkeys were frequently able to limit forelimb and hind limb joint loading via a combination of changes in limb posture and limb force distribution, potentially compensating for limited muscularity at younger ages. These results complement previous morphometric studies and suggest that immature mammals may utilize a combination of behavioral and anatomical mechanisms to mitigate ontogenetic limits on locomotor performance. However, ontogenetic changes in joint posture, not limb length per se, explained most of the variation in load arm lengths and joint loading in growing squirrel monkeys, indicating the importance of incorporating both anatomical and performance measures when studying the ontogeny of limb joint mechanics. PMID:19411552

  18. Oxidative stress in brain ischemia.

    PubMed

    Love, S

    1999-01-01

    Brain ischemia initiates a complex cascade of metabolic events, several of which involve the generation of nitrogen and oxygen free radicals. These free radicals and related reactive chemical species mediate much of damage that occurs after transient brain ischemia, and in the penumbral region of infarcts caused by permanent ischemia. Nitric oxide, a water- and lipid-soluble free radical, is generated by the action of nitric oxide synthases. Ischemia causes a surge in nitric oxide synthase 1 (NOS 1) activity in neurons and, possibly, glia, increased NOS 3 activity in vascular endothelium, and later an increase in NOS 2 activity in a range of cells including infiltrating neutrophils and macrophages, activated microglia and astrocytes. The effects of ischemia on the activity of NOS 1, a Ca2+-dependent enzyme, are thought to be secondary to reversal of glutamate reuptake at synapses, activation of NMDA receptors, and resulting elevation of intracellular Ca2+. The up-regulation of NOS 2 activity is mediated by transcriptional inducers. In the context of brain ischemia, the activity of NOS 1 and NOS 2 is broadly deleterious, and their inhibition or inactivation is neuroprotective. However, the production of nitric oxide in blood vessels by NOS 3, which, like NOS 1, is Ca2+-dependent, causes vasodilatation and improves blood flow in the penumbral region of brain infarcts. In addition to causing the synthesis of nitric oxide, brain ischemia leads to the generation of superoxide, through the action of nitric oxide synthases, xanthine oxidase, leakage from the mitochondrial electron transport chain, and other mechanisms. Nitric oxide and superoxide are themselves highly reactive but can also combine to form a highly toxic anion, peroxynitrite. The toxicity of the free radicals and peroxynitrite results from their modification of macromolecules, especially DNA, and from the resulting induction of apoptotic and necrotic pathways. The mode of cell death that prevails probably

  19. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-08-15

    The subject of this report is progress during the quarter for Phase I -- Design and Permitting, Phase II -- Coolside/LIMB Construction, Start-Up and Phase III -- Operation, Data Collection, Reporting and Disposition. Under Phase I, Task 2, Consol Technology Transfer, Consol R D continued to review the status of the Coolside installation and identified construction details which required additional action. Activities in Task 4.0 -- Permitting and Licensing have focused on finalizing a subcontract agreement for trucking the DOE Coolside/LIMB ash to a solid waste landfill. Under Phase II, Task 1, Project Management, purchase orders were placed with two (2) lime suppliers for supplying the specified hydrated lime to be used for the Coolside test program. For Subtask 2.2 -- Sorbent Feed System Installation, the construction and installation of the sorbent feed system has been completed. Under Phase III, Subtask 2.1, Optimization of the Coolside sorbent feed system, the ash recycle system and the caustic injection system were initiated. 3 figs.

  20. LDTK: Limb Darkening Toolkit

    NASA Astrophysics Data System (ADS)

    Parviainen, H.; Aigrain, S.

    2015-11-01

    We present a PYTHON package LDTK that automates the calculation of custom stellar limb-darkening (LD) profiles and model-specific limb-darkening coefficients using the library of PHOENIX-generated specific intensity spectra by Husser et al. The aim of the package is to facilitate analyses requiring custom generated LD profiles, such as the studies of exoplanet transits - especially transmission spectroscopy, where the transit modelling is carried out for custom narrow passbands - eclipsing binaries, interferometry, and microlensing events. First, LDTK can be used to compute custom LD profiles with uncertainties propagated from the uncertainties in the stellar parameter estimates. Secondly, LDTK can be used to estimate the LD-model-specific coefficients with uncertainties for the most common LD models. Thirdly, LDTK can be directly integrated into the log posterior computation of any pre-existing modelling code with minimal modifications. The last approach can be used to constrain the LD model parameter space directly by the LD profile, allowing for the marginalization over the LD parameter space without the need to approximate the constraint from the LD profile using a prior.

  1. The hind wing of the desert locust (Schistocerca gregaria Forskål). I. Functional morphology and mode of operation.

    PubMed

    Wootton, R J; Evans, K E; Herbert, R; Smith, C W

    2000-10-01

    Detailed morphological investigation, mechanical testing and high-speed cinematography and stroboscopic examination of desert locusts, Schistocerca gregaria, in flight show that their hind wings are adapted to deform cyclically and automatically through the wing stroke and that the deformations are subtly dependent on the wings' structure: their shape, venation and vein design and the local properties of the membrane. The insects predominantly fly fast forwards, generating most force on the downstroke, and the hind wings generate extra lift by peeling apart at the beginning of the downstroke and by developing a cambered section during the stroke's translation phase through the 'umbrella effect' - an automatic consequence of the active extension of the wings' expanded posterior fan. Bending experiments indicate that most of the hind wing is more rigid to forces from below than from above and demonstrate that the membrane acts as a stressed skin to stiffen the structure.

  2. Evaluation of Limb-Girdle Muscular Dystrophy

    ClinicalTrials.gov

    2014-03-06

    Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

  3. Complete mitochondrial genome of the sixblotch hind Cephalopholis sexmaculata (Pisces: Perciformes).

    PubMed

    Hsiao, Sheng-Tai; Chen, Kao-Sung; Tseng, Chen-Te; Wu, Chi-Lun

    2016-01-01

    The complete mitogenome of the sixblotch hind, Cephalopholis sexmaculata was presented in this study. This mitochondrial genome consists of 16,589 bp, with 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a noncoding control region (CR), and its gene arrangement is identical to most vertebrates. The overall base composition of the heavy strand is A, 29.35%; G, 16.08%; C, 28.56%; and T, 26.01%. The COI gene started with GTG codon and the ATP6 gene started with CTG codon. The complete mitogenomic data may provide informative for further phylogenetic approach of species of Cephalopholis and related genera belong to the Epinephelidae groupers.

  4. Determining the size of American alligators using hind-foot track length

    USGS Publications Warehouse

    Wilkinson, Philip M.; Rice, Kenneth G.

    2000-01-01

    Size distribution information is useful for crocodilian management, but can be hard to obtain. Indirect and less costly demographic inferences made from track measurements may be valuable for management decisions. We related hind-foot lengths (HF) with total length (TL) to determine if we could indirectly assess alligator size using track length. Regression showed that HF was an excellent predictor (F1,246= 15722.9, R2=0.98, P<0.01) of TL and track length was an exceptional predictor of HF (F1,14=7520.3, R2= 1.00, P<0.01). The correlation between track length and HF length also was significant (N= 15, r=0.99, P <0.01). Thus, alligator size can be accurately estimated from measures of track length at sites where capture and direct measurement is impractical.

  5. Peripheral muscle dysfunction in COPD: lower limbs versus upper limbs.

    PubMed

    Miranda, Eduardo Foschini; Malaguti, Carla; Corso, Simone Dal

    2011-01-01

    In patients with COPD, the degree of functional impairment appears to differ between the upper and lower limbs. Significant dyspnea and fatigue have been reported by these patients when performing tasks with unsupported upper limbs and two mechanisms have been proposed to explain this fact: neuromechanical dysfunction of respiratory muscles; and changes in lung volume during such activities. The neuromechanical dysfunction seen in COPD patients during this type of exercise is related to changes in the breathing pattern, as well as to the simultaneity of afferent and efferent muscle stimuli, resulting in respiratory muscle asynchrony. In addition, the increased ventilation during upper limb exercise in patients with COPD leads to dynamic hyperinflation at different workloads. During lower limb exercises, the strength and endurance of the quadriceps muscle is lower in COPD patients than in healthy subjects. This could by explained by abnormal muscle metabolism (decreased aerobic capacity), dependence on glycolytic metabolism, and rapid accumulation of lactate during exercise. In comparison with lower limb exercises, upper limb exercises result in higher metabolic and ventilatory demands, as well as in a more intense sensation of dyspnea and greater fatigue. Because there are differences between the upper and lower limb muscles in terms of the morphological and functional adaptations in COPD patients, specific protocols for strength training and endurance should be developed and tested for the corresponding muscle groups.

  6. Functional tests for myocardial ischemia

    SciTech Connect

    Levinson, J.R.; Guiney, T.E.; Boucher, C.A. )

    1991-01-01

    Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.22 references.

  7. Intracellular Signalling in Retinal Ischemia

    DTIC Science & Technology

    1990-07-01

    36) However, vascularization of the RPE is not known to occur in human diseases of photoreceptor degeneration, such as retinitis pigmentosa ...A.C. (1986) Retinitis pigmentosa and retinal neovascularization. Ophthalmology 91, 1599- 1603. Figure la: Control rat retina, 8 weeks of age, central...TITLE (Include Security Classification) Intracellular Signalling in Retinal Ischemia 12. PERSONAL AUTHOR(S) Burns, Margaret Sue; Bellhorn, Roy William

  8. Chronic Gastric Ischemia Leading to Gastric Perforation

    PubMed Central

    Lundsmith, Emma; Zheng, Matthew; McCue, Peter

    2016-01-01

    A 69-year-old man with diabetes, peripheral vascular disease, and hypertension presented with 3 months of diffuse abdominal pain that worsened with meals, weight loss, and dysphagia. Esophagogastroduodenoscopy and computed tomography revealed findings consistent with chronic gastric ischemia secondary to atherosclerosis. Gastric ischemia eventually led to perforation. We discuss causes, symptoms, diagnosis, and management of gastric ischemia, an underdiagnosed and potentially fatal condition that requires urgent diagnosis and treatment. PMID:28119945

  9. Predictive Modeling of Cardiac Ischemia

    NASA Technical Reports Server (NTRS)

    Anderson, Gary T.

    1996-01-01

    The goal of the Contextual Alarms Management System (CALMS) project is to develop sophisticated models to predict the onset of clinical cardiac ischemia before it occurs. The system will continuously monitor cardiac patients and set off an alarm when they appear about to suffer an ischemic episode. The models take as inputs information from patient history and combine it with continuously updated information extracted from blood pressure, oxygen saturation and ECG lines. Expert system, statistical, neural network and rough set methodologies are then used to forecast the onset of clinical ischemia before it transpires, thus allowing early intervention aimed at preventing morbid complications from occurring. The models will differ from previous attempts by including combinations of continuous and discrete inputs. A commercial medical instrumentation and software company has invested funds in the project with a goal of commercialization of the technology. The end product will be a system that analyzes physiologic parameters and produces an alarm when myocardial ischemia is present. If proven feasible, a CALMS-based system will be added to existing heart monitoring hardware.

  10. Severe Hypokalemia Masquerading Myocardial Ischemia

    PubMed Central

    Petrov, Daniel Bogdanov; Sardovski, Svetlozar Ivanov; Milanova, Maria Hristova

    2012-01-01

    An advanced degree of body potassium deficit may produce striking changes in the electrocardiogram (ECG). These changes can result in incidental findings on the 12-lead ECG or precipitate potentially life-threatening dysrhythmias. Although usually readily recognized, at times these abnormalities may be confused with myocardial ischemia. The object was to report a case of severe hypokalemia mimicking myocardial ischemia. A 33-year-old, previously healthy man, presented to the Emergency Department (ED) with a progressive weakness and chest discomfort. The electrocardiogram showed a marked ST-segment depression in leads II, III, aVF, V1-V6. The initial diagnosis was non ST-elevation myocardial infarction. Echocardiography was normal and troponin levels were within normal limits. A more detailed history revealed that the patient had an episode of acute gastroenteritis with diarrhea and vomiting. Serum chemistries were notable for a potassium concentration of 1,8 mmol per liter. With aggressive electrolyte correction, the ECG abnormalities reverted as potassium levels normalized. Hypokalemia induced ST-segment depression may simulate myocardial ischemia. The differential diagnosis might be difficult, especially in the cases when ST changes are accompanied with chest discomfort.

  11. Purkinje fibers after myocardial ischemia-reperfusion.

    PubMed

    García Gómez-Heras, Soledad; Álvarez-Ayuso, Lourdes; Torralba Arranz, Amalia; Fernández-García, Héctor

    2015-07-01

    The purpose of this study was to evaluate the effects of ischemia-reperfusion on Purkinje fibers, comparing them with the adjacent cardiomyocytes. In a model of heterotopic heart transplantation in pigs, the donor heart was subjected to 2 hours of ischemia (n=9), preserved in cold saline, and subjected to 24 hours of ischemia with preservation in Wisconsin solution, alone (n=6), or with an additive consisting of calcium (n=4), Nicorandil (n=6) or Trolox (n=7). After 2 hours of reperfusion, we evaluated the recovery of cardiac electrical activity and took samples of ventricular myocardium for morphological study. The prolonged ischemia significantly affected atrial automaticity and A-V conduction in all the groups subjected to 24 hours of ischemia, as compared to 2 hours. There were no significant differences among the groups that underwent prolonged ischemia. Changes in the electrical activity did not correlate with the morphological changes. In the Purkinje fibers, ischemia-reperfusion produced a marked decrease in the glycogen content in all the groups. In the gap junctions the immunolabeling of connexin-43 decreased significantly, adopting a dispersed distribution, and staining the sarcolemma adjacent to the connective tissue. These changes were less marked in the group preserved exclusively with Wisconsin solution, despite the prolonged ischemia. The addition of other substances did not improve the altered morphology. In all the groups, the injury appeared to be more prominent in the Purkinje fibers than in the neighboring cardiomyocytes, indicating the greater susceptibility of the former to ischemia-reperfusion injury.

  12. Mitochondria: mitochondrial participation in ischemia-reperfusion injury in skeletal muscle.

    PubMed

    Lejay, Anne; Meyer, Alain; Schlagowski, Anna-Isabel; Charles, Anne-Laure; Singh, François; Bouitbir, Jamal; Pottecher, Julien; Chakfé, Nabil; Zoll, Joffrey; Geny, Bernard

    2014-05-01

    Irrespective of the organ involved, restoration of blood flow to ischemic tissue is vital, although reperfusion per se is deleterious. In the setting of vascular surgery, even subtle skeletal muscle ischemia contributes to remote organ injuries and perioperative and long-term morbidities. Reperfusion-induced injury is thought to participate in up to 40% of muscle damage. Recently, the pathophysiology of lower limb ischemia-reperfusion (IR) has been largely improved, acknowledging a key role for mitochondrial dysfunction mainly characterized by impaired mitochondrial oxidative capacity and premature mitochondrial permeability transition pore opening. Increased oxidative stress triggered by an imbalance between reactive oxygen species (ROS) production and clearance, and facilitated by enhanced inflammation, appears to be both followed and instigated by mitochondrial dysfunction. Mitochondria are both actors and target of IR and therapeutic strategies modulating degree of ROS production could enhance protective signals and allow for mitochondrial protection through a mitohormesis mechanism.

  13. Acute brain ischemia as a complication of the Ehlers-Danlos syndrome, the case series.

    PubMed

    Pajak, Michal; Majos, Marcin A; Szubert, Wojciech; Stefanczyk, Ludomir; Majos, Agata

    2014-10-01

    Vascular type of Ehlers-Danlos syndrome involves many severe complications leading not only to organ-specific symptoms but often ends in a sudden death. The aim of this paper was to present a diagnostic possibilities and its efficiency rate in patients with vascular complications of Ehlers-Danlos syndrome who suffered from artery dissection resulting in acute brain or limb ischemia. We analysed three patients with diagnosed Ehlers-Danlos syndrome who were referred to radiology department for diagnostic imaging of affected vascular beds, each experienced brain ischemia. The paper also aims at offering some general recommendations for patients suffering from possible complications of type IV Ehlers-Danlos syndrome basing on our own experience and available literature data.

  14. Simulation of Upper Limb Movements

    NASA Astrophysics Data System (ADS)

    Uherčík, Filip; Hučko, Branislav

    2011-12-01

    The paper deals with controlling an upper limb prosthesis based on the measurement of myoelectric signals (MES) while drinking. MES signals have been measured on healthy limbs to obtain the same response for the prosthesis. To simulate the drinking motion of a healthy upper limb, the program ADAMS was used, with all degrees of freedom and a hand after trans-radial amputation with an existing hand prosthesis. Modification of the simulation has the exact same logic of control, where the muscle does not have to be strenuous all the time, but it is the impulse of the muscle which drives the motor even though the impulse disappears and passed away.

  15. Management of Major Limb Injuries

    PubMed Central

    Langer, Vijay

    2014-01-01

    Management of major limb injuries is a daunting challenge, especially as many of these patients have severe associated injuries. In trying to save life, often the limb is sacrificed. The existing guidelines on managing such trauma are often confusing. There is scope to lay down such protocols along with the need for urgent transfer of such patients to a multispecialty center equipped to salvage life and limb for maximizing outcome. This review article comprehensively deals with the issue of managing such major injuries. PMID:24511296

  16. Prevalence and Characteristics of Phantom Limb Pain and Residual Limb Pain in the Long Term after Upper Limb Amputation

    ERIC Educational Resources Information Center

    Desmond, Deirdre M.; MacLachlan, Malcolm

    2010-01-01

    This study aims to describe the prevalence and characteristics of phantom limb pain and residual limb pain after upper limb amputation. One-hundred and forty-one participants (139 males; mean age 74.8 years; mean time since amputation 50.1 years) completed a self-report questionnaire assessing residual and phantom limb pain experience. Prevalence…

  17. Enriched housing enhances recovery of limb placement ability and reduces aggrecan-containing perineuronal nets in the rat somatosensory cortex after experimental stroke.

    PubMed

    Madinier, Alexandre; Quattromani, Miriana Jlenia; Sjölund, Carin; Ruscher, Karsten; Wieloch, Tadeusz

    2014-01-01

    Stroke causes life long disabilities where few therapeutic options are available. Using electrical and magnetic stimulation of the brain and physical rehabilitation, recovery of brain function can be enhanced even late after stroke. Animal models support this notion, and housing rodents in an enriched environment (EE) several days after experimental stroke stimulates lost brain function by multisensory mechanisms. We studied the dynamics of functional recovery of rats with a lesion to the fore and hind limb motor areas induced by photothrombosis (PT), and with subsequent housing in either standard (STD) or EE. In this model, skilled motor function is not significantly enhanced by enriched housing, while the speed of recovery of sensori-motor function substantially improves over the 9-week study period. In particular, this stroke lesion completely obliterates the fore and hind limb placing ability when visual and whisker guidance is prevented, a deficit that persists for up to 9 weeks of recovery, but that is markedly restored within 2 weeks by enriched housing. Enriched housing after stroke also leads to a significant loss of perineuronal net (PNN) immunoreactivity; detection of aggrecan protein backbone with AB1031 antibody was decreased by 13-22%, and labelling of a glycan moiety of aggrecan with Cat-315 antibody was reduced by 25-30% in the peri-infarct area and in the somatosensory cortex, respectively. The majority of these cells are parvalbumin/GABA inhibitory interneurons that are important in sensori-information processing. We conclude that damage to the fore and hind limb motor areas provides a model of loss of limb placing response without visual guidance, a deficit also seen in more than 50% of stroke patients. This loss is amenable to recovery induced by multiple sensory stimulation and correlates with a decrease in aggrecan-containing PNNs around inhibitory interneurons. Modulating the PNN structure after ischemic damage may provide new therapies

  18. Hemodynamic and metabolic diffuse optical monitoring in a mouse model of hindlimb ischemia.

    PubMed

    Mesquita, Rickson C; Skuli, Nicolas; Kim, Meeri N; Liang, Jiaming; Schenkel, Steve; Majmundar, Amar J; Simon, M Celeste; Yodh, Arjun G

    2010-10-15

    Murine hindlimb ischemia is a useful model for investigation of the mechanisms of peripheral arterial disease and for understanding the role of endothelial cells and generic factors affecting vascular regeneration or angiogenesis. To date, important research with these models has explored tissue reperfusion following ischemia with Laser Doppler methods, methods which provide information about superficial (~mm) vascular regeneration. In this work, we employ diffuse correlation spectroscopy (DCS) and diffuse optical spectroscopy (DOS) in mice after hindlimb ischemia. We hypothesize that vascular re-growth is not uniform in tissue, and therefore, since diffuse optical methods are capable of probing deep tissues, that the diffuse optics approach will provide a more complete picture of the angiogenesis process throughout the whole depth profile of the limb. Besides increased depth penetration, the combined measurements of DCS and DOS enable all-optical, noninvasive, longitudinal monitoring of tissue perfusion and oxygenation that reveals the interplay between these hemodynamic parameters during angiogenesis. Control mice were found to reestablish 90% of perfusion and oxygen consumption during this period, but oxygen saturation in the limb only partially recovered to about 30% of its initial value. The vascular recovery of mice with endothelial cell-specific deletion of HIF-2α was found to be significantly impaired relative to control mice, indicating that HIF-2α is important for endothelial cell functions in angiogenesis. Comparison of DOS/DCS measurements to parallel measurements in the murine models using Laser Doppler Flowmetry reveal differences in the reperfusion achieved by superficial versus deep tissue during neoangiogenesis; findings from histological analysis of blood vessel development were further correlated with these differences. In general, the combination of DCS and DOS enables experimenters to obtain useful information about oxygenation, metabolism

  19. Limb displacement and brightness seismology

    NASA Astrophysics Data System (ADS)

    Emilio, Marcelo; Cunnyngham, Ian; Kuhn, Jeff; Mehret, Leandro; Bush, Rock; Scholl, Isabelle

    2015-08-01

    The Helioseismic and Magnetic Imager (HMI) abord the Solar Dynamics Observatory (SDO) has been used to obtain the most sensitive spectrally resolved observation of individual p-modes at the extreme solar limb. Such oscillation observations of the limb displacement and brightness for some spatial and temporal regimes are even competitive in signal-to-noise to full-disk doppler measurements of the p-mode spectrum. Limb measurements of 5-min p-modes, while having many similarities to full-disk doppler observations, have significantly different sensitivities to the solar rotation and the 5-min mode solar atmospheric structure. These may provide information about the solar structure which is complementary to full-disk measurements. In this work we present results from Individual spherical harmonic p-modes that were detected around solar limb with amplitudes at the micro-arcsecond level.

  20. Differentiation of cartilaginous anlage in entire embryonic mouse limbs cultured in a rotating bioreactor.

    NASA Astrophysics Data System (ADS)

    Duke, P.; Oakley, C.; Montufar-Solis, D.

    The embryonic mammalian limb is sensitive both in vivo and in vitro to changes in gravitational force. Hypergravity of centrifugation and microgravity of space decreased size of elements due to precocious or delayed chondrogenesis respectively. In recapitulating spaceflight experiments, premetatarsals were cultured in suspension in a low stress, low sheer rotating bioreactor, and found to be shorter than those cultured in standard culture dishes, and cartilage development was delayed. This study only measured length of the metatarsals, and did not account for possible changes in width and/or in form of the skeletal elements. Shorter cartilage elements in limbbuds cultured in the bioreactor may be due to the ability of the system to reproduce a more in vivo 3D shape than traditional organ cultures. Tissues subjected to traditional organ cultures become flattened by their own weight, attachment to the filter, and restrictions imposed by nutrient diffusion. The purpose of the current experiment was to determine if entire limb buds could be successfully cultured in the bioreactor, and to compare the effects on 3D shape with that of culturing in a culture dish system. Fore and hind limbs from E11-E13 ICR mouse embryos were placed either in the bioreactor, in Trowell culture, or fixed as controls. Limbbuds were cultured for six days, fixed, and processed either as whole mounts or embedded for histology. Qualitative analysis revealed that the Trowell culture specimens were flattened, while bioreactor culture specimens had a more in vivo-like 3D limb shape. Sections of limbbuds from both types of cultures had excellent cartilage differentiation, with apparently more cell maturation, and hypertrophy in the specimens cultured in the bioreactor. Morphometric quantitation of the cartilaginous elements for comparisons of the two culture systems was complicated due to some limb buds fusing together during culture. This problem was especially noticeable in the younger limbs, and

  1. Pediatric limb differences and amputations.

    PubMed

    Le, Joan T; Scott-Wyard, Phoebe R

    2015-02-01

    Congenital limb differences are uncommon birth defects that may go undetected even with prenatal screening ultrasound scans and often go undetected until birth. For children with congenital limb differences, a diagnostic evaluation should be done to rule out syndromes involving other organ systems or known associations. The most common etiology of acquired amputation is trauma. Postamputation complications include pain and terminal bony overgrowth. A multidisciplinary approach to management with the child and family can lead to a successful, functional, and fulfilling life.

  2. Earth's Dynamo: Fore- and Hind- casting Limits from a Variational Data Assimilation Approach

    NASA Astrophysics Data System (ADS)

    Dimitrova, L. L.; Egbert, G. D.; Kuang, W.; Tangborn, A.

    2010-12-01

    In the last decade, fully 3-D, nonlinear numerical dynamo models have allowed for the study of many geomagnetic field features. As the ultimate goal of geodynamo simulations is to explain the features of the real geomagnetic field, variational data assimilation (DA) techniques, in which observations are combined with the underlying dynamical principles governing the system, are a logical next step. A variational approach to DA allows inputs (e.g., initial and boundary data, and forcing) to be adjusted to simultaneously fit dynamical equations and observational data by minimizing a cost functional. The increased resolution and accuracy of geomagnetic field models and observations in recent years can be used to, on one hand, improve estimates of the geodynamo state in earlier years and, on the other hand, to produce better forecasts. Consequently, of interest is the time scales on which such fore- and hind- predictions are appropriate. Recently, Hullot et al. [2010] used a series of perturbed numerical dynamo simulations to estimate a time limit for predictability (time for forecast errors to grow to 100 nT) of 50-70 years for the geodynamo. We present our ongoing effort to develop modern variational DA methods (based on the representers, potentially allowing for weak constraint DA) for the Modular Scalable Self-consistent Three-dimensional (MoSST) geodynamo simulator. An implementation of variational DA requires developing tangent linear (TL) and adjoint (ADJ) codes for the nonlinear forcing and the three different time stepping schemes. The adjoint of the numerical time-stepping schemes is calculated in terms of adjoints of the discrete spatial operators. Because the linear parts of these operators are explicitly formed matrices, adjoints of these spatial operators are essentially matrix transposes. The non-linear terms, which must be linearized around a background state, require more care. The TL and the adjoint can be furthermore used to characterize (1) the

  3. Revising Australian Pristomerus (Hymenoptera, Ichneumonidae, Cremastinae): species with a tooth on the hind femur.

    PubMed

    Klopfstein, Seraina

    2016-09-15

    The Australian insect fauna is among the least-well studied in the world, and conservative estimates state that 75% of the species still await description. In the more species-rich groups, this percentage might be even larger, which is certainly the case in parasitoid wasps which have received very little attention by taxonomists. The genus Pristomerus of the family Ichneumonidae is distributed worldwide, with most species found in the tropics. Its members attack concealed larvae of small Lepidoptera, and several species are used in biocontrol. Five species have been reported from Australia, all of them endemic, but many more undescribed species are present in various collections.        I here revise Australian Pristomerus, focussing on the species that bear a tooth on the ventral side of the hind femur. Twenty-two species are recorded, 19 of which are described as new: Pristomerus australiensis n. sp., P. bertschmanni n. sp., P. callitrinus n. sp., P. dundeei n. sp., P. flavicephalus n. sp., P. fourecksensis n. sp., P. gracilis n. sp., P. kakaduensis n. sp., P. laetus n. sp., P. luculentus n. sp., P. lunatus n. sp., P. mangiferus n. sp., P. merus n. sp., P. nedkellyi n. sp., P. pellicius n. sp., P. periculosus n. sp., P. stellatus n. sp., P. tenebrosus n. sp., and P. venustus n. sp. A dichotomous key and an online interactive key to the known Australian species with a tooth on the hind femur are provided, including photographs of all the species.        The origin of the considerable number of Australian Pristomerus species remains unclear. They might represent Southern relict elements with affinities to South American taxa, or their ancestors might have immigrated from the Paleotropics in more recent times; this question can only be solved with a dated phylogeny of the genus. However, support for a Palaeotropic origin of at least a good portion of the taxa comes from their current distribution, as the Australian Pristomerus are found to be most

  4. Mice Hemizygous for a Pathogenic Mitofusin-2 Allele Exhibit Hind Limb/Foot Gait Deficits and Phenotypic Perturbations in Nerve and Muscle

    PubMed Central

    Bannerman, Peter; Burns, Travis; Xu, Jie; Miers, Laird; Pleasure, David

    2016-01-01

    Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of hereditary sensory motor neuropathy, is caused by mutations of mitofusin-2 (MFN2). Mitofusin-2 is a GTPase required for fusion of mitochondrial outer membranes, repair of damaged mitochondria, efficient mitochondrial energetics, regulation of mitochondrial-endoplasmic reticulum calcium coupling and axonal transport of mitochondria. We knocked T105M MFN2 preceded by a loxP-flanked STOP sequence into the mouse Rosa26 locus to permit cell type-specific expression of this pathogenic allele. Crossing these mice with nestin-Cre transgenic mice elicited T105M MFN2 expression in neuroectoderm, and resulted in diminished numbers of mitochondria in peripheral nerve axons, an alteration in skeletal muscle fiber type distribution, and a gait abnormality. PMID:27907123

  5. Low-Level Laser Therapy (904 nm) Counteracts Motor Deficit of Mice Hind Limb following Skeletal Muscle Injury Caused by Snakebite-Mimicking Intramuscular Venom Injection

    PubMed Central

    Vieira, Willians Fernando; Kenzo-Kagawa, Bruno; Cogo, José Carlos; da Cruz-Höfling, Maria Alice

    2016-01-01

    Myotoxins present in Bothrops venom disrupt the sarcolemma of muscle fibers leading to the release of sarcoplasmic proteins and loss of muscle homeostasis. Myonecrosis and tissue anoxia induced by vascularization impairment can lead to amputation or motor functional deficit. The objective of this study was to investigate the dynamic behavior of motor function in mice subjected to injection of Bothrops jararacussu venom (Bjssu) and exposed to low-level laser therapy (LLLT). Male Swiss mice received Bjssu injection (830 μg/kg) into the medial portion of the right gastrocnemius muscle. Three hours later the injected region was irradiated with diode semiconductor Gallium Arsenide (GaAs– 904 nm, 4 J/cm²) laser following by irradiation at 24, 48 and 72 hours. Saline injection (0.9% NaCl) was used as control. Gait analysis was performed 24 hours before Bjssu injection and at every period post-Bjssu using CatWalk method. Data from spatiotemporal parameters Stand, Maximum Intensity, Swing, Swing Speed, Stride Length and Step Cycle were considered. The period of 3 hours post venom-induced injury was considered critical for all parameters evaluated in the right hindlimb. Differences (p<0.05) were concentrated in venom and venom + placebo laser groups during the 3 hours post-injury period, in which the values of stand of most animals were null. After this period, the gait characteristics were re-established for all parameters. The venom + laser group kept the values at 3 hours post-Bjssu equal to that at 24 hours before Bjssu injection indicating that the GaAs laser therapy improved spatially and temporally gait parameters at the critical injury period caused by Bjssu. This is the first study to analyze with cutting edge technology the gait functional deficits caused by snake envenoming and gait gains produced by GaAs laser irradiation. In this sense, the study fills a gap on the field of motor function after laser treatment following snake envenoming. PMID:27392016

  6. Experimental measurements of the temperature variation along artery-vein pairs from 200 to 1000 microns diameter in rat hind limb.

    PubMed

    He, Qinghong; Zhu, Liang; Lemons, Daniel E; Weinbaum, Sheldon

    2002-12-01

    Theoretical studies have indicated that a significant fraction of all blood-tissue heat transfer occurs in artery-vein pairs whose arterial diameter varies between 200 and 1000 microns. In this study, we have developed a new in vivo technique in which it is possible to make the first direct measurements of the countercurrent thermal equilibration that occurs along thermally significant vessels of this size. Fine wire thermocouples were attached by superglue to the femoral arteries and veins and their subsequent branches in rats and the axial temperature variation in each vessel was measured under different physiological conditions. Unlike the blood vessels < 200 microns in diameter, where the blood rapidly equilibrates with the surrounding tissue, we found that the thermal equilibration length of blood vessels between 200 microns and 1000 microns in diameter is longer than or at least equivalent to the vessel length. It is shown that the axial arterial temperature decays from 44% to 76% of the total core-skin temperature difference along blood vessels of this size, and this decay depends strongly on the local blood perfusion rate and the vascular geometry. Our experimental measurements also showed that the SAV venous blood recaptured up to 41% of the total heat released from its countercurrent artery under normal conditions. The contribution of countercurrent heat exchange is significantly reduced in these larger thermally significant vessels for hyperemic conditions as predicted by previous theoretical analyses. Results from this study, when combined with previous analyses of vessel pairs less than 200 microns diameter, enable one estimate the arterial supply temperature and the correction coefficient in the modified perfusion source term developed by the authors.

  7. Low-Level Laser Therapy (904 nm) Counteracts Motor Deficit of Mice Hind Limb following Skeletal Muscle Injury Caused by Snakebite-Mimicking Intramuscular Venom Injection.

    PubMed

    Vieira, Willians Fernando; Kenzo-Kagawa, Bruno; Cogo, José Carlos; Baranauskas, Vitor; Cruz-Höfling, Maria Alice da

    2016-01-01

    Myotoxins present in Bothrops venom disrupt the sarcolemma of muscle fibers leading to the release of sarcoplasmic proteins and loss of muscle homeostasis. Myonecrosis and tissue anoxia induced by vascularization impairment can lead to amputation or motor functional deficit. The objective of this study was to investigate the dynamic behavior of motor function in mice subjected to injection of Bothrops jararacussu venom (Bjssu) and exposed to low-level laser therapy (LLLT). Male Swiss mice received Bjssu injection (830 μg/kg) into the medial portion of the right gastrocnemius muscle. Three hours later the injected region was irradiated with diode semiconductor Gallium Arsenide (GaAs- 904 nm, 4 J/cm²) laser following by irradiation at 24, 48 and 72 hours. Saline injection (0.9% NaCl) was used as control. Gait analysis was performed 24 hours before Bjssu injection and at every period post-Bjssu using CatWalk method. Data from spatiotemporal parameters Stand, Maximum Intensity, Swing, Swing Speed, Stride Length and Step Cycle were considered. The period of 3 hours post venom-induced injury was considered critical for all parameters evaluated in the right hindlimb. Differences (p<0.05) were concentrated in venom and venom + placebo laser groups during the 3 hours post-injury period, in which the values of stand of most animals were null. After this period, the gait characteristics were re-established for all parameters. The venom + laser group kept the values at 3 hours post-Bjssu equal to that at 24 hours before Bjssu injection indicating that the GaAs laser therapy improved spatially and temporally gait parameters at the critical injury period caused by Bjssu. This is the first study to analyze with cutting edge technology the gait functional deficits caused by snake envenoming and gait gains produced by GaAs laser irradiation. In this sense, the study fills a gap on the field of motor function after laser treatment following snake envenoming.

  8. [Ischemia-reperfusion injury after lung transplantation].

    PubMed

    Gennai, Stéphane; Pison, Christophe; Briot, Raphaël

    2014-09-01

    Lung ischemia-reperfusion is characterized by diffuse alveolar damage arising from the first hours after transplantation. The first etiology of the primary graft dysfunction in lung is ischemia-reperfusion. It is burdened by an important morbi-mortality. Lung ischemia-reperfusion increases the oxidative stress, inactivates the sodium pump, increases the intracellular calcium, leads to cellular death and the liberation of pro-inflammatory mediators. Researches relative to the reduction of the lung ischemia-reperfusion injuries are numerous but few of them found a place in common clinical practice, because of an insufficient level of proofs. Ex vivolung evaluation is a suitable technique in order to evaluate therapeutics supposed to limit lung ischemia-reperfusion injuries.

  9. A gigantic new dinosaur from Argentina and the evolution of the sauropod hind foot.

    PubMed

    González Riga, Bernardo J; Lamanna, Matthew C; Ortiz David, Leonardo D; Calvo, Jorge O; Coria, Juan P

    2016-01-18

    Titanosauria is an exceptionally diverse, globally-distributed clade of sauropod dinosaurs that includes the largest known land animals. Knowledge of titanosaurian pedal structure is critical to understanding the stance and locomotion of these enormous herbivores and, by extension, gigantic terrestrial vertebrates as a whole. However, completely preserved pedes are extremely rare among Titanosauria, especially as regards the truly giant members of the group. Here we describe Notocolossus gonzalezparejasi gen. et sp. nov. from the Upper Cretaceous of Mendoza Province, Argentina. With a powerfully-constructed humerus 1.76 m in length, Notocolossus is one of the largest known dinosaurs. Furthermore, the complete pes of the new taxon exhibits a strikingly compact, homogeneous metatarsus--seemingly adapted for bearing extraordinary weight--and truncated unguals, morphologies that are otherwise unknown in Sauropoda. The pes underwent a near-progressive reduction in the number of phalanges along the line to derived titanosaurs, eventually resulting in the reduced hind foot of these sauropods.

  10. A gigantic new dinosaur from Argentina and the evolution of the sauropod hind foot

    NASA Astrophysics Data System (ADS)

    González Riga, Bernardo J.; Lamanna, Matthew C.; Ortiz David, Leonardo D.; Calvo, Jorge O.; Coria, Juan P.

    2016-01-01

    Titanosauria is an exceptionally diverse, globally-distributed clade of sauropod dinosaurs that includes the largest known land animals. Knowledge of titanosaurian pedal structure is critical to understanding the stance and locomotion of these enormous herbivores and, by extension, gigantic terrestrial vertebrates as a whole. However, completely preserved pedes are extremely rare among Titanosauria, especially as regards the truly giant members of the group. Here we describe Notocolossus gonzalezparejasi gen. et sp. nov. from the Upper Cretaceous of Mendoza Province, Argentina. With a powerfully-constructed humerus 1.76 m in length, Notocolossus is one of the largest known dinosaurs. Furthermore, the complete pes of the new taxon exhibits a strikingly compact, homogeneous metatarsus—seemingly adapted for bearing extraordinary weight—and truncated unguals, morphologies that are otherwise unknown in Sauropoda. The pes underwent a near-progressive reduction in the number of phalanges along the line to derived titanosaurs, eventually resulting in the reduced hind foot of these sauropods.

  11. HindIII polymorphism in the human c-sis proto-oncogene

    SciTech Connect

    Fourney, R.M.; Dietrich, K.D.; Aubin, R.A.; Paterson, M.C. )

    1988-08-25

    The 2.0 kb BamH1 restriction fragment corresponding to a cDNA insert encoding the human c-sis PDGF A chain and nucleotide sequences homologous to the v-sis gene was isolated from plasmid pSM-1. An identical polymorphism was noted using the 1.2 kb PstI fragment or the 1.0 kb PstI/XbaI fragment isolated from the v-sis sequence subcloned in the plasmid pV-sis. HindIII identifies a single bi-allelic polymorphism with bands at 22.6 kb and 19.4 kb. Co-dominant segregation was demonstrated in 1 family. This polymorphism is not easily detected unless the restricted DNA is separated on 0.6-0.8% agarose gels. Resolution was optimal if gels were run until the bromophenol blue tracking dye had migrated 14 cm from the origin and Southern blotting was performed under alkaline conditions.

  12. A gigantic new dinosaur from Argentina and the evolution of the sauropod hind foot

    PubMed Central

    González Riga, Bernardo J.; Lamanna, Matthew C.; Ortiz David, Leonardo D.; Calvo, Jorge O.; Coria, Juan P.

    2016-01-01

    Titanosauria is an exceptionally diverse, globally-distributed clade of sauropod dinosaurs that includes the largest known land animals. Knowledge of titanosaurian pedal structure is critical to understanding the stance and locomotion of these enormous herbivores and, by extension, gigantic terrestrial vertebrates as a whole. However, completely preserved pedes are extremely rare among Titanosauria, especially as regards the truly giant members of the group. Here we describe Notocolossus gonzalezparejasi gen. et sp. nov. from the Upper Cretaceous of Mendoza Province, Argentina. With a powerfully-constructed humerus 1.76 m in length, Notocolossus is one of the largest known dinosaurs. Furthermore, the complete pes of the new taxon exhibits a strikingly compact, homogeneous metatarsus—seemingly adapted for bearing extraordinary weight—and truncated unguals, morphologies that are otherwise unknown in Sauropoda. The pes underwent a near-progressive reduction in the number of phalanges along the line to derived titanosaurs, eventually resulting in the reduced hind foot of these sauropods. PMID:26777391

  13. Protein synthesis rates in atrophied gastrocnemius muscles after limb immobilization

    NASA Technical Reports Server (NTRS)

    Tucker, K. R.; Seider, M. J.; Booth, F. W.

    1981-01-01

    Noting that protein synthesis declines in the gastrocnemius 6 hr after immobilization, the study sought to detect an increase of protein synthesis when the limb was freed, and to examine the effects of exercise on the rate of increase. Rats were used as subjects, with their hind legs in plaster of Paris in plantar flexion to eliminate strain on the gastrocnemius. Periods of immobilization were varied and samples of blood from the muscle were taken to track protein synthesis rates for different groups in immobilization and exercise regimens (running and weightlifting). Synthesis rates declined 3.6% during time in the cast, then increased 6.3%/day after the casts were removed. Both running and weightlifting were found to increase the fractional rate of protein formation in the gastrocnemius muscle when compared with contralateral muscles that were not exercised and were used as controls, suggesting that the mechanism controlling protein synthesis in skeletal muscles is rapidly responsive to changes in muscular contractile activity.

  14. Influence of level of nutrition during late pregnancy on reproductive productivity of red deer (2) Adult hinds gestating wapitixred deer crossbred calves.

    PubMed

    Asher, G W; Scott, I C; O'Neill, K T; Littlejohn, R P

    2005-04-01

    The present study aimed to relate feed intake of red deer hinds in the later stages of gestating wapitixred deer crossbred foetuses on dam body condition, gestation length, birth weight and calf growth. Multiparous hinds (N=18) conceiving at known dates to either wapiti (n=12) or red deer (n=6) sires were housed in individual pens from days 150-220 of pregnancy, during which time they were offered either ad libitum access to pelletised rations (n=6 crossbred-bearing hinds [HH] and n=6 red deer-bearing hinds [RH]) or a restricted offer (n=6 crossbred-bearing hinds [HL]) set at 70% of the average ad libitum intake of HH hind in the previous week. Hinds were returned to pasture at day 220 and calving was closely monitored. Liveweights, body condition score (BCS), and lactation score (LS) of hinds were recorded weekly from day 130 of pregnancy until calves were weaned at 12 weeks of age. Calves were tagged and weighed at birth, and subsequently weighed at 7 and 12 weeks of age. HH and RH hinds exhibited similar patterns and levels of MEI/kg0.75, which peaked at 7.8 MJME/kg0.75 at day 220. HL hinds peaked at approximately 5 MJME/kg0.75 and showed significantly lower rates of liveweight gain during pregnancy. Interestingly, both crossbred-bearing groups initiated mammary development in advance of the RH hinds. While there were significant effects of foetal genotype on mean gestation length (239 days versus 234 days for crossbred versus red deer) and mean birth weight (14.5 kg versus 10 kg), the nutritional contrast for gestation length of crossbred-bearing hinds (i.e. HH versus HL) was not significant but approached significance for birth weight (14.5 kg versus 11.9 kg; P=0.06). Regression analysis revealed weak relationships between changes in hind liveweight and gestation length (P>0.05) but a significant relationship with birth weight (P<0.05). However, change in hind BCS was significantly related to both gestation length and birth weight. Crossbred calves reared by

  15. Pre- and postischemic transcutaneous oxygen tension measurements and the determination of amputation level in ischemic limbs.

    PubMed

    Slagsvold, C E; Kvernebo, K; Slungaard, U; Kroese, A J

    1989-10-01

    The value of transcutaneous pO2 (TCpO2) measurements in determining amputation levels was studied in patients with atherosclerotic lower limb ischemia. A postischemic TCpO2 response did not predict healing of the amputation stump better than measurements at rest. No minimal resting or postischemic TCpO2 was found below which healing could not occur. However high TCpO2 values probably are indicative of a good healing potential. In patients with poor skin viabil