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Hind limb ischemia

Puneet Kaur Randhawa, Amteshwar Singh Jaggi
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...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Alice Brandli, Daniel M Johnstone, Jonathan Stone
Purpose: To test whether remote ischemic preconditioning (RIP) is protective to photoreceptors, in a light damage model, and to identify mechanisms involved. Methods: A pressure cuff was used to induce ischemia (2 × 5 minutes) in one hind limb of 4- to 6-month-old albino Sprague-Dawley rats raised in dim, cyclic light (12 hours 5 lux, 12 hours dark). Immediately following the ischemia, rats were exposed to bright continuous light (1000 lux) for 24 hours. After 7-day survival in dim, cyclic light conditions, retinal function was assessed using the flash electroretinogram (ERG) and retinal structure was examined for photoreceptor survival and death, as well as for stress...
October 1, 2016: Investigative Ophthalmology & Visual Science
Petra Bonova, Miroslava Nemethova, Milina Matiasova, Martin Bona, Miroslav Gottlieb
Ischemic tolerance (IT) has gained attention as an attractive strategy for improving stroke outcome. Recently, it was shown that signal responsible for rapid IT induction (tolerance induction factor- TIF) is transmitted via circulating blood. In the present paper, we have hypothesized about the role of the blood cell compartment in TIF production. We used hind limb ischemia to generate TIF as a rapid preconditioning against transient middle cerebral artery occlusion (MCAO). The essential properties of protein synthesis inhibitors actinomycin D and cycloheximide were utilized to obtain the following results: 1...
October 5, 2016: European Journal of Neuroscience
Can Tepeköylü, Daniela Lobenwein, Anja Urbschat, Michael Graber, Elisabeth Judith Pechriggl, Helga Fritsch, Patrick Paulus, Michael Grimm, Johannes Holfeld
BACKGROUND: Shock wave therapy (SWT) has been shown to induce angiogenesis in ischemic muscle. However, the mechanism of action remains unknown. Macrophages are crucial for angiogenic responses after ischemic injury. The M2 macrophage subset enables tissue repair and induces angiogenesis. We hypothesized that the angiogenic effects of SWT are at least partly caused by enhanced macrophage recruitment. METHODS: C57BL/6 mice were subjected to hind limb ischemia with subsequent SWT or sham treatment...
September 30, 2016: Journal of Tissue Engineering and Regenerative Medicine
Johanna Herajärvi, Tuomas Anttila, Henna Sarja, Caius Mustonen, Henri Haapanen, Tuomas Mäkelä, Fredrik Yannopoulos, Tuomo Starck, Mika Kallio, Hannu Tuominen, Ulla Puistola, Peeter Karihtala, Kai Kiviluoma, Vesa Anttila, Tatu Juvonen
BACKGROUND: Paraplegia is one of the most severe complications occurring after the repair of thoracic and thoracoabdominal aortic aneurysms. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurologic damage, and this study assessed its efficacy in preventing spinal cord ischemia. METHODS: The study randomized 16 female pigs into an RIPC group (n = 8) and a control group (n = 8). The RIPC group underwent four cycles of 5-minute ischemia-reperfusion episodes by intermittent occlusion of the left iliac artery...
September 22, 2016: Annals of Thoracic Surgery
Zhongjian Cheng, Venkata Garikipati, Emily Nickoloff, Chunlin Wang, David J Polhemus, Jibin Zhou, Cynthia Benedict, Mohsin Khan, Suresh K Verma, Joseph E Rabinowitz, David Lefer, Raj Kishore
BACKGROUND: -Bone marrow cell-based treatment for critical limb ischemia (CLI) in diabetic patients yielded a modest therapeutic effect due to cell dysfunction. Therefore, approaches that improve diabetic stem/progenitor cell functions may provide therapeutic benefits. Here, we tested the hypotheses that restoration of hydrogen sulfide (H2S) production in diabetic bone marrow cells (BMCs) improves their reparative capacities. METHODS: -Mouse BMCs were isolated by density-gradient centrifugation...
September 22, 2016: Circulation
Jan P Skóra, Tomasz Płonek, Piotr Barć, Dagmara Baczyńska, Agata Radwańska, Artur Pupka, Krzysztof Korta, Marek Ussowicz, Łukasz Strożecki, Diana Kupczyńska-Markiewicz, Agnieszka Hałoń
BACKGROUND: Chronic limb ischemia is a serious clinical problem. Patients who do not qualify for standard treatment may benefit from novel gene therapies. OBJECTIVES: This study evaluated angiogenesis following intramuscular injections of angiogenic plasmid Ang-1 in Fisher rats. MATERIAL AND METHODS: Twenty rats had plasmids injected intramuscularly in their hind limbs. The study group consisted of 10 animals which received the Ang-1 plasmid, while the control group consisted of 10 rats that received an empty plasmid...
July 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Hassan Albadawi, A Aria Tzika, Christian Rask-Madsen, Lindsey M Crowley, Michael W Koulopoulos, Hyung-Jin Yoo, Michael T Watkins
BACKGROUND: Obesity and type 2 diabetes are major risk factors for peripheral arterial disease in humans, which can result in lower limb demand ischemia and exercise intolerance. Exercise triggers skeletal muscle adaptation including increased vasculogenesis. The goal of this study was to determine whether demand ischemia modulates revascularization, fiber size, and signaling pathways in the ischemic hind limb muscles of mice with diet-induced obesity (DIO). MATERIALS AND METHODS: DIO mice (n = 7) underwent unilateral femoral artery ligation and recovered for 2 wks followed by 4 wks with daily treadmill exercise to induce demand ischemia...
September 2016: Journal of Surgical Research
Philippe Garrigue, Guillaume Hache, Youssef Bennis, Pauline Brige, Jimmy Stalin, Lionel Pellegrini, Lionel Velly, Francesca Orlandi, Elena Castaldi, Françoise Dignat-George, Florence Sabatier, Benjamin Guillet
BACKGROUND: endothelial colony-forming cells (ECFCs) are promising candidates for cell therapy of ischemic diseases, as less than 10% of patients suffering from an ischemic stroke are eligible for thrombolysis. We previously reported that erythropoietin priming of ECFCs increased their in vitro and in vivo angiogenic properties in mice with hind limb ischemia. OBJECTIVE: the present study aimed to evaluate whether priming of ECFCs with erythropoietin could enhance their homing into the ischemic site after transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats and potentiate their protective or regenerative effects on brain-blood barrier disruption (BBBd), cerebral apoptosis and cerebral blood flow (CBF) by Single Photon Emission/Computed Tomography (SPECT/CT) imaging...
September 8, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Fang He, Yixing Ren, Enyi Shi, Kun Liu, Lihui Yan, Xiaojing Jiang
OBJECTIVE: MicroRNA (miRNA) molecules are involved in the response of the central nervous system to ischemia and reperfusion. We sought to test the hypothesis that overexpression of miRNA-21 can induce neuroprotection on spinal cords against transient ischemia. METHODS: Overexpression of miRNA-21 in vivo was conducted by means of intrathecal injection of lentivirus vectors containing pre-miRNA-21. The vehicle or control lentivirus vectors were given to the control group and the control vector group, respectively...
August 12, 2016: Journal of Thoracic and Cardiovascular Surgery
Michael J Zhang, Brian E Sansbury, Jason Hellmann, James F Baker, Luping Guo, Caitlin M Parmer, Joshua C Prenner, Daniel J Conklin, Aruni Bhatnagar, Mark A Creager, Matthew Spite
BACKGROUND: Resolvins are lipid mediators generated by leukocytes during the resolution phase of inflammation. They have been shown to regulate the transition from inflammation to tissue repair; however, it is unknown whether resolvins play a role in tissue revascularization following ischemia. METHODS: We used a murine model of hind limb ischemia (HLI), coupled with laser Doppler perfusion imaging, microcomputed tomography, and targeted mass spectrometry, to assess the role of resolvins in revascularization and inflammation resolution...
August 30, 2016: Circulation
Wesley T Abplanalp, Daniel J Conklin, Joseph M Cantor, Mark H Ginsberg, Marcin Wysoczynski, Aruni Bhatnagar, Timothy E O'Toole
Diabetes is associated with a deficit of circulating endothelial progenitor cells (EPCs) which has been attributed to their defective mobilization from the bone marrow. The basis for this mobilization defect is not completely understood and we sought to determine if hyperglycemic conditions enhanced EPC adhesion. We found that culturing EPCs in high glucose media increased adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1β (PRKAR1β), activation of protein kinase A (PKA), and phosphorylation of α4 integrin on serine 988...
August 5, 2016: Diabetes
Abdelaziz M Hussein, Hussein F Sakr, Faris Q Alenzi
BACKGROUND: It has been documented that remote limb ischemic preconditioning (rIPC) protect kidneys against renal ischemia/reperfusion (I/R). We hypothesized that osteopontin (OPN), transforming growth factor beta (TGF-β), apoptotic proteins (survivin and caspase-3) and oxidative stress play role in the renoprotective effects of rIPC. MATERIALS AND METHODS: Fifty-four male Sprague-Dawley rats were randomized into 3 equal groups: sham group, I/R group (left renal 45 min ischemia) and rIPC group (as I/R group with 3 cycles of left hind limb ischemia just before renal ischemia)...
2016: Nephron
Dominic K T Pang, Zengxuan Nong, Brian G Sutherland, Cynthia G Sawyez, Debra L Robson, Jelena Toma, J Geoffrey Pickering, Nica M Borradaile
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...
June 2016: Pharmacology Research & Perspectives
Sungwoo Kim, Toshiyuki Kawai, Derek Wang, Yunzhi Yang
Here, we report the use of chemically cross-linked and photo-cross-linked hydrogels to engineer human umbilical vein endothelial cell (HUVEC) aggregate-induced microvascular networks to increase blood perfusion in vivo. First, we studied the effect of chemically cross-linked and photo-cross-linked chitosan-lactide hydrogels on stiffness, degradation rates, and HUVEC behaviors. The photo-cross-linked hydrogel was relatively stiff (E = ∼15 kPa) and possessed more compact networks, denser surface texture, and lower enzymatic degradation rates than the relatively soft, chemically cross-linked hydrogel (E = ∼2 kPa)...
August 3, 2016: ACS Applied Materials & Interfaces
Ye Song, Xiaoyun Xie, Yuan Gao, Guojun Gu, Peijun Wang
This study aimed to investigate whether ultrasound-induced microbubble destruction was able to promote targeted delivery of adipose-derived stem cells (ASCs) to improve hind-limb ischemia of diabetic mice. Ischemia was induced in the lower limb of db/db mice which were then randomly divided into 5 groups: PBS group, Sham group, ultrasound + microbubble group (US+MB), US+MB+ASCs group and ASCs group. Contrast-enhanced ultrasound perfusion imaging showed the ratio of blood flow in ischemic hind-limb to that in contralateral limb increased over time in five groups...
2016: American Journal of Translational Research
J W Xiao, L H Li, B Z Hong, J Q Xiao, D M Wei, Z Jin
OBJECTIVE: To investigate the therapeutic effects of erythropoietin sustained-release gelatin hydrogel microspheres (EPO-GHM) on a murine model of hindlimb ischemia and related mechanisms. METHODS: Fifty two ten weeks old male C57BL/6J mice were assigned to 5 groups: sham-operated group (the right femoral artery suture was passed through the right femoral artery but not tied, n=8); saline group (right femoral artery ligation and intramuscular injection of saline at a dose of 4 ml/kg into the right hind limb, n=12); EPO group(right femoral artery ligation and intramuscular injection of EPO at a dose of 5 000 IU/kg into the right hind limb, n=12), empty GHM group (right femoral artery ligation and intramuscular injection of empty GHM at a dose of 4 ml/kg into the right hind limb, n=8); EPO-GHM group(right femoral artery ligation and intramuscular injection of EPO-GHM at a dose of 5 000 IU/kg into the right hind limb, n=12)...
June 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
Laura M Ricles, Pei-Ling Hsieh, Nicholas Dana, Viktoriya Rybalko, Chelsea Kraynak, Roger P Farrar, Laura J Suggs
The intent of the current study was to investigate the therapeutic contribution of MSCs to vascular regeneration and functional recovery of ischemic tissue. We used a rodent hind limb ischemia model and intramuscularly delivered MSCs within a PEGylated fibrin gel matrix. Within this model, we demonstrated that MSC therapy, when delivered in PEGylated fibrin, results in significantly higher mature blood vessel formation, which allows for greater functional recovery of skeletal muscle tissue as assessed using force production measurements...
September 2016: Biomaterials
Jonathan Caron, Pierre-Antoine Michel, Jean-Claude Dussaule, Christos Chatziantoniou, Pierre Ronco, Jean-Jacques Boffa
Low-energy extracorporeal shock wave therapy (SWT) has been shown to improve myocardial dysfunction, hind limb ischemia, erectile function, and to facilitate cell therapy and healing process. These therapeutic effects were mainly due to promoting angiogenesis. Since chronic kidney diseases are characterized by renal fibrosis and capillaries rarefaction, they may benefit from a proangiogenic treatment. The objective of our study was to determine whether SWT could ameliorate renal repair and favor angiogenesis in L-NAME-induced hypertensive nephropathy in rats...
June 2016: Physiological Reports
Yan Yang, Lamei Xiao, Ni Chen, Yongjie Li, Xin Deng, Liqun Wang, Hongmin Sun, Jianbo Wu
OBJECTIVE: Coagulation factor V (FV) is distributed in plasma and platelet pools, which are distinguished by physical and functional differences. FV has been extensively studied for its roles in coagulation. The roles of FV in other physiologic pathways remain understudied. METHODS: Hind limb ischemia was produced in transgenic mice by femoral artery ligation, with different levels of FV gene expression restricted to the plasma or platelets. RESULTS: Hind limb blood flow perfusion in mice with higher platelet FV was significantly increased...
May 27, 2016: Journal of Vascular Surgery
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